Anda di halaman 1dari 206

WHO Library Cataloguing-in-Publication data

Guidelines for the management of snake-bites, 2nd edition.

1. Snake Bites education epidemiology prevention and control therapy.


2. Public Health.
3. Venoms therapy.
4. Guidelines.

ISBN 978-92-9022-530-0 (NLM classification: WD 410)

World Health Organization 2016

2nd Edition
All rights reserved. Requests for publications, or for permission to reproduce or translate WHO
publications, whether for sale or for noncommercial distribution, can be obtained from Publishing
and Sales, World Health Organization, Regional Office for South-East Asia, Indraprastha
Estate, Mahatma Gandhi Marg, New Delhi-110 002, India (fax: +91-11-23370197;
e-mail: publications@ searo.who.int).

The designations employed and the presentation of the material in this publication do not imply
the expression of any opinion whatsoever on the part of the World Health Organization concerning
the legal status of any country, territory, city or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border
lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers products does not imply that they
are endorsed or recommended by the World Health Organization in preference to others of a
similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary
products are distinguished by initial capital letters.

All reasonable precautions have been taken by the World Health Organization to verify the
information contained in this publication. However, the published material is being distributed
without warranty of any kind, either expressed or implied. The responsibility for the interpretation
and use of the material lies with the reader. In no event shall the World Health Organization be
liable for damages arising from its use.

This publication contains the collective views of an international group of experts and does not
necessarily represent the decisions or the stated policy of the World Health Organization.

Printed in India
Contents
i. Foreword 7
ii. Acknowledgement 8
iii. Preface 9

1 Executive summary 11

2 Prevention 17
Essentials 19
2.1 Reducing the risk of snakebites 19
2.2 Implementing preventive strategies for community education 22
2.3 Conclusion 23

3 Venomous snakes of the South-East Asia Region, 25


their venoms and pathophysiology of human envenoming
Essentials 27
3.1 The venom apparatus
3.2 Classification of venomous snakes 29
3.2.1 Medically important species in South-East Asia Region countries 30
3.2.2 Other medically important venomous snakes 63
3.2.3 Non-venomous snakes 64
3.3 Identification of venomous snakes 67
3.4 Snake venoms 67
3.4.1 Venom composition 67
3.4.2 Quantity of venom injected at a bite, dry bites 69
3.4.3 Variations in venom composition within 69
individual species of snakes
3.5 Pathophysiology of human envenoming 69

4 Epidemiology of snakebites in South-East Asia Region countries 73


Essentials 75
4.1 Introduction 77
4.2 Determinants of snakebite incidence and severity of envenoming 78
4.3 Epidemiological characteristics of snakebite victims 79
4.4 Circumstances of snakebites 79
4.5 Snakebite as an occupational disease 79
4.6 Death from snakebite 80
4.6.1 Factors contributing to fatal snakebite 80
4.6.2 Time between snakebite and death 80
4.7 Snakebite in different South-East Asia Region countries 80

CONTENTS 3
5 Clinical aspects of snakebites 89
Essentials 91
5.1 When venom has not been injected 94
5.2 When venom has been injected 94
5.2.1 Early symptoms and signs 94
5.2.2 Clinical patterns of envenoming by snakes in South East Asia 95
5.2.3 Local symptoms and signs in the bitten part 95
5.2.4 Generalized (systemic) symptoms and signs 96
5.3 Clinical syndromes of snakebite in South-East Asia 101
5.4 Long-term complications (sequelae) of snakebite 104
5.5 Symptoms and signs of seasnake envenoming 103
5.6 Symptoms and signs of cobra-spit ophthalmia 104
(eye injuries from spitting cobras)

6 Management of snakebites in South-East Asia 105


Essentials 107
6.1 Stages of management 115
6.2 First-aid treatment 115
6.2.1 Principles of first-aid 115
6.2.2 The danger of respiratory paralysis and shock 115
6.2.3 Recommended first-aid methods 116
6.3 Transport to hospital 117
6.4 Medical treatment in the dispensary or hospital 118
6.4.1 Rapid primary clinical assessment and resuscitation 118
6.4.2 Detailed clinical assessment 119
6.4.2.1 History 119
6.4.2.2 Physical examination 120
6.4.2.3 Neurotoxic envenoming: Bulbar and respiratory paralysis 121
6.4.2.4 Generalized rhabdomyolysis 123
6.4.2.5 Examination of pregnant women 123
6.5 Species diagnosis 123
6.6 Investigations/laboratory tests 123
6.6.1 20 minute whole blood clotting test (20WBCT) 123
6.6.2 Other tests of blood coagulation 126
6.6.3 Other laboratory tests 126
6.6.4 Other investigations 127
6.7 Antivenom treatment 128
6.7.1 What is antivenom? 128
6.7.2 Indications for antivenom treatment 129
6.7.3 Inappropriate use of antivenom 130
6.7.4 How long after the bite can antivenom be expected to be effective? 130
6.7.5 Antivenom reactions 130
6.7.5.1 Prediction of antivenom reactions 132
6.7.5.2 Contraindications to antivenom: 132
Prophylaxis in high risk patients

4 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
6.7.5.3 Prevention of antivenom reactions 132
6.7.5.4 Treatment of antivenom reactions 134
6.7.6 Supply, Selection, storage and shelf-life of antivenom 135
6.7.7 Administration of antivenom 136
6.7.8 Dosage of antivenom 138
6.7.9 Recurrence of systemic envenoming 142
6.7.10 Criteria for repeating the initial dose of antivenom 142
6.8 Conservative treatment when no antivenom is available 143
6.9 Supportive/ancillary treatment 144
6.9.1 Treatment of neurotoxic envenoming 144
6.9.2 Practical guide to airway management and respiratory support 144
6.9.3 Trial of anticholinesterase 152
6.9.4 Treatment of hypotension and shock 154
6.9.5 Treatment of oliguria and acute kidney injury 156
6.9.5.1 Oliguric phase of renal failure 156
6.9.5.2 Bleeding/ blood clotting disturbances in 159
patients with acute kidney injury
6.9.5.3 Prevention of renal damage in patients with myoglobinuria 159
or haemoglobinuria
6.9.5.4 Diuretic phase of renal failure 160
6.9.5.5 Renal recovery phase 160
6.9.5.6 Persisting renal dysfunction 160
6.10 Haemostatic disturbances 160
6.10.1 Dangers of venipuncture in patients with haemostatic abnormalities 160
6.11 Treatment of the bitten part 161
6.11.1 Wound management 161
6.11.2 Bacterial infections 161
6.11.3 Compartment syndromes and fasciotomy 161
6.12 Rehabilitation 163
6.13 Discharge advice and assessment 163
6.14 Management of cobra spit ophthalmia 164
6.15 Management of snakebites at different levels of the health service 165
6.16 Summary of current evidence for treatment of snakebite envenoming 168

7 References and further reading 169

8 Annexes 185
Annex 1 Algorithm 1: Antivenom treatment of snakebite cases 187
Annex 2 Algorithm 2: Differentiating major Asian snake species by clinical syndrome 188
Annex 3 Antivenoms for treating bites by South-East Asian snakes 191
Annex 4 Pressure-immobilization and pressure pad 195
Annex 5 Measurement of central venous pressure 197
Annex 6 Measurement of intracompartmental pressure 198
Annex 7 List of Contributors 199

CONTENTS 5
Foreword
S
nakebites are well known medical emergencies and a
cause of hospital admission in many countries. The true
scale of this problem however is unknown because of
inadequate reporting in almost every part of the world. The
South-East Asia Region is one of the worlds most affected
regions, due to its high population density, widespread
agriculture activities, presence of numerous venomous snakes
and lack of necessary community awareness to address the
problem.

Regardless of the increasing knowledge about the composition


of snake venom and its mode of action, and a sound
understanding of clinical features of envenoming, management of snakebites remains a
challenge in the Region. Appropriate and timely use of anti-snake venom reduces morbidity
and mortality. Although in the last few years production of anti-venom has increased, it is
still well below the current estimated annual requirement of 10 million vials. In addition,
available anti-venoms do not cover all the important venomous snakes of the Region.
Mechanisms need to be developed to ensure timely access and availability of anti-venom
to all needy persons. Public-private partnerships, intercountry support, involvement of
national, regional, and global agencies are vital to effectively meet the challenge.

The WHO Regional Office for South-East Asia had developed and published Guidelines for
the Management of Snakebites as a special issue of the South East Asian Journal of
Tropical Medicine and Public Health in 1999 followed by publication of the guidelines as
independent regional document in 2011. Considering the new technical advances in the
field, the guidelines have been revised with the help of regional and global experts. The
geographical area specifically covered by this publication includes the South-East Asia
Region of WHO. The venomous snake fauna of the South East Asia Region is rich and
diverse. It varies within and between countries. Countries such as Malaysia, Singapore,
Cambodia, Lao Peoples Democratic Republic, Republic of Korea, Philippines, Pakistan
and Afghanistan may share many of the same medically-important species of snakes that
occur in the South-East Asia Region and may find these guidelines useful. This publication
aims to pass on a digest of available knowledge about all clinical aspects of snake-bite to
medically trained personnel.

I am confident that these revised guidelines will help Member States to improve the
management of snakebites in the peripheral health services and thereby reduce the
morbidity and mortality due to snakebites.

Dr Poonam Khetrapal Singh


Regional Director

FOREWORD 7
Acknowledgements
Prof David Warrell, Emeritus Professor of Tropical Medicine, University of Oxford, UK,
wrote the draft of the guidelines. These were finalized through a meeting of experts
held at SEARO, New Delhi, in June 2016 and revised by Dr Warrell. The list of experts
who contributed can be seen at Annex 7. Contributions of all the experts and people
who helped in the production of this document are sincerely acknowledged.

8 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Preface
Geographical coverage
The geographical area specifically covered by this publication includes the South-East
Asia Region of WHO including eleven Member States (Bangladesh, Bhutan, Democratic
Peoples Republic of Korea, Maldives, Myanmar, Nepal, India, Indonesia, Sri Lanka,
Thailand, Timor-Leste ). Countries such as Malaysia, Singapore, Cambodia, Lao Peoples
Democratic Republic, Republic of Korea, Philippines, Pakistan and Afghanistan may share
many of the same medically important species of snakes that occur in the South-East
Asia Region. It is interesting to note that snakes inhabiting the Indonesian islands East of
Wallaces line (West Papua and Maluku Islands) are part of the Australasian elapid fauna,
differing from those West of this line.

Antivenoms are essential drugs


The only specific antidotes to snake venoms are immunoglobulin antivenoms (WHO,
2010), which are recognized as essential drugs. see http://www.who.int/medicines/
publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1.

Target readership
This publication aims to pass on a digest of available knowledge about all clinical aspects
of snakebites to medically trained personnel. The guidelines are intended for medical
doctors, nurses, paramedics, dispensers and community health workers who have the
responsibility of treating victims of snakebites, and also for medical and nursing students
and postgraduates as an educational resource. They aim to provide sufficient practical
information to allow medically trained personnel to assess and treat patients with
snakebites at all the different levels of the health service.

Levels of evidence
Recommendations are based largely on observational studies (O see below), expert
opinion (E) and, in some cases, comparative trials (T), but in only one case on formal
systematic reviews (S).

Symbols for the evidence used as the basis of each recommendation (in order of level
of evidence) are:
S formal systematic reviews, such as Cochrane Reviews of which there is only one in
the field of snakebites. These include more than one randomized controlled trial;
T comparative trials without formal systematic review;
O observational studies (e.g. surveillance or pharmacological data);
E expert opinion/consensus.

PREFACE 9
10 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
EXECUTIVE SUMMARY

VENOMOUS SNAKES OF THE searo REGION,


THEIR VENOMS, AND THE PATHOPHYSIOLOGY...
11
12 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Executive Summary
1
Epidemiology where it occurs commonly, since it is
The venomous snake fauna of the South- largely an occupational disease of food-
East Asia Region is rich and diverse. It producers such as farmers, plantation
varies within and between countries. workers, herdsmen, and fishermen, and
Widely distributed species of major also of wild life park rangers, military
medical importance, such as Russells personnel, snake restaurant workers, snake
vipers, show geographical intra-species handlers and collectors of snake skins. It is
variation in their venom composition. In recommended that snakebite should be
many countries, snakebite is an important formally recognized by the International
medical emergency and cause of hospital Labour Office as an important
admission, demanding urgent attention by occupational disease in the South-East
adequately trained medical staff. It results Asia Region (E).
in the death or chronic disability of tens
of thousands of active younger people, Prevention
especially those involved in farming Detailed consideration of community
and plantation work. The true scale of education on venomous snakes and
mortality and acute and chronic morbidity snakebite is outside the scope of this
from snakebite is only just beginning publication. However, it is clear that this
to be recognized, based on large well- is a most powerful tool and essential
designed community-based studies component in any campaign to address
(Mohapatra et al., 2011; Rahman et al., the public health challenge posed by
2010; Ediriweera et al, 2016). Persisting snakebite. It is strongly recommended
or permanent physical and psychological as the method most likely to succeed in
disability in snakebite survivors may confer reducing the risk of snakebites (E).
social stigma. The full burden of human
suffering remains uncertain because of Health system strengthening,
inadequate reporting in almost every part education and training
of the Region. To remedy this deficiency, it Some ministries of health in the Region
is strongly recommended that snakebite have begun to organise training of
be made a specific notifiable disease in all doctors and other medical workers in
countries in the South-East Asia Region (E). the clinical management of snakebite
patients. However, medical personnel
Snakebite is predominantly a rural problem throughout the Region would benefit from
that has important implications for the more formal instruction on all aspects
nutrition and economy of the countries of this subject. This should include the

EXECUTIVE SUMMARY 13
medical care at the hospital or dispensary.
Recommended first-aid methods
Most of the familiar methods for first-aid
emphasise reassurance, application of
treatment of snakebite, both western and a pressure-pad over the bite wound,
traditional/herbal, have been found immobilization of the bitten limb and
transport of the patient to a place where
to result in more harm (risk) than good they can receive medical care without
(benefit) and should be firmly discouraged. delay (O).

Diagnosis of the species of snake


responsible for the bite is important for
identification of medically important optimal clinical management. This may be
species of snake, clinical diagnosis and achieved through expert identification of
the appropriate use of antivenoms and the dead snake or a (mobile-phone) image
ancillary treatments. It is recommended of it, or by inference from the resulting
that education and training in the clinical syndrome of envenoming.
prevention and management of snakebite It is recommended that syndromic
should be included in the curriculum of approaches and algorithms for diagnosing
medical and nursing schools and should the species responsible for snakebites be
be addressed specifically through the developed in different parts of the
organization of special training courses Region (E).
and other educational events based
on nationally agreed guidelines (E). Treatment: antivenom (species-specific
These measures should be supported by hyperimmune immunoglobulin), a life-
improvements in hospital accommodation saving, WHO-recognized, essential
of snake-bitten patients (ideally in medicine, is the only effective antidote
specialized units staffed by specially for envenoming. However, there are
trained teams), basic laboratory and challenges surrounding its design,
diagnostic facilities, supply, deployment production, distribution, conservation,
and conservation/storage of antivenoms, safety, initial dosage and effectiveness. It
ambulance services and general is recommended that a critical appraisal
community awareness of the problem and of all aspects of antivenom production
its potential solutions. should be carried out in South-East Asia
Region countries. Although antivenom
Management is an essential element of the treatment
First-aid: most of the familiar methods of systemic envenoming, it may be
for first-aid treatment of snakebite, insufficient on its own to save the
both western and traditional/herbal, patients life. Antivenoms are generally
have been found to result in more harm expensive and in short supply. It is
(risk) than good (benefit) and should be recommended that antivenom should
firmly discouraged. However, in many be used in all patients with signs of
communities, traditional therapists and systemic and/or severe local envenoming
their practices are respected and it is in whom the benefits of treatment are
important to initiate a dialogue with judged to exceed the risks of antivenom
these practitioners, perhaps through reactions (E). It should not be used in
anthropologists, to encourage their the absence of evidence of envenoming.
understanding and cooperation in the Skin/conjunctival hypersensitivity testing
timely referral of envenomed patients to does not predict early or late antivenom

14 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
reactions and it is recommended that haemostatic abnormalities have been
these tests should not be carried out (T). corrected, clinical features of an intra-
Prophylactic subcutaneous adrenaline compartmental syndrome are present and
has proved effective in reducing the a consistently raised intra-compartmental
frequency and severity of early antivenom pressure has been confirmed by direct
reactions and its routine use is, therefore, measurement (E). Before discharge from
recommended unless the risk of the medical facility, patients should be
reactions associated with a particular given explanation, reassurance, and
antivenom is low (less than a few %) advice about avoiding future bites, and
(T). It is recommended that whenever the opportunity for follow-up and further
possible antivenom should be given by rehabilitation/counselling in case of
slow intravenous injection or infusion (O). late antivenom reactions and persistent
Adrenaline should always be available in physical or psychological sequelae.
readiness at the bedside in case of an early
anaphylactic antivenom reaction. When no Research: there have been fewer proper
appropriate specific antivenom is available, clinical studies of snakebite than of
judicious conservative treatment can in almost any other tropical disease, despite
many cases save the life of the patient. its causing more deaths and chronic
In the case of neurotoxic envenoming disability in the Region than all the other
with bulbar and respiratory paralysis, so-called Neglected Tropical Diseases
antivenom alone cannot be relied upon combined. It is recommended that
to prevent early death from asphyxiation. governments, academic institutions,
Artificial ventilation is essential in such pharmaceutical, agricultural and other
cases. In the case of acute kidney injury industries and other funding bodies,
associated particularly with envenoming should actively encourage, sponsor
by Russells vipers, hump-nosed pit-vipers and invest in properly designed clinical
and sea snakes, conservative management studies of all aspects of snakebite,
and, in some cases renal replacement especially community-based, nation-wide
therapy (dialysis), is an effective supportive epidemiological studies, correlation of
treatment. It is recommended that clinical syndromes with envenoming by
fasciotomy should never be carried out defined species, and antivenom dose-
in snakebite patients unless or until finding studies (E).

EXECUTIVE SUMMARY 15
16 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Prevention

VENOMOUS SNAKES OF THE searo REGION,


THEIR VENOMS, AND THE PATHOPHYSIOLOGY...
17
18 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Prevention
2
Essentials: 2.1 Reducing the risk of
Snakebites are environmental, snakebites
occupational and climatic hazards, Snakebite is an environmental,
predominantly of rural areas. Bites are occupational and climatic hazard in
usually inflicted on lower legs, ankles rural and urban areas of many South-
and feet of agricultural workers and East Asian countries where most bites
their families. Know your local snakes, are inflicted on the lower legs, ankles
their favourite habitats, and times of and feet of agricultural workers and
day and seasons when they are most their families. Attention to the following
active. Never handle, threaten or attack recommendations for community
snakes. Do not attract snakes to homes education will reduce the risk of bites.
by keeping livestock indoors or leaving Snakes have adapted to a wide range of
food unprotected, encouraging rodents. habitats and prey species. All snakes are
Sleep under a well-tuckedin mosquito predatory carnivores, none is vegetarian
net, ideally on a raised bed. Clear rubbish although some eat birds eggs. Since
and undergrowth from around the house. snakes are preyed upon by other animals,
Always use a light and prod with a stick they tend to be secretive and have
when walking outside at night, visiting the evolved many survival strategies, including
latrine or relieving yourself in the open. camouflage, making them difficult to see.
Solid shoes or boots are recommended By understanding something about snakes
especially during agricultural activities. habits, simple precautions can be adopted
Fishermen should avoid touching sea to reduce the chance of encounters,
snakes caught in their nets. and consequently bites. Know your local
snakes, the sorts of places where they
Community education reduces the risk of prefer to live and hide, the times of year
snakebites. Involve all community workers, and times of day and night, and the kinds
traditional healers and villagers. Distribute of weather when they are most likely to be
leaflets, banners and posters. Reformat active. Many species are mainly nocturnal
these SEARO recommendations for (night hunters) (e.g. kraits) while other
national or local use as guidelines, training species (e.g. Australasian brown snakes)
modules, leaflets, video clips or posters, are mainly diurnal (daylight hunters).
displayed in hospital and clinic waiting Be particularly vigilant about the risk of
areas and disseminate them via radio, TV snakebites after rains, during flooding,
and social networks. at harvest time and at night and when

PREVENTION 19
walking to and from the fields before (e.g. in the Sundarbans). Ideally, avoid
dawn and after dusk. Snakes prefer not to sleeping unprotected on the ground, but
confront large animals such as humans, if you do choose, or are forced, to sleep
and so avoid cornering them and give on the ground, or are able to sleep on a
them every opportunity to escape. raised bed, use an insecticide-impregnated
mosquito net that is well tucked-in under
Inside the house, where snakes may the mattress or sleeping mat. This will
enter in search of food or to find hiding protect against mosquitoes and other
places, do not keep livestock, especially biting insects, centipedes, scorpions, and
chickens, as they are potential prey snakes (Chappuis et al., 2007). (Fig 001)
for larger snakes and they may attract No chemical has yet been discovered that
rodents upon which many species of is effectively repellent to snakes without
snakes will prey. Store food in rodent- being so toxic as to threaten the life of
proof containers. Regularly check houses children and domestic animals.
for snakes and, if possible, avoid types
of house construction that will provide In the farm yard, compound, or
snakes with hiding places (e.g. thatched garden: Try not to provide hiding places
roofs with open eaves, mud and straw for snakes. Clear away termite mounds,
walls with large cracks and cavities, large heaps of rubbish, building materials etc.
unsealed spaces beneath floorboards). In from near the house. Do not have tree
South Asia, almost all krait (Bungarus) branches touching the house. Keep grass
bites are inflicted on people sleeping short or clear the ground around your
in their homes, usually on the floor but house and clear underneath low bushes
sometimes even in beds and under pillows so that snakes cannot hide close to the

Prevention is the mother


of cure
Himmatroo Salube Bawaskar,
Parag Himmatroo Bawaskar,
Pramodini Himmatroo Bawaskar,
bawasker Hospital and Clinical
Research Center, Mahed Raigad,
Maharashtra 402301, India
(HSB, PrHB); and Topiwala
National Medical College and
BYL NAIR Hospital, Mumbai,
India (PaHB)
Many people in India live in
villages where mosquitoes,
scorpions, and snakes flourish.
To help preven malaria, dengue
fever, chikungunya, Japanese
encephalities, and lympatic
filarias is caused by mosquitoes,
as well as life-threatening
envenoming from krait bite
poisoning and scorpion stings,
we prepared a poster to
promote the health advantage
of sleeping in bed or cot and
using mosquito nets. Our poster
uses local vernacular language
communicate this message and
was distributed and displayed
at primary health centres, rural
hospitals, panchayat offices,
and temples in the villages in
our area.

Figure 001: Protection from sleeping under a mosquito net (H Bawaskar)

20 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
house. Keep your granary away from the
house (it may attract rodents that snakes
Lamps placed at strategic locations such as
will hunt). Water sources, reservoirs, ponds
and puddles may also attract prey animals at the entrance to the house, in passages
such as frogs and toads. Listen to wild and between houses, in front of the latrine
domestic animals, especially birds, as they
mob snakes and warn of a snake nearby. outside the house or within the courtyard
Use a light when you walk outside the are valuable, provided that they are
house, visit the latrine at night, or relieve
positioned so as to avoid casting shadows
yourself in the open.
over corners and niches where snakes may
In the countryside: firewood collection
be concealed.
at night is a high risk activity. Watch
where you walk. The value of wearing
protective clothing is widely accepted,
but there are many practical difficulties, the entrance to the house, in passages
including cost, habit, inconvenience and between houses, in front of the latrine
discomfort in a tropical climate as well outside the house or within the courtyard
as cultural and superstitious objections are valuable, provided that they are
making this seem impracticable. However, positioned so as to avoid casting shadows
in Myanmar, a specially developed light- over corners and niches where snakes may
weight boots proved acceptable to be concealed. Be careful when handling
farmers for use during the high risk rice dead or apparently dead snakes even
harvesting season, although these would an accidental scratch from the fang of a
be impracticable during rice planting when snakes severed head may inject venom.
the fields are inundated (Tun Pe et al., Snake restaurants pose a threat of bites
2002). Rather than walking bare-footed to staff and customers. Many snakebites
or wearing sandals, use proper shoes or occur during ploughing, planting and
boots and long trousers, especially when harvesting and in the rainy season. Rain
walking in the dark or in undergrowth. may wash snakes and debris into gutters
This advice may not be immediately at the edges of roads, and flush burrowing
acceptable in some communities because species out of their burrows, so be careful
of cost, cultural attitudes, comfort and when walking on roads after heavy rain
convenience. However, use of protective especially after dark.
clothing (boots and gloves) should be
promoted as the most obvious means of On the road: Drivers or cyclists should
reducing occupational risk of snakebite. never intentionally run over snakes on
Step on to rocks or logs rather than the road. The snake may not be instantly
straight over them snakes may be killed and may lie injured and pose a risk
sunning themselves on the sides. Do to pedestrians. The snake may also be
not put hands into holes or nests or any injured and trapped under the vehicle,
hidden places where snakes might be from where it will crawl out once the
resting. Young boys often do this while vehicle has stopped or has been parked in
hunting for rodents. Use a light (torch, the house compound or garage.
flashlight or lamp) when walking at night
especially after heavy rains and prod the In rivers, estuaries and the sea: To
ground ahead of you with a stick. Lamps prevent sea snakebites, fishermen should
placed at strategic locations such as at avoid touching sea snakes caught in nets

PREVENTION 21
and on lines. The head and tail are not 2.2 Implementing preventive
easily distinguishable. Sea snakes are air- strategies for community
breathing and are therefore drowned if education
caught in drift or trawl nets, but, unlike Community education has been proved
fish, may survive if laid on the beach. to be an effective strategy for preventing
There is a risk of bites to bathers and snakebites. In the Terai region of Nepal,
those washing clothes in the muddy a group of villages was targeted for
waters of estuaries, river mouths and snakebite awareness sessions, involving
some coastlines. political leaders, female health volunteers,
community health workers, social workers,
General: Avoid snakes as far as possible, traditional healers and other villagers.
including those displayed by snake Many leaflets, banners and posters
charmers, who are frequently bitten. were distributed. As a result, snakebite
Displays by performers such as Austin incidence decreased from 502 bites to
Stevens and the late Steve Irwin on TV 315 bites/100 000 population in targeted
and social media have encouraged people villages (relative risk reduction 0.373
to risk pursuing, attacking and handling (95% CI = 0.2450.48) but it remained
wild snakes. This should be actively constant in the control untargeted
discouraged. Never handle, threaten or villages (Sharma et al., 2013). A similar
attack a snake and never intentionally scheme in West Bengal, India involved
trap or corner a snake in an enclosed the training of 800 health workers (Vishal
space. In many parts of the Region there Santra, Simultala Conservationists). Such
are dedicated snake catchers who will programmes should be repeated every
remove snakes found in houses and year, using well-designed posters with
gardens. For example, in New Delhi, colour photographs of the medically
if you find a snake hissing inside your significant snakes of the Region combined
house, just dont panic or cause it any with clear recommendations for
harm. All you need to do is dial a helpline preventing snakebite. In Indonesia, since
(9871963535) and dedicated snake 2013, medical staff have collaborated
trappers will be at your doorstep to help regularly with herpetologists in learning
you Wildlife SOS (WSOS). Keep young about snake identification and snakebite
children away from areas known to be management, while in West Papua, church
snake-infested. In occupations that carry a and other religious organizations have an
high risk of snakebite, such as rice farming important role in education campaigns
and fish farming, employers might be on snakebite. Designers of Information,
held responsible for providing protective Education and Communication (IEC)
clothing (boots). In Myanmar, farmers activities for preventing snakebites,
can take out special low-cost insurance to should bear in mind local infrastructure,
cover them specifically against snakebite, demography and topography. An example
and Indias National Health Assurance is given in Figure 01 from Duncan
Mission envisages free treatment for Hospital, Raxaul, Bihar, India (Longkumer
snakebite. et al., 2016).

22 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Recommendations for health care workers
Recommendation for health care workers Rationale
1 Use the months of April and May to 80% of bites occur during the months of June-
Procure the necessary stocks of ASV September so preparedness and prevention need
Train health care workers in snakebite particular attention in the time leading up to this
prevention and first aid epidemic season.
2 Envenomation should not be excluded by 3.8% of people without fang marks were envenomed.
the absence of fang marks. Krait bites, in particular, can be hard to visualise, even
a short time after the bite.
3 Consider snakebite in the differential Patients can present with symptoms of envenomation,
diagnosis of unexplained altered without any history of being bitten by a snake.
sensorium, alteration to speech and
swallowing, and abdominal pain, especially
during the rainy season.
4 Bites by an unknown predator need to be 14% of people, who were unable to identify what
taken seriously and observed for signs of predator bit them were envenomed.
envenomation.
5 Dont rely on the ability of patients or Identification of snake species is poor, although it is
relatives to identify snakes. better for cobras.
6 Antivenom should only be given to patients Envenomation of patients only occurred in 63.6% of
showing symptoms of envenomation the cases where cobras were brought. To give anti
venom without symptoms of envenomation exposes
people to the risk of adverse reactions and is costly,
especially in a setting where demand exceeds supplies.
7 Consider the production of a bivalent ASV Saw scaled and Russell's vipers are not present in this
for regions of north India and Nepal. region and a bivalent anti venom is likely to cause less
adverse reactions.

Recommendations for Community Education


Recommendation for Community Education Rationale
1 A large part of the public health education The 10-19 year old age group is the peak age interval
needs to be directed to children and young for bites. Numbers of males and females bitten are
people to both genders. almost equal.
2 Encourage the use of footwear and long 67% of bites occur on the feet and legs.
pants/trousers.
3 The use of a stick to sacare away snakes, This would decrease the number of bites where
prior to working in an area wth ones hands are put into snake micro habitats without prior
hands. visualisation of the area.
4 Improved lighting using: 40% of bites occur between 1700-2200 hours. 59.2%
Torches when walking outside of bites occur in and around the house. Lighting will
Lighting in and around houses. enable better visualisation of snakes.
5 Provision of toilets and education regarding 8% of bites occurred when people were going to the
their use. fields for the purpose of open defecation.
6 Encourage people to sleep on a bed and 10% of people were bitten while they were sleeping.
under a well tucked-in mosquito net. Sleeping on the ground, inceases your risk of
envenomation, sixfold. Sleeping under a mosquito
net, decreases your risk of envenomation, six fold.
7 Provision of buffer zones between fields 59.2% of bites occur in and around the house. Snakes
and housing areas. are attracted to the rodents who come for grain being
grown. Keeping these distances separate may help in
decreasing the encroachment of snakes in housing
areas.
8 Make sleeping areas separate from food The presence of rodents in food related areas is prone
storage, preparation and sonsumption to attract snakes. If people sleep in places away from
areas. areas of the house connected with food, theis may
decrease the risk of people connecting with snakes.

Figure 01: Community Education: recommendations for health-care workers and community education from
Duncan Hospital, Raxaul, Bihar, India (see Longkumer et al., 2016)

PREVENTION 23
Religious organizations and charities
such as Rotary and Lions Clubs might
Raising community awareness about
be persuaded to promote snakebite
prevention of snakebites is the most awareness. It is especially valuable to win
effective strategy for reducing snakebite the support of high profile media figures
such as sporting heroes, film stars,
morbidity and mortality. pop stars and politicians. Education
departments should incorporate
appropriate first-aid for snakebite in
school textbooks.
The above recommendations for
preventing snakebite could be reformatted 2.3 Conclusion
for national or local use as guidelines, Raising community awareness about
training modules, leaflets, video clips and prevention of snakebites is the most
posters (Fig 001) that can be displayed effective strategy for reducing snakebite
on the walls of hospital and clinic waiting morbidity and mortality. The current
areas for the attention of patients and burden of snakebite morbidity can also
their families. At the village level, role- be mitigated by providing region-specific
playing, drama and puppets have been guidelines and training protocols for
used successfully to portray snakebite effective case management. Support
scenarios. Media such as radio and TV materials for health-care providers at
can be used for health promotion and all levels of the health service could
advantage can be taken of FM radio help to disseminate appropriate
phone-ins to publicise the problem. scientific knowledge about snakebite
Increasingly, young people and advertisers management. Ensuring an efficient
use social networking (YouTube, Twitter) supply-chain for antivenom and other
to communicate information and mobile supplies can reduce preventable deaths
phone messaging might also be employed. from snakebite.

24 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Venomous snakes of the
South-East Asia Region,
their venoms and the
pathophysiology of human
envenoming
Venomous snakes of the South-East
3
Asia Region, their venoms and the
pathophysiology of human envenoming
Essentials: most important species medically are
The venom apparatus: venom glands cobras (Naja), kraits (Bungarus), death
of Elapidae and Viperidae are situated adders, taipan, black and brown snakes
behind the eye, surrounded by (Acanthophis, Oxyuranus, Pseudechis,
compressor muscles. The venom duct Pseudonaja) and sea-snakes.
opens at the base of the fang, conducting
venom to its tip through a groove or Viperidae (vipers) are divided into
canal. In Viperidae, but not Elapidae or typical vipers (Viperinae) and pit-vipers
Colubridae, fangs are mounted on a (Crotalinae) that have a heat-sensitive
rotatable maxilla, making them erectile. loreal pit organ situated between nostril
In Colubridae, venom secreted by and eye. Vipers are relatively short,
Duvernoys (supralabial) glands tracks thick-bodied, short-tailed snakes with
down grooves in posterior maxillary fangs. many small rough scales on the top of
Spitting cobras squeeze venom forward the head and characteristic patterns of
from tips of their fangs in a fine spray coloured markings on their backs. The
directed towards the eyes of an aggressor. most important species are: Russells
vipers (Daboia), saw-scaled vipers (Echis),
Classification/taxonomy: there are Malayan pit viper (Calloselasma), mamushis
three families of venomous snakes in (Gloydius), hump-nosed pit- vipers
South East Asia, Elapidae, Viperidae and (Hypnale), Chinese habu (Protobothrops
Colubridae. mucrosquamatus), and green pit vipers
(Trimeresurus).
Elapidae are relatively long, thin, usually
uniformly-coloured snakes with large Among Colubridae, red-necked
smooth symmetrical scales on the top keelback (Rhabdophis subminiatus) and
of the head. Cobras, raise the front yamakagashi (R. tigrinus) are dangerous.
part of their body off the ground and More than a dozen other species can
spread a hood. Venomous sea-snakes cause mild local envenoming (e.g. cat
have flattened paddle-like tails. The snakes - Boiga).

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
27
haemorrhage, plasma leakage (oedema-
Composition and antigenicity of snake formation) and autopharmacological
release of histamine and other autacoids.
venoms varies greatly between and within
species, as snakes mature, seasonally, Polypeptide postsynaptic () neurotoxins
bind to acetylcholine receptors at
between sexes, and throughout the the motor endplate. Presynaptic ()
geographical range. neurotoxins are phospholipases that
damage nerve endings irreparably.

Many bites are inflicted by non-venomous Composition and antigenicity of snake


or minimally-venomous species of medical venoms varies greatly between and within
importance because they may be mistaken species, as snakes mature, seasonally,
for venomous species, resulting in between sexes, and throughout the
unnecessary, expensive, risky and wasteful geographical range. Thus, envenoming
antivenom treatment. Large pythons by a particular species in one part of its
(Boidae), occasionally attack and even geographical range may not be responsive
swallow humans. to an antivenom raised against venom
from this same species in another area.
Identification: posters and picture cards,
with vernacular names are useful. Expert Dry bites: about 50% of venomous
identification of the snake responsible, or snakebites do not result in envenoming.
of a photo image, is recommended.
Pathophysiology of human envenoming
Snake venoms 90% of dry weight Swelling and bruising result from venom-
comprises >100 different proteins: induced increased vascular permeability
enzymes, non-enzymatic polypeptide and ischaemia caused by thrombosis, tight
toxins, and non-toxic proteins. tourniquets applied as first-aid, or swollen
Enzymes are digestive hydrolases, muscle within tight fascial compartments.
hyaluronidase (spreading factor), yellow Hypotension and shock often results
L-amino acid oxidases, phospholipases from hypovolaemia caused by leakage of
A2, and peptidases. Snake venom plasma or blood into the bitten limb and
metalloproteases (SVMPs) damage elsewhere, vasodilatation and myocardial
basement membranes, causing endothelial damage. Oligopeptides (ACE inhibitors
cell damage and spontaneous systemic and BPPs) and vasodilating autacoids cause
bleeding. Procoagulant enzymes are early transient hypotension. Procoagulant
thrombin-like, splitting fibrinogen, or enzymes cause defibrinogenation, DIC
activators of factors V, X, prothrombin and consumption coagulopathy. Venom
and other clotting factors, causing phospholipases are anticoagulant.
DIC, consumption coagulopathy and Platelet activation/inhibition and
incoagulable blood. Phospholipases sequestration causes thrombocytopenia.
A2 damage mitochondria, red blood Spontaneous systemic bleeding is
cells, leucocytes, platelets, peripheral attributable to Zn metalloproteases
nerve endings, skeletal muscle, vascular haemorrhagins. Complement activation
endothelium, and other membranes, affects platelets, blood coagulation
producing presynaptic neurotoxic activity, and other humoral mediator. With
cardiotoxicity, myotoxicity, necrosis, elapid and some colubroid venoms
hypotension, haemolysis, anti-coagulation, the alternative pathway is triggered by

28 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
cobra venom factor, while viperid The ability to inject venom into prey
venoms activate the classical pathway. animals by means of cannulated, modified
Neurotoxic polypeptides and PLA2s teeth evolved over 140 million years ago
cause paralysis by blocking transmission in bird-like dinosaurs and later in snakes
at neuromuscular junctions, but do not (Gong et al., 2010). The venom glands
cross the blood-brain-barrier; there of Elapidae and Viperidae are situated
are no direct CNS effects. Descending behind the eye, surrounded by compressor
paralysis affects bulbar and respiratory muscles (Fig 1). The venom duct opens
muscle causing fatal upper airway within the sheath at the base of the
obstruction, aspiration, or respiratory fang and venom is conducted to its tip
paralysis. Anticholinesterase drugs (e.g. through a groove or canal, as through
neostigmine) prolong activity of ACh a hypodermic needle. In Elapidae, the
at neuromuscular junctions, improving (proteroglyph) fangs are mounted on
paralytic symptoms when postsynaptic a relatively fixed maxilla at the front of
neurotoxins are involved. PLA2 myotoxins the mouth (Fig. 2a). In Viperidae, the
and metalloproteases in venoms of sea (solenoglyph) fangs are mounted on
snakes, terrestrial Australasian elapids a rotatable maxilla so that they can be
and some kraits and Russells vipers folded flat against the roof of the mouth
cause generalized rhabdomyolysis, (Fig. 2b). In Colubridae (used here in the
myoglobinaemia, myoglobinuria and broad sense, including some subfamilies
acute kidney injury. Acute kidney injury is such as Natricinae, considered by some
associated with histopathological evidence taxonomists to be separate families),
of acute tubular necrosis, proliferative venom secreted by Duvernoys (supralabial)
glomerulonephritis, bilateral renal cortical glands tracks down grooves in the anterior
necrosis, acute interstitial nephritis, toxic
mesangiolysis with platelet agglutination,
fibrin deposition and ischaemic changes.
Causes include prolonged hypotension,
hypovolaemia, DIC, direct nephrotoxicity,
haemoglobinuria, myoglobinuria, and
hyperkalaemia. Antivenom can cause
immune-complex-mediated kidney injury.
DIC may result in deposition of fibrin
on vascular endothelium that has been
activated by metalloproteases, producing
microangiopathic haemolysis and
thrombotic microangiopathy, resembling
haemolytic uraemic syndrome (HUS) and
thrombotic thrombocytopenic purpura
(TTP), but ADAMTS 13 levels are not
depleted. Generalized increase in capillary
permeability in Russells viper envenoming
is attributable to metalloproteases that
damage vascular endothelium.

3.1 The venom apparatus


(Fig 1) (Gans and Gans 1978; Junghanss Figure 1: Venom apparatus of an eastern Russells viper (Daboia siamensis)
and Bodio 1995; Weinstein et al. 2009) (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
29
surfaces of (opisthoglyph) fangs at the
posterior end of the maxilla (Fig 2c)
(Weinstein et al., 2011) . Fangs allow the
snake to introduced venom deep into
the tissues of its natural prey. If a human
is bitten, venom is usually injected
subcutaneously or intramuscularly.
Spitting cobras can squeeze the venom
out of the tips of their fangs producing
a fine spray directed towards the eyes of
an aggressor.

3.2 Classification of
venomous snakes
3.2.1 Medically important species in
South-East Asia Region countries
(Gopalakrishnakone and Chou 1990;
Williams et al., 2009; WHO 2010)

There are three families of venomous


snakes in South-East Asia, Elapidae,
Viperidae and Colubridae.
Figure 2a: Short, permanently erect, front fangs of a typical elapid
(Sri Lankan cobra - Naja naja) (Copyright DA Warrell)

Figure 2b: Long, hinged, front fangs of a typical


Figure 2c: Rear fangs of a dangerously venomous Colubrid snake, the red- viper (Thailand Russells viper Daboia russelii)
necked keelback (Rhabdophis subminiatus) ) (Copyright DA Warrell) Copyright DA Warrell)

30 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 3: Absent loreal scale in Elapid snakes: above - Rat snake Ptyas mucosus non-venomous family
Colubridae, showing 3 loreal scales (red arrows) between pre-ocular (p) and nasal (n) scales (Copyright Mark
OShea); below - Sind krait Bungarus sindanus venomous family Elapidae, showing no loreal scale between
pre-ocular (p) and nasal (n) scales (Copyright Rom Whitaker)

Elapidae: have relatively short fixed scales (Fig 3). Some, notably cobras,
front (proteroglyph) fangs (Fig 2a). raise the front part of their body off the
This family includes cobras, king cobra, ground and spread and flatten the neck to
kraits, coral snakes, Australasian snakes form a hood (Figs 4-9). Several species of
and sea snakes. Elapidae are relatively cobra can spit their venom for one metre
long, thin, uniformly-coloured snakes or more towards the eyes of perceived
with large smooth symmetrical scales enemies. Venomous sea snakes have
(plates) on the top (dorsum) of the head flattened paddle-like tails and their ventral
(Fig 3 and Fig 9). There is no loreal (belly) scales are greatly reduced in size or
scale between the pre-ocular and nasal lost (Figs 20-24).

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
31
Some important examples of the (Tun- Pe et al., 1997; Ha-Tran-Hung
Elapidae inhabiting South-East Asia et al., 2010)
Region countries (References to Greater black krait B. niger (Fig 16)
reports or reviews of bites by these (Faiz et al., 2010)
species are given in parenthesis):
Sind krait B. sindanus (Pillai et al.,
Cobras (genus Naja): 2012; in press) (Fig 17)
Common spectacled (Indian) cobra Walls krait B. walli
N. naja (Fig 4) (Theakston et al.,
1990) Spotted coral snake Calliophis
maculiceps (Fig 18)
North Indian or Oxus cobra N. oxiana
(Fig 5) MacClellands coral snake
Sinomicrurus maclellandi
Monocellate cobra N. kaouthia (Kramer 1977)
(Fig 6a-c) (Reid 1964; Warrell 1986;
Viravan et al., 1992) Australasian elapids inhabiting
Eastern Indonesia (Maluku and West
Andaman cobra Naja sagittifera Papua):
(Fig 6d)
Death adders (Genus Acanthophis):
Spitting cobras: N. siamensis (Fig 7) A. rugosus (Fig 19a) (Lalloo et al.,
(Warrell 1986; Wster et al., 1997), 1996)
N. sumatrana (Fig 8), N. sputatrix, New Guinea small-eyed snake
N. mandalayensis etc Micropechis ikaheka (Fig 19b)
King cobra: Ophiophagus hannah (Warrell et al., 1996)
(Fig 9) (Tin-Myint et al., 1991) Papuan Taipan Oxyuranus scutellatus
Kraits (genus Bungarus): canni (Fig 20) (Lalloo et al., 1995)

Common krait B. caeruleus (Fig 10) Papuan black snake Pseudechis


(Theakston et al., 1990; Ariaratnam papuanus (Fig 21) (Lalloo et al.,
et al., 2009) 1994)

Malayan krait B. candidus (Fig Brown snakes (Genus Pseudonaja)


11) (Warrell et al.,1983; Kiem-Xuan- (Fig 22)
Trinh et al., 2010) Sea snakes (Reid 1975, 1979;
Ceylon krait B. ceylonicus (Fig 12) Reid and Lim 1957; Warrell
(de Silva et al., 1993) 1994): important species include
Enhydrina schistosa (Hydrophis
Banded krait B. fasciatus (Fig 13)
schistosus) (Fig 23) (Kularatne et
Red-headed krait B. flaviceps al., 2014), Hydrophis sp. (Fig 24)
(Fig 14) (Amararasekara et al., 1994; Watt
Lesser black krait B. lividus (Kuch et and Theakston 1985), Lapemis curtus
al., 2011) (Fig 25), Pelamis platura (Fig 26)
and Laticauda colubrina (Fig 27).
Chinese krait B. multicinctus (Fig 15)

32 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]

[c]
Figures 4: Common spectacled cobra (Naja naja): (a) Sri Lanka;
(b) Pune; (c) Kolkata; (d) Bardia, Nepal (a-c Copyright DA Warrell; [d]
d Copyright Mark OShea)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
33
Figure 5: North Indian or Oxus cobra (Naja oxiana) (Copyright DA Warrell)

34 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a]

[b] [d]

[c]
Figures 6: Monocellate cobra (Naja kaouthia): (a) Thailand nuchal pattern; (b) Thailand; (c) West Bengal (Fig a-c: Copyright DA Warrell);
(d) Andamans cobra (Naja sagittifera) juvenile specimen (Fig d: Copyright Ashok Captain)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
35
[a]

[c]
Figures 7: Indo-Chinese spitting cobra (Naja siamensis)
Thailand: (a) Black and white specimen with ill-defined
spectacle marking on hood; (b, c) Brown-coloured
specimen showing spectacle marking on hood
(Copyright DA Warrell)

[b]

36 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figures 8: Sumatran spitting
cobra (Naja sumatrana):
(a) black phase Singapore
(b) golden phase Thailand
(Copyright DA Warrell)

[a]

[b]

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
37
[a] [b]

[d]

[c] [e]
Figures 9: King cobra or hamadryad (Ophiophagus hannah) (Copyright DA Warrell)
(a) The famous king cobra dance in Yangon, Myanmar; (b) Specimen from Trang, southern Thailand more than
3.5 metres in total length; (c, d) Dorsal and lateral views of head of Thai specimens showing the two large
occipital scales which distinguish this species from cobras (Naja); (e) Pune, India (Copyright DA Warrell)

38 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figures 10: Common
krait (Bungarus caeruleus):
(a) Sri Lankan specimen
showing narrow white
dorsal bands; (b) Indian
specimen showing pure
white ventrals (Copyright
DA Warrell)

[a]

Figures 11: Malayan


krait (Bungarus
candidus) Thai
specimen: (a) Showing
dorsal black saddle-
[b] shaped markings;
(b) Showing pure white
ventrals (Copyright DA
Warrell).

[a] [b]

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
39
[a]

[b]

[c]
Figures 12: Ceylon krait (Bungarus ceylonicus): (a) showing incomplete white bands (spots); (b) head;
(c) showing white bands and dark ventral scales. Perideniya, Sri Lanka (Copyright DA Warrell)

40 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]
Figures 13: Banded krait (Bungarus fasciatus) Thai specimens: (a) Showing black and yellow bands; (b) Showing circumferential
black bands and blunt-tipped tail (Copyright DA Warrell)

Figure 14: Red-headed krait (Bungarus flaviceps) Thailand (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
41
Figure 15: Chinese krait (Bungarus multicinctus) Figure 16: Greater black krait (Bungarus niger) Nepal
(Copyright DA Warrell) (Copyright F. Tillack)

[a]
Figures 17: Sind krait (Bungarus sindanus): (a) specimen from Bikaner
(Copyright Rom Whitaker); (b) head of specimen from Maharashtra, India
(Copyright DA Warrell)

[b]

42 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 18: Spotted coral snake (Calliophis maculiceps) Thai specimen (Copyright DA Warrell)

[a] [b]
Figures 19: Death adders (Acanthophis rugosus): (a) Specimen from West Irian, Indonesia; (b) Specimen from Seram, Indonesia

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
43
Figure 19c: New
Guinea small-eyed snake
(Micropechis ikaheka).
Specimen from Arso,
West Irian, Indonesia
1.69m in total length
responsible for a case
of envenoming (see
Warrell et al., 1996).;
(Copyright DA Warrell)

Figure 20: Papuan taipan (Oxuyuranus scutellatus) SaiBai Island, Torres Strait Islands (Copyright DA Warrell)

44 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 21: Papuan black snake (Pseudechis papuanus) SaiBai Island, Torres Strait Islands (Copyright DA Warrell)

Figure 22: Eastern brown snake (Pseudechis textilis) Australia Figure 23: Beaked sea snake (Enhydrina schistose or
(Copyright DA Warrell) Hydrophis schistosus) Bunapas Mission, Ramu River,
Papua New Guinea (Copyright DA Warrell)

Figure 24a:
Blue spotted sea
snake (Hydrophis
cyanocinctus)
Thailand
(Copyright DA
Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
45
Figure 24b: Banded sea snake (Hydrophis fasciatus atriceps) Thailand (Copyright DA Warrell)

Figure 24c: Flattened


paddle-like tail of sea snakes:
Hydrophis cyanocinctus
(above); Lapemis curtus
(below) Thailand
(Copyright DA Warrell)

Figure 25: Hardwicks


sea snake (Lapemis curtus)
showing tiny fangs
(Copyright DA Warrell)

46 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 26: Yellow-bellied sea snake (Pelamis platurus) Watamu, Kenya (Copyright Royjan Taylor)

[a] [b]
Figures 27: Sea krait (Laticauda colubrina) Madang, Papua New Guinea: (a) Showing blue and banded pattern
and amphibious behaviour; (b) Showing fangs (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
47
Viperidae have relatively long fangs to detect their warm-blooded prey. This
(solenoglyph) which are normally folded is situated between the nostril and the
flat against the upper jaw but, when eye (Fig. 28). Viperidae are relatively
the snake strikes, are erected (Fig 2b). short, thick-bodied snakes with many
There are two subfamilies, typical vipers small rough scales on the top (dorsum)
(Viperinae) and pit-vipers (Crotalinae). of the head and characteristic patterns of
The Crotalinae possess a special infra-red coloured markings on the dorsal surface of
heat-sensing organ, the loreal pit organ, the body (Fig 29).

Pit Viper (Trimeresurus T. Macrops)

Showing heat sensitive


pit organ (red arrow)

Figure 28: Head of a typical pit viper - dark green pit viper (Trimeresurus T. macrops) showing the pit organ
situated between the nostril and the eye (red arrow) (Copyright DA Warrell)

48 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]

[c]

[d] [e]
Figures 29: Western Russells viper (Daboia russelii): (a) Specimen from Sri Lanka; (b, c) Specimens from Tamil Nadu,
southern India; (d, e) specimens from Pune, India (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
49
Some important examples of the (Craspedocephalus) gramineus (Fig 38)
Viperidae inhabiting South-East
Malabar rock pit viper Trimeresurus
Asia Region countries (References to
(Crapedocephalus) malabaricus (Fig 39)
reports of reviews of bites by these
(Gowda et al., 2006)
species are given in parenthesis):
Palm viper Trimeresurus
Typical vipers (subfamily Viperinae):
(Craspedocephalus) puniceus (Fig 40)
Russells vipers, Western, Daboia russelii
(Fig 29 a-e) (Phillips et al., 1988; Warrell Sri Lankan viper Trimeresurus
1989; Gawarammana et al., 2009); and (Craspedocephalus) trigonocephalus (Fig
Eastern, D. siamensis (Fig 30) (Myint-Lwin 41) (Warrell 1995)
et al., 1985; Tun-Pe et al., 1987; Than- Hagens pit viper Trimeresurus (Parias)
Than et al., 1987; Than-Than et al., 1988; hageni (Fig 42)
Warrell 1989; Than- Than et al., 1989;
Popes pit viper Trimeresurus (Popeia)
Thein-Than et al., 1991; Tin-Nu-Swe et al.,
popeiorum (Fig 43)
1993; Belt et al., 1997)
Chinese bamboo viper Trimeresurus
Saw-scaled or carpet vipers Echis c.
(Viridovipera) stejnegeri (Fig 44)
carinatus (Fig 31) (Bhat 1974; Warrell and
(Warrell 1995)
Arnett 1976) and E. c. sochureki (Fig 31c)
(Kochar et al., 2007). White-lipped green pit viper Trimeresurus
(Trimeresurus) albolabris (Fig 45) (Hutton
Levantine or blunt-nosed viper
et al., 1990; Rojnuckarin et al., 1998)
Macrovipera lebetina (Fig 32) (Sharma et
al., 2008) Dark green pit viper Trimeresurus
(Trimeresurus) macrops (Fig 28, 46)
Pit vipers (subfamily Crotalinae):
(Hutton et al., 1990; Warrell 1990b)
Malayan pit viper Calloselasma
Spot-tailed green pit viper Trimeresurus
rhodostoma (Fig 33) (Reid et al., 1963a;
(Trimeresurus) erythrurus (Fig 47) (Warrell
Reid et al., 1963b;
1995)
Reid 1968; Warrell et al., 1986)
White-lipped island viper Trimeresurus
Mount Kinabalu pit viper Garthia chaseni (Trimeresurus) insularis (Fig 48)
(Fig 34) (Haile 1963; Warrell 1995)
Kanchanburi pit viper Trimeresurus
Mamushis (Genus Gloydius): G. (Trimeresurus) kanburiensis (Warrell et al.,
brevicaudus (Fig 35) (Warrell 1995) 1992)
Hump-nosed pit viper Hypnale hypnale Mangrove pit viper Trimeresurus
(Fig 36) (de Silva et al., 1994; Joseph et (Trimeresurus) purpureomaculatus (Fig 49)
al., 2007; (Warrell 1995)
Ariaratnam et al., 2008; Premawardhena Northern white-lipped pit viper
et al, 1998) and other Hypnale species Trimeresurus (Trimeresurus) septentrionalis
(Maduwage et al., 2011). (Whitaker)
Chinese habu Protobothrops Beautiful pit viper Trimeresurus
mucrosquamatus (Fig 37) (Warrell 1995) (Trimeresurus) venustus (Fig 50)
Green pit vipers, bamboo vipers, palm Waglers (temple) pit viper Tropidolaemus
vipers and habus (formerly all genus wagleri (Fig 51a) (Reid 1968)
Trimeresurus)
Banded temple viper Tropidolaemus
Indian bamboo viper Trimeresurus subannulatus (Fig 51b)

50 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]

Figures 30: Eastern


Russells viper (Daboia
siamensis): (a) Specimen
from Myanmar; (b)
Specimen from Thailand;
(c) Specimen from East
Java, Indonesia; (d)
Specimen from Flores,
Indonesia (Copyright DA
[c] [d] Warrell)

[a] [b]

Figures 31: Saw-scaled


viper (Echis carinatus):
(a) Echis carinatus
carinatus Specimen
from southern India; (b)
Echis carinatus carinatus
Specimen from Sri
Lanka; (c) Echis carinatus
sochureki Specimen from
[c] Chhattagharh Rajisthan
(Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
51
Figure 32: Levantine
viper (Macrovipera
lebetina) Specimen from
Cyprus (Copyright DA
Warrell)

[a] [b]

Figures 33: Malayan pit viper (Calloselasma rhodostoma) Thai specimens: (a) Showing characteristic posture and triangular
dorsal markings; (b) Showing supralabial markings (Copyright DA Warrell)

Figure 34: Mount Kinabalu pit viper (Garthia Figure 35: Mamushi or Fu-she (Gloydius
chaseni) (Copyright Prof RS Thorpe) brevicaudus) from China (Copyright DA Warrell)

52 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]

[c] [d]
Figures 36 a-d: Hump-nosed viper (Hynpale hypnale) (Copyright DA Warrell)
a) Specimen from Sri Lanka; (b) Specimen from Sri Lanka showing long fangs; (c) Specimen from south western India;
(d) Specimen from south western India showing upturned snout

Figure 37:
Chinese habu
(Protobothrops
mucrosquamatus)
Specimen from
China (Copyright
DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
53
Figure 38: Indian
bamboo viper
(Trimeresurus
Craspedocephalus
gramineus)
(Copyright DA Warrell)

[a]

54 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[b]
Figures 39 a, b: Malabar rock pit viper (Trimeresurus Craspedocephalus malabaricus) (Copyright DA Warrell)

Figure 40: Palm viper (Trimeresurus Craspedocephalus puniceus) Specimen from Cilacap, West Java, Indonesia
(Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
55
Figure 41: Sri Lankan pit viper (Trimeresurus Craspedocephalus trigonocephalus) (Copyright DA Warrell

56 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 42: Hagens pit
viper (Trimeresurus Parias
hageni) Trang, Thailand
(Copyright DA Warrell)

Figure 43: Popes pit viper (Trimeresurus Popeia popeiorum) Thailand (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
57
Figure 44: Chinese bamboo viper (Viridovipera stejnegeri) Specimen from China (Copyright DA Warrell)

[a] [b]
Figures 45 a,b: White-lipped green pit viper (Cryptelytrops albolabris) Thai specimen: (a) Showing colouring and distinctive
brown-topped tail; (b) Showing details of the head: note smooth temporal scales (Copyright DA Warrell)

58 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a]

[b]
Figure 46: Dark green pit viper (Trimeresurus T. macrops) Figures 47 a, b: Spot-tailed green pit viper (Cryptelytrops erythrurus) Specimen
Thai specimen (Copyright DA Warrell) from near Yangon, Myanmar: (a) Showing colouring and brown spotted tail;
(b) Showing details of head; note keeled temporal scales (Copyright DA Warrell)

Figure 48: White-lipped island viper (Trimeresurus T. insularis) specimen from Tutuala Sub-district Lautem District Timor-Leste
(Copyright Mark O'Shea)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
59
Figures 49 a,b:
Mangrove pit viper
(Trimeresurus T.
purpureomaculatus):
(a) Specimen from
Kanchanburi, Thailand;
(b) Specimen from
[a] [b] upper Myanmar
(Copyright DA Warrell)

Figure 50: Beautiful


pit viper (Cryptelytrops
venustus) specimen from
Thung Song, Thailand
(Copyright DA Warrell)

60 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 51a: Waglers pit
(temple) viper (Tropidolaemus
wagleri) specimens in the
snake temple, Penang,
Malaysia
(Copyright DA Warrell)

Figure 51b:
Banded temple viper
(Tropidolaemus
semiannulatus) Borneo

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
61
3.2.2 Other medically important
venomous snakes
Several species of medically important
Colubridae (sensu lato) have been
identified in the South-East Asia
Region. The red-necked keelback
Rhabdophis subminiatus (Fig 2c and
52a) and yamakagashi R. tigrinus
(Fig 52b) (Warrell 1995) can cause
severe life-threatening anti-haemostatic
disturbances and acute kidney injury
(Fig 52c, 52d). A case of systemic
envenoming by the Sri Lankan keelback
(Balanophis ceylonicus) with similar
Figure 52a: Red-necked keelback (Rhabdophis
features has also been reported subminiatus) Thai specimen (Copyright DA
Warrell)

Figure 52b: Yamakagashi (Rhabdophis tigrinus) (Copyright S Mishima The Snake 1974 6-1 Courtesy of Dr Y Sawai)

62 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
(Fernando et al 2015). More than a dozen
other species have proved capable of
causing local envenoming [e.g. mangrove
snake (Boiga dendrophila) (Weinstein et
al., 2014) Warrell, 1995) and other cat
snakes (Boiga species); long-nosed whip
snake (Ahaetulla nasuta) (Fig 52e); dog-
faced water snake (Cerberus rhynchops);
and water snakes/paddy field snakes
(Enhydris species) (Fig 52f and 53c).
Undoubtedly more will be described as
the concept of non-venomous is further
reviewed (Weinstein et al., 2011) Figure 52c: Extensive bruising from envenoming by R. tigrinus in Japan

CT scanning of the head: Hemorrhage in the left temporal and occipital


perforative hemorrhage into the ventricle.

Figure 52d: Intracerebral haemorrhage


(Courtesy of the late Dr Y Sawai)

Figure 52f: Paddy field snake (Enhydris plumbea)

Figure 52e: Long-nosed whip snake (Ahaetulla nasuta) Sri


Lanka (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
63
3.2.3 Non-venomous snakes
Many species of non-venomous or only
trivially-venomous species are responsible
for bites, especially those that are
aggressive, irritable or prone to strike at
humans who approach to closely or that
commonly inhabit urban and rural gardens
and compounds.

Apart from the taxa mentioned above,


these include paradise or flying snakes
(Chrysopelea species) (Fig 52g), striped
keelbacks (Amphiesma species) (Fig 52h),
kukri snakes (Oligodon species) (Fig 52i),
checkered keelbacks or Asian water snake
(Xenochrophis species) (Fig 52j), wolf
snakes (Lycodon or Dinodon species)
(Fig 52k), bridle snakes (Dryocalamus)
(Fig 52m) and rat snakes (Ptyas, Elaphe,
Coelognathus, Goniosoma etc.) (Fig 52n).
Their medical importance is that they
may be mistaken for venomous species
(notably the krait mimics Lycodon and
Dryocalamus), resulting in unnecessary and
wasteful antivenom treatment (Viravan et
al., 1992; Ariaratnam et al., 2009).

Large pythons (Boidae), notably the


reticulated python Python reticularis in
Indonesia, have been reported to attack
and even ingest humans, usually inebriated
Figure 52g: Paradise or flying snakes (Chrysopelea ornata)
farmers (Fig 52o).
(Copyright Mark OShea)

Figure 52i: Kukri snakes (Oligodon cyclurus)


Figure 52h: Striped keelbacks (Amphiesma stolatum) (Copyright Mark OShea) (Copyright DA Warrell)

64 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 52k: Wolf snakes (Lycodon aulicus) (Copyright DA Warrell)

Figure 52l: Yellow-necked wolf snake (Lycodon flavicollis) biting


(Copyright DA Warrell)

Figure 52j: Chequered keelback (Xenochrophis piscator) Figure 52m: Bridle snake (Dryocalamus davisoni)
brought by bite victim Chittagong Bangladesh (Copyright DA Warrell)

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
65
Figure 52n: Rat snake (Ptyas mucosus) (Copyright Marl O'Shea)

Figure 52o: Reticulated python (Python reticularis) containing the body of a farmer it had swallowed at Palu,
Sulawesi, Indonesia (Copyright Excel Sawuwu)

66 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
3.3 Identification of 3.4.1 Venom composition
venomous snakes Modern techniques of venomics
Unfortunately, there is no simple rule for (proteomics as applied to venoms) such as
identifying a dangerous venomous snake. high performance liquid chromatography,
However, public educational materials SDS-PAGE, and mass spectrometry are
such as posters and cards with pictures revealing the enormous complexity of
of medically significant species of that snake venoms (Warrell et al., 2013). More
region with short one line or two line than 90% of snake venom (dry weight) is
notes of identifying features below the protein. Each venom contains more than
pictures in the local language will be very a hundred different proteins: enzymes
useful. In a dead snake, a needle may (constituting 80-90 % of viperid and 25-
be drawn along the upper jaw from the 70 % of elapid venoms), non-enzymatic
angle of the jaw to the snout to snag and polypeptide toxins, and non-toxic proteins
reveal the fangs. Some harmless snakes such as nerve growth factor. Nonprotein
have evolved to look almost identical to ingredients include carbohydrates and
venomous ones. Examples are various metals (often part of glycoprotein
species of Lycodon, Dryocalamus and metalloprotein enzymes), lipids, free amino
Cercaspis that mimic the appearance of acids, nucleosides, and biogenic amines
the kraits B. candidus, B. caeruleus and such as serotonin and acetylcholine.
B. ceylonicus; Cylindropis ruffus, whose
tail raising display and colouring may Venom enzymes
mimic coral snakes (Calliophis species), These include digestive hydrolases
and Boiga multomaculata that mimics (proteinases, exopeptidase,
Daboia siamensis. However, some of endopeptidases, phosphodiesterases,
the most notorious venomous snakes metalloproteinases, and phospholipases),
can be recognized by their size, shape, hyaluronidase (spreading fator), and
colour, pattern of markings, behaviour activators or inactivators of physiological
and the sound they make when they feel processes, such as kininogenases. Most
threatened. For example, the defensive venoms contain l-amino acid oxidase
behaviour of the cobras is well known (Fig (containing a riboflavin 5-phosphate
4-9): they rear up, spread a hood, hiss prosthetic group that confers the yellow
and make repeated strikes towards the colour of many venoms), phospho mono-
aggressor. Colouring can vary enormously. and di- esterases, 5'-nucleotidase, DNAase,
However, some patterns, like the NAD-nucleosidase, phospholipase A2, and
longitudinal rows of large, dark-rimmed, peptidases.
pale-centred spots of the Russells vipers
(Figs 29, 30), or the alternating black Zinc metalloproteinases/
and yellow circumferential bands of the metalloproteases (metalloproteinase-
banded krait (Fig 13), are distinctive. The like, disintegrin-like, cysteine-rich)
blowing hiss of the Russells viper and the haemorrhagins (snake venom
grating rasp of the saw-scaled viper are metalloproteinases, SVMPs): degrade
warning and identifying sounds, even in basement membrane components,
the dark. leading to endothelial cell damage and
contributing to spontaneous systemic
3.4 Snake venoms bleeding.
(Bucherl et al., 1968,1971; Gans and Gans
1978; Lee 1979; Harvey 1991; Mnez Procoagulant enzymes: venoms
2003; Mackessy 2009; Warrell 2010) of Viperidae and some Elapidae and

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
67
Acetylcholinesterases: although
found in most elapid venoms, may cause
Envenoming by juvenile and adult fasciculation.
snakes may cause qualitatively different
Hyaluronidase: promotes the spread
clinical effects of venom through tissues by increasing
permeability but can also contribute to
tissue damage.
Colubridae contain serine proteases and
other procoagulant enzymes that are Proteolytic enzymes
thrombin-like or activate factors V, X, (metalloproteinases, endopeptidases
prothrombin and other clotting factors. or hydrolases) and polypetide
These enzymes stimulate blood clotting cytotoxins (cardiotoxins): increase
with formation of fibrin in the blood vascular permeability causing oedema,
stream. Paradoxically, this process results blistering, bruising and necrosis at the site
in incoagulable blood because most of of the bite.
the fibrin clot is broken down immediately
by the bodys own plasmin fibrinolytic Venom polypeptide toxins
system. Sometimes within 30 minutes (neurotoxins)
of the bite, the levels of clotting factors Postsynaptic () neurotoxins such as
have been so depleted that the blood will -bungarotoxin and cobrotoxin, consist of
not clot (consumption coagulopathy). 60-62 or 66- 74 amino acids. They bind
Some venoms contain multiple anti- to acetylcholine receptors at the motor
haemostatic factors. For example, Russells endplate. Presynaptic () neurotoxins such
viper venom contains toxins that activate as -bungarotoxin, and taipoxin, contain
factors II (prothrombin), V, X, IX and 120-140 amino-acids and a phospholipase
XIII, fibrinolysis and protein C, and cause A subunit. These release acetylcholine
platelet aggregation, anticoagulation and at the nerve endings at neuromuscular
haemorrhage. junctions and then damage the endings,
preventing further release of transmitter.
Phospholipases A2 (lecithinase):
are most widespread and extensively Variation in venom composition
studied of all venom enzymes. They within species
damages mitochondria, red blood The composition of snake venoms, and
cells, leucocytes, platelets, peripheral hence their antigenicities in inducing
nerve endings, skeletal muscle, vascular specific neutralizing antibodies during
endothelium, and other membranes, antivenom manufacture, varies greatly
producing presynaptic neurotoxic between different species, but also within
activity, cardiotoxicity, myotoxicity, an individual species, as the snake matures
necrosis, hypotension, haemolysis, (ontogenic variation), seasonally, between
haemorrhage, plasma leakage (oedema- sexes, and throughout the geographical
induction), opiate-like sedative effects and range (Warrell, 1997; Mackessy et al.,
autopharmacological release of histamine 2003). The two important implications
and other autacoids. They are anti- of venom variation are 1- envenoming
coagulant, either by hydrolysing plasma by juvenile and adult snakes may cause
or platelet membrane phospholipids, or qualitatively different clinical effects and 2-
by interacting with different coagulation envenoming by a snake in one part of its
factors. geographical range may not be neutralized

68 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
by an antivenom raised using venom from
another part of the range. Recommendations: Bites
by small snakes should not
3.4.2 Quantity of venom injected at a be ignored or dismissed.
bite, dry bites They should be taken just as
This is very variable, depending on seriously as bites by large
the species and size of the snake, the snakes of the same species
mechanical efficiency of the bite, whether (O). Design and manufacture
one or two fangs penetrated the skin and of antivenoms should take
whether there were repeated strikes. The account of geographical and
average dry weight of venom injected ontogenic variation in venom
at a strike is approximately 60 mg in N. composition within individual
naja, 13 mg in E. carinatus and 63 mg species (O).
in D. russelii. In the case of D. siamensis
in Myanmar, the total yield of desiccated
venom extracted by milking ranged from
21-268 mg (127 +/- 13 mg, mean +/- 3.5 Pathophysiology of
1SE) in adults (mean total length 111 human envenoming
+/- 1.8 cm) and 8-79 mg (45 +/- 7 mg) Local envenoming
in juveniles (mean total length 79 +/- 2.8 Swelling and bruising result from increased
cm). Adults inject 45% of the venom vascular permeability attributable to
glands' content in the first bite (Tun-Pe venom endopeptidases, metalloproteinase
and Khin-Aung Cho, 1986). Either because hemorrhagins, membrane-damaging
of mechanical inefficiency or the snakes polypeptide toxins, phospholipases,
control of venom discharge, a proportion and endogenous autacoids released by
of bites by venomous snakes does not the venom, such as histamine, 5-HT,
result in the injection of sufficient venom and kinins. Local tissue necrosis results
to cause clinical effects. About 50% of from the direct action of myotoxins
bites by Malayan pit vipers and Russells and cytotoxins, and ischemia caused
vipers, 30% of bites by cobras and 5-10% by thrombosis; compression of blood
of bites by saw-scaled vipers do not result vessels by first-aid methods such as
in any symptoms or signs of envenoming. tight tourniquets; or by swollen muscle
Snakes do not exhaust their store of within a tight fascial compartment.
venom, even after several strikes, and they Myotoxins damage the muscle cell plasma
are no less venomous after eating their membrane directly. Most are PLA2s, either
prey (Tun-Pe et al., 1991). enzymatically active (aspartate-49) or
enzymatically inactive (lysine-49). Cobra
3.4.3 Variations in venom cardiotoxins are low-molecular weight
composition within individual polypeptides with cytotoxic action.
species of snakes
Although large snakes tend to inject more Hypotension and shock
venom than smaller specimens of the same After viper bites, leakage of plasma or
species, the venom of smaller, younger blood into the bitten limb and elsewhere,
vipers may be richer in some dangerous or massive gastrointestinal haemorrhage,
components, such as those affecting may cause hypovolaemia. Vasodilation,
haemostasis because venom composition especially of splanchnic vessels, and a direct
varies (ontogenically) with the snakes age effect on the myocardium may contribute
and hence size (Tun-Pe et al., 1995a). to hypotension. Profound hypotension

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
69
is part of the autopharmacological Neurotoxicity
syndrome that occurs within minutes Neurotoxic polypeptides and PLA2s of
of bites by D. siamensis, D. russelii, and snake venoms cause paralysis by blocking
Australasian elapids, attributable to transmission at the neuromuscular
oligopeptides (ACE inhibitors and BPPs) junction. Patients with paralysis of
and vasodilating autacoids. In some cases, the bulbar muscles may die of upper
direct myocardial effects of venom may airway obstruction or aspiration, but
be suggested by electrocardiographic the most common mode of death after
(ECG) changes and autopsy findings of neurotoxic envenoming is respiratory
epicardial or endocardial haemorrhages paralysis. By prolonging activity of
and histopathological evidence of cardiac ACh at neuromuscular junctions,
myonecrosis. anticholinesterase drugs may improve
paralytic symptoms in patients bitten
Bleeding and blood clotting by snakes with neurotoxins that are
disturbances predominantly postsynaptic in their
Snake venoms affect haemostasis in action (e.g., cobras and Australasian
several ways. Procoagulant enzymes death adders [genus Acanthophis]). Some
activate intravascular coagulation, patients bitten by elapids or vipers are
producing consumption coagulopathy drowsy in the absence of respiratory or
and incoagulable blood. Procoagulants of circulatory failure. This is unlikely to be an
Colubridae, Australasian Elapidae, Echis, effect of neurotoxic polypeptides, which
and Daboia species activate prothrombin, do not cross the blood-brain barrier.
whereas those in venoms of Daboia russelii
and D. siamensis also activate factors V Myotoxicity
and X. Thrombin-like enzymes in pit-viper PLA2 myotoxins and metalloproteinases are
venoms have a direct action on fibrinogen. principally responsible. They are present
Some venoms cause defibrinogenation in venoms of most species of sea snakes,
by activating the endogenous fibrinolytic many terrestrial Australasian elapids, some
(plasmin) system. Anticoagulant activity species of krait (Bungarus), and Viperidae,
is attributable to venom phospholipases. such as the Sri Lankan Russells viper (D.
Platelet activation or inhibition results russelii). Release into the bloodstream of
in thrombocytopenia in victims of myoglobin, muscle enzymes, uric acid,
Trimeresurus and Viridovipera species, potassium, and other muscle constituents
Calloselasma rhodostoma, Deinagkistrodon is an effect in humans of presynaptic
acutus, and Daboia siamensis. Potentially neurotoxins. Patients may die of bulbar
lethal spontaneous systemic bleeding is and respiratory muscle weakness, acute
attributable venom haemorrhagins (Zn hyperkalaemia, or acute kidney injury.
metalloproteases).
Acute kidney injury
Complement Activation A wide range of renal histological changes
Elapid and some colubroid venoms has been described after snakebite. Acute
activate complement via the alternative tubular necrosis is the most common, but
pathway (cobra venom factor is the proliferative glomerulonephritis, interstitial
snakes C3b), whereas some viperid nephritis, toxic mesangiolysis with platelet
venoms activate the classic pathway. agglutination, fibrin deposition, ischaemic
Complement activation affects platelets, changes, and distal tubular damage
the blood coagulation system, and other (lower nephron nephrosis), suggesting
humoral mediators. direct venom nephrotoxicity attributable

70 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
to venom PLA2 and metalloproteases , was an early sign of oliguric renal
and bilateral renal cortical necrosis with failure. Snake venominduced DIC may
subsequent calcification are also reported. result in deposition of fibrin on vascular
Antivenom can cause immune-complex- endothelium that has been activated
mediated kidney injury. Acute tubular by, for example, metalloproteinases,
necrosis may result from prolonged producing microangiopathic haemolysis.
hypotension and hypovolaemia, DIC, direct Although the clinical picture is reminiscent
toxic effect of the venom on the renal of haemolytic uraemic syndrome (HUS)
tubules, haemoglobinuria, myoglobinuria, and thrombotic thrombocytopenic
and hyperkalaemia. Russells viper purpura (TTP), there is no evidence of
venom produces hypotension, DIC, depleted ADAMTS-13 levels and, therefore
direct nephrotoxicity, and, in Sri Lanka no justification for cryosupernatant
and India, intravascular haemolysis and plasmapheresis (Ho et al., 2010).
rhabdomyolysis.In Burmese patients
envenomed by Russells vipers (D. Generalized increase in capillary
siamensis), high urinary concentrations permeability
of 2-microglobulin, retinal binding Venoms of some Viperidae, such as
protein, and N-acetyl glucosaminidase D. russelii and D. siamensis, can cause
suggested failure of proximal tubular a generalized increase in vascular
reabsorption and tubular damage. permeability, resulting in pulmonary
High plasma concentrations of active oedema, serous effusions, conjunctival,
renin suggested that renal ischaemia periorbital, facial and retinal oedema,
with activation of the renin-angiotensin bilateral parotid enlargement, albuminuria,
system was involved in development of and haemoconcentration. The likely cause
renal failure. A massive but transient is metalloproteases that damage vascular
capillary and glomerular leak of albumin endothelium.

Venomous snakes of the South-East Asia Region, their


venoms and the pathophysiology of human envenoming
71
72 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Epidemiology of snakebite
in South-East Asia Region
countries

Epidemiology of snakebite
in South-East Asia Region countries
73
74 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Epidemiology of snakebite in
4
South-East Asia Region countries
Essentials: venomous snake cause no envenoming
Most published data, based on hospital (dry bites), a figure ranging 5-80% with
returns, are incomplete because many different species.
patients are treated by traditional healers.
However, three large, well-designed, national, Snakebite epidemics follow flooding,
community-based studies from Bangladesh, cyclones and invasion of snakes habitats
India and Sri Lanka have produced reliable for road building, irrigation schemes
estimates. Data are inadequately reported and logging. These activities cause long
and so snakebite should be made a notifiable term changes in climate and ecology and
disease in all South-East Asia Region encourage influx of human settlers.
countries. Death certification should use
International Classification of Diseases code Males are more often bitten than females.
T63.0 (Toxic effect of contact with venomous Peak incidence is in children and young
animals snake venom and sea-snake adults. Pregnant women and their fetuses
venom) (ICD-10 Version:2015 http://apps. are at increased risk of dying. Snakebite
who.int/classifications/icd10/browse/2015/ is an occupational disease of farmers,
en#/T63.0) plantation workers, herders, hunters,
fishermen, fish farmers, snake restaurant
Incidence of snakebite varies diurnally and workers and snake charmers. Factors
seasonally. It is highest during agricultural contributing to fatal snakebite include
activities and seasonal rains. Most bites problems with choice and dosage of
are inflicted on the feet and ankles of antivenom, delay from visiting traditional
bare-footed agricultural workers who healers, transportation difficulties,
tread on snakes inadvertently while death in transit, airway obstruction,
walking in the dark or working in fields failure to attempt assisted ventilation or
and plantations. Snake species differ in problems in carrying it out, failure to treat
their inclination to strike when disturbed. hypovolaemia, complicating infections,
Notoriously irritable species include failure to observe deterioration in hospital.
Russells and saw-scaled vipers. Cobras and Hours usually elapse between bite and
kraits enter human dwellings. Kraits bite neurotoxic deaths from elapid envenoming
people who are asleep on the ground at and several days or longer, from viper
night. On average, about 50% of bites by envenoming.

Epidemiology of snakebite
in South-East Asia Region countries
75
Snakebite in different South-East Asia Direct estimate of deaths attributable to
Region countries snakebite in 2005 was 46 000 (99%CI 41
Bangladesh: medically important species 000-51 000), (1 snakebite death for every
include B. caeruleus, B. niger, B. walli; 2 HIV/AIDS deaths). Snakebites caused
N. kaouthia, N. naja; D. russelii and T. (T.) 0.5% of all deaths, 3% in 5-14 year-olds.
erythrurus. 97% died in rural areas, only 23% in health
facilities. The highest numbers of deaths
In 2009, 9000 people were questioned in were in Uttar Pradesh (8,700), Andhra
about 4000 randomly selected households Pradesh (5,200), and Bihar (4,500).
throughout all 6 administrative divisions.
589,919 snakebites and 6,041 deaths per Indonesia: medically important species
year were estimated in rural areas (case- throughout the >18 000 islands include
fatality 1%). B. candidus, N. sputatrix, N. sumatrana,
C. rhodostoma , T. (T.) albolabris; D.
Green pit vipers cause many bites, some siamensis and, in West Papua and Maluku,
morbidity but few deaths. D. russelii Acanthophis laevis. Hundreds of bites each
is restricted to western and southern year are treated in Sumatra, Java, East
areas. B. niger, previously unknown Kalimantan, Sulawesi, Wetar and West
in Bangladesh, has caused deaths. N. Papua.
kaouthia causes most cobra bites.
Maldives: there is one species of sea
Bhutan: medically-important species snake but no terrestrial venomous snake.
include cobras, kraits and pit-vipers. No No recent data on bites.
recent data on bites.
Myanmar: medically important
Democratic Peoples Republic of species include B. magnimaculatus,
Korea: medically-important species B. multicinctus; N. kaouthia, N.
include adders (Vipera berus and V. mandalayensis; Trimeresurus (T.) albolabris,
sachalinensis), several species of mamushi T. (T.) erythrurus; D. siamensis
(genus Gloydius) and Rhabdophis tigrinus. In 2014, 15,080 bites with 305 deaths
No recent data on bites. were reported to the Ministry of Health
(case-fatality 2.02%). D. siamensis causes
India: medically important species include 90% of bites.
N. naja, N. kaouthia; B. caeruleus; D.
russelii, E. carinatus; Hypnale hypnale, Nepal: medically important species
Trimeresurus. Registrar General of Indias include B. caeruleus, B. niger, B. walli; N.
Million Death Study assigned causes of naja, N. kaouthia; D. russelii and Ovophis
all deaths in about 7000 randomly chosen monticola. In the Eastern Terai, there were
sample areas, each with a population 162 snakebite deaths/100 000/year. Only
of about 1000 throughout the whole 20% of deaths occurred in hospitals. Most
country. Verbal autopsy (questioning were attributed to krait. National totals of
bereaved relatives and neighbours about between 1000 bites and 200 deaths and
the circumstances of the deceaseds 20 000 bites and 1000 deaths/year have
death), proved reliable for an event as been suggested. In 2000, the Ministry of
distinctive, dramatic and memorable Health reported 480 bites with 22 deaths,
as snakebite fatality. Results were while 4,078 bites with 81 deaths were
independent of hospital underreporting recorded at 10 hospitals in eastern Nepal
and were nationally representative. (case-fatality 3-58%).

76 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Sri Lanka: medically important species
include B. caeruleus; N. naja; D. russelii,
The total number of snakebites each year
Echis carinatus and Hypnale hypnale. Bites
are caused by D. russelii, (30%), H. hypnale might exceed 5 million with a snakebite
(22%), N. naja (17%) and B. caeruleus. A mortality of 125 000 each year in the world
recent community-based, countrywide
survey of snakebite included nearly 1% of as a whole. (Chippaux,1998)
the countrys population. The incidence
of bites, envenoming and mortality from
snakebite was found to be 398 (95% been made to assess global snakebite
CI: 356441), 151 (130173) and 2.3 mortality. In 1954, Swaroop and Grab
(0.2 4.4)/100 000/year, respectively, of the Statistical Studies Section, WHO,
amounting to more than 80 000 bites, 30 estimated that among half a million
000 envenomings and 400 deaths in the snakebites and between 30 000 and 40
country each year. 000 snakebite deaths each year in the
world as a whole, with between 25 000
Thailand: medically important species and 35 000 deaths in Asia. Their analysis
include B. candidus; N. kaouthia, N. was based on registration of deaths in
siamensis; C. rhodostoma; Trimeresurus different countries, but they recognized
(T.) albolabris and D. siamensis. Incidence the following deficiencies in this method:
of bites has declined from 9,071 bites
(14.5/100 000) in 2002 to 457 (0.7/100 1. Available statistical data are known to
000) in 2015. Mortality has declined from be unreliable and, at best, can serve to
an average of 178/year in the 1950s to provide only an approximate and highly
fewer than 2/year since 2008 (case-fatality conservative estimate of the relative
<0.5%). Calloselasma rhodostoma causes magnitude of the snakebite problem.
38% of attributable bites, Trimeresurus
(T.) albolabris and T. (T). macrops 30 %, 2. The chance of snakebite deaths being
Naja kaouthia and N. siamensis 23% missed are perhaps even greater than
and Daboia siamensis 2%. B. candidus for deaths occurring from several other
causes as many fatalities as the far better causes.
recognized Calloselasma rhodostoma).
3. The recorded figures of snakebite
Timor-Leste: T. (T.) insularis causes bites deaths may therefore be regarded as
and a few fatalities. underestimates of the total fatality
from this cause, the degree of
4.1 Introduction underrecording varying from place to
It is generally recognized that the place.
epidemiology of snakebite in the South-
East Asia Region has not been adequately In 1998, Chippaux published an appraisal
studied and that the published data, based of the global situation, again based mainly
almost exclusively on hospital returns on hospital records or health authority
to ministries of health, are likely to be statistics, quoting 114 publications. He
unreliable and therefore misleading. One speculated that the total number of
reason is that many snakebite victims are snakebites each year might exceed 5
treated not in hospitals but by traditional million with a snakebite mortality of 125
healers (Warrell, 1992). In the past 000 each year in the world as a whole,
half century, only three attempts have including 4 million snakebites, 2 million

Epidemiology of snakebite
in South-East Asia Region countries
77
snakebite envenomings, and 100 000 The continuing inadequacies in the
snakebite deaths each year in Asia. reporting of snakebite incidence, morbidity
and mortality, prompts the following
In 2008 Kasturiratne et al estimated 237 recommendation.
3791 184 550 envenomings with
15 385 - 57 636 deaths in the Asia-
Pacific region (South 14 112-33 666 Recommendation: To
rate 0.912- 2.175/100 000/year; East remedy the deficiency in
462-4 829 rate 0.033- 0.347/100 000/ reliable snakebite data, it is
year). Their most conservative estimate strongly recommended that
of the highest number of deaths due to snakebites should be made
snake bite was 14 000 in South Asia. a specific notifiable disease
Various studies suggest that bites with in all countries in the South-
envenoming constitute 12-50% of the East Asia Region and that
total number of bites in Asia and 18-30% death certification should
in India and Pakistan. use the specific International
Classification of Diseases code
A fundamental problem throughout T63.0 (Toxic effect of contact
much of the Region is that snakebite with venomous animals snake
treatment has remained in the domain venom and sea-snake venom)
of traditional, herbal or ayurvedic (ICD-10 Version:2015 http://
practitioners, so that the majority of apps.who.int/classifications/
snakebite victims are not seen or recorded icd10/browse/2015/en#/T63.0 (E)
in western-style hospitals or dispensaries. (T63.0) Snake venom
For example, in Wat Promlok, Nakorn
Srithamarat, Thailand, one moor glang
baan (traditional therapist) treated 72-
393 snakebite victims each year between 4.2 Determinants of
1985 and 2002. snakebite incidence and
severity of envenoming
In the Terai of Nepal, a community-based The incidence of snakebites depends
study established the high fatality rate of critically on the frequency of contact
161/100 000/year, attributable mainly to between snakes and humans. Except at
krait bites (Sharma et al., 2004). Few other times of flooding, snakes are elusive and
community studies have been attempted reclusive and so contact with humans is
(Hati et al 1992). In some countries, such likely only when humans move into the
as Sri Lanka, there has, over the last two snakes favoured habitat (rice fields in
decades, been a dramatic shift in patients the case of Russells vipers and cobras;
preference for treatment from ayurvedic to rubber and coffee plantations in the case
western medicine. of Malayan pit vipers) or when nocturnally
active snakes are trodden upon by people
The true scale of mortality from snakebite walking along paths in the dark. Seasonal
is just beginning to be revealed, thanks to peaks of snakebite incidence are usually
three large, well-designed, community- associated with increases in agricultural
based studies that have recently been activity or seasonal rains, perhaps
published from India (Mohapatra et al., coinciding with unusual movements and
2011), Bangladesh (Rahman et al., 2010) activity by the snakes. Different species
and Sri Lanka (Ediriweera et al, 2016). of snake vary in their willingness to strike

78 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
when disturbed. Typically irritable is in young children and the elderly. In
species are Russells vipers (Daboia russelii pregnant women, snakebite carries
and D. siamensis) and saw-scaled vipers definite but largely unquantified risks to
(Echis). Bites may be inflicted in the home mother (perhaps 4-5% case-fatality) and
by peri-domestic species such as cobras fetus (perhaps 20% case-fatality), mainly
(Naja) which may live in roof spaces or from bleeding and stillbirth/abortion
under the floor and by kraits (Bungarus) (Seneviratne at al, 2002; Langley, 2010).
which enter human dwellings at night Most snakebites are inflicted on the feet
in search of their prey and may bite and ankles of agricultural workers.
people who move in their sleep. Bites in
which a venomous snakes fangs pierce 4.4 Circumstances of
the skin but no envenoming results are snakebites
known as dry bites. The incidence of Most snakebites happen when the snake
dry bites varies with the species, from is trodden on, either in the dark or in
5-80%, average about 50% (Reid et al., undergrowth, by someone who is bare-
1963a; de Rezende et al., 1998; Silveira footed or wearing only sandals. The
and Nishioka, 1995). The explanation for snake may be picked up, unintentionally
dry bites is either mechanical inefficiency in a handful of foliage or intentionally
of the venom apparatus striking at an by someone who is unwise or boastful.
unnatural angle or through clothing, or Some bites occur when the snake (usually
perhaps voluntary defensive retention a krait) comes in to the home at night in
(metering) of venom by the snake. search ofits prey (other snakes, lizards,
frogs, mice) and someone sleeping on
Snakebite epidemics follow flooding the floor rolls over onto the snake in their
(India, Bangladesh, Myanmar and sleep. Not all snakebites happen in rural
Indonesia), cyclones and invasion of areas. For example, in some large cities,
snakes habitats for road building, such as Jammu in India, people who
irrigation schemes (e.g. Mahaweli Ganga sleep in small huts (jhuggies) are bitten
Irrigation Project in Sri Lanka) and by kraits during the night and wake with
logging. These activities cause long-term paralysis (Saini et al., 1986). In parts of
changes in climate and ecology that may India, Hindu pilgrims travel bare-footed
encourage influx of venomous snakes though overgrown and mountainous
and human settlers into deforested areas areas in the dark of early morning to
that have been developed for farming reach a holy place and are at increased
and plantations. There was no immediate risk of snakebites (e.g. Sabarimala in the
increase in snakebites in Myanmar after Periyar Tiger Reserve, Kerala, India). Sea
Cyclone Nargis, but there was in the snakebites usually occur when fishermen
aftermath 9-12 months later. pick the animals out of their hand nets
or when people are bathing or washing
4.3 Epidemiological clothes in estauaries.
characteristics of snakebite
victims 4.5 Snakebite as an
Males are more often bitten than occupational disease
females, except where the work force In South-East Asia Region countries, the
is predominantly female (e.g. tea and risk of snakebite is strongly associated
coffee picking). The peak age for bites with occupations: farming (rice),
is in children and young adults. There plantation work (rubber, coffee), herding,
is some evidence that peak case fatality hunting, fishing and fish farming,

Epidemiology of snakebite
in South-East Asia Region countries
79
(Calloselasma rhodostoma) and cobras
(Naja species) (Looareesuwan et al., 1988).
Inadequacies in ambulance transport
Factors identified as contributing to a
from rural locations to properly fatal outcome included problems with
equipped hospitals is an important antivenom use (inadequate dose or use
of a monospecific antivenom for a bite
cause of death. by a different species), delayed hospital
treatment resulting from prolonged visits
to traditional healers and problems with
catching and handling snakes for food transportation, death on the way to
(in snake restaurants), displaying and hospital, inadequate artificial ventilation or
performing with snakes (snake charmers), failure to attempt such treatment, failure
manufacturing leather (especially sea to treat hypovolaemia in shocked patients,
snakes), and in the preparation of airway obstruction, complicating infections,
traditional (Chinese) medicines. and failure to observe patients closely
after they had been admitted to hospital.
Inadequacies in ambulance transport
Snakebite: from rural locations to properly equipped
an occupational disease in hospitals is an important cause of death
South-East Asia (Gimkala et al., 2016). In India, the
majority of deaths occur outside a hospital
Farmers (rice, etc.,)
facility (Mohapatra et al. 2011). Peripheral
Plantation workers (rubber, hospitals often have inadequate medical
coffee, cacao, oil palm etc.) and nursing staffing. It is very important
Herdsmen that relatives be effectively deployed to
monitor snakebite victims, particularly
Hunters
those with neurotoxic envenoming, to
Snake handlers (snake charmers detect progression of weakness and early
and in snake restaurants and signs of respiratory paralysis.
traditional Chinese
pharmacies) 4.6.2 Time between snakebite
and death
Fishermen and fish farmers
Although very rapid death after snakebite
Sea-snake catchers (for sea-snake has, rarely, been reported (e.g. reputedly
skins, leather) a few minutes after a bite by the king
cobra Ophiophagus hannah), it is clear
from studies of large series of snakebite
deaths that many hours usually elapse
4.6 Death from snakebite between bite and death in the case of
4.6.1 Factors contributing to fatal elapid envenoming, and several days,
snakebite or even longer, in the case of viper
Few attempts have been made to examine envenoming (Reid 1968; Warrell 1995).
the factors responsible for death in cases
of bites by identified species of snakes. 4.7 Snakebite in different
In a study of 46 cases of identified South-East Asia Region
snakebite in Thailand, the three species countries
causing most deaths were Malayan krait For each South-East Asia Region country,
(Bungarus candidus), Malayan pit viper some information about the estimated

80 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
incidence of snakebite is reviewed below, large disparities between the results of
based on published and unpublished these two surveys must be explained by
reports. The most important snake their design and assumptions made in
species from a medical point of view calculating the national estimates.
are given in the boxes, according to the
following definitions (WHO, 2010): In 1988-1989, a study had discovered
records of 764 bites and 168 deaths (22%
CATEGORY 1: Highest Medical case fatality). 34% were cobra (Naja naja,
Importance - highly venomous snakes N. kaouthia) bites, carrying a 40% case
that are common or widespread and cause fatality. A total of 8000 bites per year
numerous snakebites, resulting in high across Bangladesh was estimated (Sarkar
levels of morbidity, disability or mortality. et al., 1999). A postal survey suggested
4.3 bites/100 000/year, rising to 7 per 100
CATEGORY 2: Secondary Medical 000 in areas like Chittagong Division, with
Importance - highly venomous snakes an overall case fatality of 20% (Huq et al.,
capable of causing morbidity, disability 1995). Forty-five percent of victims are
or death, but for which (a) exact said to be farmers and 23% housewives.
epidemiological or clinical data are lacking Most patients are treated by traditional
or (b) are less frequently implicated healers (ozhas) and 20% of fatal cases
because of their behaviour, habitat receive no conventional medical treatment
preferences or occurrence in areas remote (Ali Reza Khan. Indo-Asian News Service,
from large human populations. Dhaka October 12, 2001). In one five-
year study of 336 cases of snakebite at
Bangladesh: In 2003, about 170 Mymensingh Medical College Hospital,
000 households were surveyed in 12 70% of cases were aged 11-30 years and
randomly selected districts. A national 75% were males (Bhuiyan WHO New Delhi
total was estimated of 15 372 bites 1981, unpublished). During the severe
and 1709 deaths (Case Fatality 11%). flooding of July-August 2007, there were
The risk in rural areas was 10.54 times 76 cases of snakebite with 13 deaths.
that in urban areas. 94% victims lived
under poor socioeconomic conditions Only 3% of bite victims attend hospital
and 61% sought immediate treatment or seek help from a trained doctor, 6%
from traditional healers (Hossain et al., seek assistance from village doctors and
2016). In 2009, a survey, funded by the most of the rest used traditional healers
government and World Bank, questioned Ojhas. About 75 % of snakebite victims
9000 people questioned in about 4000 receive some kind of treatment within
randomly selected households throughout two hours of being bitten. Peak snakebite
all 6 administrative divisions. Results incidence is during May-October. It was
suggested an incidence of 623.4 (95% highest in Barisal (2667/100 000/year) and
CI 513.4789.2) snakebites per 100 000 lowest in Sylhet (321/100 000/year). In
person-years. There were an estimated Dhaka, incidence was 440/100 000/year.
710 159 episodes of snakebites occur A study carried out in 4 tertiary referral
annually in rural Bangladesh. An estimated hospitals estimated the economic cost
589 919 individuals are bitten by snakes of snakebite to the victims families. The
and 6041 die from snakebites every year total expenditure related to snakebite was
in rural (Case Fatality 1%) (Rahman et al., mean US$124 (4 2294) with a mean
2010). This is a much higher incidence income loss of US$93. Cost of a venomous
than formerly had been imagined. The snakebite was US$231, 7 times higher

Epidemiology of snakebite
in South-East Asia Region countries
81
than for a non-venomous snakebite.
Cat 1: Elapidae: Bungarus
Treatment imposes a major economic
caeruleus, Bungarus niger,
burden on affected families, especially
Bungarus walli; Naja kaouthia;
in venomous snakebite cases (Hasan et
Viperidae: Daboia russelii,
al., 2012).
Trimeresurus (T.) erythrurus

Green pit vipers Trimeresurus


(Trimeresurus) erythrurus cause many
Cat 2: Elapidae: Bungarus
bites and some morbidity but few if any
fasciatus, Bungarus lividus; Naja
fatalities. Russells Viper (Daboia russelii)
naja; Ophiophagus hannah;
appears to be rare. It is restricted to
Viperidae: Trimeresurus (T.)
western and southern parts of the
purpureomaculatus, Trimeresurus
country. There are recent reports of
(T.) septentrionalis
envenoming in the Rajshahi area (Ghose
and Faiz, 2015; Ghose et al., 2015).
Kraits are responsible for many bites
and fatalities. The importance of the Bhutan: In 2000, 2085 bites and stings
greater black krait (Bungarus niger), were reported. Five elapid species have
a species previously unreported from been reported from lowland regions
Bangladesh, has only recently emerged. of Bhutan (less than 500 metres above
Based on their frequencies among mean sea level): cobra (Naja naja), king
proven krait bites in Bangladesh and cobra (Ophiophagus hannah) and two
their geographical distribution, it is species of krait (Bungarus niger and B.
estimated that Walls krait (Bungarus fasciatus). Other venomous species such
walli) causes about 40% of all krait bites as N. kaouthia, Sinomicrurus macclellandi,
in the country, greater black krait Daboia russelii (Bhutan Hills according
(B. niger) and common krait (B. to MA Smith 1943), and several pit vipers
caeruleus) about 28% each, and banded may well occur there as well. There is no
(B. fasciatus) and lesser black kraits published information on snakebites in
(B. lividus) very few. In Bangladesh, Bhutan but there are said to be many
B. lividus is known only from the bites causing local pain and swelling and
northwest, B. walli and B. caeruleus are there were a minimum of 2 fatalities in
absent from southeastern Bangladesh, one year. Antivenom is imported from
but B. fasciatus and B. niger occur India (200 vials each year). No recent data
throughout the country. Monocled on bites.
cobras Naja kaouthia occur throughout
the country and cause most cobra
bites. They are the only cobras found Cat 1: Elapidae: Bungarus niger;
in southeastern Bangladesh (including Naja naja
Chittagong, Coxs Bazar and Chittagong
Hill Tract Districts). Spectacled cobras Cat 2: Elapidae: Bungarus
Naja naja occur around Dhaka and fasciatus; Ophiophagus hannah;
to the west and north of the capital. Viperidae: Trimeresurus (T.)
King cobras (Ophiophagus hannah) erythrurus; Daboia russelii
occur wherever relatively undisturbed
bamboo stands and forests remain
in Bangladesh, but have not caused Democratic Peoples Republic of
documented bites in recent years. Korea: Two species of adders

82 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
(Vipera berus and V. sachalinensis), several
species of mamushi (genus Gloydius) and
The direct estimate of deaths attributable
the yamakagashi (Rhabdophis tigrinus)
occur in North Korea but there is no to snakebite in India in 2005 was 46 000
information on snakebites. (99%CI 41 000-51 000), or 1 snakebite
Published data are restricted to the death for every 2 HIV/AIDS deaths.
Republic of (South) Korea (eg Soh et al.,
1978; Sawai,1993). No recent data on
bites. figure from health facilities and more
than 4 times higher than WHO-sponsored
guesstimate (Kasturiratne et al, 2008).
Cat 1: Gloydius brevicaudus Snakebites caused 0.5% of all deaths,
but 3% in the age group 5-14 years. The
Cat 2: Gloydius intermedius; proportion of victims dying in rural areas
Gloydius ussuriensis; Vipera berus was 97%. Only 23% had died in a health
facility. The highest number of deaths were
in Uttar Pradesh (8700), Andhra Pradesh
India: the numbers of snakebite fatalities (5200), and Bihar (4500).
in India has long been controversial.
The Government of Indias web-site Previous studies had included a field
reported an average of only 1350 deaths/ survey in randomly selected villages in
year between 2003 and 2008, whereas Barddhaman (Burdwan) District, West
Kastururatne et al., 2008 estimated about Bengal that suggested that among the
11 000 deaths/year. Estimates as low as 61 total population of nearly 5 million people,
507 bites and 1124 deaths in 2006 and 76 nearly 8000 were bitten and 800 killed
948 bites and 1359 deaths in 2007 and by snakes each year, an average incidence
as high as 50 000 deaths each year have of 16.4 deaths/100 000/year (Hati et al.,
been published. The Registrar General of 1992). In Maharashtra State, between
Indias Million Death Study, 2001-2003, 1974 and 78, there was an average of
assigned causes of all deaths, using verbal 1224 deaths/year (2.43 deaths/100 000/
autopsy, in about 7000 randomly chosen year). The big four medically important
sample areas, each with a population species had been considered to be Naja
of about 1000 throughout the whole naja, Bungarus caeruleus, Daboia russelii
country. Verbal autopsy (questioning and Echis carinatus but other species have
bereaved relatives and neighbours about now been proved important in particular
the circumstances of the deceaseds areas, such as Naja oxiana (north), N.
death), proved reliable for an event as kaouthia (north east), Hypnale hypnale
distinctive, dramatic and memorable as (south-west coast and Western Ghats
snakebite fatality (Mohapatra et al., 2011). (Joseph et al., 2007)), Echis carinatus
The results were independent of hospital sochureki (Rajisthan) (Kochar et al., 2007)
underreporting and were nationally and Trimeresurus (Craspedocephalus)
representative. The direct estimate of malabaricus (Hassan District, Mysore,
deaths attributable to snakebite in 2005 Karnataka). Bites by non-venomous
was 46 000 (99%CI 41 000-51 000), or species such as checkered keelback/Asiatic
1 snakebite death for every 2 HIV/AIDS water snake (Xenochrophis piscator) are
deaths. This figure was more than 20 common and may cause confusion among
times higher than Government of Indias medical staff and lead to inappropriate

Epidemiology of snakebite
in South-East Asia Region countries
83
antivenom treatment. There is variation (Trimeresurus) albolabris, Bungarus
in the pattern of syndromes across India, candidus (Kuch and Mebs 2007), spitting
with predominance of haemotoxic viper cobras (Naja sumatrana and N. sputatrix),
bites in south India and neurotoxic elapid Calloselasma rhodostoma (Java, Madura),
bites in north India. Syndrome-species Daboia siamensis (East Java, Komodo,
correlation studies in Tamil Nadu suggest Flores and Lomblen) and death adders
the validity of the main syndromes in (Acanthophis spp.)(West Irian). The
identifying the four main venomous snakes national antivenom producer BioFarma
in this geographical region: haemotoxicity manufactures a trivalent antivenom
without acute kidney injury (Echis against Naja sputatrix, Bungarus fasciatus
carinatus); haemotoxicity and neurotoxicity and Calloselasma rhodostoma. No
with or without renal failure (Daboia cases of B. fasciatus bites are known
russelii); neurotoxicity with local swelling but deaths from B. candidus (Java), D.
(Naja naja); and neurotoxicity without local siamensis (Java, Flores, Komodo) and
swelling (Bungarus caeruleus). Acanthophis (West Irian) have been
reported.

Cat 1: Elapidae: Bungarus Sumatra: in Bengkulu, 2-4 case of


caeruleus; Naja kaouthia (east), Naja snakebite /week; Java (West): in
naja (throughout); Semarang 1-3 case/week, in Serang, 5-8
Viperidae: Daboia russelii; Echis case /week, in Madiun 1-3 case/week, in
carinatus; Hypnale hypnale (south-west) Jogjarkarta 5-6 case/week; Java East: in
Surabaya and Sidoarjo 2-5 case/week,
Cat 2: Elapidae: Bungarus in Bondowoso, 148 cases of snakebite
fasciatus, Bungarus niger, Bungarus were treated between March 2015 and
sindanus, Bungarus walli; Naja May 2016 (15 months): Trimeresurus
oxiana (north west), Naja sagittifera (T.) insularis - 85 cases, Bungarus sp 5,
(Andaman Islands); Ophiophagus Naja sp -15, Calleselasma rhodostoma
hannah (south, north-east, 2, non-venomous snakes - 5, unidentified
Andaman Islands); snakes 36; Lombok: 5-8 case/week;
Viperidae: Trimeresurus (T.) East Kalimantan, Borneo: in Samarinda
albolabris (northeast); Trimeresurus 1-4 case/week; Sulawesi: in Palu 1-2
(T.) erythrurus (northeast); case/week; Weta: 5-8 case/week; West
Trimeresurus (T.) purpureomaculatus Papua: in Timika 1-3 case/week (Dr Tri
(east); Trimeresurus Maharani, personal communication).
(Craspedocephalus) malabaricus
(south-west), Trimeresurus Indonesia (Sumatra, Java, Borneo,
(Craspedocephalus) gramineus (south Sulawesi & Lesser Sunda Islands but
India, Andaman & Nicobar Islands), West of Wallaces line i.e. excluding West
Macrovipera lebetina (north) Papua and Maluku Islands):

Indonesia: Although fewer than 20 Cat 1: Elapidae: Bungarus


snakebite deaths are registered each year candidus (Sumatra, Java, east to
in this vast archipelago of more than Bali); Naja sputatrix (Java & Lesser
18 000 islands, several thousand deaths Sunda Islands), Naja sumatrana
are suspected to occur. Species responsible (Sumatra & Borneo);
for most bites include Trimeresurus

84 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
and is now the 12th leading cause of
Viperidae: Calloselasma rhodostoma death in this country. In 1991, there were
(Java, Madura); Trimeresurus (T.) 14 000 bites with 1000 deaths and in
albolabris (Java, Sumatra, Borneo); 1997, 8000 bites with 500 deaths. From
Daboia siamensis (formerly D. s. 2005 until 2008, 8994-11172 bites were
limitis and D.s . sublimitis) reported annually with 748-794 deaths.
In 2012, there were 13 867 snakebites in
Cat 2: Elapidae: Bungarus the whole country with 285 deaths (case-
fasciatus, Bungarus flaviceps fatality 2.06%). In 2014, there were 15
(Sumatra & Borneo); Calliophis 080 bites with 305 deaths (case-fatality
bivirgatus; Ophiophagus hannah 2.02%). Russells vipers (Daboia siamensis)
(Sumatra, Borneo & Java); cause 90% of bites. Other important
Viperidae: Trimeresurus (T.) insularis species are cobras (Naja kaouthia and N.
(Java, Bali, Komodo, Wetar, Bangka, mandalayensis), kraits (Bungarus spp.)
Sumatra, Sulawesi), Trimeresurus (T.) and green pit vipers [Trimeresurus (T.)
purpureomaculatus (Sumatra) erythrurus]. In the recent past, antivenom
has been imported from Thailand and
India to supplement national production.
Indonesia (East of Wallaces line, i.e. West However, the latest annual production by
Papua and Maluku): Myanmar Pharmaceutical Factory (Insein)
is 73 000 vials of Russells viper and 7000
vials of Cobra antivenom, with a predicted
Cat 1: Elapidae: Acanthophis production of 100 000 vials of antivenom
laevis in 2016-2017 financial year that will fulfil
national requirements.
Cat 2: Elapidae: Acanthophis
rugosus; Micropechis ikaheka;
Oxyuranus scutellatus; Pseudechis Cat 1: Elapidae: Bungarus
papuanus, Pseudechis rossignolii; magnimaculatus, Bungarus
Pseudonaja textilis multicinctus; Naja kaouthia, Naja
mandalayensis;
Viperidae: Trimeresurus (T.)
Maldives: Only one species of sea snake albolabris, Trimeresurus (T.)
(Pelamis platurus) and two species of erythrurus; Daboia siamensis
harmless land snakes (Lycodon aulicus
or L. capucinus and Typhlops brahminus) Cat 2: Elapidae: Bungarus
occur. There have been no reports of bites. candidus; Ophiophagus hannah;
A living specimen of Naja kaouthia was Viperidae: Calloselasma
found in the wild. It had presumably been rhodostoma (southern
imported in cargo from South Asia. No Peninsula); Trimeresurus (T.)
recent data on bites. purpureomaculatus; Ovophis
monticola, Protobothrops kaulbacki,
Myanmar: In the 1930s the annual Protobothrops mucrosquamatus
snakebite mortality reported in Burma
exceeded 2000 (15.4/100 000/year). Thirty
years later it was still estimated to exceed Nepal: Sixteen species of known or
1000 (3.3/100 000/year). Russells viper potential medical importance occur in
(Daboia siamensis) bite was once the 5th Nepal (Sharma et al, 2013). The highest

Epidemiology of snakebite
in South-East Asia Region countries
85
fasciatus; Bungarus lividus;
According to the Epidemiology Unit, Ministry
Bungarus walli; Ophiophagus
of Health, reported snakebite numbers hannah; Hemibungarus
increased from 12 175 per year in 1991 to (Sinomicrurus) macclellandii
Viperidae: Trimeresurus (T.)
peak at 37 244 in 2002 and 36 861 in 2005. septentrionalis; Cryptelytrops
Trimeresurus (T.) albolabris;
Trimeresurus (T.) erythrurus;
recorded focal incidence, for Nepal or Trimeresurus (Crapedocephalus)
for the whole world, was 162 snakebite gramineus; Gloydius himalayanus;
deaths/100 000/year, determined in the Ovophis monticola; Himalayophis
Eastern Terai (Sharma et al., 2004). In this tibetanus; Protobothrops jerdonii;
study, only 20% of the deaths occurred Trimeresurus (Viridovipera)
in hospitals. Increased risk of fatality was stejnegeri; Trimeresurus
associated with being bitten inside the (Viridovipera) yunnanensis
house while resting between 2400 and
0060 hr, suggesting bites by the common
krait (Bungarus caeruleus) (see below). Sri Lanka: According to the
Other risk factors were an initial visit to a Epidemiology Unit, Ministry of Health,
traditional healer and delayed transport reported snakebite numbers increased
to hospital. Medically important species from 12 175 per year in 1991 to peak
include Naja naja, Bungarus caeruleus, B. at 37 244 in 2002 and 36 861 in 2005.
walli and Daboia russelii. In the Kathmandu Fatalities peaked at 194 in 2000 and
valley and foothills of the Himalaya, there were 134 in 2005. There are
Ovophis monticola and Trimeresurus pit- currently 30 000 35 000 bites and
vipers cause some bites. Russells viper (D. 100-150 deaths each year. In hospitals,
russelii) causes bites in a few parts of the case fatality decreased from 3.5% in
Terai (e.g. Nawalparasi). In the country 1985 to 0.2% in 2006. However, these
as a whole, 1000 bites and 200 deaths data are based on hospital returns which
have been estimated but one survey are likely to miss at least 5% of deaths.
suggested 20 000 bites and 1000 deaths/ Comparison of hospital data with death
year (Bhetwal et al., 1998). In 2000, the certifications in Monaragala District
Ministry of Health reported 480 bites with during a 5-year period (1999-2003)
22 deaths, while 4078 bites with 81 deaths revealed a 63% underestimate by hospital
were recorded at 10 hospitals in eastern records of the true number of snakebite
Nepal. The case-fatality varied from 3 to deaths (Fox et al., 2006), partly explained
58% in different hospitals (Sharma, 2003). by the fact that 36% of snakebite
victims did not seek or achieve hospital
treatment. In Kandy district, snakebite
Cat 1: Elapidae: Bungarus fatality based on death certification
caeruleus, Bungarus niger; was 2/100 000/year during the period
Naja naja; Naja kaouthia 1967-1987, amounting to about 0.5%
Viperidae: Daboia russelii of all deaths. Bites are caused by Daboia
russelii, (30%), hump-nosed viper
Cat 2: Elapidae: Elapidae: (Hypnale hypnale) (22%), Naja naja (17%)
Bungarus bungaroides, Bungarus and kraits (mainly Bungarus caeruleus but
a few B. ceylonicus ) (15%).

86 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
A recent community based, countrywide
survey of snakebite included nearly 1% of Cat 1: Elapidae: Bungarus
the countrys population. The incidence candidus; Naja kaouthia, Naja
of bites, envenoming and mortality from siamensis; Viperidae: Calloselasma
snakebite was found to be 398 (95% rhodostoma; Trimeresurus (T.)
CI: 356441), 151 (130173) and 2.3 albolabris; Daboia siamensis
(0.2 4.4)/100 000/year, respectively. This
Cat 2: Elapidae: Bungarus
amounts to more than 80 000 bites, 30
fasciatus, Bungarus flaviceps; Naja
000 envenomings and 400 deaths in the
sumatrana; Ophiophagus hannah;
country each year (Ediriweera et al, 2016).
Viperidae: Trimeresurus (T.) macrops,
Trimeresurus (T. ) purpureomaculatus

Cat 1: Elapidae: Bungarus


caeruleus; Naja naja; Viperidae: Timor-Leste: the white-lipped island viper
Daboia russelii; Hypnale hypnale Trimeresurus (T.) insularis is very common
on the main island of Timor, on the small
Cat 2: Elapidae: Bungarus Ataro Island to the north and on at least
ceylonicus; Viperidae: Echis 18 other islands in Indonesia. On Timor
carinatus; Hypnale nepa, Hypnale LEste, it does cause bites including a few
walli; Trimeresurus trigonocephalus fatalities. The spitting cobra (Naja sputatrix)
is still unconfirmed but suspected and
ophthalmic injuries from spitting have been
Thailand: Improved surveillance rumoured (http://www.markoshea.info/
explained the reporting of increasing timor.php) No recent data on bites.
numbers of snakebite cases from an
average of 2316/year in the 1950s
to 9071 (14.5/100 000) in 2002 and Cat 1: Viperidae: Trimeresurus (T.)
8299 (13.25/100 000) in 2006. Cases insularis
have subsequently declined from 7835
(12.35/100 000) in 2008 to 5077 (7.9/100 Cat 2: Elapidae: Naja sputatrix
000) in 2012, 1962 (3.06/100 000) in (unconfirmed)
2013, 1219 (1.88/100 000) in 2014 and
457 (0.7/100 000) in 2015. Mortality has
declined from an average of 178/year Summary: There is great diversity
in the 1950s to fewer than 2/year since of venomous snake species in
2008. Over the last 5 years, both incidence the Region. There are in excess
and case fatality have declined to 500 of one million envenomings
5000 bites/year (1-10/100 000/year) with and 75 000 deaths/year in the
an admirably low case fatality less than Region. Important species
0.05%. Calloselasma rhodostoma causes include Naja naja, N. kaouthia,
38% of attributable bites, Trimeresurus N. oxiana, Bungarus caeruleus,
(T.) albolabris and T. (T). macrops 30 %, B. multicinctus, Daboia russelii,
Naja kaouthia and N. siamensis 23% and D. siamensis, Echis carinatus,
Daboia siamensis 2%. However, Calloselasma rhodostoma,
Bungarus candidus causes as many Hypnale hypnale, Trimeresurus
fatalities as the far better recognized (T.) albolabris and Trimeresurus
Calloselasma rhodostoma) (Looareesuwan (Craspedocephalus) gramineus. (O)
et al., 1988).

Epidemiology of snakebite
in South-East Asia Region countries
87
88 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Clinical effects of snakebite

Clinical effects of snakebite 89


90 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Clinical effects of snakebite
5
Essentials: usually painless), local swelling spreading
In patients with suspected snakebite there proximally, tender, painful swelling of
may be 1-Puncture mark(s) only, caused regional lymph nodes draining bite
by dry bite from venomous snake, bite site. Other signs: fang mark, persistent
by non-venomous snake, bite/scratch by local bleeding, bruising, lymphangitis,
another animal (lizard, fish, rodent, spider inflammation (swelling, redness, heat),
etc.), or puncture by sharp vegetation; blistering (blebs, bullae, vesicles), infection,
2-Local pain/swelling at bite site that may abscess formation, necrosis.
be transient, persistent or complicated by
necrosis or infection leading to permanent Systemic envenoming: nausea, vomiting,
disability; 3-Local and/or systemic malaise, abdominal pain, weakness,
envenoming affecting organs and tissues drowsiness, prostration.
distant from bite site that may be transient,
persistent, life-threatening or permanently Cardiovascular (Viperidae): visual
debilitating; 4-Signs of extreme anxiety disturbances, dizziness, faintness, collapse,
prompted by the frightening experience: shock, hypotension, cardiac arrhythmias,
hyperventilation, acroparaesthesiae, tetany, myocardial damage. Generalized increase
dizziness/syncope, vasovagal shock with in capillary permeability: facial, periorbital,
profound bradycardia, diarrhoea and conjunctival oedema (chemosis), bilateral
vomiting, agitation, irrational behaviour, parotid enlargement, pleural and
hypertension, tachycardia, sweating, pericardial effusions, pulmonary oedema,
trembling that may mislead medical massive albuminuria, haemoconcentration.
staff and lead to persistent psychological Bleeding and clotting disorders (Viperidae):
morbidity; 5-Effects of first-aid and local traumatic bleeding from recent and
other pre-hospital treatments such as partly-healed wounds and venepuncture
pain, swelling and congestion from tight sites; spontaneous systemic bleeding
tourniquet and effects of herbal and other (gums, epistaxis, haematemesis,
traditional remedies. meningism from subarachnoid
haemorrhage, lateralising signs and/
Summary of symptoms and signs or coma from cerebral haemorrhage/
General: fear and foreboding are very thrombosis), haemoptysis, haematemesis,
common rectal bleeding or melaena, haematuria,
vaginal bleeding, subconjunctival
Local envenoming: increasing local haemorrhages, skin petechiae, purpura,
pain at the site of the bite (krait bites discoid haemorrhages, ecchymoses.

Clinical effects of snakebite 91


Neurological (Elapidae, Viperidae eg SYNDROME 4: Paralysis with minimal
Russells viper D. russelii, Gloydius or no local envenoming:
species): bilateral ptosis, external Bitten on land while sleeping on the
ophthalmoplegia, descending paralysis ground with/without abdominal pain
progressing to generalized flaccid = krait
paralysis. Generalized rhabdomyolysis:
muscles stiff, tender, painful on passive Bitten in the sea, estuary and some
stretching, trismus, dark brown urine. freshwater lakes = sea snake
Acute kidney injury: loin (lower back)
pain, haematuria, haemoglobinuria, Bitten in Indonesia Maluku or West
myoglobinuria, oliguria/anuria, uraemia Papua with/without bleeding/clotting
(acidotic breathing, hiccups, nausea, disturbance = Australasian elapid
pleuritic chest pain, encephalopathy).
SYNDROME 5: Paralysis with dark
Acute pituitary insufficiency (Russells brown urine and acute kidney injury:
viper): acute - shock, hypoglycaemia; Bitten on land (with bleeding/clotting
chronic - weakness, loss of secondary disturbance) = Russells viper, Sri Lanka
sexual hair, loss of libido, amenorrhoea, or South India
testicular atrophy, hypothyroidism etc.
Bitten on land while sleeping indoors
Clinical syndromes of snakebite in South- = krait (B. niger, B. candidus, B.
East Asia: although there may be overlap multicinctus), Bangladesh, Thailand
of clinical features caused by venoms
of different species of snake, especially Bitten in the sea, estuary and some
as knowledge advances, a syndromic freshwater lakes (no bleeding/clotting
approach is useful, especially when the disturbances) = sea snake
snake has not been identified and only
monospecific antivenoms are available. Long term complications: at the
bite site - tissue loss, amputation,
SYNDROME 1: Local envenoming chronic ulceration (risk of malignant
(swelling etc) with bleeding/clotting change), infection, osteomyelitis,
disturbances = Viperidae (all species) arthritis, arthrodesis, contracture
and hypertrophic or keloid scars
SYNDROME 2: Local envenoming cause permanent physical disability.
(swelling etc) with bleeding/clotting Chronic kidney disease, chronic
disturbances, shock or acute kidney panhypopituitarism, chronic
injury = Russells viper; with conjunctival neurological deficits after strokes.
oedema (chemosis) and acute pituitary Chronic psychological morbidity
insufficiency = Russells viper, Myanmar (depression, anxiety, impaired function,
and South India with bilateral ptosis, post-traumatic stress disorder,
external ophthalmoplegia, facial paralysis unexplained residual physical disability).
etc. and dark brown urine = Russells
viper, Sri Lanka and South India Cobra-spit ophthalmia: there is
immediate intense pain, profuse
SYNDROME 3: Local envenoming watering with whitish discharge,
(swelling etc.) with paralysis = cobra or congested conjunctivae and spasm and
king cobra swelling of eyelids.

92 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Victims of snakebite may suffer any or all snakes in which no venom was
of the following: injected. Patients who develop no
1. No physical effects other than the fang/ or negligible local swelling and no
tooth puncture. This is explained by systemic envenoming are identified
bites by non-venomous snakes, animals by clinical evaluation. They can be
other than snakes (e.g. lizards, fish, managed at the most peripheral
rodents, spiders see Fig 53), by being level of the health service without
impaled on a thorn or other sharp referral to higher centres (Harris et
object, or dry bites by venomous al., 2010).

[a] [b]

[c] [d]

[e] [f]
Figures 53: Animal bite marks: (a) venomous European adder (Vipera berus); (b) venomous Western Russells viper (Daboia russelii) (fatal
case); (c) non-venomous back-fanged rice paddy or plumbeous water snake (Enhydris plumbea); (d) rat; (e) Brazilian wandering spider
(Phoneutria nigriventer); (f) catfish (Siluridae) (Copyright DA Warrell)

Clinical effects of snakebite 93


2. Local envenoming confined to the part slowing of the heart. Others may become
of the body that has been bitten. These highly agitated and irrational and may
effects may be transient, resolving in develop a wide range of misleading
hours or a few days; persistent for symptoms. Blood pressure and pulse rate
weeks; or debilitating, sometimes may increase and there may be sweating
permanently, due to locally necrotic and trembling. Others may vomit and have
effects of venom and complicating diarrhoea.
infections.
Another source of symptoms and signs
3. Systemic envenoming involving organs not caused by snake venom is first aid and
and tissues distant from the part of traditional treatments (Harris et al., 2010).
the body that has been bitten. These Constricting bands or tourniquets may
effects may be transient, persistent, cause pain, swelling and congestion that
life threatening and debilitating, suggest local envenoming. Ingested herbal
sometimes permanently. remedies may cause vomiting. Instillation
of irritant plant juices into the eyes may
4. Effects of anxiety prompted by the cause conjunctivitis. Forcible insufflation
frightening experience of being bitten of oils into the respiratory tract may lead
(real or imagined) and by exaggerated to aspiration pneumonia, bronchospasm,
beliefs about the potency and speed ruptured ear drums and pneumothorax.
of action of snake venoms. These Incisions, cauterisation, immersion in
symptoms can be misleading for scalding liquid and heating over a fire can
medical personnel. They may persist result in devastating injuries.
causing psychological morbidity
(Williams et al., 2011). 5.2 When venom has
been injected
5. Effects of first-aid and other pre- 5.2.1 Early symptoms and signs
hospital treatments that may cause Following the immediate pain of
misleading clinical features. These may mechanical penetration of the skin by the
be debilitating and rarely even life- snakes fangs, and the fear associated
threatening. (Harris et al., 2010) with such a terrifying experience as being
bitten by a snake, there may be increasing
5.1 When venom has not local pain (burning, bursting, throbbing)
been injected at the site of the bite, local swelling that
Some people who are bitten by snakes gradually extends proximally up the bitten
or suspect or imagine that they have limb and tender, painful enlargement of
been bitten, may develop quite striking the regional lymph nodes draining the
symptoms and signs, even when no site of the bite (in the groin - femoral or
venom has been injected. This results inguinal, following bites in the lower limb;
from an understandable fear, and at the elbow epitrochlear - or in the
foreboding about the consequences of a axilla following bites in the upper limb).
real venomous bite. Anxious people may However, bites by kraits, sea snakes and
over breathe so that they develop pins and Philippine cobras may be virtually painless
needles (paraesthesiae) of the extremities, and may cause negligible local swelling.
stiffness or tetany of their hands and Someone who is sleeping may not even
feet and dizziness. Others may develop wake up when bitten by a krait and there
vasovagal shock after the bite or suspected may be no detectable fang marks or signs
bite - faintness and collapse with profound of local envenoming.

94 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
5.2.2 Clinical patterns of envenoming which may suggest which species was
by snakes in South East Asia responsible.
Symptoms and signs vary according to
the species of snake responsible for the 5.2.3 Local symptoms and signs in the
bite and the amount of venom injected. bitten part
Sometimes the identity of the biting
fang marks (Fig 54a)
snake can be confirmed by examining
the dead snake or an image of the snake local pain
sent by mobile phone; it may be strongly
local bleeding (Fig 54b)
suspected from the patients description
or the circumstances of the bite or from bruising (Fig 54c)
knowledge of the clinical effects of the spreading local swelling (Fig 55)
venom of that species. This information
will enable the doctor to choose an lymphangitis
appropriate antivenom, anticipate the lymph node enlargement
likely complications and therefore take
appropriate action. If the biting species inflammation (swelling, redness, heat)
is unknown, the patient should be blistering (Fig 54c, 54d, 54e)
observed closely to allow recognition of
local infection, abscess formation
the emerging pattern of symptoms, signs
(Fig 56)
and results of laboratory tests (the clinical
syndrome), together with other evidence, necrosis (Fig 57)

[a] [b]

[d] [e] [c]


Figures 54: Local signs of envenoming: (a) Fang marks 2.5 cm apart inflicted by a large Russells viper in Sri Lanka; (b) Persistent
local bleeding from fang marks 40 minutes after a bite by a Malayan pit viper; (c) Swelling, blistering and bruising following a
bite by a Malayan pit viper; (d) Blistering with early necrosis at the site of a monocellate cobra bite; (e) blistering and early tissue
necrosis following a bite by an Indo-Chinese spitting cobra (Naja siamensis) in south Viet Nam. (Copyright DA Warrell)

Clinical effects of snakebite 95


Figure 55: Local swelling after a saw-scaled viper (Echis ocellatus) bite on the hand rapidly extending proximally (Copyright DA Warrell)

[a]

Figure 56: Local


abscess at the site of a 5.2.4 Generalized (systemic)
Western Russells viper
(Daboia russelii) bite in symptoms and signs
Sri Lanka
(Copyright DA Warrell)
General
Fear, anxiety, nausea, vomiting, malaise,
abdominal pain, weakness, drowsiness,
prostration.

Cardiovascular (Viperidae)
Visual disturbances, dizziness, faintness,
collapse, shock, hypotension, cardiac
arrhythmias, myocardial damage (reduced
ejection fraction).

Generalized increase in capillary


permeability (capillary leak
syndrome) (Russells vipers: D.
siamensis in Myanmar (Myint-
Lwin et al., 1985) and D. russelii in
India; Facial and conjunctival oedema
(chemosis) (Fig 58), bilateral parotid [b]
enlargement (Fig 59 a, b) (Chakraborty
and Bhattachcharjee, 2010; Deepak et al., Figures 57: Local necrosis that required
2013), pleural and pericardial effusions, surgical debridement: (a) after Malayan pit viper
(Calloselasma rhodostoma) bite in Thailand;
pulmonary oedema, massive albuminuria, (b) after spectacled cobra (Naja naja) bite in Sri
haemoconcentration. Lanka (Copyright DA Warrell)

96 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 58 Bilateral conjunctival oedema (chemosis) after bite of Eastern Russels viper (Daboia siamensis) in Myanmar (Copyright DA Warrell)

Bleeding and clotting disorders


(Viperidae)
- traumatic bleeding from recent wounds
(including prolonged bleeding from the
fang marks (Fig 54b, venipunctures etc)
and from old partly-healed wounds -
spontaneous systemic bleeding - from gums
(Fig 60a), epistaxis, bleeding into the tears,
intracranial haemorrhage (meningism from
subarachnoid haemorrhage - Fig 60b,
lateralising signs and/or coma from cerebral
haemorrhage Fig 61), haemoptysis (Fig
62), haematemesis), rectal bleeding or
melaena, haematuria, vaginal bleeding,
bleeding into the mucosae (eg conjunctivae [a] [b]
Fig 63), skin (petechiae, purpura, discoid
Figure 59 a, b: Bilateral parotid gland enlargement (vipers head appearance)
haemorrhages Fig 64 and ecchymoses. after bite of Western Russels viper (Daboia russelii) in Kerala, India
(Copyright Dr Joseph K Joseph)

[A]
[b]
Figures 60: Spontaneous systemic bleeding: (a) from gingival sulci in a patient
[a] bitten by a Malayan pit viper; (b) neck stiffness (meningism) from sub-arachnoid
haemorrhage after a saw-scaled viper bite (Copyright DA Warrell)

Clinical effects of snakebite 97


[a] [b] [c]
Figures 61: Strokes after Russells viper bites: (a) fatal cerebral haemorrhage in Myanmar (Copyright Dr U Hla Mon); (b) intra cerebral
haemorrhages in Maharashtra, India; (c) ischaemic/thrombotic stroke in Maharashtra, India (b, c, Copyright Dr Suvarna Patil)

Figure 62: Haemoptysis from a Figure 63: Subconjunctival haemorrhages in a patient bitten by a Burmese Russells viper
tuberculous lung cavity in a patient (Copyright DA Warrell)
bitten by a Malayan pit viper
(Copyright DA Warrell)

Figure 64: Cutaneous


signs: (a) lymphangitic
lines extending towards
regional lymph nodes
(b) Cutaneous discoid
haemorrhages in a
patient bitten by a
Malayan pit viper in
Viet Nam
(Copyright DA Warrell)

98 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Cerebral arterial thrombosis (Russells Neurological (Elapidae, Viperidae
vipers Daboia russelii and D. siamensis) eg Russells viper D. russelii,
Thrombotic strokes, confirmed by Gloydius species)
angiography or imaging, are increasingly Drowsiness, paraesthesiae,
recognized after envenoming by D. abnormalities of taste and smell,
russelii in India (Fig 61c), Sri Lanka heavy eyelids, ptosis (Fig 65a,b),
(Gawarammana et al., 2009) and Taiwan. external ophthalmoplegia (Fig 66),

[a] [b]
Figures 65a,b: Bilateral ptosis: (a) in a patient bitten by a common krait in Sri Lanka; (b) in a patient bitten by a
Russells viper in Sri Lankan (Copyright DA Warrell)

Figure 66: External


ophthalmoplegia in
a patient bitten by a
Russells viper in Sri
Lanka. The patient is
attempting to look to his
right. The eyes must be
held open becauseof the
bilateral ptosis
(Copyright DA Warrell)

Clinical effects of snakebite 99


paralysis of facial muscles and other niger and B. candidus, western
muscles innervated by the cranial nerves, Russells viper Daboia russelii)
nasal voice or aphonia, regurgitation
through the nose, difficulty in swallowing Generalized pain, stiffness and
secretions, respiratory and generalized tenderness of muscles, pain on
flaccid paralysis. passive stretching (Fig 71b) trismus,
myoglobinuria (Fig 67, 71c),
Skeletal muscle breakdown (sea hyperkalaemia, cardiac arrest, acute
snakes, some krait species Bungarus kidney injury.

Figure 67: Patient bitten by a Russells viper in Sri Lanka. She began to pass dark brown urine containing myoglobin and haemoglobin 8
hours after the bite. (Copyright DA Warrell)

Renal (Viperidae, sea snakes) Endocrine (acute pituitary/adrenal


Loin (lower back) pain (Tin-Nu-Swe et al. insufficiency from infarction of the anterior
1993), haematuria, haemoglobinuria, pituitary (Fig 68 a,b) (Russells viper in
myoglobinuria, oliguria/anuria, symptoms Myanmar and several parts of India) (Eapen at
and signs of acute kidney injury/ uraemia al., 1976; Tun-Pe et al., 1987; Bandyopadhyay
(acidotic breathing, hiccups, nausea, et al 2012; Chatterjee et al., 2008; Golay et
pleuritic chest pain etc., see below). al., 2014; Murthy et al., 2002)

100 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]

Figures 68: Haemorrhagic infarction of the anterior pituitary resulting in Sheehans-like syndrome (pan-hypopituitarism) after Russells
viper bite in Myanmar: (a) appearances at the base of the brain at autopsy in a patient who died acutely after the bite (Copyright Dr U
Hla Mon); (b) Patient presenting with symptoms and signs of panhypopituitarism three years after severe envenoming by Russells viper.
There is loss of secondary sexual hair and testicular atrophy (Copyright DA Warrell)

Acute phase: shock, hypoglycaemia example, some elapid venoms, such as


Chronic phase (months to years after the those of Asian cobras, can cause severe
bite): weakness, loss of secondary sexual local envenoming (Fig 54d, 54e, 57b,
hair, loss of libido, amenorrhoea, testicular 66), formerly thought to be an effect only
atrophy, hypothyroidism etc (Fig 68b). of viper venoms. In Sri Lanka and India,
Russells viper venom causes paralytic
Hyponatraemia has been observed in signs (ptosis etc.) (Figs 65b, 66, 67),
victims of krait bites in the area of Hanoi suggesting elapid neurotoxicity, and
and around Ho Chi Minh City in Viet muscle pains and dark brown urine (Fig
Nam (Bungarus nr. multicinctus/candidus) 67), suggesting sea-snake rhabdomyolysis.
(Hung and Hjer 2009; Kiem-Xuan-Trinh Envenoming by the greater black
et al., 2010; Hjer et al., 2010), implying krait (B. niger) can cause generalized
natriuretic hormone like activity in the rhabdomyolysis leading to acute kidney
venom. injury (Faiz et al., 2010). Although there
may be considerable overlap of clinical
5.3 Clinical syndromes of features caused by venoms of different
snakebite in South-East Asia species of snake, a syndromic approach
Limitations of syndromic approach: may still be useful, especially when the
The more carefully the clinical effects snake has not been identified and only
of snakebites are studied, the more it monospecific antivenoms are available (see
is realised that the range of activities Annexes 1 and 2) (Pathmeswaran et al,
of a particular venom is very wide. For 2006; Ariaratnam et al., 2009).

Clinical effects of snakebite 101


SYNDROME 1: Local envenoming SYNDROME 5: Paralysis with dark
(swelling etc) with bleeding/clotting brown urine and acute kidney injury:
disturbances = Viperidae (all species)
Bitten on land (with bleeding/clotting
SYNDROME 2: Local envenoming disturbance) = Russells viper, Sri
(swelling etc) with bleeding/clotting Lanka or South India
disturbances, shock or acute kidney injury
= Russells viper with conjunctival Bitten on land while sleeping indoors =
oedema (chemosis) and acute pituitary krait (B. niger, B. candidus,
insufficiency = Russells viper, B. multicinctus), Bangladesh,
Myanmar and South India with ptosis, Thailand
external ophthalmoplegia, facial paralysis
etc. and dark brown urine = Russells Bitten in the sea, estuary and some
viper, Sri Lanka and South India freshwater lakes (no bleeding/clotting
(?Myanmar) disturbances) = sea-snake

SYNDROME 3: Local envenoming 5.4 Long term complications


(swelling etc) with paralysis = cobra or (sequelae) of snakebite
king cobra At the site of the bite, loss of tissue
may result from sloughing or surgical
SYNDROME 4: Paralysis with minimal or dbridement of necrotic areas or
no local envenoming: amputation: chronic ulceration, infection,
Bitten on land while sleeping on the osteomyelitis or arthritis may persist
ground with/without abdominal pain causing severe physical disability (Fig
= krait 70a). Malignant transformation may
occur in skin ulcers after a number of
Bitten in the sea, estuary and some years (Marjolins ulcer) (Fig 70b).
freshwater lakes = sea snake
Chronic kidney disease (renal failure)
Bitten in Indonesia Maluku or West may occur after bilateral cortical necrosis
Papua with/without bleeding/clotting (Russells viper and hump-nosed pit viper
disturbance = Australasian elapid bites) (Ariaratnam et al., 2008b); and

[a] [b]
Figures 70: Chronic physical handicap resulting from necrotic envenoming by Malayan pit vipers: (a) Deformity and dysfunction
after a snakebite and subsequent necrosis of the calf; (b) Squamous cell carcinoma arising at the site of a chronic skin ulcer with
osteomyelitis 8 years after the bite (Copyright DA Warrell)

102 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
chronic panhypopituitarism or diabetes ulcer, and persisting lump to amputations.
insipidus after Russells viper (Daboia (Jayawardene et al., submitted for
russelii and D. siamensis) bites in India publication). Unexplained residual
(Golay et al., 2014) and Sri Lanka and, symptoms have also been reported
most commonly, in Myanmar, following snakebite in Tamil Nadu, India
(Fig 68b). Chronic neurological deficit is (Vaiyapuri et al, 2013).
seen in patients who survive intracranial
haemorrhages and thromboses 5.5 Symptoms and signs
(Viperidae). of sea-snake envenoming
(Reid, 1979; Warrell, 1994)
Abnormalities of electrophysiological Envenoming by sea snakes (Hydrophiinae)
tests can persist for over 12 months and sea kraits (Laticaudinae): the bite is
following elapid bites in Sri Lanka (Bell et usually painless and may not be noticed
al, 2010). by the wader or swimmer. Fangs and
other teeth may be left in the wound.
Delayed psychological morbidity has been
reported one to four years after snakebite
envenoming in Sri Lanka. Depression
and anxiety, impaired functioning, post-
traumatic stress disorder and unexplained
residual physical disability were
reported (Williams et al, 2011). Chronic
musculoskeletal disabilities have been
reported following snake envenoming
in Sri Lanka. The disabilities involved
mostly the lower limbs. They ranged from
swelling, muscle wasting, stiff joints,
reduced muscle power, impaired balance,
fixed deformities, chronic non-healing [c]

[a] [b]
Figures 71: Sea-snake bite in North-west Malaysia: (a) Ptosis, facial paralysis and trismus; (b) Generalised myalgia making
passive movement of the limbs extremely painful; (c) myoglobinuria (Copyright the late H Alistair Reid)

Clinical effects of snakebite 103


conscious until the respiratory muscles are
sufficiently affected to cause respiratory
If the spat venom enters the eyes,
failure. Myoglobinaemia and myoglobinuria
there is immediate and persistent develop 38 hours after the bite (Fig 71c).
intense burning, stinging pain, followed These are suspected when the serum/
plasma appears brownish and the urine
by profuse watering of the eyes with dark reddish brown (Coca-Cola-coloured).
production of whitish discharge, congested Bedside sticks tests will appear positive
for haemoglobin/blood in urine containing
conjunctivae, spasm and swelling of the myoglobin. Myoglobin and potassium
eyelids, photophobia, clouding of vision released from damaged skeletal muscles
may contribute to acute kidney injury, while
and temporary blindness.
hyperkalaemia developing within 612
hours of the bite may precipitate cardiac
arrest.
There is minimal or no local swelling
and involvement of local lymph nodes is 5.6 Symptoms and signs of
unusual. Generalized rhabdomyolysis is cobra-spit ophthalmia
the dominant effect of envenoming by (eye injuries from spitting cobras)
these snakes although patients without (Fig 72)
this feature have been described. Early If the spat venom enters the eyes, there is
symptoms include headache, a thick immediate and persistent intense burning,
feeling of the tongue, thirst, sweating stinging pain, followed by profuse watering
and vomiting. Generalized aching, of the eyes with production of whitish
stiffness and tenderness of the muscles discharge, congested conjunctivae, spasm
becomes noticeable between 30 minutes and swelling of the eyelids, photophobia,
and 3 hours after the bite. Trismus is clouding of vision and temporary blindness.
common (Fig 71a). Passive stretching of Corneal ulceration, permanent corneal
the muscles is painful (Fig 71b). Later, scarring and secondary endophthalmitis
there is progressive flaccid paralysis are recognized complications of African
starting with ptosis, as in other neurotoxic spitting cobra venom but have not been
envenomings. The patient remains described in Asia.

Figure 72: Bilateral conjunctivitis in a patient who had venom spat into both eyes by an Indo-Chinese spitting cobra
(Naja siamensis) (Copyright DA Warrell)

104 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Management of snakebites
in South-East Asia

ManageMent of snakebites
in south-east asia
105
106 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Management of snakebites
6
in South-East Asia
Essentials: asphyxiated patients. Clear airway, give
First-aid should be carried out immediately oxygen, establish intravenous access,
after the bite, by the victim or others monitor vital signs. Beware of removing
present. Most traditional methods are tight tourniquets before antivenom and
useless and harmful. To prevent deaths resuscitation facilities are available.
from respiratory paralysis or shock before
victims reach medical care, delay venom Key questions: Where (in which part of
spread with pressure-pad or pressure- your body) were you bitten? Point to the
bandage plus immobilization, accelerate place; When were you bitten and what
transport to hospital (improve ambulance were you doing then?; Where is the
services), and train accompanying medical snake that bit you? or What did it look
workers in airway management, assisted like; did anyone take a picture?; How
ventilation and resuscitation. The snake are you feeling now?
is valuable evidence, but should not be
pursued, killed or handled. Close-up Examination of the bitten part: extent
mobile phone images are useful. of tenderness/swelling, lymph nodes
draining bitten limb, early signs of
Recommended first-aid: reassurance, necrosis (blistering, demarcated altered
immobilization of the whole patient, pigmentation, putrefaction odour.
especially their bitten limb, accelerated General: blood pressure (postural drop
transport to medical care (summoned by indicates hypovolaemia), gingival sulci,
emergency telephone helpline) ideally in nose, skin and mucosae for evidence
recovery position. Unless neurotoxic elapid of bleeding, chemosis, abdominal
bite can be excluded, apply pressure-pad tenderness, loin pain and tenderness,
(simpler, more practicable than pressure- meningism, lateralising neurological
bandage immobilization). Never use, signs (asymmetrical pupils), impaired
recommend or condone tight (arterial) consciousness, bilateral ptosis, diplopia,
tourniquets. external ophthalmoplegia, mouth opening/
closing, trismus, tongue protrusion, facial
Medical treatment in dispensary or hospital muscles, gag reflex neck flexors broken
Rapid clinical assessment accompanies neck sign, swallowing, paradoxical
urgent resuscitation of shocked or respiration, fasciculations or myokymia,

ManageMent of snakebites
in south-east asia
107
measure ventilatory capacity. If adequately measuring INR and D-dimer unreliable in
ventilated, totally paralysed patient are snakebite victims.
fully conscious and can communicate by
flexing a digit. Conventional tests of brain Other laboratory tests: haemoglobin
death misleading. Generalised tender, concentration/haematocrit,
painful muscles and dark brown urine thrombocytopenia, neutrophil leucocytosis,
suggest rhabdomyolysis. Pregnant women: fragmented red cells (helmet cell,
suspect antepartum or postpartum schistocytes) signifying microangiopathic
haemorrhage, vaginal bleeding, premature haemolysis. Observe spontaneously
labour, fetal distress, intra-uterine fetal sedimented plasma for haemoglobinaemia/
death, abortion/stillbirth. myoglobinaemia.

Species diagnosis: expert identification Biochemical abnormalities: plasma


of dead snake or a mobile phone photo creatinine, urea/blood urea nitrogen and
image is useful. Otherwise, infer species potassium concentrations raised in acute
from the patients description and kidney injury (Russells viper, hump-nosed
circumstances of bite (e.g. nocturnal bite pit-viper, sea-snake envenoming). Elevated
while sleeping on ground suggests krait) aminotransferases and muscle enzymes
and clinical syndrome. (creatine kinase, aldolase etc.) indicate
local and generalized muscle damage (sea
Investigations/laboratory tests: 20 minute snakes, some kraits, some Australasian
whole blood clotting test (20WBCT) Elapidae and Russells viper bites).
is a simple, informative bedside test Hyponatraemia associated with krait bites.
requiring only a new, clean, dry, ordinary
glass tube, bottle, vial or syringe. Positive Urine examination: dipsticks test for
(non-clotting) result indicates severe blood, haemoglobin or myoglobin
consumption coagulopathy and need and proteinuria. Microscopy to detect
for immediate antivenom treatment. erythrocytes and red cell casts, indicating
False positive (non-clotting) 20WBCT glomerular bleeding, eosinophilia
results from use of plastic, polystyrene or suggesting acute interstitial nephritis.
polypropylene rather than ordinary glass,
or glass cleaned with detergent, soap Other investigations: chest radiography
or washing fluid that destroy surface- for detecting pulmonary oedema,
activation of blood coagulation. If new haemorrhages, infarcts, pleural effusions,
glass tubes not available, re-use ordinary secondary bronchopneumonia; ultrasound
glass vessels (e.g. antibiotic bottles), for assessing local envenoming, deep
washed with normal 0.9% saline for vein thrombosis, pleural and pericardial
intravenous infusion, without detergent or effusion and bleeding; echocardiography
other cleaning agent, dried in hot air. for myocardial dysfunction; CT and
MRI imaging for intracranial and
Other more sensitive laboratory tests spinal haemorrhages and infarcts and
of blood coagulation: International osteomyelitis at the bite site; ECG for
Normalized Ratio (INR) based on arrhythmias, myocardial damage, evidence
prothrombin time (PT) (> or =1.2 is of hyperkalaemia.
abnormal), activated partial thromboplastin
time (aPPT), fibrin(ogen) related antigens Antivenom treatment
(fibrin degradation products -FDP) or Antivenom (= antivenin, anti-snakebite
D-dimer. Point-of-care (bedside) devices for serum, ASV etc.) is the only specific

108 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
antidote to snake venom. A most
important decision in managing
A most important decision in managing
snakebite victims is whether or not they
need antivenom. It is immunoglobulin snakebite victims is whether or not they
[usually pepsin-refined F(ab)2 fragments
need antivenom.
of whole IgG] purified from plasma
of horses or sheep hyperimmunised
with venoms of one (to make mono-
specific antivenom) or more (to make haemolysis/generalized rhabdomyolysis);
poly-specific antivenom) snake species, supporting laboratory evidence.
medically the most important species in a Local envenoming: local swelling involving
particular geographical area. Paraspecific more than half bitten limb (in absence
neutralization of venoms of closely related of tourniquet) within 48 hr of the bite;
species is possible but not certain. Indian swelling after bites on digits; rapid
polyvalent anti-snake venom serum extension of swelling beyond wrist/ankle
(ASV) is raised against venoms of their big within few hours of bites on hand/foot);
four species: spectacled cobra (N. naja); enlarged tender lymph node draining
common krait (B. caeruleus), Russells viper bitten limb
(D. russelii), saw-scaled viper (E. carinatus),
but other species, now recognized as Antivenom should be given only
being important, are not covered. Thai when benefits exceeds risks. Since it is
Red Cross Society manufactures neuro expensive and in limited supply, it must
polyvalent snake antivenin covering 4 not be used indiscriminately. It should be
elapids and haemato polyvalent snake given as soon as it is indicated and as long
antivenin covering 3 vipers. as anti-haemostatic abnormalities persist,
even two weeks after the bite. It is unlikely
Design, quantity, quality, stability, safety to prevent/limit local tissue damage
and dosage guidelines of antivenoms unless given within a few hours of
require review and improvement. the bite.

Antivenom treatment is indicated Antivenom reactions: many patients


if/when patients with proven/ develop early (within a few hours) or
suspected snakebite develop one late (after 5 days or more) reactions.
or more of the following signs. Depending on type of antivenom and
Systemic envenoming: haemostatic dose, the incidence may be as high as
abnormalities [spontaneous systemic 81% (43% severe) of early anaphylactic
bleeding, coagulopathy (+ve non-clotting or pyrogenic reactions or as low as 3.5%.
20WBCT, INR >1.2, or prothrombin time IgE-mediated Type I hypersensitivity after
>4-5 seconds longer than control), or previous exposure to equine serum is
thrombocytopenia; neurotoxicity (bilateral uncommon.
ptosis, external ophthalmoplegia, paralysis
etc.); cardiovascular abnormalities Early anaphylactic reactions (1 - 180
(hypotension, shock, cardiac arrhythmia, minutes after starting antivenom) can
abnormal ECG); Acute kidney injury have all classic features of anaphylaxis
(oliguria/anuria, rising blood creatinine/ from urticaria to life-threatening shock,
urea); haemoglobin-/myoglobin-uria bronchospasm and angio-oedema. Most
(dark brown/black urine, +ve urine are attributable to complement activation
dipsticks, other evidence of intravascular by IgG aggregates/residual Fc fragments,

ManageMent of snakebites
in south-east asia
109
or stimulation of mast cells/basophils by intramuscular injection of
antivenom proteins. 0.1% adrenaline, initial adult dose
0.5 ml/mg (0.01 mg/kg body weight for
Pyrogenic (endotoxin) reactions (within 1-2 children). Since severe, life-threatening
hours) involve rigors, fever (risk of febrile anaphylaxis can evolve rapidly, adrenaline
convulsions in children), vasodilatation, must be available at the bed-side
hypotension and a fall in blood pressure. and should be given at the first sign
Attributable to pyrogen contamination of anaphylaxis (e.g. when itching,
during manufacture. tachycardia, restlessness develop and a
few spots of urticaria appear). Repeat
Late (serum sickness-type) reactions (1-12, adrenaline every 5-10 minutes if reaction
mean 7, days after treatment) involve persists or worsens. Adrenaline safe in
fever, nausea, vomiting, diarrhoea, itching, pregnancy. In case of asthmatic symptoms,
recurrent urticaria, arthralgia, myalgia, given salbutamol bronchodilator. After
lymphadenopathy, periarticular swellings, adrenaline, give intravenous antihistamine
mononeuritis multiplex, proteinuria, anti-H1 blocker (e.g. chlorphenamine
immune complex nephritis, rarely maleate, adults 10 mg, children 0.2 mg/
encephalopathy. kg intravenously) and hydrocortisone
(adults 100 mg, children 2 mg/kg body
Prediction: skin and conjunctival weight). Anaphylactic shock unresponsive
hypersensitivity tests, often to adrenaline is treated by laying
recommended in package inserts patient supine, legs elevated, and giving
predict acquired IgE-mediated Type intravenous volume replacement (0.9%
I hypersensitivity to horse/sheep saline, adults 1-2 litres rapidly). Consider
proteins, but not large majority of early intravenous adrenaline infusion (adults
(anaphylactic) or late (serum sickness type) 1mg/1.0 ml of 0.1% solution in 250 ml
antivenom reactions. Their use is strongly IV fluid) infused at 1560 drops/min
discouraged. using micro-dropper burette chamber, or
dopamine. Unresponsive bronchospasm
Prevention: or angioedema is treated with optimal
A powerful, well-designed study in Sri nebulised/inhaled and/or parenteral
Lanka showed that adrenaline (0.25 ml/ bronchodilator and oxygen.
mg of 0.1% solution subcutaneously)
given before antivenom was started Pyrogenic reactions are treated by
reduced severe reactions by 43% (95% physical cooling (undressing, tepid
CI 2567) at 1 h and by 38% (95% CI sponging, fanning) and giving antipyretic
2649) up to and including 48 h after paracetamol. Intravenous fluids should be
antivenom administration; hydrocortisone given to correct hypovolaemia. Patients
(200 mg intravenously) and promethazine with features of anaphylaxis should be
(25 mg intravenously) were ineffective. given adrenaline.
Hydrocortisone negated benefit of
adrenaline. Dilution and slow infusion After recovery from early reactions,
(10-120 minutes) does not alter risk of cautiously resume and complete
reactions. administration of the dose of antivenom.

At the earliest sign of early anaphylactic Late (serum sickness) reactions respond
antivenom reaction, temporarily suspend to 5-day course of oral antihistamine or,
antivenom administration and give failing that, 5-day course of prednisolone.

110 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Supply, selection, storage and shelf-life of Geographical intra-species variation, in
antivenom venom composition and antigenicity,
explains why antivenoms raised against
Polyvalent (polyspecific) antivenoms are venom of a species (e.g. Russells viper) from
preferred in many countries because one area (e.g. Tamil Nadu, India) may not
of problems with specific diagnosis. be effective in patients envenomed by the
Antivenom should be given only if its same species elsewhere in its geographical
stated range of specificity and paraspecific range (e.g. Kerala, Maharashtra). Regional
neutralization includes the species known polyspecific antivenoms may not cover
or suspected to have been responsible for all medically important snakes (e.g. N.
the bite. Lyophilised antivenoms (shelf life kaouthia, H. hypnale, T. (Craspedocephalus)
about 5 years) are stored <25C, liquid malabaricus, T (T.) erythrurus in parts of
antivenoms (shelf life 2-3 years) at 2-8 India).
C. Ideally, antivenoms should be used
before stated expiry dates, antivenoms Response to antivenom includes rapid
retain useful activity for months or even decrease in general malaise (?placebo
years after these dates. In patients with effect), cessation of spontaneous systemic
severe envenoming, recently expired bleeding (in 15-30 minutes), restoration
antivenoms may be considered if there is of blood coagulability (in 3-9 hours),
no alternative. normalisation of blood pressure in shocked
patients (in 30-60 minutes) and sinus
Intravenous administration is mandatory, rhythm, reversal of post-synaptic type
either by slow push injection (maximum neurotoxicity (after cobra bite) (after 30
2ml/minute) or by intravenous infusion, minutes), cessation of active haemolysis
diluted in 5 ml of isotonic fluid/kg and rhabdomyolysis (within a few hours).
body weight, over 30-60 minutes.
Intramuscularly administered antivenom is After an initial response to antivenom,
poorly bioavailable. This route should be signs of systemic envenoming may recur
considered only in the absence of anyone within 24-48 hours. Improved perfusion of
capable of giving an intravenous injection. the bite site following correction of shock/
hypovolaemia increases venom absorption
Initial dose of antivenom: from bite site depot and redistribution
Guidance on average initial dose of a of venom from tissues to vascular space at
particular antivenom, appropriate for a time when therapeutic antivenom has
envenoming of different severities, in been eliminated.
patients bitten by different species based
on clinical trials is rarely available. Usually, After the first dose of antivenom, the
dosages quoted on manufacturers initial dose should be repeated 6 hours
package inserts are based on laboratory later if blood remains incoagulable, or
mouse LD50s and ED50s which are 1 hour later if spontaneous systemic
unreliable clinically. In practice, choice of bleeding continues, or neurotoxic or
initial dose is usually empirical. Regimens cardiovascular signs persist or deteriorate.
based on a higher initial (loading) dose are However, further doses of antivenom have
more logical than low doses repeated over no proven value in paralysed patients who
several days. are being ventilated.

Antivenom failure (ineffectiveness) may be When no appropriate antivenom is


due to batch-to-batch variations in potency. available, patients must be treated

ManageMent of snakebites
in south-east asia
111
For acute airway obstruction (e.g.
angioedema) perform cricothyroidotomy.
if patient is unresponsive, summon
assistanceby phone, open and maintain Resuscitation: if patient is unresponsive,
airway using head tilt - chin lift or jaw summon assistanceby phone, open and
maintain airway using head tilt - chin lift
thrust manoeuvres to improve air flow or jaw thrust manoeuvres to improve air
by dislodging tongue and reopening flow by dislodging tongue and reopening
upper airway. Remove foreign material
upper airway. from upper airway (suction or forceps, not
finger) and insert oropharyngeal (Guedel)
airway. Administer oxygen by any available
conservatively. Respiratory paralysis: means and assess breathing. If breathing
try anticholinesterases, but without is adequate, lay victim in recovery position
delaying assisted ventilation. Haemostatic (important because of venom-induced
abnormalities: rest in bed to avoid trauma, vomiting, bleeding and hypersalivation
transfuse cryoprecipitate, fresh frozen with loss of airway-protective reflexes), but
plasma, fresh whole blood and platelets. check breathing every 2 minutes.
Shock, myocardial damage: correct
hypovolaemia and consider vasopressor If breathing is inadequate or not
drugs. In hypotension with bradycardia, try discernible, respiratory rate low,
atropine. Acute kidney injury: conservative respirations shallow, patient taking agonal
treatment or renal replacement therapy. (gasping) breaths, central cyanosis, finger
Rhabdomyolysis: correct hypovolaemia oximeter oxygen saturation <90%, end-
with intravenous fluid, acidosis with tidal PCO2 high or increasing - assisted
sodium bicarbonate. Severe local ventilation is required.
envenoming: surgical intervention,
prophylactic broad spectrum antimibiotics. Techniques:
If no health facilities are immediately
Supportive/ancillary treatment available - Expired Air Resuscitation
Neurotoxic envenoming
Indications for intubation: imminent In health care centre - Non-invasive
respiratory arrest (respiratory distress, ventilation using bag-mask/bag-mask-valve
breathing absent/inadequate); neck ventilation
muscle weakness with shallow respiration
or paradoxical breathing; secretions In hospital - Invasive Ventilation (intubation
pooling in pharynx with loss of gag/ and mechanical ventilation) for Type
cough reflexes; upper airway obstruction I respiratory failure (primary failure of
with stridor (secondary to anaphylaxis oxygenation as in pulmonary oedema
angioedema); oxygen saturation <90% in Russells viper envenoming) and Type
(equivalent to Pa02 <60 mmHg) despite II respiratory failure (primary ventilatory
high flow oxygen; respiratory acidosis failure due to respiratory muscle paralysis
(hypoxia PaO2 < 60 mm Hg with PaCO2 or obstruction as in elapid envenoming).
> 45 mm Hg)
Indications for invasive ventilation:
Insert cuffed endotracheal tube using patients who, despite receiving oxygen by
laryngoscope under sedation,or laryngeal mask or nasal catheters remain tachpnoeic
mask airway or i-gel supraglottic airway. (respiratory rate > 25/min), have

112 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
paradoxical respirations and deteriorating (nausea, vomiting, acidotic breathing,
ventilatory capacity, hypoxia, respiratory hiccups, fetor, drowsiness, confusion,
acidosis. Sedate them with fentanyl and coma, flapping tremor, muscle twitching,
midazolam, or morphine and lorazepam. convulsions, pericardial friction rub, signs
Ensure adequate hydration, nutrition, of fluid overload). Patients with any of
physiotherapy, regular turning to prevent these features should be monitored for
pressure areas and lung collapse, eye care other clinical signs of uraemic syndrome,
and safe weaning from ventilation. pulse rate, postural blood pressure, height
of jugular venous pulse, respiratory rate,
Trial of anticholinesterase: temperature, auscultation of lung bases
after making baseline observations, give for crepitations, fluid balance chart and/or
atropine sulphate intravenously followed daily weight.
by intramuscular neostigmine (or, ideally,
slow intravenous injection of short-acting Most patients with AKI become oliguric
edrophonium chloride Tensilon, but (urine output < 400 ml/day or < 30 ml
rarely available), and observe over next (children < 0.5ml/kg bodyweight /hour).
10-60 minutes for disappearance of ptosis Conservative management may tide the
or improved ventilatory capacity. Treat patient over, avoiding the need for renal
patients who respond convincingly with replacement therapy (dialysis).
repeated neostigmine and atropine.
In patients with intravascular volume
Hypotension and shock depletion: establish intravenous access,
Primary causes are anaphylaxis, give cautious fluid challenge (adult 250-
vasodilatation, cardiotoxicity, 500 ml of isotonic saline over one hour).
hypovolaemia; secondary causes are Stop challenge immediately if pulmonary
antivenom reactions, respiratory failure, oedema develops. If the urine output does
acute pituitary adrenal insufficiency, not improve, perform furosemide stress/
septicaemia challenge test, if that fails to increase
urine output, switch to conservative
Measure postural change in blood pressure management.
or passive leg raising test to determine
fluid responsiveness. Control fluid therapy Conservative management of AKI: no
using jugular/central venous pressure, further diuretics, restrict fluid intake to
respiratory rate, detection of crepitations. previous days output plus insensible
Selective vasoconstrictor such as dopamine losses (500-1000 ml/day) and refer to
may be used. renal unit. Diet bland, high calorie, normal
protein, low potassium, low in salt.
Acute pituitary/adrenal insufficiency
may occur in victims of Russells viper Measure serum/plasma urea,
bites (Myanmar, India, Sri Lanka). creatinine and electrolytes daily until
Hydrocortisone is life-saving in these cases. renal failure is resolving. Examine ECG
for evidence of hyperkalaemia, for which
Oliguria and acute kidney injury (AKI) emergency treatments include calcium
Impending AKI signalled by abrupt gluconate, 2 agonist aerosol inhaler,
reduction in kidney function over 48 50% dextrose with insulin and sodium
hours: decreasing/no urine output, bicarbonate, followed by a low potassium
increased/increasing serum creatinine diet. Severe acidosis is corrected with
concentration, clinical uraemia syndrome sodium bicarbonate.

ManageMent of snakebites
in south-east asia
113
Renal replacement therapy/dialysis secondary infections involve aerobic and
Patient with clinical uraemia anaerobic bacteria from the snakes oral
(encephalopathy, pericarditis etc.), fluid flora, patients skin and asterile incisions.
overload not responding to diuretics, Tetanus toxoid booster and prompt
hyperkalaemia or hyperkalaemic ECG antibiotic treatment of necrotic wounds is
changes, symptomatic acidosis, raised recommended.
plasma/serum creatinine and/or urea
should be transferred to a health facility Compartmental syndromes are often
where they can receive renal replacement misdiagnosed and fasciotomies performed
therapy. unnecessarily. Since classical signs of
compartment syndrome are difficult
In patients with AKI associated with to assess in snake-bitten limbs, direct
thrombotic microangiopathy, there is measurement of intracompartmental
no evidence for plasmapheresis using pressure is mandatory and fasciotomy
cryosupernatant. In patients with must not be attempted before
myoglobinuria or haemoglobinuria, haemostatic disturbances have been
correct hypovolaemia, maintain urine corrected by antivenom.
output 200-300 ml/hour, correct severe
acidosis with bicarbonate, promote Rehabilitation: conventional
alkalinise diuresis, continuing until CK physiotherapy accelerates functional
level <5000 U. recovery of the bitten limb, but is often
forgotten.
Diuretic phase of AKI: some patients
develop persistent polyuria of 5-10 Discharge assessment: discussion,
litres/24 hours and may become volume encouragement, follow-up, warning
and electrolyte depleted. about late serum sickness-type reactions
and advice about reducing risk of future
Chronic kidney disease: oliguria and snakebites are important.
dialysis-dependence for more than 4
weeks demands referral to nephrologist Management of cobra spit ophthalmia:
to consider kidney biopsy. first aid is irrigation of affected eyes and
other mucous membranes with liberal
Haemostatic disturbances: usually quantities of water; medical treatment
corrected by antivenom, but recurrent involves analgesia, exclusion of corneal
coagulopathy is possible. Exceptionally, in abrasions and application of prophylactic
patients already treated with antivenom topical antibiotics.
but who have persistent severe bleeding
or require urgent surgery, restoration Management of snakebites at different
of coagulability can be accelerated with levels of the health service: all levels
blood products. of the health service can contribute
to the management of patients with
Treatment of the bitten part: suspected snakebite. In rural areas, where
Nurse painful, swollen limb in the most snakebites are most common, transfer
comfortable position, avoiding excessively to a hospital may not be feasible, and
elevation. Leave blisters, aspirate so a lower level of health facility must
abscesses and culture pus. Necrotic tissue cope with these medical emergencies.
demands early surgical dbridement Training of doctors, nurses, dispensers,
and split-skin grafting. Primary and health assistants and paramedics in

114 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
diagnosis (including snake identification), Unfortunately, most of the traditional,
early management and indications for and popular, available and affordable first aid
practicalities of administering antivenom is methods have proved to be useless or
essential. even frankly dangerous. These methods
include: making local incisions or pricks/
Snakebite treatment in developing punctures (tattooing) at the site of the
countries is challenging, creating many bite or in the bitten limb, attempts to
management problems. It is, therefore, of suck the venom out of the wound, use
utmost importance to train doctors and of (black) snake stones, tying tight bands
other health- care workers in the effective (tourniquets) around the limb, electric
care of snakebite patients. shock, topical instillation or application of
chemicals, herbs or ice packs. Local people
6.1 Stages of management may have great confidence in traditional
The following steps or stages are often (herbal) treatments, but they must not be
involved: allowed to delay medical treatment or to
do harm.

Management of snakebite
First-aid treatment Aims of first aid
Transport to hospital reassure the snakebite victim
Rapid clinical assessment and attempt to delay systemic
resuscitation absorption of venom
Detailed clinical assessment and preserve life and prevent
species diagnosis complications before the patient
Investigations/laboratory tests can receive medical care at a
Antivenom treatment dispensary or hospital
Observing the response to control distressing or dangerous
antivenom early symptoms of envenoming
Deciding whether further dose(s) arrange the transport of the
of antivenom are needed patient to a place where they
Supportive/ancillary treatment can receive medical care
Treatment of the bitten part ABOVE ALL, AIM TO DO NO
HARM!
Rehabilitation
Treatment of chronic
complications
6.2.2 The danger of respiratory
Advising how to avoid future bites paralysis and shock
The greatest fear is that a snakebite victim
might develop fatal respiratory paralysis
6.2 First-aid treatment or shock before reaching a place where
6.2.1 Principles of first-aid they may be resuscitated (Looareesuwan
First-aid treatment is carried out et al., 1988). This risk may be reduced
immediately or very soon after the bite, by speeding up transport to hospital,
before the patient reaches a dispensary by improving free ambulance services
or hospital. It can be performed by the (Gimkala et al., 2016) or by recruiting
snakebite victim himself/herself or by village-based motor cyclist volunteers
anyone else who is present and able. who transport the victim propped

ManageMent of snakebites
in south-east asia
115
hands as even a severed head can
bite! Several close-up mobile phone
images of the snake should be taken if
possible to allow expert identification.

MOST TRADITIONAL FIRST-AID


METHODS SHOULD BE DISCOURAGED:
THEY DO MORE HARM THAN GOOD!

6.2.3 Recommended first-aid methods


Reassure the victim who may be
very anxious. Reassurance will drive
away their fear and excitement, slow
the patients heart rate and reduce
the spread of venom. Grounds for
reassurance include the possibility
of a dry bite even if the snake was
venomous, the usually slow evolution
Figure 73: Evacuation of a snakebite victim showing early signs of paralysis by
a village-based motorcycle volunteer in the Terai region of Nepal. The victim is of severe envenoming allowing time
supported between the driver and a pillion passenger (Copyright Dr Sanjib Sharma) for treatment, and the effectiveness
[CAUTION - If this method of transport has to be employed, because of local
conditions and the terrain, ideally helmets should be worn and the legs of the
of modern medical management of
passengers protected from exhaust burns] snakebite.

upright between the driver in front and Immobilize the whole of the patients
a supporting pillion passenger behind. body by laying him/her down in a
This has proved effective in villages in the comfortable and safe position, ideally
Nepal Terai (Sharma et al., 2013) (Figure in the recovery position (lying prone
73). Medical workers can be trained on the left side in case vomiting
in airway management and assisted threatens to result in aspiration), and
ventilation (see below). The special danger immobilize the bitten limb with a splint
of rapidly developing paralytic envenoming or sling. Any movement or muscular
after bites by some elapid snakes has contraction, even undressing or
prompted the use of pressure-bandage walking, will increase absorption and
immobilization (Sutherland et al., 1979) spread of venom by squeezing veins
and pressure-pad immobilization (Anker and lymphatics.
1982; Tun-Pe et al.,1995b )(ANNEX 4).
Pressure bandage immobilization requires Unless the possibility of an elapid
equipment (long elasticated bandages and bite can confidently be excluded,
splints) (Canale et al., 2009; Currie et al., apply pressure-pad immobilization
2008 ) and skill. (See ANNEX 4), or, if the necessary
equipment and skills are available,
As far as the snake is concerned - do pressure-bandage immobilization. In
not attempt to kill it as this may be Myanmar, the pressure-pad method
dangerous.However, if the snake has has proved effective in reducing spread
already been killed, it should be taken to of venom in victims of Russells viper
the dispensary or hospital with the patient bite (Tun Pe et al., 1995b). Pressure-
in case it can be identified. However, do bandage immobilization has not
not handle the snake with your bare become widely used in this Region,

116 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Figure 74: Gangrenous
because provision of the necessary 6.3 Transport to hospital limb caused by a tight
equipment (long, wide elasticated Emergency Helpline Numbers tourniquet after a bite by
Malayan pit viper
bandages), training and skills required Linkage with an emergency helpline (Copyright DA Warrell)
to apply it safely and reliably have number (e.g. in India 108 see http://
proved impossible to achieve. The www.emri.in/) can speed up the
pressure-pad immobilization method is transport of a patient to a higher
preferred and recommended as being referral centre when emergency
simpler and more practicable (O). treatment is required. This will decrease
delays in accessing emergency care and
Avoid any interference with the bite reduce mortality. Information about
wound (incisions, rubbing, vigorous helpline numbers could be widely
cleaning, massage, application of herbs disseminated.
or chemicals) as this may introduce
infection, increase absorption of the The patient must be transported to a
venom and increase local bleeding. place where they can receive medical
care (dispensary or hospital) as quickly,
CAUTION Delay the release of tight but as safely and comfortably as
bands, bandages and ligatures: if the possible. Any movement, but especially
patient has already applied these very movement of the bitten limb, must be
popular methods of first-aid, they should reduced to an absolute minimum to
not be released until the patient is under avoid increasing the systemic absorption
medical care in hospital, medical staff and of venom. Any muscular contraction
resuscitation facilities are available and will increase spread of venom from the
antivenom treatment has been started site of the bite in veins and lymphatics.
(Watt et al., 1988) see Caution below. Where a conventional motor vehicle
ambulance is not available or feasible,
Tight (arterial) tourniquets must stretcher, bicycle, motorbike (Patel
never be recommended or condoned! and Ekkiswata, 2010) - by recruiting
Traditional tight (arterial) tourniquets. village-based motorbike owners/
If applied tightly around the upper part cyclists (Sharma et al., 2013) (Fig 73),
of the limb, these bands, bandages or cart, horse, train or boat may have to
ligatures are extremely painful as the limb be considered, or the patient can be
becomes ischaemic and are very dangerous carried (e.g. using the firemans lift
if left in place for long periods. Many method). If possible, patients should be
gangrenous limbs have resulted! placed in the recovery position during
(Fig 74) transit, in case they vomit.

ManageMent of snakebites
in south-east asia
117
6.4 Treatment in the
dispensary or hospital Rapid primary clinical assessment
(Warrell 1990; 1995) and resuscitation: ABCDE
approach
Airway
Medical management of
envenomed patients in dispensary Breathing (respiratory movements)
or hospital Circulation (arterial pulse)
Rapid primary clinical assessment Disability of the nervous system (level
and resuscitation of consciousness)
Detailed clinical history, physical Exposure and environmental control
examination and species diagnosis (protect from cold, risk of drowning
Simple test of blood coagulability etc)
[20-minute-whole-blood-clotting-
test (20WBCT)]
Airway patency, respiratory movements,
Antivenom: indications, initial arterial pulse and level of consciousness
and repeated dosage, response, must be checked immediately. Record the
reactions vital signs.
Treatment of organ and system
failures The Glasgow Coma Scale cannot be used
to assess the level of consciousness of
Treatment of the bitten limb
patients paralysed by neurotoxic venoms
Rehabilitation, restoration of (see below).
function
Advice at discharge from hospital Clinical situations in which
and follow-up snakebite victims might require
urgent resuscitation:
Preventive health education a) Profound hypotension and shock:
towards reducing risk of future resulting from direct cardiovascular
bites effects of the venom or secondary
effects, such as hypovolaemia, release
of inflammatory vasoactive mediators,
6.4.1 Rapid primary clinical haemorrhagic shock or rarely primary
assessment and resuscitation anaphylaxis induced by the venom itself.
Snakebite is a medical emergency:
history, symptoms and signs must be b) Terminal respiratory failure: from
obtained rapidly so that appropriate, progressive neurotoxic envenoming
urgent and life-saving treatment can that has led to paralysis of the
be given respiratory muscles; or simple airway
obstruction.
Cardiopulmonary resuscitation may be
needed, including administration of c) Respiratory distress: from
oxygen and establishment of intravenous generalized increase in capillary
access. permeability (Russells viper bite victims)

118 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
d) Sudden deterioration: or rapid
development of severe systemic
A common early symptom of systemic
envenoming after releasing a tight
tourniquet or compression bandage envenoming is vomiting and, after bites
(see Caution above). by some species, fainting and collapsing
e) Cardiac arrest: precipitated by (sometimes causing injury) with transient
hyperkalaemia resulting from skeletal unconsciousness and features of anaphylaxis
muscle breakdown (rhabdomyolysis)
after bites by sea snakes, certain kraits
(angioedema etc.)
and Russells vipers.

f) Late results of severe envenoming: take a picture? If the snake has been
in someone arriving days/weeks after the killed and brought, or an adequate
bite: with severe bleeding/blood clotting photo image is available (e.g. taken
disturbances, acute kidney injury or by mobile phone at the scene of the
septicaemia complicating local necrosis. bite), its correct identification can be
very helpful. If it is obviously a harmless
6.4.2 Detailed clinical assessment and species (or not a snake at all!), the
species diagnosis patient can be quickly reassured and
discharged from hospital. If it was
6.4.2.1 History killed and left at home, send someone
A precise history of the circumstances to fetch it, in whatever condition!
of the bite and the progression of local 4. How are you feeling now?
and systemic symptoms and signs is very
important. Have any symptoms of envenoming
developed?
Four useful initial questions:
1. Where (in what part of your body) were A common early symptom of systemic
you bitten? Point to the place Observe envenoming is vomiting and, after
any local signs fang marks, swelling, bites by some species, fainting and
bruising, persistent bleeding, pre- collapsing (sometimes causing injury)
hospital traditional treatment. with transient unconsciousness and
features of anaphylaxis (angioedema etc.).
2. When were you bitten and what were Patients who become defibrinogenated
you doing when were you bitten? If or thrombocytopenic may begin to bleed
the bite was very recent, there may not from old, partially-healed wounds as well
have been time for signs of envenoming as bleeding persistently from the fang
to develop. If the patient was bitten at marks. The patient should be asked how
night while asleep, a krait was probably much urine they have passed since the bite
implicated; if in a paddy field, a cobra or and whether it was a normal colour or very
Russells viper; if while tending fruit trees, dark (implying haemoglobin/myoglobin
a green pit viper; if while swimming or uria). Patients who complain of sleepiness,
wading in water a cobra (fresh water) or drooping eyelids or blurred or double
sea snake (sea or estuary). vision may have neurotoxic envenoming.
An important early symptom of sea snake
3. Where is the snake that bit you? envenoming that may develop as soon as
or What did it look like; did anyone 30 minutes after the bite is generalized

ManageMent of snakebites
in south-east asia
119
pain, tenderness and stiffness of muscles lines noted. A bitten limb may be
and trismus. tensely oedematous, cold, immobile,
painful on passive movement and
with impalpable arterial pulses. These
Early clues that a patient has appearances may suggest intravascular
severe envenoming: thrombosis, which is exceptionally rare
after snakebite, or a compartmental
Snake identified as a very
syndrome, which is uncommon. If
dangerous one or a large
possible, intracompartmental pressure
specimen
should be measured (see Annex 5) and
Widely spaced fang puncture the blood flow and patency of arteries
marks or evidence of multiple and veins assessed (e.g. by doppler
strikes ultrasound). Early signs of necrosis may
Rapid early extension of local include blistering, demarcated darkening
swelling from the site of the bite (easily confused with bruising) (Fig 54
d, e, Fig 69) or paleness of the skin, loss
Early tender enlargement of local of sensation and a smell of putrefaction
lymph nodes, indicating spread of (rotting flesh).
venom in the
lymphatic system General examination: Measure the
blood pressure (sitting up and lying
Early systemic symptoms:
to detect a postural drop indicative of
collapse (hypotension, shock),
hypovolaemia see 14 Management
nausea, vomiting, diarrhoea,
of hypotension and shock) and heart
severe headache, heaviness
rate. Examine the skin and mucous
of the eyelids, inappropriate
membranes for evidence of petechiae,
(pathological) drowsiness or early
purpura, discoid haemorrhages (Fig
ptosis/ophthalmoplegia
64b) and, ecchymoses, the conjunctivae,
Early spontaneous systemic for haemorrhages (Fig 63) and
bleeding chemosis (Fig 58), and the optic fundi
No urine passed since the bite for retinal haemorrhages. Examine
the gingival sulci thoroughly, using a
Passage of dark brown/black urine torch and spatula/tongue depressor, as
these may show the earliest evidence
of spontaneous systemic bleeding (Fig
6.4.2.2 Physical examination 60a), a very valuable sign. Examine
This should start with careful assessment the nose for epistaxis. Abdominal
of the site of the bite and signs of local tenderness may suggest gastrointestinal
envenoming. or retroperitoneal bleeding. Loin (low
back) pain and tenderness suggest
Examination of the bitten part: The acute renal ischaemia (Russells viper
extent of swelling, which is usually also bites). Subarachnoid haemorrhage is
the extent of tenderness to palpation suggested by neck stiffness (meningism)
(start proximally and squeeze gently (Fig 60b). Intracranial haemorrhage is
while watching the patients expression), suggested by lateralising neurological
should be recorded. Lymph nodes signs, asymmetrical pupils, convulsions or
draining the limb should be palpated and impaired consciousness (in the absence
overlying ecchymoses and lymphangitic of respiratory or circulatory failure).

120 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
5.4.2.3 Neurotoxic envenoming:
Bulbar and respiratory paralysis
To exclude early neurotoxic envenoming,
ask the patient to look up and observe
whether the upper lids retract fully
(Fig 75). Ask about diplopia and test
eye movements for evidence of early
external ophthalmoplegia (Fig 66).
Check the size and reaction of the
pupils. Ask the patient to open their
mouth wide and protrude their tongue;
early restriction in mouth opening may
indicate trismus (sea snake envenoming)
(Fig 71a) or, more often, paralysis of
pterygoid muscles (Fig 76).

Check other muscles innervated by the


cranial nerves (facial muscles, tongue,
gag reflex etc.).

The muscles flexing the neck may be


paralysed, giving the broken neck sign Figure 75: Examination for ptosis in a patient with
neurotoxic envenoming by a Papuan taipan. This is
(Fig 77). usually the earliest sign of neurotoxic envenoming
(Copyright DA Warrell)

Figure 77: Broken neck sign in a child envenomed by a krait in Sri Lanka Figure 76: Examination for ability to open the mouth
(Copyright DA Warrell) and protrude the tongue in a patient with neurotoxic
envenoming from the Malayan krait (Copyright DA Warrell)

Can the patient swallow or are (abdomen expands rather than the chest
secretions accumulating in the pharynx, on attempted inspiration) indicates
an early sign of bulbar paralysis? Ask that the diaphragm is still contracting
the patient to take deep breaths in but that the intercostal muscles and
and out. Paradoxical respiration accessory muscles of inspiration are

ManageMent of snakebites
in south-east asia
121
profound generalized flaccid paralysis from
neurotoxic envenoming are fully conscious
(Fig 78).

Lifting their paralysed upper eyelids allows


them to see their surroundings which
they find very reassuring. If asked, they
may still be able to flex a finger or toe,
allowing simple communication. However,
because their eyes are closed and they do
not move or speak, they are commonly
assumed to be unconscious or even dead.
Conventional tests of brain death can
prove misleading (Dayal et al., 2014) and
there are media reports of a child with
snakebite paralysis who was about to be
placed on a funeral pyre before she was
seen to be breathing and of snakebite
victims being rescued when they were
about to be buried alive.

Test the tone and power of limb muscles


and the superficial and deep tendon
reflexes. Look for lateralising signs
suggesting intracranial haemorrhage
or thrombosis. Observe involuntary
movements such as fasciculations/
myokymia (as in anticholinesterase
Figure 78: Generalized flaccid paralysis in a patient envenomed by a common overdose or organo-phosphate poisoning)
krait in Sri Lanka. The patient was fully conscious and was able to communicate by
flexing his index fingers (Copyright DA Warrell)
and writhing choreo-athetotic movements
suggesting hypoglycaemia (Russells viper
envenoming).
paralysed. Where possible, serial objective
measurements of ventilatory capacity
are very useful. Use a peak flow metre, Do not assume that snake-bitten
spirometer (to measure FEV1 and FVC) patients are unconscious or even
or ask the patient to blow into the tube irreversibly brain dead just
of a sphygmomanometer (mercury or because their eyes are closed,
aneroid) to record the maximum expiratory they are unresponsive to painful
pressure (mmHg) or use the single-breath stimuli, are areflexic, or have
counting test (SBC). SBC measures how fixed dilated pupils. They may
far the patient can count at two numbers merely be paralysed! They may
per second in a normal speaking voice be severely paralysed and lack
after taking a maximal inhalation (Ali et motor responses or spontaneous
al., 2011). A finger oximeter will detect eye movements mimicking coma
decreasing arterial oxygen saturation. (locked-in syndrome). Check pulse,
Remember that, provided their lungs heart sounds and, if possible, ECG.
are adequately ventilated, patients with

122 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
6.4.2.4 Generalized rhabdomyolysis carinatus) bites in SW India (Joseph et
In victims of envenoming by sea snakes, al., 2007); or mistaken for Russells viper
some species of kraits (B. niger and B. (Daboia russelii) bites in Sri Lanka, since
candidus), some Australasian elapids and available polyvalent antivenoms do not
Russells vipers in Sri Lanka and South cover the venom of this species. An
India, muscles, especially of the neck, image of the dead snake may be taken
trunk and proximal part of the limbs, may and then easily sent by mobile phone,
become tender and painful on active or Whats App, or internet to a local,
passive movement (Fig 71b) and later national or international snake expert or
may become paralysed. In sea snakebite Poisons Information Centre for definitive
envenoming, there is pseudotrismus that identification. Otherwise, the species
can be overcome by sustained pressure responsible must be inferred indirectly
on the lower jaw. Myoglobinuria may be from the patients description of the
evident 3 hours after the bite (Figs 67, snake, circumstances of the bite (e.g.
71c). nocturnal bites by kraits in people sleeping
on the ground, Ariaratnam et al., 2008),
6.4.2.5 Examination of pregnant and the clinical syndrome of symptoms
women and signs (see above and Annexes 1
Potential complications of envenoming and 2). This was particularly important
in pregnancy include antepartum and in countries where only monospecific
postpartum hemorrhage indicated by antivenoms are available.
vaginal bleeding, premature labour,
abortion/stillbirth, fetal distress or intra- 6.6 Investigations/
uterine fetal death. If possible, uterine laboratory tests
contractions and fetal heart rate should 6.6.1 20 minute whole blood
be monitored continuously. Fetal distress clotting test
may be signalled by fetal bradycardia, (20WBCT) (Warrell et a., 1977;
tachycardia, or late deceleration after Sano-Martins et al., 1994) (Fig 79)
each uterine contraction. If there is This very useful and informative bedside test
vaginal bleeding or the need for imminent requires very little skill and only one piece of
surgery, correction of antihaemostatic
abnormalities after antivenom treatment
should be accelerated using blood
products. Lactating women should be
encouraged to continue breastfeeding.

6.5 Species diagnosis


If the dead snake has been brought, it can
be identified, but this requires skill and
even experienced medical personnel may
mistake harmless mimics for venomous
snake, or they may confuse different
venomous species (Viravan et al., 1992;
Ariaratnam et al., 2009). As a result,
the patient may be given antivenom
unnecessarily, as in the case of hump-
Figure 79: 20 minute whole blood clotting test in a patient still bleeding from
nosed pit viper (Hypnale hypnale) bites incisions made at the site of the bite. The blood is icoagulable indicating venom-
mistaken for saw-scaled viper (Echis induced consumption coagulopathy (Copyright DA Warrell)

ManageMent of snakebites
in south-east asia
123
apparatus - a new, clean, dry, ordinary glass these cases, surface activation of blood
vessel (tube, bottle or syringe). coagulation by the glass surface, mediated
by Hageman Factor XII is lacking or has
been destroyed by cleaning with the result
20 minute whole blood clotting
that blood coagulation is not activated and
test (20WBCT)
the blood will not clot.
Place 2 mls of freshly sampled
venous blood in a small, new, dry,
A major difficulty is that many hospitals/
glass vessel
dispensaries in countries where snakebites-
Leave undisturbed for 20 minutes
are common, cannot afford to provide a
at ambient temperature
new, unwashed, un-recycled bottle, tube,
Tip the vessel once
syringe or other vessel for each test and
If the blood is still liquid
ordinary glass tubes/vessels may be difficult
(unclotted) and runs out, the
to purchase in this age of plastic. However,
patient has hypofibrinogenaemia
the commonly used recycled glass
(incoagulable blood) as a result
antibiotic bottles can be made suitable and
of venom-induced consumption
reliable, provided that they are cleaned
coagulopathy
by washing with normal 0.9% saline
In the South-East Asia Region,
for intravenous infusion, without any
incoagulable blood is diagnostic
added detergent of other cleansing agent,
of a viper bite and rules out an
followed by hot air drying.
elapid bite
Warning! If the vessel used
Variants of the 20WBCT, such as the 30
for the test is not made of
minute WBCT, 2,3,5 syringe test used in
ordinary glass, or if it has
Myanmar, or the capillary tube test have
been cleaned with detergent,
not been standardised or validated and
its wall may not stimulate
are susceptible to the same risks of false
clotting of the blood sample
positivity outlined above.
(surface activation of factor
XII Hageman factor) and test
False negative results: a false
will be invalid
negative (i.e. clotting) 20WBCT may
If there is any doubt, repeat the
occur in patients with milder degrees
test in duplicate, including a
of coagulopathy. The 20WBCT is less
healthy control (blood from a
sensitive to mild depletion of fibrinogen
healthy person such as a relative)
and other clotting factors, in the early
stages of evolving snake venom induced
Problems with the 20WBCT DIC and consumption coagulopathy, than
False positive results: a false positive laboratory tests such as prothrombin time
(i.e. non-clotting) 20WBCT in a patient (PT), activated partial thromboplastin time
who is not envenomed and has normal (aPPT), and fibrinogen assay. The 20WBCT
blood coagulation, results from the use of becomes positive (i.e. non-clotting) at
a tube, bottle, syringe or other vessel that is plasma fibrinogen concentrations below
made of plastic, polystyrene, polypropylene 0.5g/L (Sano-Martins et al., 1994). A
rather than ordinary glass, or a glass vessel study of 20WBCT in victims of taipan bites
that has been cleaned with detergent, soap (Oxyuranus scutellatus) in Papua New
or washing fluid or is wet or contaminated, Guinea found that a positive 20WBCT
or in the case of some glass syringes, (i.e. non-clotting) was associated with
has a lubricant that is anticoagulant. In a median PT of 120.0s (IQR 24.4-200s),

124 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
median aPTT of 132 sec (IQR=69.1-180s)
and median fibrinogen concentration of
0.01 g/L (IQR=0.01-0.18 g/L). A positive Every effort should be made to eliminate
(i.e. non-clotting) 20WBCT had a positive false positive (non-clotting) results by
predictive value of 89.7%, negative
predictive value of 93.5%, sensitivity ensuring that ordinary glass is used, that
of 92.9% and specificity of 90.6% for recycled glass vessels are not cleaned with
fibrinogen concentrations of <0.5 g/L.
(Paiva et al., 2015). However, a study in
detergents or other cleansing fluids and
Sri Lanka that is open to many criticisms that a normal control blood is used for
found that in some patients bitten by
comparison in cases where the 20WBCT
Russells vipers, whose 20WBCTs were
negative (i.e. clotting) on admission result is inconsistent with the patients
to hospital, blood samples taken up clinical condition.
to one hour later, frozen and flown to
Australia for testing, showed prolonged
prothrombin times [International
Normalized Ratio (INR) >1.5 see below].
This was not a comparison of 20WBCT
and INR in blood sample taken at the same Recommendation: in the absence
time. In every case, the INR sample was of an alternative simple bed-
taken later than the 20WBCT sample, by side test of blood coagulability
which time the process of venom-induced available in hospitals in the
DIC and consumption coagulopathy developing world, the 20WBCT
in the envenomed patient would have should continue to be used.
evolved. The authors considered that the However, every effort should
use of the 20WBCT was associated with be made to eliminate false
an unacceptable level of false negative positive (non-clotting) results by
(clotting) results and that it consequently ensuring that ordinary glass is
delayed antivenom treatment. However, used, that recycled glass vessels
if blood clots in the 20WBCT, the sample are not cleaned with detergents
must contain sufficient clotting factors, or other cleansing fluids and
albeit at reduced levels, to make this that a normal control blood is
possible, indicating that haemostasis is used for comparison in cases
maintained. However, no evidence was where the 20WBCT result is
adduced that this false negative result inconsistent with the patients
was in any way deleterious to the patients clinical condition. Accepting
whose antivenom treatment was delayed that the 20WBCT may remain
until their 20WBCTs became positive (i.e. negative (clotting) in patients
non-clotting) some hours later (Isbister with evolving venom-induced
et al., 2013). The authors admitted DIC, the test should be repeated
that prothrombin times could not be frequently and antivenom
performed in Sri Lankan hospitals and, treatment should not be delayed
unfortunately, they were unable to suggest if there is other evidence of anti-
any practicable alternative to the 20WBCT haemostatic disturbances (e.g.
for the many provincial and rural hospitals spontaneous systemic bleeding
in tropical developing countries where distant from the bite site)
snakebites are common.

ManageMent of snakebites
in south-east asia
125
6.6.2 Other tests of blood haematocrit: a transient increase
coagulation indicates haemoconcentration resulting
More sensitive laboratory tests that are from a generalized increase in capillary
rapid and relatively simple to perform permeability (e.g. in Russells viper bite).
are plasma prothrombin time (PT) or
activated partial thromboplastin time More often, there is a decrease reflecting
(aPPT) and measurement of fibrin(ogen) blood loss or, in the case of Indian,
related antigens, also known as fibrin Thai and Sri Lankan Russells viper bite,
degradation products (FDP) or fibrin intravascular haemolysis.
split products (FSP), by agglutination of
sensitized latex particles or of D-dimer Platelet count: this may be decreased
(cross-linked fibrin fragments) by assays in victims of envenoming by vipers and
using monoclonal antibodies that detect Australasian elapids.
an epitope that is present in the factor
XIIIacrosslinked fragment D domain of White blood cell count: an early
fibrin. The International Normalized Ratio neutrophil leucocytosis is evidence of
(INR) is the patients PT divided by the systemic envenoming by any species.
laboratory control PT (normal range 0.8 Lymphopenia has been described in
- 1.2). An abnormal INR result, indicating patients envenomed by Australasian
coagulopathy, is 1.2 or above. Point of Elapidae.
care (bed-side) devices for measuring
INR and D-dimer are expensive and are Blood film: fragmented red cells
unreliable in snakebite victims (Cubitt (helmet cell, schistocytes) are seen
et al., 2013). Measurement of plasma when there is microangiopathic
concentrations of fibrinogen and other haemolysis or thrombotic
individual clotting factors are more microangiopathy (TMA). Haemolytic
demanding in time and laboratory skills. uraemic syndrome (HUS) consists of
persistent, profound thrombocytopenia,
Thrombo-elastography (TEG) and microangiopathic haemolytic anaemia
thromboelastometry (TEM, ROTEG, (fragmented red cells, helmet cells,
ROTEM) have been suggested as a or schistocytes) and acute kidney
simple bed-side method for assessing injury. It is associated with envenoming
coagulopathy in snakebite victims but the by Russells vipers, hump-nosed pit
equipment is expensive. Analysis of the vipers and Australian Elapidae. The
TEG tracing provides measures of time pathophysiology of TMA is unknown,
to initiation of clotting, speed of clot but in other diseases, such as thrombotic
formation and clot strength that reflect thrombocytopenic purpura (TPP), it is
coagulation factor activity, fibrinolysis thought to be due to deficiency of the
and platelet function. In a study of metalloproteinase ADAMTS 13 which
envenomed children in South Africa, cleaves von Willebrand multimers. These
TEG predicted severe bleeding diathesis multimers initiate platelet activation
in 50% of patients with 94% sensitivity and formation of microthrombi which
(Hadley et al., 1999). It has also been is the key factor in the development of
used in envenomed dogs (Armentano et acute kidney injury. In an Australian tiger
al., 2014). snake (Notechis scutatus) bite victim
with TMA, ADAMTS 13 levels were
6.6.3 Other laboratory tests normal before and after plasmapheresis
Haemoglobin concentration/ with cryosupernatant (Ho et al., 2010).

126 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Plasma/serum in blood samples to an arterial PO2 of less than 60 mmHg
allowed to sediment spontaneously (8.8 kPa).
(without centrifugation) may be stained
pinkish or brownish if there is gross Urine examination: the urine
haemoglobinaemia or myoglobinaemia. should be tested by dipsticks for
blood or haemoglobin or myoglobin.
Biochemical abnormalities: plasma Standard dipsticks do not distinguish
creatinine, urea/blood urea nitrogen and blood, haemoglobin and myoglobin.
potassium concentrations are raised in Haemoglobin and myoglobin can be
the acute kidney injury of Russells viper, separated by immunoassays but there is
hump-nosed pit-viper and sea-snake no easy or reliable test. Microscopy will
envenoming. Aminotransferases and confirm whether there are erythrocytes in
muscle enzymes (creatine kinase, aldolase the urine.
etc.) will be elevated if there is severe
local damage or, particularly, if there is Red cell casts indicate glomerular
generalized muscle damage (sea-snakes, bleeding. Massive proteinuria is an
some kraits, some Australasian Elapidae early sign of the generalized increase in
and Sri Lankan, Indian, Bangladeshi and capillary permeability in Russells viper
Myanmar Russells viper bites). Mild envenoming and an early indicator of
hepatic dysfunction is reflected in slight acute kidney injury. Urine eosinophilia
increases in other serum enzymes. Bilirubin suggests acute interstitial nephritis, but
is elevated following massive extravasation this can be confirmed only by renal biopsy
of blood. Early hyperkalaemia may be (Priyamvada et al., 2016).
seen following extensive rhabdomyolysis
in sea snakebites. Bicarbonate will be low 6.6.4 Other investigations
in metabolic acidosis (e.g. acute kidney Radiography: chest radiography is
injury). Hyponatraemia is reported in useful for detecting pulmonary oedema
victims of krait bites in northern Viet Nam (e.g. after bites by Vipera and Daboia
(Bungarus near candidus). species), pulmonary haemorrhages and
infarcts, pleural effusions, and secondary
Arterial blood gases and pH may show bronchopneumonia.
evidence of respiratory failure (neurotoxic
envenoming) and acidaemia (respiratory or Ultrasound: ultrasonography was found to
metabolic acidosis). be useful for assessing local envenoming,
including deep vein thrombosis in a case
of Russells viper bite in Pondicherry, India,
Warning: arterial puncture is and for detecting pleural and pericardial
contraindicated in patients effusion and bleeding into serous cavities.
with haemostatic abnormalities
(Viperidae and some Australasian Echocardiography has proved useful in
Elapidae) detecting reduced left ventricular ejection
fraction in hypotensive and shocked
patients envenomed by Russells vipers in
Desaturation: arterial oxygen saturation Sri Lanka..
can be assessed non-invasively in patients
with respiratory failure or shock using a Imaging: CT and MRI imaging is
finger pulse oximeter. Remember that an increasingly available in the Region. It has
oxygen saturation below 90% is equivalent detected haemorrhages and ischaemic

ManageMent of snakebites
in south-east asia
127
infarcts in the brain (subarachnoid, that has been immunised with the venoms
subdural, cerebral, cerebellar, brainstem) of one or more species of snake. Specific
(Figs 61b, 61c, 52d), spinal cord, antivenom, implies that the antivenom
peritoneum and elsewhere in Russells has been raised against the venom of the
viper victims in India, Sri Lanka and snake that has bitten the patient and that
Myanmar. Cerebral imaging has shown it can therefore be expected to contain
pituitary shrinkage in cases of chronic specific antibody that will neutralize that
panhypopituitarism and unexplained particular venom and perhaps the venoms
haemorrhagic and demyelinating of closely related species (paraspecific
leucoencephalopathies after Russells viper neutralization). Monovalent (monospecific)
bites in India. Imaging can show oedema antivenom neutralizes the venom of
and haemorrhage in fascial compartment only one species of snake. Polyvalent
muscles and the degree of osteomyletis (polyspecific) antivenom neutralizes
and soft tissue changes in chronic the venoms of several different species
snakebite ulcers that have undergone of snakes, usually the most important
malignant change to squamous cell species, from a medical point of view, in a
carcinomas (Marjolins ulcers). particular geographical area.

Electrocardiography: ECG abnormalities For example, the Indian antivenom


reported in snakebite victims include manufacturers polyvalent anti-snake
tachyarrhythmias, sinus bradycardia, venom serum is raised in horses, using
ST-T wave changes, varying degrees the venoms of the four most important
of atrioventricular block, and evidence venomous snakes in India (Indian cobra,
of hyperkalaemia. Shock may induce Naja naja; Indian krait, Bungarus caeruleus;
myocardial ischaemia or infarction in Russells viper, Daboia russelii; saw-scaled
patients with diseased coronary arteries. viper, Echis carinatus), although the
validity of the concept of the big four is
6.7 Antivenom treatment increasingly challenged by the discovery
that other species are also important
in certain regions [e.g. Echis carinatus
Antivenom is the only specific sochureki in Rajasthan (Kochar et al.,
antidote to snake venom. 2007); H. hypnale in SW India (Joseph et
A most important decision in al., 2007); Trimeresurus (Craspedocephalus)
the management of a snakebite malabaricus in southern India; Trimeresurus
victim is whether or not to give (Peltopelor) macrolepis (ref) in hilly regions
antivenom. of Tamil Nadu and Kerala; Trimeresurus
(T.) erythrurus in Assam and Sikkim; Naja
kaouthia in North east India; Bungarus
6.7.1 What is antivenom? sindanus in W and NW India (Pillai et al.,
(WHO 2010) 2012); B. walli and possibly B. niger in NE
Antivenom treatment for cobra bites India (Faiz et al., 2010)] (Whitaker and
was introduced by Albert Calmette at Martin 2014; Whitaker 2015). Antibodies
the Institut Pasteur in Saigon, Viet Nam raised against the venom of one species
in the 1890s (Bon and Goyffon 1996). may have cross-neutralizing activity against
Antivenom is immunoglobulin [usually other venoms, usually from closely related
pepsin-refined F(ab)2 fragment of whole species. This is known as paraspecific
IgG] purified from the plasma of a horse, activity. For example, the manufacturers
mule or donkey (equine) or sheep (ovine) of Haffkine polyvalent anti-snake venom

128 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
serum claim that this antivenom also
neutralizes venoms of two Trimeresurus
There is an urgent need to improve the
species.
design (species cover), quantity, and quality
The Thai Red Cross Society now of antivenoms produced in South-East Asia
manufactures two polyvalent antivenoms
to cover the venoms of neurotoxic Elapidae Region countries, in the interests of reducing
(Naja kaouthia, O. hannah, Bungarus snakebite mortality and morbidity.
candidus, B. fasciatus) and haematotoxic
Viperidae (Daboia russelii, Calloselasma
rhodostoma, Trimeresurus (T.) albolabris).
Systemic envenoming
In Indonesia, Biofarma produces a Haemostatic abnormalities:
polyvalent antivenom to cover venoms spontaneous systemic bleeding
of neurotoxic Naja sputatix, Bungarus distant from the bite site (clinical),
fasciatus (that rarely, if ever, bites humans) coagulopathy [+ve (non-clotting)
and Calloselasma rhodostoma, but, 20WBCT or other laboratory tests
unaccountably, ignores important species such as INR >1.2 or patients
such as Bungarus candidus, Daboia prothrombin time >4-5 seconds
siamensis, Trimeresurus species and all the longer than laboratory control value]
Eastern Indonesian Australasian Elapidae. or thrombocytopenia [<100 x 109/
litre, or <100 000/cu mm, or (India)
There is an urgent need to improve the < 1.0 lakh per microlitre of blood)]
design (species cover), quantity, and (laboratory)
quality of antivenoms produced in South-
East Asia Region countries, in the interests Neurotoxic signs: ptosis, external
of reducing snakebite mortality and ophthalmoplegia, paralysis etc (clinical)
morbidity.
Cardiovascular abnormalities:
6.7.2 Indications for antivenom hypotension, shock, cardiac arrhythmia
treatment (see also Annexes 1 and 2) (clinical), abnormal ECG

Antivenom should be given only Acute kidney injury (renal failure):


to patients in whom its benefits oliguria/anuria (clinical), rising blood
are considered likely to exceed creatinine/ urea (laboratory)
its risks. Since antivenom is
relatively costly and often in Haemoglobin-/myoglobin-uria:
limited supply, it should not be dark brown urine (clinical), urine
used indiscriminately. The risk of dipsticks, other evidence of
reactions should always be taken intravascular haemolysis or generalized
into consideration. rhabdomyolysis (generalized muscle
aches, pains, tenderness, pain on
passive stretching (hyperkalaemia)
Indications for antivenom (clinical, laboratory)
Antivenom treatment is recommended
if and when a patient with proven or Supporting laboratory evidence of
suspected snakebite develops one or more systemic envenoming (see above) Local
of the following signs: envenoming

ManageMent of snakebites
in south-east asia
129
Local swelling involving more than half give antivenom for as long as evidence
of the bitten limb (in the absence of of the coagulopathy persists. Whether
a tourniquet) within 48 hr of the bite antivenom can prevent local necrosis
Swelling after bites on the digits (toes remains controversial, but there is some
and especially fingers) clinical evidence that, to be effective in
this situation, it must be given within the
Rapid extension of swelling (for first few hours after the bite (Warrell et
example beyond the wrist or ankle al., 1976; Tilbury 1982).
within a few hours of bites on the
hands or feet) 6.7.5 Antivenom reactions
A substantial proportion of patients
Development of an enlarged tender develop reactions, either early (within
lymph node draining the bitten limb a few hours) or late (5 days or more)
after being given antivenom. In Sri
6.7.3 Inappropriate use of antivenom Lanka, Indian polyvalent antivenoms
In some parts of the world, a small incur reactions in as many as 81% of
standard dose of antivenom is given recipients and severe reactions in as
routinely to any patient claiming to many as 43% (Ariaratnam et al. 2001,
have been bitten by a snake, irrespective de Silva et al, 2016). In India, these
of symptoms or signs of envenoming. antivenoms cause reactions in 5.6 to
Sometimes the local community are 56% of recipients, 10-15% of which are
so frightened of snakebite that they moderate to severe (Srimannarayana
compel the doctor to give antivenom et al., 2004; Deshpande et al., 2013;
against medical judgement. Even doctors Cherian et al., 2013; Menon et al.,
themselves may administer antivenom to 2016a). Other antivenoms have much
patients envenomed by snakes against lower reported reaction rates. In
which the antivenom is known to be Thailand, among 254 patients receiving
ineffective (Seneviratne et al, 2000). Thai Red Cross (TRC) antivenoms during
19972006, early reactions occurred
in 9 (3.5%) including 3 (1.2%) with
Inappropriate use of antivenom hypotension. Most patients were being
should be strongly discouraged treated for Trimeresurus (84%) and Naja
as they expose patients who may (13%) bites, in whom the incidence
not need treatment to the risks of reactions was 2.3% and 12.5%
of antivenom reactions; they also respectively, reflecting the difference
waste valuable and scarce stocks in dose (3 and 10 vials respectively)
of antivenom. (Thiansookon and Rojnukarin, 2008).
In Australia, use of CSL antivenoms
incurred early anaphylactic reactions
6.7.4 How long after the bite in 25% and severe raections in 5% of
can antivenom be expected to be recipients (Isbister et al., 2008). The risk
effective? of antivenom reactions is dose-related,
Antivenom treatment should be given except in rare cases in which there has
as soon as it is indicated. It may reverse been sensitisation (IgE-mediated Type
systemic envenoming even when this has I hypersensitivity) by previous exposure
persisted for several days or, in the case to animal serum, for example to equine
of haemostatic abnormalities, for two or antivenom, tetanus-immune globulin or
more weeks. It is, therefore, appropriate to rabies-immune globulin.

130 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[b]

[a]
Figures 80: Early anaphylactic reaction to antivenom: (a, b) urticaria and pruritus of the
trunk and face; (c) life-threatening angioedema of face tongue, gums, throat, neck and
upper airway (Copyright DA Warrell)

1. Early anaphylactic reactions: basophils by antivenom


usually within minutes and up to 180 protein are more likely
minutes after starting antivenom, the mechanisms for these
patient begins to itch (often over the reactions.
scalp) and develops urticaria
(Fig 80 a,b), dry cough, fever, nausea, 2. Pyrogenic
vomiting, abdominal colic, diarrhoea (endotoxin)
and tachycardia. A minority of these reactions: usually
patients may develop severe life- develop 1-2 hours after [c]
threatening anaphylaxis: hypotension, treatment. Symptoms
bronchospasm and angio-oedema include shaking
(Fig 80c). chills (rigors), fever, vasodilatation
and a fall in blood pressure. Febrile
Fatal reactions have probably been convulsions may be precipitated in
under-reported as death after snakebite children. These reactions are caused
is usually attributed to the venom by pyrogen contamination during
and patients may not be monitored the manufacturing process. They are
carefully after treatment. commonly reported.

In most cases, these reactions are 3. Late (serum sickness type)


not truly allergic. They are not reactions: develop 1-12 (mean 7)
IgE-mediated type Ihypersensitivity days after treatment. Clinical features
reactions to horse or sheep proteins include fever, nausea, vomiting,
as there is no evidence of specific diarrhoea, itching, recurrent urticaria,
IgE, either by skin testing or arthralgia, myalgia, lymphadenopathy,
radioallergosorbent tests (RAST). periarticular swellings, mononeuritis
Complement activation by IgG multiplex, proteinuria with immune
aggregates or residual Fc fragments complex nephritis and rarely
or direct stimulation of mast cells or encephalopathy. Patients who suffer

ManageMent of snakebites
in south-east asia
131
(adrenaline) *adult dose 0.25mg of 0.1%
solution is given just before antivenom
Adrenaline (epinephrine) is the most
treatment is started (see below), followed
effective treatment for anaphylactic by an intravenous anti-H1antihistamines
reactions, by reducing bronchospasm and such as chlorphenamine. In asthmatic
patients, prophylactic use of an inhaled
capillary permeability. adrenergic 2 agonist such as salbutamol
may prevent bronchospasm.

6.7.5.3 Prevention of antivenom


early reactions that are treated with reactions
antihistamines and corticosteroid are One of only two systematic reviews
less likely to develop late reactions. carried out in the field of snakebite
treatment (Nuchpraryoon and
6.7.5.1 Prediction of antivenom Garner, 2000) concluded that routine
reactions prophylactic adrenaline for antivenom
known to have high adverse event rates
Skin and conjunctival hypersensitivity seemed sensible, based on only one
tests can only detect IgE mediated trial (Premawardhena et al., 1999) and
Type I hypersensitivity to horse or that antihistamine appeared to be of
sheep proteins. However, the large no obvious benefit, again based on one
majority of early (anaphylactic) or trial (Fan et al., 1999). Since then, more
late (serum sickness type) antivenom definitive data have been published.
reactions result from direct dose-
related complement activation rather 1. Prophylactic drugs (adrenaline,
than from non-dose-related IgE- antihistamine anti-H1 blockers,
mediated hypersensitivity, and so these corticosteroids)
tests are not predictive. Since they may Adrenaline (epinephrine) is the most
delay treatment and can in themselves effective treatment for anaphylactic
be sensitising, these tests should not reactions, by reducing bronchospasm
be used. and capillary permeability. However, the
risks of adrenaline make it less attractive
for prophylaxis (Rusznak and Peebles,
6.7.5.2 Contraindications to 2002). Premawardhena et al. (1999)
antivenom: Prophylaxis of high risk used premedication with subcutaneous
patients adrenaline in 105 snakebite victims
There is no absolute contraindication to and found a reduction from 43% to
antivenom treatment, but patients who 11% (p=0.04) in the incidence of
have reacted to horse (equine) or sheep acute adverse reactions compared
(ovine) serum in the past (for example after to placebo.No adverse reactions to
treatment with equine anti-tetanus serum, the adrenaline were observed in this
equine anti-rabies serum or equine or study. However, a subsequent fatality
ovine antivenom) and those with a strong (Dassanayake et al., 2002) raised
history of atopic diseases (especially severe concerns about intracranial bleeding
asthma) are at high risk of severe reactions (a known complication of systemic
and should therefore be given antivenom envenoming following bites by vipers and
only if they have signs of systemic Australian elapid snakes), hypertension
envenoming. Subcutaneous epinephrine and arrhythmias if adrenaline prophylaxis

132 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
were to be used routinely especially reactions to antivenom by 43% (95%
in children, pregnant women and in CI 2567) at 1 h and by 38% (95%
patients with heart disease who had been CI 2649) up to and including 48
excluded from the trial.Gawarammana et h after antivenom administration;
al. (2004) tested parallel pre-antivenom hydrocortisone and promethazine did
infusion of placebo, hydrocortisone not. Adding hydrocortisone negated the
alone, or hydrocortisone plus benefit of adrenaline. The plasma half-
chlorphenamine in 52 patients. Reactions life of adrenaline is about 2-3 minutes.
were reduced from approximately 80% However, when given by subcutaneous
in the first two groups to 52% in the or intramuscular injection, local
premedicated group though the results vasoconstriction may delay absorption so
did not achieve statistical significance that the effects may last longer than the
and the study was underpowered.A half-life suggests.
randomized placebo-controlled trial
of 101 patients in Brazil by Fan et al. 2. Speed and dilution of intravenous
(1999) showed that premedication antivenom administration
with intramuscular promethazine had The in vitro anti-complementary activity
no significant effect on the high rate of several commercial antivenoms
(68%) of anaphylactic reactions to led Sutherland (1977) and others to
antivenom.A review of 10 years of advocate dilution and slow infusion of
experience with various premedication antivenom (Reid, 1980; WHO, 1981).
regimens in Papua New Guinea (Williams However, in a small randomized study,
et al., 2007) further illustrates the Malasit et al. (1986) found no difference
heterogeneity and lack of standardization in rate or severity of reactions in patients
of snakebite victim care in developing given diluted antivenom over 30 minutes
countries where most venomous compared to those in whom intravenous
snakebites occur but suggested efficacy push injection over 10 minutes was used.
of some prophylactic regimes, as did the In Ecuador, Caron et al., 2009 found a
study of Caron et al., 2009 in Ecuador. strikingly lower incidence of reactions
in a group of patients premedicated
A large and well-designed study was with intravenous hydrocortisone and
carried out in Sri Lanka. In total, 1,007 diphenhydramine and given antivenom
patients were randomized, using a 2 by infusion over 60 minutes compared
x 2 x 2 factorial design, in a double- to a group of historical controls who
blind, placebo-controlled trial of had been given no prophylaxis and in
adrenaline (0.25 ml of a 0.1% solution whom antivenom had been injected
subcutaneously), promethazine (25 intravenously over 10 minutes. In Sri
mg intravenously), and hydrocortisone Lanka, 104 patients were randomly
(200 mg intravenously), each alone allocated to receive antivenom by
and in all possible combinations. The intravenous infusion over 20 minutes and
interventions, or matching placebo, 94 by infusion over 2 hours. There was
were given immediately before infusion no difference in the incidence of early
of antivenom. Patients were monitored severe anaphylactic reactions in the two
for mild, moderate, or severe adverse groups (32% vs. 35%; difference 3%;
reactions for at least 96 h. (de Silva et 95% CI: -10% to +17%; p = 0.65). The
al., 2011). Compared with placebo, frequency of mild/moderate reactions
adrenaline significantly reduced severe was also similar (Isbister et al., 2012).

ManageMent of snakebites
in south-east asia
133
Additional treatment: After epinephrine
Recommendation: based on (adrenaline), patients with bronchospasm
the results of a powerful and should be given an inhaled short-acting 2
well-designed trial in Sri Lanka, agonist bronchodilator such as salbutamol
routine use of prophylactic or terbutaline ideally by oxygen-
adrenaline is recommended driven nebuliser) and an antihistamine
before antivenom treatment, anti-H1 blocker can be given, such as
except in those older patients chlorphenamine maleate (adults 10
in whom there is evidence mg, children 0.2 mg/kg by intravenous
or suspicion of underlying injection over a few minutes). Intravenous
cerebrovascular disease and hydrocortisone (adults 100 mg, children
when the particular antivenom in 2 mg/kg body weight) can be given,
use has a proven low incidence but it is unlikely to act for several hours.
of reactions (<5%). The adult Corticosteroids do not reduce the risk of
dose of epinephrine (adrenaline) recurrence (biphasic) anaphylaxis (Grunau
is 0.25ml of 0.1% solution (0.25 et al., 2015).
mg) by sub-cutaneous injection
(children 0.005 ml/kg body Anaphylaxis unresponsive to
weight of 0.1% solution) (T). intramuscular epinephrine
(adrenaline): a few patients may not
Use of histamine anti-H1 and respond to single or repeated doses of
anti-H2 blockers, corticosteroid, intramuscular epinephrine (adrenaline).
and the rate of intravenous
infusion of antivenom (between Patients who remain shocked and
10 and 120 minutes), do not hypotensive should be laid supine with
affect the incidence or severity of their legs elevated and given intravenous
early antivenom reactions (T,O). volume replacement with 0.9% saline
(1-2 litres rapidly in an adult). Intravenous
epinephrine (adrenaline) infusion should
6.7.5.4 Treatment of antivenom be considered [adult dose 1mg (1.0 ml)
reactions of 0.1% solution in 250 ml 5% dextrose
Early anaphylactic antivenom or 0.9% saline - i.e. 4 (micro) g/ml
reactions: Epinephrine (adrenaline) is concentration) - infused at 14 (micro)
given intramuscularly (ideally into the g/minute (1560 drops/min usin a
upper lateral thigh) in an initial dose microdropper burette chamber), increasing
of 0.5 mg for adults, 0.01 mg/kg body to maximum 10 (micro) g/min] and,
weight for children. Because severe, in patients who remain hypotensive, a
life-threatening anaphylaxis can evolve vasopressor agent such as dopamine [dose
so rapidly, epinephrine (adrenaline) 400mg in 500ml 5% dextrose or 0.9%
should be given at the very first sign of saline infused at 25 (micro) g/kg/min].
a reaction, even when only a few spots
of urticaria have appeared or at the start Patients who remain dyspnoeic, with
of itching, tachycardia or restlessness. bronchospasm or angioedema, should
The dose can be repeated every 5-10 be propped up at 45 degrees and given
minutes if the reaction persists or the supplemental oxygen by any available
symptoms become worse. Adrenaline has route together with optimal nebulised/
proved safe in pregnant women, whereas inhaled and/or parenteral bronchodilator
anaphylaxis can induce abortion. (2 agonist) (Kemp and Kemp 2014).

134 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Pyrogenic reactions: the patient must 6.7.6 Supply, selection, storage and
be cooled physically (remove clothing, shelf-life of antivenom
tepid sponging with fanning) and given an Supply: it is important to determine
antipyretic (e.g. paracetamol by mouth or how much antivenom remains unused
suppository). Intravenous fluids should be at the end of each year in different parts
given to correct hypovolaemia. Patients who of the country, to allow the calculation
also exhibit features of anaphylaxis should of antivenom requirements, and the
be given adrenaline as well (see above). efficient deployment of adequate stocks
of this scarce resource to areas where it
is most needed. Adequate buffer stocks
At the earliest sign of a reaction: are mandatory in areas where natural
disasters, such as the annual floods
Antivenom administration in Bangladesh, cause epidemics of
must be temporarily snakebite. These provisions will reduce
suspended preventable deaths. Adequate training
Epinephrine (adrenaline) of medical personnel in the rational use
(0.1% solution, 1 in of antivenom is important to reduce
1 000, 1 mg/ml) given by mortality and morbidity and minimise
intramuscular injection is wastage.
the effective treatment for
early anaphylactic antivenom Selection: Polyvalent (polyspecific)
reactions antivenoms are preferred in many
countries because of the difficulty
in identifying species responsible for
Completion of administration of bites. They can be just as effective
antivenom dose: as monovalent (monospecific) ones.
After the patient has recovered from the An antivenom should be given only
early anaphylactic or pyrogenic reaction, the if its stated range of specificity and
indications for antivenom therapy should paraspecific neutralization includes
be critically re-examined. If antivenom is the species known or suspected to
still indicated, intravenous administration have been responsible for the bite. If
should be cautiously resumed until the total the biting species is known, the ideal
dose has been given. treatment may be with a monovalent
(monospecific) antivenom, as this may
Treatment of late (serum sickness) be less expensive and may involve
reactions: Late (serum sickness) reactions administration of a lower dose
may respond to a 5-day course of oral of antivenom protein than with a
antihistamine. Patients who fail to respond polyvalent (polyspecific) antivenom.
within 24-48 hours should be given a However, immunisation of a horse or
5-day course of prednisolone. sheep with venoms of several related
species of snakes (e.g. Viperidae)
Doses: Chlorphenamine: adults 2 mg six may produce an enhanced antibody
hourly, children 0.25 mg/kg /day in divided response to common antigens, making
doses. the resulting polyvalent antivenom
more rather than less potent than a
Prednisolone: adults 5 mg six hourly, monovalent antivenom (Raweerith
children 0.7 mg/kg/day in divided doses and Ratanabanangkoon, 2005; WHO,
for 5-7 Days 2010).

ManageMent of snakebites
in south-east asia
135
Storage and shelf-life: to retain their Freeze-dried (lyophilised) antivenoms
full potency within the limits of stated are reconstituted, usually with 10 ml of
expiry dates, lyophilised antivenoms sterile water for injection per ampoule.
(shelf life about 5 years) should be stored If the freeze-dried protein is difficult to
at below 25C and liquid antivenoms dissolve, it may have been denatured by
(shelf life 2-3 years) should be stored a faulty freeze-drying technique during
at 2-8 C and not frozen. Ideally, manufacture (WHO, 2010).
antivenoms should be used before the
stated expiry dates but, provided that Two methods of administration are
they have been properly stored, they can recommended:
be expected to retain useful activity for
months or even years after these dates 1. Intravenous push injection:
(WHO, 1981; OLeary et al., 2009). TRC reconstituted freeze-dried antivenom
antivenoms retain their potency after 5 or neat liquid antivenom is given by
years even when stored temperatures slow intravenous injection (not more
of 25-50 C (Prof Sumana Komvilai, than 2 ml/minute). This method has
personal communication). the advantage that the doctor, nurse,
or dispenser giving the antivenom must
In patients with severe envenoming, remain with the patient during the
recently expired antivenoms may time when some early reactions may
be used if there is no alternative. develop. It is also economical, saving
However, liquid antivenoms that have the use of intravenous fluids, giving
become opaque or which contain sets, cannulae etc.
visible particles should not be used
as precipitation of protein indicates 2. Intravenous infusion: reconstituted
loss of activity and an increased risk of freeze-dried or neat liquid antivenom is
reactions. diluted in about 5 ml of isotonic fluid
per kg body weight (i.e. about 250 ml
6.7.7 Administration of antivenom of isotonic saline or 5% dextrose in the
case of an adult patient) and is infused
at a constant rate over a period of
Epinephrine (adrenaline) about 30-60 minutes.
should always be available
at the bed-side, ideally
drawn up in readiness, Patients must be closely observed
before antivenom is for at least one hour after
administered. starting intravenous antivenom
administration, so that early
Antivenom should be given anaphylactic antivenom reactions
by the intravenous (iv) route can be detected and treated early
whenever possible, either with epinephrine (adrenaline).
by slow iv push injection
(maximum 2 ml/minute) Local administration of antivenom
or by iv infusion diluted in at the site of the bite is not
about 5 ml of isotonic fluid recommended! Although this
per kg body weight over route may seem rational, it
about 30-60 minutes. should not be used as it is

136 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
extremely painful, may increase 1 Vial Fab Antivenom I.V.I. Compared with 1 Vial I.M.I.
intracompartmental pressure and (9 patients via each route)
proved to be much less effective
0.5
than by the intravenous route (O). Fab AV I.V. Fab AV I.M.

0.4

Fab antivenom (ul/ml)


Intramuscular injection of antivenom:
0.3
Antivenoms are large molecules, [F(ab)2
fragments or sometimes whole IgG] which,
after intramuscular injection, are absorbed 0.2

slowly via lymphatics. Bioavailability is


poor, especially after intragluteal injection, 0.1
and blood levels of antivenom never reach
those achieved rapidly by intravenous 0
0 1 3 6 12 24 48
administration (Fig 81) Theakston
Time after antivenom (hr)
RDG, Warrell DA unpublished). Other
disadvantages are the pain of injection of
large volumes of antivenom and the risk
of haematoma formation in patients with
Figure 81: Comparison of intravenous and intramuscular administration of an
haemostatic abnormalities. Fab fragment antivenom. Antivenom administered intramuscularly appeared slowly
in the bloodstream (dashed line) compared to that given by the intravenous route
(solid line). (RDG Theakston and DA Warrell unpublished data).
The only situations in which
intramuscular administration might
be considered is in the absence
of anyone capable of giving an Antivenom should never be
intravenous injection: injected into the gluteal region
(upper outer quadrant of
1. at a peripheral first aid station, before the buttock) as absorption is
a patient with obvious envenoming is exceptionally slow and unreliable
put in an ambulance for a journey to and there is always the danger
hospital that may last several hours of sciatic nerve damage when
(Win-Aung et al., 1996); the injection is given by an
2. on an expedition exploring a remote inexperienced operator.
area very far from medical care;
3. when intravenous access has proved
impossible. Under these exceptional circumstances,
the dose of antivenom should be divided
Although the risk of antivenom reactions between a number of sites in the upper
is less with intramuscular than intravenous anterolateral region of both thighs. A
administration, epinephrine (adrenaline) maximum of 5-10 ml should be given at
must be readily available each site by deep intramuscular injection
followed by massage to aid absorption.
Local bleeding and haematoma formation
Antivenom must never be given is a problem in patients with incoagulable
by the intramuscular route if it blood. Finding enough muscle mass to
could be given intravenously. contain such large volumes of antivenom
is particularly difficult in children.

ManageMent of snakebites
in south-east asia
137
6.7.8 Dosage of antivenom push injection, is followed by infusion
(Table 1 and Annex 3) of 4 vials over 4 hours, and, as long as
Initial dose of antivenom signs of envenoming persist, 4 vials over
A fundamental piece of information for 4 hours every 4 hours for a further 12
those treating envenomed patients is hours, followed by 2 vials over 4 hours,
the average initial dose of a particular repeated until recovery. Following this
antivenom appropriate for different regimen, cumulative doses may reach 140
levels of clinical severity in patients bitten vials (1000 ml) in patients with neurotoxic
by different species. Unfortunately, envenoming by kraits (Magar et al., 2013).
these data, based on clinical trials, are A recent study in Nepal compared the
rarely available. In any case, since the effectiveness and safety of this regimen
neutralizing power of antivenoms varies with a single higher initial dose of 10
from batch to batch, and between vials given over 1 hour in patients with
different antivenoms, the results of a neurotoxic envenoming. There was no
clinical trial may soon become obsolete if statistically significant difference between
the manufacturers change the strength the two regimens in the proportion of
of their antivenom. This happened patients reaching the primary endpoint
in Myanmar in the 1990s, when the (48.7% in the low initial dose arm
national producer arbitrarily halved the versus 38.5% in the high initial dose
strength of their antivenom. As a result, arm, p=0.264). Likewise, there was no
medical personnel must usually rely difference in the incidence of antivenom
on manufacturers recommendations reactions (53.8% of patients given the
stated in the package insert. These high dose compared to 52.6% given the
are usually based on laboratory assays low initial dose). Among the 51 patients
in which venom and antivenom are in whom the snake species could be
incubated in vitro before being injected identified, 29 had been bitten by cobras
into the test animals, usually mice. The (Naja spp) and 22 by kraits (Bungarus
recommended dose is usually the amount spp.). Patients bitten by kraits were more
of antivenom required to neutralize the severely envenomed and recovered less
average venom yield when captive snakes often (40.9% versus 96.5%, p<0.001)
are milked of their venom, but, quite and more slowly (mean recovery time 18
apart from many theoretical objections hours versus 5 hours, p<0.001) than did
to this protocol, the maximum venom patients bitten by cobras. These findings
yield may be seriously underestimated suggested that there was no difference in
(Tun Pe and Khin Aung Cho, 1986). effectiveness and safety between initially
In practice, the choice of an initial low and high doses of antivenom for
dose of antivenom is usually empirical. neurotoxic snakebite in southern Nepal,
Some antivenom dosage regimens and that systemic envenoming due to krait
recommended in national management bites was less responsive to antivenom
guidelines seem illogical, based on what than that following cobra bites (Alirol E,
is known of the pharmacokinetics and Sharma SK et al., in press). Since the high
pharmacodynamics of venom-antivenom single initial dose was non-inferior to the
interactions. low initial dose (but much higher total
dose), the former is preferred on grounds
Nepal: the Nepalese national guidelines of cost and convenience.
recommend prolonged and repeated
dosage of antivenom. An initial dose India: there have been many publications
of 2 vials of antivenom given by IV on treatment of snakebite with national

138 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
polyvalent antivenoms, but there is little
reliable evidence to guide initial dosage.
In clinical practice, the dose of antivenom
Manufacturers recommendations are
based on the amount of venom (mg) used is very variable. In government
neutralized by 1 ml of antivenom. The hospitals where antivenom is freely
Indian national snakebite protocol
(Directorate General of Health Services, available, higher doses of antivenom are
2009) and previous editions of WHO prescribed, often exceeding 20 vials.
guidelines recommend immediate
administration of 5 vials, and a recent
consensus 4-6 vials (Menon et al., 2916b) was effective in permanently restoring
in the case of Echis carinatus; and 10 blood coagulability. Subsequently, in
vials for patients envenomed by the 2003-4, a retrospective study of 225 C.
other species, with repeated dosing if the rhodostoma victims suggested that 4-9
patient fails to improve, to a maximum vials of Thai Red Cross (TRC) Malayan Pit
of 20 vials. There are no adequately Viper antivenin was effective in correcting
designed dose finding studies that selected coagulopathy and systemic symptoms
snakebites by identified species, controlled but appeared to do little to counteract
for clinical severity, were randomised local tissue necrosis (Wongtongkam et
and employed defined clinical end points al., 2005). In a small observational study,
including measurement of antigaenemia an average dose of 165 (+/- 59.3) ml of
(Warrell, 2011). In clinical practice, the TRC Russells Viper antivenin corrected
dose of antivenom used is very variable. In blood incoagulability in a group of 38
government hospitals where antivenom is patients envenomed by D. siamensis. The
freely available, higher doses of antivenom authors recommended that 60 ml of this
are prescribed, often exceeding 20 vials. antivenom should be administered at
Other non-profit rural hospitals use a low 6-hour intervals until blood coagulability
dose regimen of less than 10 vials in view was restored (Karnchanachetanee et
of the high cost and scarcity of antivenom. al., 1994). In the case of cobra (Naja
Several randomised controlled trials from kaouthia) bite victims with respiratory
such hospitals claimed to demonstrate paralysis, envenoming, treated between
that lower doses were equally effective 1981 and 1991, a single dose of 100 ml
in victims of predominantly haemotoxic of TRC Cobra antivenin reduced time on
snakebites in South India in (Thomas and a respirator from approximately 40 h if
Jacob, 1985; Tariang et al., 1999; Paul et no antivenin or an inadequate dose was
al., 2004; Srimannarayana et al., 2004; used to 10h (Pochanagool et al., 1997).
Cherian et al., 2013). However, these Increasing the dose did not lead to added
studies, without exception, had severe benefits. In victims of Trimeresurus (T.)
limitations in patient slection and case albolabris or T.(T.) macrops, 50 ml of TRC
definition, snake species identification, Green Pit Viper antivenin rapidly corrected
design, end-points and power, rendering coagulopathy (Hutton et al., 1990). A
their results uninterpretable. large retrospective review of patients
envenomed by these species found that
Thailand: in 1984, a small randomised TRC Green Pit Viper antivenin given on
controlled trial was carried out in patients average 21 hours after the bite for the
with systemic C. rhodostoma envenoming, treatment of severe coagulopathy did not
comparing three antivenoms that were affect the risk of their developing local
then available. An initial dose of 5 vials necrosis (Chotenimitkhun and Rojnuckarin,

ManageMent of snakebites
in south-east asia
139
2008). A randomized, double-blind, geographical intra-species venom
placebo-controlled trial of TRC Green Pit variation, lack of adequate neutralizing
Viper antivenin in patients bitten by these antibodies against key toxic venom
Trimeresurus species who had marked proteins, inability of the antibodies to
limb swelling, but no severe coagulopathy neutralize toxins that are tissue bound or
suggested that antivenom accelerated to reverse the pathological consequences
resolution of local swelling, although not of tissue injury. Envenoming by the larger
to a clinically useful degree (Rojnukarin et northern sub-species of saw-scaled viper
al., 2006). (Echis carinatus sochureki) requires larger
antivenom doses (Kochar et al., 2007)
and envenoming by Russells vipers in
Reasons for antivenom Kerala and Maharashtra require higher
ineffectiveness antivenom doses (Warrell et al., 2013).
Biochemical studies have shown variations
There is an urgent need for in venom composition in different parts
well-designed and adequately- of India for Naja naja (Mukherjee and
powered national clinical dose- Maity., 1998; Shashidharamurthy and
finding studies to establish Kemparaju, 2007) and Daboia russelii
initial doses of antivenom for (Jayanthi and Gowda, 1988; Prasad et al.,
patients with different severities 1999). Antivenom raised against venom
of envenoming by the major from one geographical location may not
medically important species in be as effective against envenoming in
the Region. These should focus other geographical locations. In India,
on bites by reliably-identified most of the venom used for antivenom
species, should be randomised, manufacture is obtained from the Irula
comparing two doses of the cooperative in Mammallapuram (Warrell
same antivenom or two different et al., 2013). A recent comparison of two
antivenoms, should have commercially available antivenoms showed
objective end-points to assess that one had a higher protein content, and
effectiveness and safety, and antibody binding and neutralizing capacity
should, ideally, be blinded to for Echis carinatus and Daboia russellii
exclude bias. venom. Indian polyvalent antivenoms
are raised against venoms of the classic
big four species and may not neutralize
There have been anecdotal and venoms of other medically important
unpublished reports of clinical snakes, such as monocellate cobra (N.
ineffectiveness of individual batches of kaouthia) in the North-East and any of the
antivenom. The variable efficacy may Indian pit-vipers, notably the hump-nosed
be due to lower antibody titre, reduced pit-viper (Hypnale hypnale) and Malabar
antibody binding specificities and lack pit-viper (Trimeresurus (Craspedocephalus)
of antibodies to low molecular weight malabaricus) of the south-west coast.
proteins. Studies have shown batch
to batch variability in effectiveness Suggested initial doses of some of
of Indian antivenoms, manifested by the available antivenoms are given in
increased complications and mortality Table 1 (by species of snake), based
with particular batches (Zachariah A, on clinical experience; and in Annex 3
personal communication; Zacharaiah, (by country),based on manufacturers
2015). Possible explanations include recommendations.

140 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Table 1: Guide to initial dosage of some antivenoms for treating bites by medically-important
snakes in the South-East Asia Region, based on clinical experience, rather than manufacturers
recommendations (E)

Latin name English Name Manufacturer, antivenom Approximate


average initial
dose

Acanthophis species death adder CSL1 Death Adder or Polyvalent Antivenom 1-3 vials

Bungarus caeruleus common krait Indian manufacturers2 polyvalent 100 ml

Bungarus candidus Malayan krait TRC Malayan Krait Antivenin Mono


3
50-100 ml
OR TRC3 Neuro Polyvalent 100 ml

Bungarus fasciatus banded krait TRC3 Malayan Krait Antivenin 50-100 ml


OR TRC3 Neuro Polyvalent 100 ml

Bungarus multicinctus Chinese krait Shanghai Vaccine & Serum Institute 5 vials
NIPM Taipei Naja-Bungarus antivenin 5 vials

Calloselasma (Agkistrodon) Malayan pit viper TRC3 Malayan Pit Viper Antivenin
Monovalent 30-50 ml
rhodostoma OR TRC3 Hemato Polyvalent 30-30 ml

Daboia russelii Western Russells viper Indian manufacturers2 polyvalent 100 ml

Daboia siamensis Eastern Russells viper Myanmar Pharmaceutical Factory 80 ml


TRC3 Russells Viper Antivenin Monovalent 30-50 m
OR TRC3 Hemato Polyvalent 30 ml

Echis carinatus India saw-scaled viper Indian manufacturers4 polyvalent 50 ml


Gloydius (Agkistrodon) Chinese Mamushi Shanghai Vaccine & Serum Institute
brevicaudus Mamushi antivenom 1 vial

Hydrophiinae sea snakes CSL1Sea Snake Antivenom 1-10 vials

Micropechis ikaheka New Guinean CSL1 Polyvalent Antivenom 2 vials


small-eyed snake

Naja kaouthia monocellate Thai cobra TRC3 Cobra Antivenin Mono 100 ml
OR TRC3 Neuro Polyvalent 100 ml
Naja naja, N oxiana Indian cobras Indian manufacturers2 polyvalent 50 ml

Ophiophagus hannah king cobra TRC3 King Cobra Antivenin Mono 100 ml
OR TRC3 Neuro Polyvalent 100 ml

Oxyuranus scutellatus Australian/Papuan CSL1 Taipan or Polvalent Antivenom 1-6+ vials


taipans

Pseudonaja species Australian brown CSL1 Brown Snake or Polyvalent 1-2 vials
snakes Antivenom\

Pseudechis species Australian black snakes CSL1 Black Snake Antivenom 1-3 vials

Rhabdophis tigrinus, Japanese yamakagashi, Japanese Snake Institute, Nitta-gun


R. subminiatus SE Asian red-necked Yamakagashi antivenom 1-2 vials
keelback

Trimeresurus (T.) albolabris Green pit-vipers TRC3 Green Pit Viper Antivenin 30-50 ml
T. (T.) macrops etc. OR TRC3 Hemato Polyvalent 30-50 ml

1
CSL, Parkville, Australia http://www.toxinology.com/fusebox.cfm?staticaction=generic_static_files/avp-csl-01.html
2
Indian Manufacturers: Bharat Serums & Vaccines, Mumbai https://www.bharatserums.com/; Central Research Institute, Kasauli http://www.
nti.org/learn/facilities/145/ ; Haffkine Biopharma, Mumbai; Serum Institute of India, Pune http://www.seruminstitute.com/content/products/
product_list.htm ; Vins Bioproducts, Hyderabad: Premium Serums and Vaccines, Narayangaon http://www.premiumserums.com/
3
Thai Red Cross, Queen Saovabha Memorial Institute, Bangkok, Thailand http://www.snake-antivenin.com/

ManageMent of snakebites
in south-east asia
141
f) Active haemolysis and
Snakes inject the same dose rhabdomyolysis may cease within a
of venom into children and few hours and urine colour returns to
adults. Children must therefore normal.
be given exactly the same
dose of antivenom as adults 6.7.9 Recurrence of systemic
Antivenom manufacturers, health envenoming
institutions and medical research In patients envenomed by vipers,
organizations should encourage after an initial response to antivenom
and promote the proper clinical (cessation of bleeding, restoration of
testing of antivenoms as with blood coagulability), signs of systemic
other therapeutic agents. This envenoming may recur within 24-48 hours.
is the only reliable guide to the
initial dose (and safety) of an This is attributable to:
antivenom. 1. continuing absorption of venom from
the depot at the site of the bite,
perhaps promoted by improved blood
Observation of the response to supply following correction of shock,
antivenom: If an adequate dose of hypovolaemia etc., after elimination
an appropriate antivenom has been of antivenom (range of elimination
administered, the following responses may half-lives: IgG 45 hours; F(ab)2 80-100
be seen. hours; Fab 12-18 hours) (Ho et al.,
1986; Ho et al., 1990)
a) General: the patient feels better.
Nausea, headache and generalized 2. redistribution of venom from the
aches and pains may disappear very tissues into the vascular space, as the
quickly. This may be partly attributable result of antivenom treatment (Rivire
to a placebo effect. et al.,1997).
b) Spontaneous systemic bleeding
(e.g. from the gums) usually stops Recurrent neurotoxic envenoming after
within 15-30 minutes. treatment of cobra bite has also been
c) Blood coagulability (as measured described.
by 20WBCT) is usually restored in 3-9
hours. Bleeding from new and partly 5.7.10 Criteria for repeating the initial
healed wounds usually stops much dose of antivenom
sooner than this.
d) In shocked patients, blood pressure
Criteria for giving more
may increase within the first 30-60
antivenom
minutes and arrhythmias such as sinus
bradycardia may resolve. Persistence or
e) Neurotoxic envenoming of the post- recurrence of blood
synaptic type (cobra bites) may begin incoagulability after 6 hr or
to improve as early as 30 minutes after of bleeding after 1-2 hr
antivenom (Faiz et al., cobra bites in
Deteriorating neurotoxic
press), but may take several hours.
or cardiovascular signs
Envenoming by presynaptic toxins
after 1 hr
(kraits and sea snakes) will not respond
in this way.

142 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
If the blood remains incoagulable periods of more than one month. Manual
(as measured by 20WBCT) six hours ventilation (anaesthetic bag) by relays
after the initial dose of antivenom, the of doctors, medical students, relatives
same dose should be repeated. This is and nurses has been effective where
based on the observation that, if a large no mechanical ventilator was available.
dose of antivenom (more than enough Anticholinesterases should always be tried
to neutralize the venom procoagulant (see below).
enzymes) is given initially, the time taken
for the liver to restore coagulable levels of Haemostatic abnormalities - strict bed
fibrinogen and other clotting factors is 3-9 rest to avoid even minor trauma including
hours. intramuscular injections; transfusion of
clotting factors and platelets; ideally, fresh
In patients who continue to bleed frozen plasma (FFP) or cryoprecipitate
briskly, the dose of antivenom should be with platelet concentrates or, if these are
repeated within 1-2 hours. not available, fresh whole blood. The
indications for these blood components
In case of deteriorating neurotoxicity are the same as those for antivenom
or cardiovascular signs. There is no administration for bleeding tendency, but
evidence to guide the exact timing for it is important to recognize that, in the
repeating the dose of antivenom for presence of un-neutralized circulating
paralysis or shock, but it seems reasonable venom procoagulant toxins, administered
to repeat the initial dose after 1 hour if the clotting factors will be rapidly consumed,
patients condition is deteriorating. Full with the potential danger of formation of
supportive treatment must be considered. microthrombi.
Repeating doses of antivenom after the
patient is paralysed and being ventilated Shock, myocardial damage:
has no proven value, increases the risk hypovolaemia should be corrected
of reactions, is expensive and wastes a with colloid/crystalloids, controlled by
valuable resource. observation of the central venous pressure.
Ancillary pressor drugs (dopamine or
6.8 Conservative treatment epinephrine-adrenaline) may also be
when no antivenom is needed. Patients with hypotension
available associated with bradycardia should be
This will be the situation in many parts of treated with atropine.
the Region, where supplies of antivenom
run out or where the bite is known to Acute kidney injury: conservative
have been inflicted by a species against treatment or dialysis (see below).
whose venom there is no available specific
antivenom. Dark brown urine (myoglobinuria or
haemoglobinuria): correct hypovolaemia
The following conservative measures are with intravenous fluid, correct acidosis
suggested: with a slow intravenous infusion of 50-100
mmol of sodium bicarbonate.
Neurotoxic envenoming with
respiratory paralysis: assisted Severe local envenoming: local
ventilation. This has proved effective, necrosis, intracompartmental syndromes
and has been followed by complete and even thrombosis of major vessels
recovery, even after being maintained for is more likely in patients who cannot

ManageMent of snakebites
in south-east asia
143
be treated with antivenom. Surgical antivenom and fresh-frozen
intervention may be needed but the risks plasma or clotting factors will be
of surgery in a patient with consumption needed to control bleeding after this
coagulopathy, thrombocytopenia and procedure.)
enhanced fibrinolysis must be balanced
against the life threatening complications In urgent situations where acute airway
of local envenoming. Prophylactic broad obstruction has developed and where
spectrum antimicrobial treatment is the patient cannot be intubated,
justified (see below). cricothyroidotomy will establish an airway
faster than tracheostomy.
6.9 Supportive/ancillary
treatment
Antivenom treatment can be expected to Although artificial ventilation was
neutralize free circulating venom, prevent first suggested for neurotoxic
progression of envenoming and allow envenoming 140 years ago,
recovery. However, these processes take patients continue to die of
time and the severely envenomed patient asphyxiation because some
may require life support systems such as doctors believe that antivenom
treatment of shock, assisted ventilation alone is sufficient treatment.
and renal dialysis until the severely
damaged organs and tissues have had
time to recover. 6.9.2 Practical guide to airway
management and respiratory support
6.9.1 Treatment of neurotoxic The following guidelines have been
envenoming produced specifically to aid health care
workers in the acute management
of snakebite patients. However, it is
Antivenom treatment alone important to recognize that the techniques
cannot be relied upon to save the described below are applicable to the care
life of a patient with bulbar and of all critically ill patients.
respiratory paralysis.
The techniques discussed below are not
complicated. However, expert instruction
Death may result from aspiration, airway is desirable, ideally from a fully trained
obstruction or respiratory failure. A doctor, nurse, first-aid worker or other
clear airway must be maintained. Once health professional, with experience in
there is loss of gag reflex and pooling resuscitation, airway management, use
of secretions in the pharynx, failure of of the necessary equipment, intubation
the cough reflex or respiratory distress, and assisted ventilation. These techniques
a cuffed endotracheal, laryngeal mask must be practised frequently, under
airway or i-gel supraglottic airway should supervision, using a manikin (dummy/
be inserted. If this is impossible for model see Fig 82a) or, but only where
any reason, or the need for prolonged appropriate and culturally acceptable, a
ventilation is anticipated, a tracheostomy dead body in the mortuary, to acquire
should be performed and a snugly- essential understanding of the anatomy
fitting or cuffed tracheostomy tube of the upper airway and the techniques
inserted (Caution in patients with themselves, and to maintain an adequate
uncorrected coagulopathy, more baseline level of skill (Fig 82b).

144 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Importance of training (Fig 82a)

Figure 82b: Anatomy of the upper airway

Resuscitation
This follows the general principles of life
support given below:

DRABCDE
D - DANGER
R - RESPONSE
A - AIRWAY
B BREATHING
C - CIRCULATION
D - DISABILITY
Figure 82: Treatment of neurotoxic envenoming: (a) Training health workers in
E EXPOSE THE PATIENT techniques of endrotracheal intubation and airway management in Papua New
(Only DRAB are discussed here) Guinea (Copyright DJ Williams)

D - DANGER - Scene safety: The If there is no response, or limited response,


rescuer should ensure that there is no summon assistance. Call out for help, send
risk of exposure to danger of a further someone for medical assistance, or make a
snakebite to the victim, to themselves, very quick telephone call.
or to other helpers by observing
standard precautions possible under the Making an emergency call
circumstances (e.g. removing the victim If the victim does not respond:
from undergrowth and, in the case of 1. In a field situation: emergency medical
sea snakebite, removal from the water services (EMS) are activated by calling
to avoid drowning) and ensuring that the local emergency number (either
any snake brought to hospital with the by a second rescuer or by the first
patient, for identification, will not bite rescuer him/herself). The response
another person. team (ambulance) is asked to bring the
necessary resuscitation equipment (also
R - RESPONSE -The rescuer checks termed code cart or code blue cart
responsiveness of the victim (e.g. vocal - in some hospitals/clinics), including an
Are you all right?, with gentle shaking). automated external defibrillator (AED).

ManageMent of snakebites
in south-east asia
145
2. In a health centre: emergency cart catheter (attempts should not be longer
and defibrillator are summoned. Once than 10 seconds) or by using forceps.
the EMS/emergency cart has been Use of a gloved finger is discouraged
summoned, the rescuer starts airway as this may push the material or object
management further down the airway and may put
the rescuer at risk of being bitten.
A AIRWAY PROTECTION AND
MANAGEMENT Finally, insert an oropharyngeal (Guedel)
Basic Airway Management (BAM) airway (OPA), measured to suit the
Opening and maintaining the airway: patient (from the corner of the mouth
The airway can be opened using the to the angle of the jaw), being sure to
head tilt - chin lift manoeuvre (Fig avoid causing trauma to the lips and
82c), bringing the patients head into the mouth, especially if there is evidence of
sniffing position. If there is any suspicion bleeding or the if the patient has been
of cervical spine trauma, jaw thrust should bitten by a snake which causes bleeding
be used rather than this procedure. abnormalities. While nasopharyngeal
airway (NPA) devices are better tolerated
by semi-conscious patients, who may
still have a gag reflex, or in those who
have trismus, they are more likely to
cause nasal bleeding, and so are not
preferred.

If an OPA device cannot be inserted


because of trismus (rigidity of the
chewing muscles, preventing opening of
the mouth), the patient may have one of
Figure 82c: Head-tilt, chin-lift (left) and jaw-thrust manoeuvres (right)
the following life-threatening conditions,
which must be urgently treated:
If this does not improve air flow, the jaw
thrust manoeuvre (Fig 82c) should be Severe hypoxia;
performed as the tongue may have fallen Hypoglycaemia;
or been sucked backwards, obstructing the Seizure;
oropharynx. Jaw thrust helps to lift the Active rhabdomyolysis affecting
tongue forward, and is often effective in the masseter muscles (e.g. in sea-
improving air flow as lifting the patients snakebite envenoming)
chin and extending their neck serves to Or they may, in fact, be awake and
dislodge the tongue and reopen the upper simply resisting you.
airway.
Advanced Airway Management
Next look inside the victims mouth. (AAM)
There may be blood, vomit or excessive AAM is defined as the use of more
oral secretions contributing to airway advanced techniques in airway
obstruction and putting the patient at management. It may be used in the
risk of aspirating (inhaling) this material following circumstances:
into their lungs. Remove any foreign
material by suction, using a suitable To maintain (keep open) the airway
suction catheter, such as a Yankeur suction over long periods;

146 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
To protect the airway (prevent the
inhalation/pulmonary aspiration of
saliva, vomit or blood):

To ventilate a paralysed patient (such as


after a bite by a snake with neurotoxic
venom);

To allow high concentrations of oxygen


(up to 100%) to be delivered;

To remove, and control the


concentration of, carbon dioxide in the Figure 82d: Supraglottic (above the larynx) devices Laryngeal mask airway,
introduction and position
blood.

work, but they may not be freely available


Indications for intubation in peripheral hospitals. They do not require
[insertion of endotracheal tube special equipment to insert them, and
(ETT) or other airway]: even medically untrained people can be
taught to insert them successfully after
a. Imminent respiratory arrest minimal (as little as one hours) tuition,
(breathing is absent or making them potentially ideal in a low-skill
inadequate) setting. However, they not provide good
b. Neck muscle weakness protection of the airway as, potentially,
with shallow respiration or fluids can still leak past them into the
paradoxical breathing patients lungs. They do not permit high
c. Upper airway obstruction ventilation/airway pressures, and require
with stridor (secondary to a gastric tube to reduce the risk of gastric
anaphylaxis) insufflation (distension with gas) and the
d. Oxygen saturation <90% risk of gastro-oesophageal reflux.
(equivalent to Pa02 <60
mmHg) despite high flow i-gel supraglottic airway. i-gel
oxygen airways are made of a thermoplastic
e. Blood gas measurement elastomer, which is soft, gel-like and
showing respiratory acidosis transparent. They are designed to create
(hypoxia PaO2 < 60 mm Hg a non-inflatable anatomical seal of the
with PaCO2 > 45 mm Hg) pharyngeal, laryngeal and perilaryngeal
structures. Insert with the i-gel cuff outlet
facing towards the patients chin with
The devices used for this type of airway head extended and neck flexed in the
management are divided into 2 categories: sniffing position (see above). Glide
the device downwards and backwards
Supraglottic (above the larynx) along the hard palate with a continuous
devices (Fig 82d) but gentle push until a definitive
Laryngeal mask airways. Many resistance is felt. At this point the tip of
models with different features benefits the airway should be located into the
and disadvantages are now available, upper oesophageal opening and the cuff
depending on the country in which you should be located against the laryngeal

ManageMent of snakebites
in south-east asia
147
(Fig 82e) i-gel supraglottic airway and hence the risk of hypoxia) experience
is required.

Induction/intubation drugs should be


used, though these may not be available
or the staff may not be experienced in
their safe use.

Discussion of the actual techniques


involved is beyond the scope of this
document. However, essentially an
endotracheal tube is inserted under
laryngoscopic vision between the vocal
cords so that its tip lies in the mid trachea
(Fig 82f).

An endotracheal tube is inserted under


laryngoscopic vision between the vocal
Figure 82e: Treatment of neurotoxic envenoming i-gel supraglottic airway cords so that its tip lies in the mid trachea.
Intubation is more invasive than supra-
glottic devices and needs laryngoscopy
framework. The incisors should be resting and more skill to perform.
on the integral bite-block.
Surgical airway devices
Infraglottic (extending below the (tracheostomy)
larynx) devices: These are discouraged and are rarely
The most familiar, and by far the most necessary because:
readily available, is the endotracheal tube
(ETT), typically a cuffed tube for adults and Patients rarely require ventilation beyond
an uncuffed tube for children, though the a week, once the correct type and dose
use of cuffed (low pressure, high volume) of antivenom has been given; Many
tubes for children is becoming more patient venom-induced bleeding disorders
acceptable. and will bleed excessively from any such

These do provide protection of the lower


airway (the lungs) against contamination
by fluids and also permit higher ventilation
pressures and the highest inspired oxygen
concentrations.

However, they require a laryngoscope of


some sort to permit visualization of the
laryngeal structures, and even the most
basic of these are not available in small
health centres.

To insert these devices safely and quickly


(to reduce the period of no ventilation, Figure 82f: Insertion of an endotracheal tube

148 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
intervention. Therefore, tracheostomy If breathing stops at any time, lay the
is a term that should be removed from victim supine, go through the airway
snakebite management protocols. opening manoeuvres again, and then
provide breathing artificially, if required.
B BREATHING Assessing breathing:
Place your ear near the victims mouth If breathing is absent or inadequate, such
and nose, keeping your gaze towards as if:
the victims chest. Look for chest to rise
and fall, listen for air escaping during
exhalation, feel for the flow of air against
your cheek. Take at least 5 seconds but
no more than 10 seconds to make this
assessment.

If oxygen is available, it should be


Figure 82g: The recovery position
administered by any available means (nasal
prongs/catheters, mask, bag-valve-mask
etc.) between each suctioning attempt No breathing is discernible within 10
(which should not be prolonged). [Arterial seconds (or 5 seconds in a child, 2
Peripheral oxygen saturation (SpO2) seconds in a baby);
should be monitored by digital oximeter, if
available.] The respiratory rate is low (a general
idea of normal ranges of age-related
Positioning the patient to protect airway respiratory rates and other basic
patency (Dangers of vomiting and physiological parameters is required
aspiration) of all health care workers, or this
information should be readily available
If breathing is present and adequate (with to them);
or without airway opening manoeuvres),
put the victim in the recovery position (Fig The depth of respiration is inadequate
82g) and keep checking for breathing (shallow) (the tidal volume is low);
every 2 minutes. This position and a chin-
up tilt can be maintained using pillows, The patient is taking agonal (gasping)
sand bags or an assistant, often the breaths;
patients relative. The recovery position is
especially important in envenomed patients The patient is cyanosed centrally (blue
because vomiting is such a common early lips, ears, or tongue) (this might not
symptom, oral bleeding is common if be visible if the patient is very anaemic,
there is a bleeding disorder, there may be such as from malnutrition, chronic
hypersalivation and, since patients with malaria or chronic gastrointestinal
neurotoxicity cannot cough or swallow, parasite infestation), or
they are at increased risk of inhaling any of
these secretions and fluids. However, when The measured blood peripheral oxygen
the patient is placed in the correct recovery saturation is low (a poor trace, and
position, these fluids will drain harmlessly so a potentially low reading, may
from their mouth. The recovery position be obtained if the patient has cold
will also help to stop the tongue from peripheries or a low blood pressure
falling back and blocking the airway. -shock);

ManageMent of snakebites
in south-east asia
149
patients mouth and deliver a breath over
a second, enough to see the chest rise,
If chest movement is inadequate, a
and allowing 4 seconds for exhalation
correctly-sized OPA should be inserted. before giving a second breath. In the case
This will usually assist with air flow in and of a small child the mouth and nose may
be covered by the rescuers mouth.
out of the lungs. If there is no bleeding
disorder, a NPA (or 2) may be used instead Assisted ventilation by this means will
provide a maximum of approximately only
of, or in addition to, an OPA. 16% inspired oxygen concentration (FIO2
0.16).

The end-tidal CO2, by whichever The risk of communicable disease


method is being used, is high, or transmission to the rescuer is low, but can
climbing; be diminished further by the use of:

ASSISTED VENTILATION IS REQUIRED! A special EAR face shield,


How this is delivered will depend on: manufactured for this purpose;
A mask of the type used with Bag-
The clinical circumstances, i.e. whether Valve-Mask (devices);
the patient is in the bush, in an small A piece of cloth thin enough to allow
health centre or in a hospital; for the free passage of air.
The skills of the rescuer;
The availability of assistants; If the patient does not begin to breathe, or
Equipment available. to breathe more effectively, at this point,
the decision will need to be made about
Methods for providing assisted how long to continue this method of
ventilation assisted ventilation.
Expired Air Resuscitation (EAR) (no health
facilities immediately available): This will depend on:

Deliver 2 initial rescue breaths as follows The clinical circumstances, e.g. the
(Fig 82h): close the patients nose with likely diagnosis, the age of the patient
one hand and pull the jaw down with (the rescuer might reasonably persist
the other, and place your mouth over the for longer if the patient is a small
child), or the distance from medical
assistance or from more advanced
health care facilities;

The presence of effective cardiac


activity; as determined by the presence
of a carotid pulse (palpate on both
sides before determining that this is
absent), more advanced tests such as
auscultation of audible heart sounds,
or visible cardiac contraction on
ultrasound; are supportive tests which
Figure 82h: Technique of giving rescue breaths may be available.

150 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
The presence of electrical activity, as
determined using a cardiac monitor of
some kind, with no demonstrable cardiac
output or pulse (so-called pulse-less
electrical activity) usually carries a very
poor prognosis, though there is a list of
potentially reversible conditions which
may cause this. This topic is not covered in
these guidelines, but should be covered in
any advanced life support course material.
Figure 82i: bag-mask/Bag-Valve-Mask (BVM)
(resuscitator bag)
Non-invasive ventilation:
Bag-mask/Bag-mask-valve ventilation: In term respiratory support but if there is no
a health-care centre, a commonly used breathing or inadequate breathing that
method for providing initial respiratory needs longer term support, the airway
assistance is with a bag-mask/Bag-Valve- needs to be secured more definitively and
Mask (BVM) (resuscitator bag) (Fig 82i) even the bag may have to be replaced
Even the simplest health-care centre with a ventilator. However, many snakebite
should have these, with different sizes patients around the developing world have
required for different ages of patients, been kept alive for days, or week, using
and the staff should be well versed in how simply an OPA and a BVM, or with an ETT
to check that the device is functioning and a BVM, using relatives to squeeze the
correctly and know how to use it correctly bag, though this is far from ideal.
and safely.
Invasive Ventilation:
The rescuer positions him/herself at the Indications for intubation and mechanical
victims head end. Holding the bag with ventilation are Type I respiratory failure
one hand, he/she places the mask on the (primary failure of oxygenation as in
victims face with the apex of the mask pulmonary oedema in Russells viper
on the bridge of the nose and its base on envenoming) and Type II respiratory
the groove over the chin. With the other failure (primary ventilatory failure due to
hand, he/she seals the mask around the respiratory muscle paralysis or obstruction
victims nose and mouth, tilts (extends) as in elapid envenoming). Suggestive
the victims head, lifts the jaw forward clinical features in patients receiving
and gives breaths at approximately the oxygen by mask or nasal catheters include
normal respiratory rate for the patient by tachpnoea (respiratory rate > 25/min) or
squeezing/pressing the bag, looking for paradoxical respirations (abdomen moves
visible chest rise. Any chest movement is out on inspiration) and deteriorating
usually adequate, especially in children. ventilatory capacity (see above); hypoxia
(central cyanosis, SpO2 < 90%, arterial
If chest movement is inadequate, a PO2 < 50 mm Hg, < 6.7 kPa); and
correctly-sized OPA should be inserted. respiratory acidosis (arterial PCO2 > 50
This will usually assist with air flow in and mm Hg, < 6.7 kPa, arterial pH <7.36).
out of the lungs. If there is no bleeding Supraglottic or infraglottic devices are
disorder, a NPA (or 2) may be used instead used to open the airway and assist with
of, or in addition to, an OPA. both the supply of oxygen to the lungs
and removal of carbon dioxide from the
Bag-mask breathing suffices for short- lungs. Generally, and where possible,

ManageMent of snakebites
in south-east asia
151
endotracheal intubation (insertion of Physiotherapy (including chest
an ETT) should be performed and the physiotherapy, regular turning to
patient placed on a ventilator, attended prevent pressure areas and lung
constantly by a suitably qualified nurse, collapse, and maintenance of the range
with a suitably qualified doctor always of motion of paralysed, immobile
on call to provide additional assistance, if joints and muscles, as well as limbs
required. Tube blockages are a frequent where significant cytotoxicity and tissue
cause of morbidity and mortality. They damage has occurred).
are prevented by regular suctioning,
humidification and training of staff to Eye care (synthetic tears and closure
recognize the symptoms of a blocked tube. of the eyelids to prevent drying and
damage to corneas in patients on
Sedation for patients being ventilators).
mechanically ventilated: fentanyl 2-40
microg/hour and midazolam 2-4 mg/hour Safe and effective weaning from
OR (to avoid acute kidney injury) morphine ventilation.
1-5 mg/hour with lorazepam 1-2 mg/hour.
Always be careful to minimize trauma
Adequacy of respiratory assistance can to the airway of a snakebite patient; this
be assessed by reversal of clinical signs of includes the insertion of basic airway
inadequate respiration and stabilization devices, advanced airway devices and
of SpO2 and end-tidal CO2 (where gastric tubes. Orogastric tubes are much
available) and improvement in the victims preferred over nasogastric ones the
level of consciousness if respiratory latter often lead to bleeding which is
failure was the sole cause of his/her difficult to deal with in the patient who
unresponsiveness. However, assessing the has a coagulopathy, and may even
level of consciousness of a patient with lead inexperienced staff to give more
neurotoxic envenoming can be difficult antivenom or blood products when these
because of their often generalized flaccid are not necessary.
paralysis, such that the normal method of
ascertaining the level of consciousness (the Such care also applies to the insertion of
Glasgow Coma Scale GCS) is irrelevant intravenous catheters and urinary (urethral)
since the patient is unable to open their catheters. Central venous lines may be
eyes, unable to speak and often unable inserted, if required and possible, but the
to obey commands. They are, contrary insertion site will depend on the presence
to common belief, awake, able to hear or absence of a bleeding disorder. Intra-
everything which is said around them. They arterial lines may be useful in many
should be sedated during the period of respects, but, again, are discouraged in
their ventilation. the presence of a bleeding disorder.

Other important aspects of the care of a 6.9.3 Trial of anticholinesterase


ventilated patient include: Anticholinesterase drugs have a variable,
but potentially very useful effect in
Adequate hydration, monitoring of patients with neurotoxic envenoming,
renal function and of fluid balance; especially those bitten by cobras (Banerji
et al., 1972; Watt et al., 1986; Watt et al.,
Nutrition (in addition to the minimal 1989; Faiz et al., cobra in press), but not
nutrition contained in normal IV fluids); usually in those envenomed by kraits (Anil

152 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
et al., 2010). However, recent claims that
intra-nasal neostigmine might provide a
universal first-aid method for snakebite
victims have achieved a high media profile
but are unsubstantiated, misleading and
fanciful (Lewin et al., 2013; Lewin et al.,
2014).

[a] [b]
A trial of anticholinesterase Figures 83: Anti-cholinesterase: (a) Before and (b) after intravenous atropine
followed by intravenous edrophonium chloride in a patient envenomed by a
(e.g. Tensilon test) should Malayan krait (Bungarus candidus) (Copyright DA Warrell)
be performed in every patient
with neurotoxic envenoming,
as it would be in any patient 10-20 minutes (edrophonium) for
with suspected myasthenia signs of improved neuromuscular
gravis. However, this should not transmission. Ptosis may disappear
delay antivenom treatment or (Fig 83) and ventilatory capacity
endotracheal intubation. Patients (peak flow, FEV-1 or maximum
must be observed closely as they expiratory pressure) may improve.
may deteriorate while the trial
of anticholinesterase is being 4. Patients who respond convincingly
carried out can be maintained on neostigmine
methylsulphate, 0.5-2.5 mg every
1-3 hours up to 10 mg/24 hours
Procedure maximum for adults or 0.01-0.04
1. Baseline observations or mg/kg every 2-4 hours for children
measurements are made against by intramuscular, intravenous or
which to assess the effectiveness of subcutaneous injection together
the anticholinesterase. with atropine to block muscarinic
side effects. Patients able to swallow
2. Atropine sulphate (0.6 mg for tablets may be maintained on
adults; 50 g/kg for children) or atropine 0.6 mg twice each day,
glycopyrronium is given by intravenous neostigmine 15 mg four times each
injection followed by neostigmine day or pyridostigmine 60 mg four
bromide or methylsulphate times each day.
(Prostigmin) (or distigmine,
pyridostigmine, ambenomium etc. in
appropriate doses) by intramuscular Anticholinesterase (e.g.
injection 0.02 mg/kg for adults, 0.04 Tensilon) test
mg/kg for children. Short acting Baseline observations
edrophonium chloride (Tensilon) is Give atropine intravenously
ideal for this test but is rarely available Give anticholinesterase
in the Region. It is given by slow drug (e.g. neostigmine
intravenous injection in an adult dose intramuscularly)
of 10 mg, or 0.25 mg/kg for children. Observe effect
If positive, institute regular
3. The patient is observed over the atropine and neostigmine
next 30-60 minutes (neostigmine) or

ManageMent of snakebites
in south-east asia
153
Suggested method: in a patient with
bilateral ptosis from neurotoxic snake-bite,
the distance between the upper and lower
lid margins of both eyes (palpebral fissures)
is measured using a mm ruler. Digital
pressure is applied to the frontalis muscle to
avoid its influencing upper eyelid retraction.
An ice-filled plastic glove or frozen ice pack
is then gently applied to one eyelid for 2
minutes, after which the palpebral fissures
of both eyes are immediately re-measured.
A more-than-2mm difference in palpebral
fissure between the cooled and control
eyelids might be considered a positive result
(Fig 84).

6.9.4 Treatment of Hypotension


and shock
This is usually the result of hypovolaemia
[from loss of circulating volume into the
swollen limb, as a result of generalized
increase in capillary permeability (e.g.
Russells viper envenoming in Myanmar)
or internal/external haemorrhage], venom-
induced vasodilatation or direct myocardial
effects with or without arrhythmias.

Postural (orthostatic) blood pressure


measurement: hypovolaemia is best
detected by measuring blood pressure
with the patient lying supine, and
repeating the measurement when the
patient is propped up, ideally in a fully
Figure 84: Ice test sitting position but, depending on their
recovery of ptosis in the
left eye after applying The ice pack test as a possible condition, at 45 degrees if 90 degrees
an ice pad that inhibits alternative to the Tensilon test is not tolerated (Fig 85). A clinically
intrinsic cholinesterase in a
patient with post-synaptic
(Golnik et al., 1999). significant fall in blood pressure during
blockade of neuro- In patients with myasthenia gravis who have this procedure (orthostatic hypotension) is
muscular transmission.
ptosis, cooling of the ptotoc (drooping) a fall in systolic blood pressure of 20 mm
(Delaney Y, Khooshabeh R,
Benjamin L (2002). Acute eyelid results in improvement in ptosis, Hg or diastolic blood pressure of 10 mm
severe ocular myasthenia due to inhibition of intrinsic cholinesterase Hg or more.
in a 92-year-old woman.
Eye (Lond);16(3):323-4). (Golnik et al., 1999). This quick and simple
test might obviate the need for the Tensilon Passive leg raising test (fig.
test in predicting the effectiveness of 85c): another way of assessing fluid
anticholinesterase (neostigmine) treatment. responsiveness is to sit the patient in a 45
However, it has not yet been evaluated in degrees head-up semi-recumbent position.
patients with neurotoxic envenoming. This Lower their upper body to the horizontal
study must be done! and passively raise their legs at 45 degrees

154 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
[a] [b]
Figures 85 a, b: measurement of postural change in blood pressure as evidence of hypovolaemia: (a) supine;
(b) sitting up (Copyright DA Warrell)

transfer of blood from


the legs and abdominal
compartments

= test for fluid


responsiveness

Passive leg raising


Passive leg raising. The passive leg raising test consists in measuring the hemodynamic effects of a leg elevation up to
45. A simple way to perform the postural maneuver is to transfer the patient from the semirecumbent posture to the
passive leg raising position by using the automatic motion of the bed.

Figure 85. c: Passive leg raising test to guide fluid therapy


(see Marik et al., 2011)

up, increasing circulating volume by may be given by intravenous infusion,


about 150-300ml. The maximal effect preferably into a central vein (starting dose
of this auto-infusion occurs at 30-90 2.5-5 (micro) g/kg/minute).
seconds, measured by clinical features of
improved cardiac output (e.g. increase in
Snakebite: causes of hypotension
pulse pressure and decrease in heart rate)
and shock
(Boulain et al., 2002; Marik et al., 2014).
1 Anaphylaxis
Treatment with crystalloids should Vasodilatation
be controlled by observation of the Cardiotoxicity
fluid status (jugular venous pressure, Hypovolaemia
respiratory rates and crepitations, see 2 Antivenom reaction
Annex 6). Excessive volume replacement Respiratory failure
may cause pulmonary oedema when Acute pituitary adrenal
plasma extravasated in the bitten limb insufficiency
and elsewhere is reabsorbed into the Septicaemia
circulation.

In patients with evidence of a generalized In victims of Russells viper bites in


increase in capillary permeability, a Myanmar, India and Sri Lanka, acute
selective vasoconstrictor such as dopamine pituitary adrenal insufficiency resulting

ManageMent of snakebites
in south-east asia
155
from haemorrhagic infarction of the In patients with any of the above
anterior pituitary may contribute to features, the following should be
shock, while neurological manifestations monitored
of hypoclycaemia, such as impaired
consciousness, extensor posturing and other signs of uraemia syndrome
other involuntary movements, may be pulse rate
presenting signs that respond to a test blood pressure, lying and sitting, to
dose of intravenous 50% dextrose injection detect postural hypotension (see 14
(Warrell, 2009) (Tun-Pe et al., 1987) (Fig Treatment of hypotension and shock)
52a). Hydrocortisone, fluid and electrolyte respiratory rate
replacement may needed acutely in these temperature
patients. In chronic cases, addition of height of jugular venous pulse
thyroxin, oestrogen or testosterone may be auscultation of lung bases for
needed (Antonypillai et al., 2011; Jeevagan crepitations
et al., 2013). fluid balance chart and/or daily weight

6.9.5 Treatment of oliguria and acute 6.9.5.1 Oliguric phase of renal failure
kidney injury Most, but not all, patients with acute
(Sitprija and Boonpucknavig 1979; renal failure are oliguric, defined as a
Chugh 1989) urine output of less than 400 ml/day or
less than 30 ml/hour (children less than
0.5ml/kg bodyweight /hour). Conservative
Detection of acute kidney injury management may tide the patient over,
avoiding the need for renal replacement
Abrupt (within 48h) reduction therapy (dialysis).
in kidney function (Acute
Kidney Injury Network criteria) If the patient has intravascular volume
Decreasing or no urine output depletion, indicated by supine or postural
(<0.5 mL/kg/h for more than hypotension, or empty neck veins,
6 h) proceed as follows:
Increase in serum creatinine
concentration [serum 1. Establish intravenous access
creatinine 26.5 mol/L (0.3
mg/dL)] or increasing by 150 2. Give a cautious fluid challenge: an
- 200% (x 1.5 - 2) compared to adult patient can be given 250-500
baseline [?urea] ml of isotonic saline over one hour
or, until the jugular venous pressure/
Clinical uraemia syndrome: central venous pressure has risen to
nausea, vomiting, 8-10 cm above the sternal angle (with
acidotic (Kussmaul) the patient propped up at 45). The
breathing patient must be closely observed while
hiccups, fetor, this is being done. The fluid challenge
drowsiness, confusion, coma, must be stopped
flapping tremor, muscle immediately if pulmonary oedema
twitching, convulsions develops. If the urine output does not
pericardial friction rub, improve it is reasonable to perform a
signs of fluid overload furosemide stress/challenge test (see
below for details).

156 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Note in some patients it can be 5. Conservative management for acute
difficult to determine the height of kidney injury: if the urine output does
the central venous pressure by clinical not improve, despite these challenges,
examination. Direct measurement of no further diuretics should be given
central venous (superior vena caval) and fluid intake should be restricted
pressure through a long catheter, to a total of the previous days output
preferably inserted at the antecubital plus insensible losses (500-1000 ml/
fossa (see Annex 6), can be helpful day). If possible, the patient should be
in this circumstance. The catheter is referred to a renal unit. The diet should
connected to a saline manometer, be bland, high in calories (1800/
the 0 point of which must be placed day), normal in protein (0.8-1 g/day),
at the same level as the right atrium low in potassium (avoid fruit, fruit
(that is, at the sternal angle when the juices, energy drinks and potassium-
patient is propped up at 45). This containing drugs) and low in salt.
measurement is reliable only if the Infections will cause tissue breakdown
level varies freely with respiration and and increase urea levels. They should
the zero point is correctly positioned. be prevented or treated promptly with
non-nephrotoxic antibiotics (i.e. avoid
In a patient who is obviously volume- aminoglycosides such as gentamicin).
depleted, resuscitation should start
immediately, and not be delayed 6. Biochemical monitoring: In patients
until a central venous line has been with acute kidney injury it is
inserted. recommended that serum/plasma
urea, creatinine and electrolytes be
3. Insert a urethral catheter (full sterile monitored daily if possible, until renal
precautions!) but in male patients, try failure is resolving. Serum potassium,
using a condom catheter first. urea, creatinine and, if possible, pH,
bicarbonate, calcium and phosphate
4. Furosemide (frusemide) stress/ should be measured. If this is not
challenge: once the patient has been possible the electrocardiogram (ECG)
given adequate fluid replacement should be examined for evidence of
1-1.5 mg/kg of furosemide is injected hyperkalaemia, especially following
slowly (4-5 mg/minute) intravenously bites by sea snakes, or Sri Lankan,
and urine output is monitored for 2 Indian, Bangladeshi or Myanmar
h. A urine output of < 200 ml in hour Russells vipers or if the patient is
(100 ml/hour) predicts progression passing dark brown urine, suggestive
of renal failure (Chawla et al., 2013). of rhabdomyolysis or intravascular
In this case, the patient is likely to haemolysis.
progress to acute kidney injury and
requires conservative management. 7. Detection and management of
Results of a small study done in hyperkalaemia (UK Renal Association,
Myanmar, showed a statistically 2014)
significant lower requirement for renal
replacement therapy (acute peritoneal ECG evidence of hyperkalaemia: tall
dialysis) in patients given furosemide peaked T waves, prolonged P-R interval,
infusion compared to those given absent P waves, wide QRS complexes.
placebo (Kyaw San Lwin, personal Emergency treatments, which will
communication, 2012). control hyperkalaemia for 3-6 hours

ManageMent of snakebites
in south-east asia
157
only, should be given if serum potassium profoundly acidotic (deep sighing
>6.5 mmol/l or ECG changes Kussmaul respirations, very low
plasma bicarbonate concentration
Calcium Gluconate 10%: 0.5 ml/kg or very low pH - <7.10),Sodium
10 ml slow intravenous injection over bicarbonate should be given.
2-5 minutes if haemodynamically Based on volume of distribution of
unstable, or over 15-20min if stable bicarbonate which is 40% of body
(onset of action 3 minutes). Check weight, bicarbonate deficit can be
for normalisation of ECG. Repeat if calculated. Usually 2-3 ampoules
necessary. (40 ml. of 8.4% sodium bicarbonate
equivalent to 1 mmol/ml) in 5%
2 agonist aerosol by inhaler (e.g. dextrose water, or half of the
salbutamol nebulisation 5mg q 1-2h calculated deficit can be replaced in
- onset of action 30 minutes - up to 3-4 hours. Severe acidosis in snakebite
10-20 mg. is usually associated with acute renal
failure. Volume expansion by sodium
Give 50 ml of 50% dextrose with 10 bicarbonate can cause fluid overload.
units of soluble insulin intravenously Therefore, if there is no clinical
(onset of action 15 minutes) improvement dialysis is required.
Caution: Intravenous bicarbonate may
Sodium Bicarbonate 8.4% 1 ml/kg IV precipitate profound hypocalcaemia
slow over 5 minutes and fitting, especially in patients with
rhabdomyolysis.
Followed by a low potassium diet.
8. Management of severe acidosis 9. Renal replacement therapy Dialysis
If the patient is hypotensive and (Fig 86)

Figures 86: Dialysis for


treatment of acute kidney
injury: (a) Peritoneal
dialysis in a township
hospital in Myanmar;
(b) Haemodialysis in a
district hospital in India [a] [b]
(Copyright DA Warrell)

158 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Transfer the patient who has developed 6.9.5.2 Bleeding/ blood clotting
the following indications to a health disturbances in patients with acute
facility where they can receive renal kidney injury
replacement therapy. Most patients with acute kidney injury
associated with snakebite will have been
envenomed by Viperidae, notably Daboia,
Indications for dialysis Hypnale and Trimeresurus species. The
only major exception is sea snakebites.
a) clinical uraemia Viper-bite victims may have venom-
(encephalopathy, pericarditis induced bleeding and blood coagulation
etc.) disturbances although in most Daboia
b) fluid overload not cases these will have been corrected by
responding to diuretics antivenom before acute kidney injury has
c) plasma potassium developed. However, patients who still
concentration > 7 mmol/l (or have active bleeding/clotting disturbances
hyperkalaemic ECG changes) require fresh frozen plasma and platelet
d) symptomatic acidosis infusions to cover insertion of dialysis
e) blood biochemistry - one or catheters and dialysis.
more of the following
Creatinine > 4 mg/ dl (354 In patients with snakebite related
micromol/l) thrombotic microangiopathy with acute
Urea > 130 mg/ dl (46 kidney injury, the role of plasmapheresis
mmol/l) using cryosupernatant (by analogy with
Caution: biochemical criteria thrombotic thrombocytopenic purpura/
alone is not sufficient to start haemolytic uraemic syndrome) is not clear
dialysis and has no sound theoretical basis.

6.9.5.3 Prevention of renal damage


The choice between peritoneal dialysis in patients with myoglobinuria or
and haemodialysis depends on haemoglobinuria
availability. Haemodialysis is referred for
management of hyperkalaemia, fluid
overload and hypercatabolic patients. To minimise the risk of renal
Each dialysis session should be decided damage from excreted myoglobin
based on daily clinical assessment (fluid and/or haemoglobin:
status, urine output and biochemical correct hypovolaemia (see
data). In patients who are hypotensive, above) and maintain urine
slow efficiency daily dialysis (SLEDD) or output of 200-300 ml/hour.
continuous renal replacement therapy correct severe acidosis with
(CRRT [dialysis over 24 hours]) is bicarbonate
preferred. However, these are available promote alkalinise diuresis
only in well-equipped ICUs. In patients (urine pH > 6.5)
with acute kidney injury, dialysis may be continue these measures
required for up to 3 weeks. After that until there is evidence that of
time, the kidney should be biopsied rhabdomyolysis is decreasing
to establish the diagnosis and indicate (CK level <5000 U).
prognosis.

ManageMent of snakebites
in south-east asia
159
6.9.5.4 Diuretic phase of renal failure urgent surgery, once specific antivenom
Some patients will develop polyuria that is has been given to neutralize venom
as important and as life-threatening as the procoagulants and other antihaemostatic
oliguric phase. Urine output increases to toxins, restoration of coagulability and
5-10 litres/24 hours following the period platelet function can be accelerated by
of anuria. The patient may become volume giving fresh frozen plasma, cryoprecipitate
depleted so that salt and water must be (fibrinogen, factor VIII), fresh whole blood
carefully replaced. or platelet concentrates.
Hypokalaemia may develop, in which case
a diet rich in potassium (fruit and fruit
juices) is recommended. Heparin is ineffective against
venom-induced thrombin and
6.9.5.5 Renal recovery phase may cause bleeding on its own
The diuretic phase may last for months account. It should never be used
after Russells viper bite. in cases of snakebite.

6.9.5.6 Persisting renal dysfunction


In Myanmar, persistent tubular Antifibrinolytic agents are not effective
degenerative changes were observed in and should not be used in victims of
Russells viper bite victims who showed snakebite.
continuing albuminuria, hypertension and
nocturia for up to 11 months after the 6.10.1 Dangers of venipuncture
bite, despite apparent recovery in renal in patients with haemostatic
function. In India, 20-25% of patients abnormalities
referred to renal units with acute kidney In patients with incoagulable blood, any
injury following Russells viper bite injection (subcutaneous, intramuscular)
suffered oliguria for more than 4 weeks and, particularly venipuncture, carries a
suggesting the possibility of bilateral renal risk of persistent bleeding and haematoma
cortical necrosis and the need for referral formation.
to a nephrologist. Patients with patchy
cortical necrosis show delayed and partial Arterial puncture is contraindicated
recovery of renal function but those with in such patients.
diffuse cortical necrosis require regular Repeated venipuncture can be avoided by
maintenance dialysis and eventual renal using an indwelling cannula and three-
transplantation. way tap system. When blood coagulability
has been restored, the dead space should
6.10 Haemostatic be filled with heparinised saline, but
disturbances beware! If this is not flushed out before
Bleeding and clotting disturbances usually blood sampling, misleading results will be
respond satisfactorily to treatment with obtained in clotting tests, including the
specific antivenom, but the dose may 20WBCT.
need to be repeated several times, at six
hourly intervals, before blood coagulability In patients with coagulopathy, sites
(assessed by the 20WBCT) is finally and of venous access and placement of
permanently restored. intravenous cannulae or catheters should
be chosen where haemostasis by external
In exceptional circumstances, such as pressure is most likely to be effective, eg
persistent severe bleeding or imminent the antecubital fossa. If possible, avoid

160 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
jugular, subclavian and femoral vein and Enterococcus), aerobic gram-negative
puncture. A pressure pad must be applied bacterial (E. coli, Klebsiella, Pseudomonas,
at the site of any venipuncture. Enterobacter, Morganella morganii),
anaerobic bacteria (Peptostreptococcus
6.11 Treatment of the and Bacteroides fragilis) (Theakston et
bitten part al., 1990; Chena et al., 2011; Garg et al.,
The bitten limb, which may be painful 2009). Infection at the time of the bite
and swollen, should be nursed in the with organisms from the snakes venom
most comfortable position, but not and buccal cavity is a problem with some
excessively elevated as this may reduce species such as the Malayan pit viper
arterial perfusion pressure in a tensely (Calloselasma rhodostoma) and severe and
swollen limb and increase the risk of intra- fatal tetanus has been reported. However,
compartmental ischaemia. prophylactic antibiotics were not effective
in a controlled study in Brazil (Jorge et
6.11.1 Wound management al., 2004). Interference with the wound
Blisters/bullae/blebs may be large and (incisions made with an unsterilised razor
tense but they should not be de-roofed blade/knife etc.) creates a risk of secondary
and require aspiration only if they threaten bacterial infection and justifies the use
to rupture. Abscesses should be aspirated of immediate broad spectrum antibiotics
with a needle and the pus cultured (e.g. gentamicin with benzyl penicillin,
(see below infection). Once frank skin amoxycillin or a cephalosporin plus a single
necrosis is detected (demarcated, hypo/ dose only of gentamicin to avoid the
hyperpigmented areas with an odour of risk of kidney injury- plus metronidazole)
putrefaction), surgical dbridement is and tetanus prophylaxis. Other possible
indicated to remove the risk of anaerobic antibiotics include amoxycillin/caluvulenic
sepsis. During debridement, all unhealthy acid, piperacillin/tazobactam, ciprofloxacin
tissue should be excised till viable tissue and third generation cephalosporin
margins are achieved. However, bruised (Mao et al., 2016). Mao YC, Liu PY, Hung
muscle may appear dead but should DZ, Lai WC, Huang ST, Hung YM, Yang
not be excised as muscle fibres may CC. Bacteriology of Naja atra Snakebite
regenerate. Amputation may be indicated Wound and Its Implications for Antibiotic
in case of gangrene of toes or limbs. Therapy. Am J Trop Med Hyg. 2016 May
4;94(5):1129-35Later infections in patients
6.11.2 Bacterial infections treated in hospital include nosocomial
The oral flora of wild snakes includes pneumonias and urinary tract infections.
aerobic and anaerobic bacteria, especially
the faecal gram-negative rods as their prey 6.11.3 Compartmental syndromes
may defecate while being ingested. Oral and fasciotomy
and venom cultures from American snakes (Fig 83) (Matsen 1980; Mars and Hadley
yielded Enterobacteriaceae including 1998; Mars et al., 1991)
Morganella spp., Escherichia coli, Group
D streptococci, Aeromonas spp., and The appearance of an immobile, tensely-
anaerobes such as Clostridium spp. swollen, cold and apparently pulseless
snake-bitten limb may suggest to
In Asia, local bite wound infections may surgeons the possibility of increased
be due to single or multiple bacteria intracompartmental pressure, especially
including gram-positive aerobes (Staph. if the digital pulp spaces or the anterior
aureus, coagulase-negative Staphylococcus tibial compartment are involved. Swelling

ManageMent of snakebites
in south-east asia
161
[a] [b]
Figure 87: Results of unnecessary fasciotomies in snakebite victims in Thailand: (a)
profuse bleeding in a patient with mild local envenoming but severe coagulopathy
following bites by green pit vipers (Trimeresurus T. albolabris); (b) Residual skin loss
and exposure of tendons following fasciotomy for mild local envenoming in a patient
bitten by a green pit viper (Trimeresurus T. albolabris) (Copyright the late Sornchai
Looareesuwan); (c) Persistent bleeding for 10 days, resulting in haemorrhagic shock
despite transfusion of 20 unites of blood, in a victim of Malayan pit viper bite in whom
fasciotomy was performed before adequate antivenom treatment had been given to
correct the coagulopathy (Copyright DA Warrell)

of envenomed muscle
Clinical features of a
within such tight fascial
compartmental syndrome
compartments could
Disproportionately severe pain
result in an increase
Weakness of intracompartmental
in tissue pressure
muscles
above the venous
Pain on passive stretching of
pressure, resulting in
intracompartmental muscles
ischaemia. However,
Hypoaesthesia of areas of skin
the classical signs of
supplied by nerves running
an intracompartmental
through the compartment
pressure syndrome
Obvious tenseness of the
may be difficult to
compartment on palpation
assess in snakebite
victims and many
unnecessary, dangerous
and debilitating Detection of arterial pulses by palpation
fasciotomies are or doppler ultrasound probes, does not
performed, especially exclude intracompartmental ischaemia.
where surgeons The most reliable test is to measure
rather than physicians intracompartmental pressure directly
have the primary through a cannula introduced into the
[c]
responsibility for compartment and connected to a pressure
managing snakebite transducer or manometer (Annex 5). In
cases (Fig 87). Fasciotomy is generally orthopaedic practice, intracompartmental
falling out of favour for the treatment of pressures exceeding 40 mmHg (less in
snake-bitten limbs (Cumpston, 2011). children) may carry a risk of ischaemic

162 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
necrosis (eg Volkmanns ischaemia or 6.12 Rehabilitation
anterior tibial compartment syndrome). In patients with severe local envenoming,
However, envenomed muscle may not the limb should be maintained in a
be saved by fasciotomy. Animal studies functional position. For example, in the
have suggested that muscle sufficiently leg, equinus deformity of the ankle should
envenomed and swollen to cause be prevented by application of a back slab
intracompartmental syndromes, may and avoiding the pressure of heavy bed
already be irreversibly damaged by the clothes.
direct effects of the venom (Garfin et al.,
1984). In any case, fasciotomy should Functional effects of local envenoming
not be contemplated until haemostatic range from persistent stiffness and
abnormalities have been corrected, induration due to sclerosis of veins,
otherwise the patient may bleed to death lymphatics and tissue planes through
(Fig 66c). which the venom has spread, to severe
deformity, arthrodeses, contractures,
Among 105 cases of rattle snakebites tissue loss, especially dermonecrosis and
in USA in which fasciotomy was either chronic ulceration requiring skin grafting,
just discussed or actually carried out, and gangrene requiring dbridement
the 28 patients given surgery showed and amputation. Restoration of normal
no advantage in morbidity, but spent on function in the bitten part should be
average 2 extra days in hospital (Darracq et started by simple exercises while the
al., 2015). patient is still in hospital. After the patient
has been discharged from hospital
In green pit viper bite (genus Trimeresurus) rehabilitation is rarely supervised but
victims, antivenom not only reversed relatives can be instructed and given a
coagulopathy, but also reducing severe time table of rehabilitating activities.
limb oedema (Rojnuckarin et al., 2006). Conventional physiotherapy may accelerate
However, corticosteroids are not effective functional rec overy of the bitten limb.
in ameliorating local effects of envenoming
and, since they carry the risk of side-effects, 6.13 Discharge assessment
they should not be used (Reid et al., 1963; Before the patient leaves hospital, discuss
Nuchprayoon et al., 2008). the following topics with them and their
accompanying family members.
Early treatment with antivenom
remains the best way of preventing Implications of having had a snakebite:
irreversible muscle damage. most patients can be assured of a full
recovery in time.

Criteria for fasciotomy in snake- Rehabilitation exercises: encourage


bitten limbs them to continue until normal function
haemostatic abnormalities have been is restored to the bitten limb.
corrected (antivenom with or without
clotting factors) Follow-up appointment: encourage the
clinical evidence of an patient to return after an interval of 1-2
intracompartmental syndrome weeks to check on their progress and
intracompartmental pressure >40 to allow further reassurance.
mmHg (in adults)
Late serum sickness-type reactions:

ManageMent of snakebites
in south-east asia
163
effective but, by rendering the eye
temporarily insensitive, may allow
Consists of urgent irrigating the affected eyes
trauma to the cornea. They should be
and other mucous membranes with liberal applied only once and the eye must
quantities of water, saline, Ringers lactate, be protected until sensation returns.
By overcoming blepharospasm,
milk or any other available bland liquid. these drugs may allow more efficient
irrigation.

warn them of the symptoms and 3. Corneal abrasions must be excluded


reassure them that this complication of by fluorescein staining and/or slit
antivenom can be treated. lamp examination

Reducing the risk of further bites: 4. Endophthalmitis or blinding corneal


provide advice, ideally in the form of opacities must be prevented
a leaflet, explaining the principles of by application of prophylactic
snakebite prevention (see Section 1 topical antibiotics (eg tetracycline,
above), to be shared with their families chloramphenicol, 0.5% framycetin
and neighbours. Soframycin, ciprofloxacin, penicillin-
streptomycin ointment, polymixin
6.14 Management of cobra B sulphate, gatifloxacin, and
spit ophthalmia moxifloxacin).
(Chu et al., 2010)
First aid: consists of urgent irrigating 5. Posterior synechiae, ciliary spasm and
the affected eyes and other mucous discomfort can be prevented with
membranes with liberal quantities of topical cycloplegics (e.g. 2% atropine,
water, saline, Ringers lactate, milk or any scopolamine or homatropine).
other available bland liquid (even urine However, beware, these mydriatics
has been used). No medicines, oils or may precipitate acute glaucoma.
traditional ointments should be put in
the eye(s) and there should be no delay 6. Allergic kerato-conjunctivitis may
in going to hospital. The spitting cobra develop in those previously sensitised
should not be pursued or killed as this may by spitting or other habitual exposure
result in further multiple spits. to snake venoms. It is treated with
antihistamines.
Medical treatment consists of:
1. Further urgent decontamination is Instillation of diluted antivenom
achieved by copious irrigation causes irritation and is of no benefit
since any residual venom in the
2. Pain is intense. Topical vasoconstrictors conjunctival sac is removed by liberal
with weak mydriatic activity [e.g. irrigation.
instillation of 0.5% epinephrine
(adrenaline) drops] relieve pain and Topical corticosteroids are
inflammation. However, topical local contraindicated because of the risk of
anaesthetics (eg 0.4% oxybuprocaine Herpes simplex keratitis.
hydrochloride (Novesin), 4%
lidocaine hydrochloride or tetracaine Some ophthalmologists recommend the
hydrochloride (Decicaine) are more use of a dressing pad to close the eye.

164 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
6.15 Management of patient to medical care as quickly,
snakebites at different levels safely and passively as possible by
of the health service vehicle, boat, bicycle, motorbike,
(refer to sections above for details of stretcher etc. Ideally the patient should
treatments etc.) lie in the recovery position (prone,
All levels of the health service can contribute on the left side) with his/her airway
to the management of patients with protected to minimise the risk of shock
suspected snakebite. Since the treatment of and inhalation of vomit.
severe envenoming is a medical emergency
that may require a range of medical skills, 5. Snake: if the snake responsible has
equipment, antivenom and other medicines, already been caught or killed take it
referral should be to the highest level of (safely in a bag or container) with the
care that is readily available. However, in patient or take images on a mobile
the rural areas where snakebites are most phone , but ensure safety by avoiding
frequent, transfer to a hospital may not direct contact.
be feasible within the reasonable time
frame of a few hours. In that case, a lower 6. Traditional treatment: discourage
level of health facility must cope with the time-wasting and potentially dangerous
emergency as suggested below. Ideally, a traditional treatments such as tight
specialist team and a defined area or ward ligatures (tourniquets), incisions,
should be allocated for the management suction and application of herbs, ice,
of snakebite victims. Training of doctors, chemicals, snakestones etc.
nurses, dispensers, health assistants
and paramedics in all the skills B. At the Rural Clinic, Dispensary,
required for diagnosis (including snake Health Post, or Primary Health Centre
identification) and early management 1. Assess for signs of local and
of snakebite patients (including systemic envenoming: carry out a
indications for and practicalities of simple medical assessment including
administering antivenom) is essential history and simple physical examination
at every level. local swelling, painful tender
enlarged local lymph glands, persistent
A. At community or village level bleeding from the bite wound, blood
1. Assess: check history of snakebite pressure, pulse rate, bleeding (gums,
and look for obvious evidence of a bite nose, vomit, stool or urine), level of
(fang puncture marks, swelling of the consciousness, drooping eyelids (ptosis)
bitten part). and other signs of paralysis. Monitor
these signs hourly.
2. Reassure
2. Check: 20 minute whole blood
3. First-aid: immobilize the whole clotting test (20WBCT), urine
patient as far as possible by laying him/ examination (appearance, sticks testing
her down in a relaxed but safe position for blood etc.). Identify the snake or a
(e.g. recovery position), immobilize photo of it (if brought).
the bitten limb with a splint and apply
pressure-pad. 3. Analgesia: give analgesia by mouth if
required: paracetamol (acetaminophen)
4. Transport: Arrange (by emergency (adult dose 500 mg to 1 g maximum
contact number) transport of the 4 g in 24 hours; children 10-15 mg/

ManageMent of snakebites
in south-east asia
165
kg maximum 100mg/kg/day) or 9. Assess the need and feasibility of
codeine phosphate (adult dose 30-60 transporting the patient to a higher
mg maximum 240 mg in 24 hours; level of the health service (see A above)
children more than 2 years old, 0.5 especially in case of:
mg/kg, maximum 2 mg/kg/day) can
be given every 4-6 hours by mouth as a. Substantial bleeding, 20WBCT still
required (not aspirin or non-steroidal positive (non-clotting) 6 hours after
anti-inflammatory drugs which can initial antivenom dose
cause bleeding). b. Progressive paralysis (muscle weakness)
or respiratory difficulty
4. Antivenom: if the patient fulfils c. Reduced urine output
criteria for antivenom treatment and d. Anaphylaxis unresponsive to
if the necessary skills, equipment, adrenaline
antivenom, adrenaline and other e. Shock/hypotension- unresponsive to
necessary drugs are available, give fluids
antivenom. These skills include f. Severe local necrosis or signs suggestive
ability to diagnose local and systemic of compartment syndrome
envenoming, set up intravenous
infusion or intravenous injection, 10. Discourage the use of ineffective
identify the early signs of anaphylaxis and potentially harmful drugs (e.g.
and treat it with intramuscular corticosteroids, antihistamines, and
adrenaline. Reasess for repeated heparin).
dose(s) of antivenom. If no antivenom
is available, transfer to a hospital. C. At the District Hospital
Proceed as in B above plus:
5. If the patient is shocked/
hypotensive: give cautious 1. Assessment: carry out a more
intravenous fluid challenge (adult detailed clinical and laboratory
250-500 ml of 0.9% saline) to correct assessment including biochemical and
hypovolaemic shock. haematological measurements, ECG or
radiography, as indicated.
6. If the patient has evidence of
respiratory paralysis: give oxygen 2. Antivenom: if no antivenom is
by mask, consider atropine and available, transfer to a hospital that has
neostigmine, and transfer to hospital. antivenom or treat conservatively; this
It is assumed that assisted ventilation may require transfusion of blood or
other than by a tight-fitting face mask fresh frozen plasma (see above).
connected to an anaesthetic (Ambu)
bag will not be possible at this level. 3. Analgesia: (see B above) and, if
required, consider stronger parenteral
7. If the patient is oliguric: initiate opioid drugs as required all with
conservative management. great caution (e.g. subcutaneous,
intramuscular or even intravenous
8. The bite wound: if necrotic, tampered pethidine, initial adult dose 50-
with (incisions etc.) or obviously 100 mg; children 1-1.5 mg/kg; or
septic, give antibiotics and tetanus morphine, initial adult dose 5-10 mg;
prophylaxis. children 0.03-0.05 mg/kg,).

166 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
4. If the patient has evidence of local be improved at various levels. The
necrosis (gangrene): give tetanus government must develop a policy for
toxoid booster, antibiotics and do snakebite, making it a notifiable disease,
surgical dbridement of dead tissue. developing a snakebite programme that
includes standard treatment guidelines,
5. If the patient has evidence of bulbar training of health personnel and ensures
or respiratory paralysis: insert an adequate supply, distribution and
endotracheal tube, laryngeal mask storage of good quality antivenom.
airway or i-gel aiway. If there is Strengthening of public health systems
evidence of respiratory failure, assist
ventilation manually by anaesthetic
Figure 88 Health system strengthening
(Ambu) bag or mechanical ventilator.

6. If the patient has evidence of acute Government


kidney injury: treat with peritoneal
Snakebite policy
dialysis. If this is not available, transfer
1. Making snakebite reportable
to a specialized hospital.
2. Developing a snakebite programme
3. Standard treatment guidelines
7. If the patient is bleeding severely or is
4. Ensuring production and supply of adequate
already seriously anaemic: cross-match
quantity and quality of antivenom
and transfuse.
5. Training of health personnel at all levels
6. Research
8. Rehabilitation: encourage exercising of
bitten limb.
HEALTH SYSTEM
D. At the Referral (Specialized)
Hospital TERTIARY REFERRAL
Proceed as in B and C above plus: HOSPITAL
Infrastructure- dialysis and ICU,
surgical set up, coagulation lab
1. More advanced surgical management of Personnel- physician, surgeon,
local necrosis (e.g. split skin grafting). nephrologist, anaesthetist
Strengthening of health
2. More advanced investigations including DISTRICT HOSPITAL system
bacterial cultures and imaging (CT Infrastructure- blood bank, 1. Training of all levels of
scans) as indicated. ICU, surgical set up health system
Personnel- physician, surgeon
2. Ensuring infrastructure at
3. If the patient has evidence of acute each level
renal failure peritoneal or haemodialysis PRIMARY HEALTH CENTRE 3. Antivenom availability
Infrastructure- basic emergency
or haemofiltration. 4. Epidemiological
care and resuscitation,
airway and Ambu bag, monitoring of snak-bite,
4. Implement rehabilitation by antivenom administration deaths, complications and
physiotherapists. Personnel- doctor, nurse antivenom reactions
5. Community education
Conclusions: Strengthening of health VILLAGE
system in managing snakebite Infrastructure- ambulance
Transport
Personnel- health aid, health
To reduce complications and deathsfrom worker, paramedic
snakebites, health systems need to

ManageMent of snakebites
in south-east asia
167
requires an appropriate infrastructure of 4. Antihistamines (H1 blockers) and
facilities and drugs at each level, training corticosteroids
of personnel, epidemiological monitoring Benefits: late serum sickness-type
and community education. reactions

6.16 Summary of current 5. Antibiotics


evidence for treatment of Benefits: treating secondary and primary
snakebite envenoming bite wound infections, prophylaxis in
Currently proposed treatment and necrotic wounds or those that have
their likely benefit been tampered with using non-sterile
instruments
1. Antivenom:
Benefits: recommended for treatment 6. Renal replacement therapy and
of bleeding/blood clotting disturbances, assisted ventilation:
shock/hypotension, post-synaptic Benefits: life-saving in patients with
neurotoxicity (cobras, death adders, acute kidney injury and respiratory failure
rhabdomyolysis (sea snakes). Optimal
initial dosage largely unknown 7. Anticolinesterase (neostigmine)
with atropine
Risks: early anaphylactic and pyrogenic Benefits: can rapidly improve neuro
reactions, late serum sickness-like reactions muscular transmission in some patients
with post-synaptic neurotoxicity (cobras,
2. Adrenaline (epinephrine) Australasian death adders)
Benefits: recommended for prevention
and treatment of early antivenom Risks: muscarinic side-effects,
reactions cholinergic crisis

Risks: cerebral haemorrhage in elderly 8. Traditional first-aid methods


patients with underlying cerebrovascular (incisions, tourniquets, suction, tattooing,
disease topical herbal remedies, black snake-
stone, electric shocks etc.)
3. Blood clotting factors
Benefits: recommended to speed up Risks: harmful and useless should never
restoration of normal haemostasis in be used
patients already treated with antivenom
and for conservative treatment of 9. First-aid pressure pad
bleeding/blood clotting disturbances, immobilization, rapid transport to
when antivenom is not available medical care
Benefits: reduces venom spread and risk
Risks: fatalities reported (reactions and of early death
possibly thromboses)

168 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
References and further reading
7
Ali SS, O'Connell C, Kass L, Graff G Single- Ariaratnam CA, Sjstrm L, Raziek Z, Kularatne
breath counting: a pilot study of a novel SA, Arachchi RW, Sheriff MH, et al. An open,
technique for measuring pulmonary randomized comparative trial of two
function in children. Am J Emerg Med. antivenoms for the treatment of envenoming by
2011 Jan;29(1):33-6. Sri Lankan Russell's viper (Daboia russelii
russelii). Trans R Soc Trop Med Hyg. 2001 Jan-
Amarasekera N, Jayawardena A, Feb;95(1):74-80. .
Ariyaratnam A, Hewage UC, de Silva A.
Bite of a sea snake (Hydrophis spiralis): a Ariaratnam CA, Sheriff MH, Theakston RD,
case report from Sri Lanka. J Trop Med Warrell DA. Distinctive epidemiologic and
Hyg. 1994;97(4):195-8. clinical features of common krait (Bungarus
caeruleus) bites in Sri Lanka. Am J Trop Med
Hyg. 2008 Sept;79(3):458-62.
Anil A, Singh S, Bhalla A, Sharma N,
Agarwal R, Simpson ID. Role of neostigmine
Ariaratnam CA, Thuraisingam V, Kularatne SA,
and polyvalent antivenom in Indian
Sheriff MH, Theakston RD, de Silva A, et al.
common krait (Bungarus caeruleus) bite.
Frequent and potentially fatal envenoming by
Journal of Infection and Public Health.
hump-nosed pit vipers (Hypnale hypnale and H.
2010;3(2):83-7.
nepa) in Sri Lanka: lack of effective antivenom.
Trans R Soc Trop Med Hyg.2008 Nov;
Anker RL, Straffon WG, Loiselle DS, Anker 102:1120-6.
KM. Retarding the uptake of "mock
venom" in humans: comparison of three Ariaratnam CA, Sheriff MH, Arambepola C,
first-aid treatments. Med J Aust. 1982 Theakston RD, Warrell DA. Syndromic approach
Mar 6;1(5):212-4. to treatment of snakebite in Sri Lanka based on
results of a prospective national hospital-based
Antonypillai CN, Wass JA, Warrell DA,
survey of patients envenomed by identified
Rajaratnam HN. Hypopituitarism
snakes. Am J Trop Med Hyg. 2009
following envenoming by Russell's vipers
Oct;81(4):725-31.
(Daboia siamensis and D. russelii)
resembling Sheehan's syndrome: first Armentano RA, Bandt C, Schaer M, Pritchett J,
case report from Sri Lanka, a review of Shih A. Thromboelastographic evaluation of
the literature and recommendations for hemostatic function in dogs treated for crotalid
endocrine management. QJM. 2011 snake envenomation. J Vet Emerg Crit Care (San
Feb;104(2):97-108. Antonio). 2014 Mar-Apr;24(2):144-53.

ManageMent of snakebites
in south-east asia
169
Bandyopadhyay SK, Bandyopadhyay R, Caron EJ, Manock SR, Maudlin J, Koleski J,
Dutta A, Pal SK. Hypopituitarism Theakston RD, Warrell DA, et al. Apparent
following poisonous viperbite. J Indian marked reduction in early antivenom
Med Assoc. 2012 Feb;110(2):120, reactions compared to historical controls:
122. was it prophylaxis or method of
administration? Toxicon. 2009
Banerji RN, Sahni AL, Chacko KA. Nov;54(6):779-83.
Neostigmine in the treatment of
Elapidae bites. J Ass Physicins India.
Chappuis F, Sharma SK, Jha N, Loutan L,
1972 Jul 20(7):503-9.
Bovier PA. Protection against snakebites by
Bell DJ, Wijegunasinghe D, Samarakoon S, sleeping under a bed net in southeastern
Palipana H, Gunasekera S, de Silva HA,et al. Nepal. Am J Trop Med Hyg. 2007;
Neurophysiological findings in patients one 77(1):197-9.
year after snakebite induced neurotoxicity in
sri lanka. Transactions of the Royal Society of
Chakraborty PP, Bhattacharjee R. Bilateral
Tropical Medicine and Hygiene 2010
parotid swelling: an unusual complication
May;104(5): 351-6.
of viper bite. J Assoc Phys India.2010 Jul;
58: 460.
Belt PJ, Malhotra A, Thorpe RS, Warrell DA,
Wuster W. Russells viper in Indonesia:
snakebite and systematics. In: Thorpe RS, Chatterjee P, Mukhopadhyay P, Pandit K,
Wster W, Malhotra A editions, Venomous Roychowdhury B, Sarkar D, Mukherjee S, et
snakes. Ecology, evolution and al. Profile of hypopituitarism in a tertiary
snakebite.Oxford:, Clarendon Press,1997.p. care hospital of eastern India--is quality of
219-34. life different in patients with growth
hormone deficiency?.J Indian Med Assoc.
2008 Jun;106(6):384-5, 388.
Bhat RN. Viperine snakebite poisoning in
Jammu. J Indian Med Assoc. 1974 Dec 16;
63(12): 383-92. Chawla LS, Davison DL, Brasha-Mitchell E,
Koyner JL, Arthur JM, Shaw AD, et al.
Bhetwal BB, OShea M, Warrell DA.Snakes Development and standardization of a
and snakebite in Nepal. Tropical Doctor. furosemide stress test to predict the
1998 Oct; 28(4): 193-5. severity of acute kidney injury. Crit Care.
2013 Sep 20; R207.

Bon C, Goyffon M. Envenomings and their


treatments. Lyon: Ed. Fondation Marcel Chen CM, Wu KG, Chen CJ, Wang CM.
Mrieux ;1995. 343 p. Bacterial infection in association with
snakebite: a 10-year experience in a
Bcherl W, Buckley EE & Deulofeu V (eds) . northern Taiwan medical center. J
Venomous animals and their venoms. Vols Microbiol Immunol Infect. 2011
1 and 2. Academic Press, New York. (1968, Dec;44(6):456-60.
1971)

Canale E, Isbister GK, Currie BJ. Cherian AM, Girish TS, Jagannati M,
Investigating pressure bandaging for Lakshmi M. High or Low- A Trial of Low
snakebite in a simulated setting: Dose Anti Snake Venom in the
bandage type, training and the effect of Treatment of Poisonous Snakebites.J
transport. Emerg Med Australas. 2009 Assoc Physicians India. 2013 Jun;
Jun; 61(6):387-9, 396.
21(3):184-90.

170 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Chippaux JP. Snakebites: appraisal of Dassanayake AS, Karunanayake P, Kasturiratne
the global situation. Bull World Health KT, Fonseka MM, Wijesiriwardena B, Gunatilake
Organ. 1998;76(5):515-24. SB et al. Safety of subcutaneous adrenaline as
prophylaxis against acute adverse reactions to
Chotenimitkhun R, Rojnuckarin P. anti-venom serum in snakebite. Ceylon Med J.
Systemic antivenom and skin necrosis 2002;47:48-9.
after green pit viper bites. Clin Toxicol
(Phila). 2008 Feb;46(2):122-5. Dayal M, Prakash S, Verma PK, Pawar M.
Neurotoxin envenomation mimicking brain death
in a child: A case report and review of literature.
Chu ER, Weinstein SA, White J, Warrell
Indian J Anaesth. 2014 Jul;58(4):458-60.
DA. Venom ophthalmia caused by
venoms of spitting elapid and other
snakes: Report of ten cases with review Deepak M, Basavaprabhu A, Ramapuram JT,
of epidemiology, clinical features, Nithyananda C, Mahalingam S. Bilateral parotid
pathophysiology and management. enlargement following snakebite : A rare sign.
Toxicon. 2010; 56(3):259-72. Asian PAc J Trop Biomed. 2013;3(2):154-5.

Chugh KS. Snakebite-induced


acute renal failure in India. Kidney de Rezende NA, Torres FM, Dias MB,
International. 1989; 35: 891-907. Campolina D, Chavez-Olortegui C, Amaral CF.
South American rattlesnakebite (Crotalus
durissus SP) without envenoming: insights on
Cubitt M, Armstrong J, McCoubrie D,
diagnosis and treatment. Toxicon. 1998
White J, Williams V, Isbister GK . Point-
Dec;36(12):2029-32.
of-care testing in snakebite: an
envenomed case with false negative
coagulation studies. Emerg Med
de Silva A, Mendis S, Warrell DA. Neurotoxic
Australas. 2013; 25(4):372-3.
envenoming by the Sri Lankan krait (Bungarus
ceylonicus) complicated by traditional treatment
Cumpston KL. Is there a role for and a reaction to antivenom. Trans R Soc Trop
fasciotomy in Crotalinae envenomations Med Hyg. 1993;87(6):682-4.
in North America? Clin Toxicol (Phila).
2011; 49(5):351-65.
de Silva HA, Pathmeswaran A, Ranasinha CD,
Currie BJ, Canale E, Isbister GK. Jayamanne S, Samarakoon SB, Hittharage A, et
Effectiveness of pressure-immobilization al. Low-dose adrenaline, promethazine, and
first aid for snakebite requires further hydrocortisone in the prevention of acute
study. Emerg Med Australas. 2008 Jun; adverse reactions to antivenom following
20(3):267-70. snakebite: a randomised, double-blind,
placebo-controlled trial. PLoS Med.
2011May;8(5):e1000435.
Darracq MA, Cantrell FL, Klauk B,
Thornton SL. A chance to cut is not
always a chance to cure- fasciotomy
de Silva HA, Ryan NM, de Silva HJ. Prevention
in the treatment of rattlesnake
and treatment of adverse reactions to snake
envenomation: A retrospective poison
antivenom. British Journal of Clinical
center study. Toxicon.
Pharmacology. 2016; 81: 446-452.
2015;101:23-6.

ManageMent of snakebites
in south-east asia
171
Deshpande RP, Motghare VM, Padwal SL, Fan HW, Marcopito LF, Cardoso JL, Frana FO,
Pore RR, Bhamare CG, Deshmukh VS, et al. Malaque CM, Ferrari RA, et al.Sequential
Adverse drug reaction profile of anti-snake randomised and double blind trial of
venom in a rural tertiary care teaching promethazine prophylaxis against early
hospital. Journal of Young Pharmacists. anaphylactic reactions to antivenom for
2013 June; 5(2):4145. bothrops snakebites. BMJ. 1999 May
29;318(7196):1451-2.

Fan HW, Marcopito LF, Cardoso JL, Frana FO,


Directorate General of Health Services
Malaque CM, Ferrari RA, et al.Sequential
Ministry of Health and Family Welfare
randomised and double blind trial of
Government of India. National Snakebite
promethazine prophylaxis against early
Management Protocol [internet]. New
anaphylactic reactions to antivenom for
Delhi;2009. Available from
bothrops snakebites. BMJ. 1999 May
http://164.100.130.11:8091/
29;318(7196):1451-2.
nationalsnakebitemanagementprotocol.pdf
Fernando WK, Kularatne SA, Wathudura SP, de
Silva A, Mori A, Mahaulpatha D. First reported
Eapen CK, Chandy N, Kochuvarkey KL, case of systemic envenoming by the Sri Lankan
Zacharia PK, Thomas PJ, Ipe TI. Unusual keelback (Balanophis ceylonensis). Toxicon.
complication of snakebite : hypopituitarism 2015;93:20-3.
after viper bites. In Ohsaka A, Hayashi K,
Sawai Y, editors. Animal, plant and Fox S, Rathuwithana AC, Kasturiratne A, Lalloo
microbial toxins.2nd edition. New York: DG, de Silva HJ. Underestimation of snakebite
Plenum;1976. P. 467-473. mortality by hospital statistics in the
Monaragala District of Sri Lanka. Trans R Soc
Trop Med Hyg. 2006;100:693-5.
Ediriweera DS, Kasturiratne A,
Pathmeswaran A, Gunawardena NK, Gans C,Gans KA. eds. Biology of the reptilia.
Wijayawickrama BA, Jayamanne SF, et al. Vol 8. London: Academic Press;1978.782 p.
Mapping the risk of snakebite in Sri Lanka-
A national survey with geospatial analysis. Garg A, Sujatha S, Garg J, Acharya NS,
PLoS Negl Trop Dis. 2016 July; Chandra Parija S. Wound infections secondary
10(7):e0004813. to snakebite. J Infect Dev Ctries. 2009 Apr
30;3(3):221-3.

Gawarammana IB, Kularatne SA, Dissanayake


Faiz A, Ghose A, Ahsan F, Rahman R, Amin
WP, Kumarasiri RP, Senanayake N, Ariyasena H.
R, Hassan MU, et al. The greater black krait
Parallel infusion of hydrocortisone +/-
(Bungarus niger), a newly recognized cause
chlorpheniramine bolus injection to prevent
of neuro-myotoxic snakebite envenoming in
acute adverse reactions to antivenom for
Bangladesh. Brain. 2010;133(11):3181-93.
snakebites. Med J Aust. 2004 Jan 5; 180:20-3.

Garfin SR, Castilonia RR, Mubarak SJ . Rattle


Faiz, MA, Ahsan MF, Ghose A, Rahman
snakebites and surgical decompression: results
MR, Amin R, Hossain, M,et al. Bites by the
using a laboratory model. Toxicon.
monocled cobra, Naja kaouthia, in
1984;22:17782.
Chittagong Division, Bangladesh:
epidemiology, clinical features of
Gawarammana I, Mendis S, Jeganathan K.
envenoming and management of 70
Acute ischemic strokes due to bites by Daboia
identified cases. (in press)
russelii in Sri Lanka - first authenticated case
series. Toxicon. 2009;54:421-8.

172 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Ghose A, Faiz MA. Snake envenomation in Gopalakrishnakone P, Chou LM . Snakes of
Bangladesh. In: Gopalakrishnakone P, Faiz medical importance (Asia-Pacific
SM, Gnanathasan CA, Habib AG, Fernando Region).Singapore: National University of
R, Yang CC. Clinical Toxinology in Asia Singapore Press;1990.
Pacific and Africa [internet].Netherlands.
Springer ;2015. Chapter 11. Available Gowda CD, Rajesh R, Nataraju A,
from : http://link.springer.com/ Dhananjaya BL, Raghupathi AR, Gowda
referencework/10.1007/978-94-007-6288- TV, et al. Strong myotoxic activity of
6/page/2 DOI: Trimeresurus malabaricus venom: role of
10.1007/978-94-007-6288-6_25-1ISBN: metalloproteases. Mol Cell Biochem.
978-94-007-6288-6 2006 Jan; 282(1-2):147-55.

Ghose A, Amin MR, Haq MA, Islam A, Grunau BE, Wiens MO, Rowe BH, McKay R,
Chowdhury FR, Miah T, et al. Russells Viper Li J, Yi TW, et al.. Emergency Department
(Daboia russelii): A newly recognized cause Corticosteroid Use for Allergy or Anaphylaxis
of neuro-myo-renal toxic envenomation in Is Not Associated With Decreased Relapses.
Bangladesh. In Proceeding 18th World Ann Emerg Med. 2015 Oct;66(4):381-9.
Congress of the International Society on Available from : http://
Toxinology ; 2015 Sept 25-30; oxford www.ncbi.nlm.nih.gov/pubmed/25820033
(United Kingdom) ; c2015. P. 91 DOI: 10.1016/j.annemergmed.2015.03.003

Gimkala A, Ramana Rao GV, Bharti OK. Gutirrez JM, Warrell DA, Williams DJ,
Transporting Snakebite Victims to Jensen S, Brown N, Calvete JJ, et al. Global
Appropriate Health Facility within Golden Snakebite Initiative. The need for full
Hour through Toll Free Emergency integration of snakebite envenoming within
Ambulance Service in India, Save Lives. Int J a global strategy to combat the neglected
Trop Dis Health. 2016; 17(2): 1-12. tropical diseases: the way forward. PLoS
Negl Trop Dis. 2013 Jun 13;7(6):e2162.

Golay V, Roychowdhary A, Dasgupta S,


Pandey R. Hypopituitarism in patients with
Haile NS. Snakebites man: two
vasculotoxic snakebite envenomation
recent Borneo cases. Sarawak Mus J.
related acute kidney injury: a prospective
1963;11:291-8.
study on the prevalence and outcomes of
this complication. Pituitary. 2014;
17(2):125-31. Harris JB, Faiz MA, Rahman MR, Jalil MM,
Ahsan MF, Theakston RD, et al. Snakebite
in Chittagong Division, Bangladesh: a study
Golnik KC, Pena R, Lee AG, Eggenberger
of bitten patients who developed no signs
ER. An ice test for the diagnosis of
of systemic envenoming. Trans R Soc Trop
myasthenia gravis. Ophthalmology.
Med Hyg. 2010 May;104(5):320-7.
1999;106:12826.

Gong E, Martin LD, Burnham DA, Falk, Harvey AL. Snake toxins. New York:
AR. The birdlike raptor Sinornithosaurus Pergamon Press, 1991.
was venomous. PNAS. 2009; 107:766
768.

ManageMent of snakebites
in south-east asia
173
Hasan SM, Basher A, Molla AA, Sultana Huq F, Islam MA, Sarker MH, Chowdhury B,
NK, Faiz MA . The impact of snakebite on Ali MW, Kabir MM. Epidemiology of
household economy in Bangladesh. Trop snakebite in Bangladesh. Bangladesh J Zool.
Doct. 2012; 42(1):41-3. 1995; 23:61-4.

Hati AK, Mandal M, De MK, Mukherjee H,


Hutton RA, Looareesuwan S, Ho M, Silamut
Hati RN. Epidemiology of snakebite in the
K, Chanthavanich P, Karbwang J, et al.
district of Burdwan, West Bengal. J Indian
Arboreal green pit vipers (genus
Med Assoc. 1992 Jun; 90:145-7.
Trimeresurus) of South-East Asia: bites by T
albolabris and T macrops in Thailand and a
Ho M, Warrell DA, Looareesuwan S,
review of the literature. Trans R Soc Trop
Phillips RE, Chanthavanich P, Karbwang J,
Med Hyg. 1990 Nov-Dec; 84(6):866-74.
et al. Clinical significance of venom
antigen levels in patients envenomed by
the Malayan pit viper (Calloselasma Isbister GK, Brown SG, MacDonald E, White
rhodostoma). American J Trop Med Hyg. J, Currie BJ. Current use of Australian snake
1986 May; 35(3): 579-87. antivenoms and frequency of immediate-
type hypersensitivity reactions and
Ho M, Silamut K, White NJ, et al. anaphylaxis. Med J Aust. 2008;188(8):
Pharmacokinetics of three commercial 473-476.
antivenoms in patients envenomed by
the Malayan pit viper (Calloselasma
rhodostoma) in Thailand. AmJ Trop Med Isbister GK, Maduwage K, Shahmy S,
Hyg. 1990; 42: 260-6. Mohamed F, Abeysinghe C, Karunathilake
H, et al. Diagnostic 20-min whole blood
clotting test in Russell's viper envenoming
Ho WK, Verner E, Dauer R, Duggan J. delays antivenom administration. QJM.
ADAMTS-13 activity, microangiopathic 2013;106(10):925-32.
haemolytic anaemia and
thrombocytopenia following snakebite
envenomation. Pathology. 2010 Isbister GK, Shahmy S, Mohamed F,
Feb;42(2):200-2. Abeysinghe C, Karunathilake H, Ariaratnam
A . A randomised controlled trial of two
Hjer J, Tran Hung H, Warrell D. Life- infusion rates to decrease reactions to
threatening hyponatremia after krait antivenom. PLoS One. 2012; 7(6):e38739.
bite envenoming - a new syndrome. Clin
Toxicol (Phila). 2010;48(9):956-7.
Jayanthi GP, Gowda TV Geographical
variation in India in the composition
Hossain J, Biswas A, Rahman F, Mashreky and lethal potency of Russell's viper
SR, Dalal K, Rahman, A. Snakebite (Vipera russelli) venom. Toxicon.
Epidemiology in BangladeshA National 1988;26(3):257-64.
Community Based Health and Injury
Survey. Health. 2016; 8, 479-86.
Jeevagan V, Katulanda P, Gnanathasan CA,
Warrell DA. Acute pituitary insufficiency
Hung HT, Hjer J, Du NT. Clinical features and hypokalaemia following envenoming
of 60 consecutive ICU-treated patients by Russell's viper (Daboia russelii) in Sri
envenomed by Bungarus multicinctus. Lanka: Exploring the pathophysiological
Southeast Asian J Trop Med Public mechanisms. Toxicon. 2013 Mar
Health. 2009 May; 40(3):518-24. 1;63:78-82.

174 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Jorge MT, Malaque C, Ribeiro LA, Fan HW, Kochar DK, Tanwar PD, Norris RL, Sabir M,
Cardoso JL, Nishioka SA, et al. Failure of Nayak KC, Agrawal TD, et al. Rediscovery of
chloramphenicol prophylaxis to reduce the severe saw-scaled viper (Echis sochureki)
frequency of abscess formation as a envenoming in the Thar desert region of
complication of envenoming by Bothrops Rajasthan, India. Wilderness Environ Med.
snakes in Brazil: a double-blind randomized 2007;18(2):75-85.
controlled trial. Trans R Soc Trop Med Hyg.
2004 Sep; 98(9):529-34. Kramer E. Zur Schlangenfauna Nepals. Rev
suisse Zool. 1977; 84 (3): 721-61.
Joseph JK, Simpson ID, Menon NC, Jose MP,
Kulkarni KJ, Raghavendra GB, et al. First Kuch U, Sharma SK, Alirol E, Chappuis F.
authenticated cases of life-threatening Fatal neurotoxic envenomation from the
envenoming by the hump-nosed pit viper bite of a Lesser Black Krait (Bungarus lividus)
(Hypnale hypnale) in India. Trans R Soc Trop in Nepal. Southeast Asian J Trop Med Public
Med Hyg. 2007 Jan;101(1):85-90. Health. 2011 Jul; 42(4):960-4.

Junghanss T, Bodio M. Notfal-Handbuch Kuch U, Mebs D. The identity of the Javan


Gifttiere. Diagnose-Terapie-Biologie. Krait, Bungarus javanicus Kopstein, 1932,
Stuttgart: Georg Thieme Verlag. 1995. (Squamata: Elapidae): evidence from
mitochondrial and nuclear DNA sequence
Karnchanachetanee C, Hanvivatvong O, analyses and morphology. 2007; Zootaxa
Mahasandana S. Monospecific antivenin 1426: 126.
therapy in Russell's viper bite. J Med Assoc
Thai. 1994 Jun;77(6):293-7. Kularatne SA, Hettiarachchi R, Dalpathadu J,
Mendis AS, Appuhamy PD, Zoysa HD, et al.
Kasturiratne A, Wickremasinghe AR, de Enhydrina schistosa (Elapidae: Hydrophiinae)
Silva N, Gunawardena NK, Pathmeswaran the most dangerous sea snake in Sri Lanka:
A, Ranjan Premaratna et al. The global three case studies of severe envenoming.
burden of snakebite: a literature analysis Toxicon. 2014 Jan;77:78-86.
and modelling based on regional estimates
of envenoming and deaths. PLoS Med. Lalloo D , Trevett A , Black J , Mapao J ,
2008 Nov 4; 5(11):e218. Naraqi S , Owens D et al. Neurotoxicity
and haemostatic disturbances in patients
Kellum JA. KDIGO Clinical Practice envenomed by the Papuan black snake
Guideline for Acute Kidney Injury Kidney (Pseudechis papuanus). Toxicon.1994;
International Supplements volume 2 32(8):927-36.
[internet]. Brussell, International Society of
Nephrology; 2012. 138 p. Available from Lalloo DG, Trevett AJ, Korinhona A, Nwokolo
http://www.kdigo.org/ N, Laurenson IF, Paul M, et al. Snakebites by
clinical_practice_guidelines/pdf/KDIGO% the Papuan taipan (Oxyuranus scutellatus
20AKI%20Guideline.pdf DOI:10.1038/ canni). Paralysis, hemostatic and
kisup.2012.1 electrocardiographic abnormalities, and
effects of antivenom. Am J Trop Med Hyg.
Kemp AM, Kemp SF. Pharmacotherapy in 1995 Jun; 52(6): 525-31.
refractory anaphylaxis: when intramuscular
epinephrine fails. Curr Opin Allergy Clin
Immunol. 2014;14(4):371-8. Lalloo DG, Trevett AJ, Black J, Mapao J,
Saweri A. Neurotoxicity, anticoagulant activity
Kiem-Xuan-Trinh, Le-Khac-Quyen, Long- and evidence of rhabdomyolysis in patients
Xuan-Trinh, Warrell DA. Hyponatraemia, bitten by death adders (Acanthophis sp.) in
rhabdomyolysis, alterations in blood pressure southern Papua New Guinea. QJM. 1996;
and persistent mydriasis in patients 89:25-35.
envenomed by Malayan kraits (Bungarus
candidus) in southern Viet Nam. Toxicon.
ManageMent of snakebites 175
2010 Nov;56(6):1070-5
in south-east asia
Langley RL. Snakebite during pregnancy: a Magar CT, Devkota K, Gupta R, Shrestha RK,
literature review. Wilderness Environ Med. Sharma SK, Pandey DP. A hospital based
2010 Mar;21(1):54-60. epidemiological study of snakebite in
Western Development Region, Nepal.
Lee C-Y. Snake venoms. Handbook of Toxicon. 2013 Jul;69:98-102.
experimental pharmacology. Berlin :
Springer-Verlag Berlin Heidelberg.1979.
1132 p. Malasit P, Warrell DA, Chanthavanich
P, Viravan C, Mongkolsapaya J,
Lewin MR, Bickler P, Heier T, Feiner J, Singhthong B, et al. Prediction,
Montauk L, Mensh B. Reversal of prevention and mechanism of early
experimental paralysis in a human by (anaphylactic) antivenom reactions in
intranasal neostigmine aerosol suggests a victims of snakebites. Br Med J (Clin
novel approach to the early treatment of Res Ed). 1986 Jan 4; 292(6512):
neurotoxic envenomation. Clin Case Rep. 17-20.
2013;1(1):7-15.

Lewin MR, Samuel SP, Wexler DS, Bickler P, Mao YC, Liu PY, Hung DZ, Lai WC,
Vaiyapuri S, Mensh BD. Early Treatment Huang ST, Hung YM, et al.
with Intranasal Neostigmine Reduces Bacteriology of Naja atra Snakebite
Mortality in a Mouse Model of Naja naja Wound and Its Implications for
(Indian Cobra) Envenomation. J Trop Med. Antibiotic Therapy. Am J Trop Med
2014;131835. Hyg. 2016 May 4;94(5):1129-35.

Longkumer T, Armstrong LJ, Santra V, Finny


P. Human, snake, and environmental factors Marik PE, Lemson J. Fluid
in human-snake conflict in North Bihar - A responsiveness: an evolution of
descriptive study [internet]. Christian Journal our understanding. Br J Anaesth.
for Global Health. 2016 May;3(1) available 2014 Apr;112(4):617-20
from: http://
journal.cjgh.org/index.php/cjgh/article/
view/77/290 Marik PE, Monnet X, Teboul JL.
Hemodynamic parameters to guide fluid
therapy. Ann Intensive Care. 2011 Mar
Looareesuwan S, Viravan C, Warrell DA.
21;1(1):1.
Factors contributing to fatal snakebite in the
rural tropics: analysis of 46 cases in Thailand.
Trans Roy Soc Trop Med Hyg. 1988; 82(6):
Mars M, Hadley, GP. Raised
930-4.
intracompartmental pressure and
compartment syndromes.
Mackessy SP, Williams K, Ashton KG. Injury.1998. 29 (6), 403 11.
Ontogenetic variation in venom composition
and diet of Crotalus oreganus concolor: A
case of venom paedomorphosis. Copeia.
Mars M, Hadley GP, Aitchison JM. Direct
2003;4:76982.
intracompartmental pressure
measurement of snakebites in children. S
Maduwage K, Kularatne K, Wazil A, Afr Med J. 1991;80: 227-8.
Gawarammana I. Coagulopthy, acute
kidney injury and death following
Hypnale zara envenoming: the first Matsen FA. Compartmental syndromes.
case report from Sri Lanka. Toxicon. New York: Grune & Stratton.1980
2011;58(8):641-3.

176 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Mnez A. The subtle beast. Snakes, Nuchprayoon I, Garner P. Interventions
from myth to medicine. London: Taylor for preventing reactions to snake
and Francis. 2003. 176 p. antivenom. Cochrane Database of
Systematic Reviews. 1999 Jul 6; 4. Art.
No.: CD002153.

Menon JC, Joseph JK, Jose MP, Dhananjaya


BL, Oommen OV. Clinical Profile and Nuchprayoon I, Pongpan C, Sripaiboonkij N.
laboratory parameters in 1051 Victims of The role of prednisolone in reducing limb
Snakebite from a Single Centre in Kerala, oedema in children bitten by green pit
South India. J Assoc Physicians India. 2016 vipers: a randomized, controlled trial. Ann
Aug; 64:18-26. Trop Med Parasitol. 2008;102:643-9.

O'Leary MA, Kornhauser RS, Hodgson WC,


Isbister GK. An examination of the activity
Menon JC, Joseph JK, Jose MP, Punde D, of expired and mistreated commercial
Mazumdar DB, Bawaskar HS, et al. Australian antivenoms. Trans R Soc Trop
Management protocol of venomous Med Hyg. 2009 Sep;103(9):937-42.
snakebite in India: a consensus statement.
Toxin Reviews. 2016 May 24;
35(3-4):147-51. Pathmeswaran A, Kasturiratne A, Fonseka
M, Nandasena S, Lalloo DG, de Silva HJ.
Identifying the biting species in snakebite
Mohapatra B, Warrell DA, Suraweera W,
by clinical features: an epidemiological tool
Bhatia P, Dhingra N, Jotkar RM, et al.
for community surveys.Trans R Soc Trop
Snakebite mortality in India: a nationally
Med Hyg. 2006 Sep; 100(9): 874-8.
representative mortality survey. PLoS Negl
Trop Dis. 2011 Apr 12;5(4):e1018.
Patel FN, Ekkiswata MM. Motor cycle
ambulance: a cheaper and faster
alternative. Indian J Appl Basic Med Sci.
Mukherjee AK, Maity CR. The composition
2010; 126: 50-54.
of Naja naja venom samples from three
districts of West Bengal, India. Comp
Biochem Physiol A Mol Integr Physiol. 1998
Paul V, Pratibha S, Prahlad KA, Earali J,
Feb;119(2):621-7.
Francis S, Lewis F. High-dose anti-snake
venom versus low-dose anti-snake venom
in the treatment of poisonous snakebites--
Murthy GL, Krishanaprasad A, Srinivasan a critical study. The Journal of the
VR, Sundaram S. Acute pituitary necrosis Association of Physicians of India. 2004
following snake envenomation. J Assoc Jan;52:14-7.
Physicians India. 2002 Mar; 50:452-3.

Phillips RE, Theakston RD, Warrell DA,


Myint-Lwin, Warrell DA, Phillips RE, Tin- Galigedara Y, Abeysekera DT,
Nu-Swe, Tun-Pe, Maung-Maung-Lay. Dissanayaka P. Paralysis, rhabdomyolysis
Bites by Russells viper (Vipera russelli and haemolysis caused by bites of
siamensis) in Burma: haemostatic, vascular Russells viper (Vipera russelli pulchella)
and renal disturbances in response to in Sri Lanka: failure of Indian (Haffkine)
treatment. Lancet. 1985 Dec 7;2(8467): antivenom. Q J Med. 1988 Sep; 68:
1259-64. 691-716.

ManageMent of snakebites
in south-east asia
177
Pillai LV, Ambike D, Husainy S, Khaire Reid HA, Thean PC, Chan KE, Baharom AR.
A, Captain A, Kuch U. Severe Clinical effects of bites by Malayan viper
Neurotoxic Envenoming and Cardiac (Ancistrodon rhodostoma). Lancet. 1963
Complications after the Bite of a 'Sind Mar 23; 1(7282): 617-21.
Krait' (Bungarus cf. sindanus) in
Maharashtra, India. Trop Med Health.
2012 Sep;40(3):103-8. Reid HA, Chan KE & Thean PC. Prolonged
coagulation defect (defibrination
Pochanugool C, Limthongkul S, Wilde syndrome) in Malayan viper bite. Lancet.
H. Management of thai cobra bites 1963 Mar 23;281(7282): 621-26.
with a single bolus of antivenin.
Wilderness Environ Med. 1997
Feb;8(1):20-3. Reid HA. Cobra bites. Br Med J. 1964 Aug
29; 2(5408): 540-5.
Prasad NB, Uma B, Bhatt SK, Gowda VT.
Comparative characterisation of Russell's
Reid HA. Antivenom reactions and efficacy.
viper (Daboia/Vipera russelli) venoms
Lancet. 1980;1:1024-5.
from different regions of the Indian
peninsula. Biochim Biophys Acta. 1999
Aug 5;1428(2-3):121-36. Reid HA. Symptomatology, pathology and
treatment of land snakebite in India and
Premawardena AP, Seneviratne SL, South-East Asia. In: Bcherl W, Buckley EE &
Gunatilake SB, de Silva HJ. Excessive Deulofeu V, editors. Venomous Animals and
fibrinolysis: the coagulopathy following their Venoms. New York. Academic Press;
Merrem's hump-nosed viper (Hypnale 1968. p. 611-42.
hypnale) bites. Am J Trop Med Hyg.
1998 Jun;58(6):821-3.
Reid HA. Symptomatology, pathology and
treatment of the bites of sea snakes. In: Lee
Premawardhena AP, de Silva CE, Fonseka
C Y, editor. Snake Venoms. Handbook of
MM, Gunatilake SB, de Silva HJ. Low dose
Experimental Pharmacology. Berlin: Springe
subcutaneous adrenaline to prevent acute
Berlin Heidelberg; 1979.p.92255.
adverse reactions to antivenom serum in
people bitten by snakes: randomised,
placebo controlled trial. BMJ. 1999 Apr Reid HA. Epidemiology of sea snakebites. J
17; 318(7190):1041-3. Trop Med Hyg. 1975 May; 78(5): 106-13.

Priyamvada PS, Shankar V, Srinivas BH,


Rajesh NG, Parameswaran S. Acute Reid HA & Lim KJ. Sea snakebite. A survey of
Interstitial Nephritis Following Snake fishing villages in northwest Malaya. BMJ.
Envenomation: A Single-Center Experience. 1957; 2: 1266-72.
Wilderness Environ Med. 2016
Jun;27(2):302-6. Reid HA, Thean PC & Martin WJ. Specific
antivenene and prednisone in viper bite
Rahman R, Faiz MA, Selim S, Rahman B, poisoning: controlled trial. BMJ. 1963; 2:
Basher A, Jones A. Annual incidence of 1378-80.
snakebite in rural Bangladesh. PLoS Negl
Trop Dis. 2010 Oct 26; 4(10): e860. Rivire G, Choumet V, Audebert F,
Sabouraud A, Debray M, Scherrmann JM, et
Raweerith R, Ratanabanangkoon K. al. Effect of antivenom on venom
Immunochemical and biochemical pharmacokinetics in experimentally
comparisons of equine monovalent and envenomed rabbits: toward an optimization
polyvalent snake antivenoms. Toxicon. of antivenom therapy. J Pharmacol Exp Ther.
2005 Mar 1;45(3):369-75. 1997 Apr; 281(1): 18

178 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Rojnuckarin P, Mahasandana S, Seneviratne SL, de Silva CE, Fonseka MM,
Intragumthornchai T, Sutcharitchan P, Pathmeswaran A, Gunatilake SB, de Silva
Swasdikul D. Prognostic factors of green HJ. Envenoming due to snakebite during
pit viper bites. Am J Trop Med Hyg. 1998 pregnancy. Trans R Soc Trop Med Hyg.
Jan;58(1):22-5. 2002 may-Jun ;96(3):272-4.

Rojnuckarin P, Chanthawibun W,
Sharma LR, Lal V, Simpson ID. Snakes of
Noiphrom J, et al. A randomized, double-
medical significance in India: the first
blind, placebo-controlled trial of
reported case of envenoming by the
antivenom for local effects of green pit
Levantine viper (Macrovipera lebetina).
viper bites. Trans R Soc Trop Med Hyg.
Wilderness Environ Med. 2008;
2006;100:87984.
19(3):195-8.

Rusznak C, Peebles RS. Anaphylaxis and


anaphylactoid reactions. A guide to Sharma SK, Alirol E, Ghimire A, Poncet A,
prevention, recognition, and emergent Mostaguir K, Combescure C, et al. editors.
treatment. Postgrad Med. 2002 A randomized, double blind, clinical trial of
May;111(5):101-4, 107-8, 111-4. two dose regimens of VINS polyvalent
antivenom for the treatment of snakebite
with neurotoxic envenomation in Nepal In:
Saini RK, Singh S, Sharma S, Rampal V,
18th World Congress of the International
Manhas AS, Gupta VK. Snakebite poisoning
Society IST 2015; Sept 25-30; London
presenting as early morning neuroparalytic
(United Kingdom).
symptoms in jhuggi dwellers. 1986 Jun;J
Assoc Physicians India 34(6): 415-7.
Sharma SK, Chappuis F, Jha N, Bovier PA,
Sano-Martins IS, Fan HW, Castro SC, Loutan L, Koirala S. Impact of snakebites
Tomy SC, Franca FO, Jorge MT, et al and determinants of fatal outcomes in
(1994). Reliability of the simple 20 minute southeastern Nepal. Am J Trop Med Hyg.
whole blood clotting test (WBCT20) as an 2004 Aug;71(2):234-8.
indicator of low plasma fibrinogen
concentration in patients envenomed by Sharma SK, Bovier P, Jha N, Alirol E, Loutan
Bothrops snakes. Toxicon; 1994 Sep; L, Chappuis F. Effectiveness of rapid
32(9): 1045-50. transport of victims and community health
education on snakebite fatalities in rural
Sarkar MSU, Sarkar NJ, Patwary MS. Nepal. Am J Trop Med Hyg. 2013
Epidemiological Survey of Snakebite in Jul;89(1):145-50.
Bangladesh. Dhaka (Bangladesh): Ministry of
Science and Technology, Government of the
Peoples Republic of Bangladesh; 1999. Sharma SK, Khanal B, Pokhrel P, Khan A,
Koirala S.Snakebite-reappraisal of the
Sawai Y. Clinical problem of snakebites in situation in Eastern Nepal. Toxicon. 2003
Southeast Asia. In: Tu AT, editors. Toxin- Mar 1;41(3):285-9.
related diseases. New Delhi: Oxford and IBH
Publishing Co;1993. P.445-69. Sharma SK, Pandey DP, Shah KB, Tillack F,
Chappuis F, Thapa CL,et al. Venomous
Seneviratne SL, Opanayaka CJ, Ratnayake Snakes of Nepal, A Photographic Guide
NS, Kumara KE, Sugathadasa AM, [internet]. Dharan: B.P. Koirala Institute of
Weerasuriya N, et al. Use of antivenom Health Sciences;2013. 78 p. Available from
serum in snakebite: a prospective study http://www.bik-f.de/files/publications/
of hospital practice in the Gampaha kuch_venomous_snakes_of_nepal_-
district. Ceylon Med J. 2000 _english_edition.pdf
Jun;4(2):65-8.
ManageMent of snakebites
in south-east asia
179
Shashidharamurthy R, Kemparaju K. Region- Sutherland SK, Tibballs J. Australian animal
specific neutralization of Indian cobra (Naja toxins: The creatures, their toxins and care
naja) venom by polyclonal antibody raised of the poisoned patient. 2nd edition.
against the eastern regional venom: A Melbourne: Oxford University Press; 2001.
comparative study of the venoms from three
different geographical distributions. Int Swaroop S, Grab B. Snakebite mortality
Immunopharmacol. 2007 Jan;7(1):61-9. in the world. Bull World Health Org.
1954; 10:35-76.

Silveira PV, Nishioka Sde A. Venomous Tariang DD, Philip PJ, Alexander G,
snakebite without clinical envenoming ('dry- Macaden S, Jeyaseelan L, Peter JV, et al.
bite'). A neglected problem in Brazil. Trop Randomized controlled trial on the
Geogr Med. 1995;47(2):82-5. effective dose of anti-snake venom in cases
of snakebite with systemic envenomation. J
Assoc Physicians India 1999;47(4):369-71.
Soh C-T, et al. Current status of snakebite
in Korea. Yonsei Reports on Trop Med.
Than-Than, Khin-Ei-Han, Hutton RA, Myint-
1978; 9:48-56.
Lwin,, Tin-Nu-Swe, Phillips RE, et al.
Evolution of coagulation abnormalities
Sitprija V, Boonpucknavig V. Snake venoms following Russells viper bite in Burma.
and nephrotoxicity. In: Lee C-Y, editors. British J Haematology. 1987; 65: 193-198.
Snake venoms. Handbook of Experimental
Pharmacology. Berlin: Springer Verlag;
Than-Than, Hutton RA, Myint-Lwin, Khin-
1979. p.997-1018
Ei-Han, Soe-Soe, Tin-Nu-Swe, et al.
Haemostatic disturbances in patients bitten
Smith MA. The Fauna of British India, by Russells viper (Vipera russelli siamensis)
Ceylon and Burma, inlcuding the whole of in Burma. British J Haematology. 1988
the Indo-Chinese subregion. Reptilia and Aug;69(4): 513-520.
Amphibia. Vol III Serpentes. London: Taylor
and Prancis; 1943. p. 482-5. Than-Than, Francis N, Tin-Nu-Swe, Myint-
Lwin, Tun-Pe, Soe-Soe, et al. Contribution
of focal haemorrhage and microvascular
Srimannarayana J, Dutta TK, Sahai A,
fibrin deposition to fatal envenoming by
Badrinath S. Rational use of anti-snake
Russells viper (Vipera russelli siamensis) in
venom: Trial of various regimens in
Burma. Acta Trop. 1989 Jan; 46(1):23-38.
Hemotoxic Snake envenomation. J Assoc
Phys India. 2004 Oct;52:788-93.
Theakston RDG, Phillips RE, Looareesuwan
S, Echeverria P, Makin T, Warrell DA.
Bacteriological studies of the venom and
Sutherland SK. Serum reactions. An analysis
mouth cavities of wild Malayan pit vipers
of commercial antivenoms and the possible
(Calloselasma rhodostoma) in southern
role of anticomplementary activity in de-
Thailand. Trans Roy Soc Trop Med Hyg.
novo reactions to antivenoms and
1990; 84: 875-9.
antitoxins. Med J Aust. 1977; 1:613-5.

Theakston RD, Phillips RE, Warrell DA,


Galagedera Y, Abeysekera DT, Dissanayaka
Sutherland SK, Coulter AR, Harris RD.
P, et al. Envenoming by the common krait
Rationalisation of first-aid measures for
(Bungarus caeruleus) and Sri Lankan cobra
elapid snakebite. Lancet. 1979;
(Naja naja naja): efficacy and complications
313(8109):183-6.
of therapy with Haffkine antivenom. Trans
R Soc Trop Med Hyg. 1990 Mar-Apr;
84(2): 301-8.

180 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Thein T, Tin T, Hla P, Phillips RE, Myint L, Tun-Pe, Ba-Aye, Aye-Aye-Myint, Tin-Nu-Swe,
Tin Nu S, et al. Development of renal Warrell DA. Bites by Russells viper (Daboia
function abnormalities following bites by russelii siamensis) in Myanmar: effect of snakes
Russells vipers (Daboia russelii siamensis) length and recent feeding on venom
in Myanmar. Trans R Soc Trop Med Hyg. antigenaemia and severity of envenoming. Trans
1991;85:404409. Roy Soc Trop Med Hyg. 1991 Nov-Dec;85(6) 85:
804-8.

Thiansookon A, Rojnuckarin P. Low


Tun-Pe, Nu-Nu-Lwin, Aye-Aye-Myint, Kyi-May-
incidence of early reactions to horse-
Htwe, Khin-Aung-Cho. Biochemical and
derived F(ab')(2) antivenom for
biological properties of the venom from Russell's
snakebites in Thailand. Acta Trop.
viper (Daboia russelli siamensis) of varying ages.
2008 Feb;105(2):203-5.
Toxicon. 1995;33(6):817-21.

Thomas PP, Jacob J. Randomised trial of Tun-Pe, Aye-Aye-Mying, Khin-Aye-Han, et al.


antivenom in snake envenomation with Local compression pads as a first-aid measure
prolonged clotting time. British medical for victims of bites by Russells viper (Daboia
journal (Clinical research ed.) 1985 russelii siamensis) in Myanmar. Trans Roy Soc
Aug;291(6489):177-8. Trop Med Hyg. 1995; 89:293-5.

Tilbury CR. Observations on the bite of the Tun-Pe, Aye-Aye-Myint, Khin-Aye-Kyu, Maung-
Mozambique spitting cobra (Naja Maung-Toe . Acceptability study of protective
mossambica mossambica). S African Med boots among farmers of Taungdwingyi
J 1982;27 Feb:308-313. township. New Delhi: WHO Regional Office for
South-East Asia; 2002. pp. 711.
Tin-Nu-Swe, Tin-tun, Myint-Lwin, Thein-
than, Tun-pe, Robertson JL, et al. Renal Vaiyapuri S, Vaiyapuri R, Ashokan R, Ramasamy
ischaemia, transient glomerular leak and K, Nattamaisundar K, Jeyaraj A,et al. Snakebite
acute renal tubular damage in patients and its socioeconomic impact on the rural
envenomed by Russells vipers (Daboia population of Tamil Nadu, India. PLoSOne.
russelii siamensis) in Myanmar. Trans Roy 2013 Nov 21;8(11):e80090.
Soc Trop Med Hyg. 1993; 87: 678-81.

Viravan C, Veeravat U, Warrell MJ, et al. ELISA-


Tin-Myint, Rai-Mra, Maung-Chit, Tun-Pe,
confirmation of acute and past envenoming by
Warrell DA. Bites by the king cobra
the monocellate Thai cobra (Naja kaouthia).
(Ophiophagus hannah) in Myanamar:
American J Trop Med Hyg. 1986; 35(1):
successful treatment of severe neurotoxic
173-181.
envenoming. QJM. 1991; 80(3): 751-62.
Viravan C, Looareesuwan S, Kosakarn W,
Tun Pe, Khin Aung Cho. Amount of venom Wuthiekanun V, McCarthy CJ, Stimson AF, et
injected by Russell's viper (Vipera russelli). al. A national hospital-based survey of snakes
Toxicon. 1986;24(7):730-3. responsible for bites in Thailand. Transactions
Roy Soc Trop Med Hyg. 1992 Jan-Feb;86(1):
100-6.
Tun-Pe, Phillips RE, Warrell DA, Moore RA,
Tin-Nu-Swe, Myint-Lwin, et al. Acute and Warrell DA. Tropical snakebite: clinical studies
chronic pituitary failure resembling in South-East Asia. In: Harris JB ,editors.
Sheehans syndrome following bites by Natural Toxins. Animal, plant and microbial.
Russells viper in Burma. Lancet. 1987 Oct Oxford: Clarendon Press; 1986. p. 25-45.
3;2(8562): 763-7.

ManageMent of snakebites
in south-east asia
181
Warrell DA. Russells viper: biology, venom Warrell DA. Snakebite. Lancet. 2010 Jan
and treatment of bites. Trans Roy Soc Trop 2; 375(9708): 77-88.
Med Hyg. 1989 Nov-Dec; 83(6): 732-40.
Warrell DA. Snakebite: a neglected problem
in twenty-first century India. Natl Med J India.
Warrell DA. Treatment of snakebite in the 2011 Nov-Dec; 24(6):321-4.
Asia-Pacific Region: a personal view. In:
Gopalakrishnakone P, Chou LM, editions. Warrell DA, Arnett C. The importance of bites
Snakes of medical importance (Asia-Pacific by the saw-scaled or carpet viper (Echis
region). Singapore:National University of carinatus). Epidemiological studies in Nigeria
Singapore Press; 1990. p. 641-670. and a review of the world literature. Acta
Tropica Basel, 1976; 33: 307-41.

Warrell DA. Bites by dark green pit vipers in Warrell DA, Greenwood BM, Davidson NM,
Bangkok. Am. J. Trop. Med Hyg.1990;42: Ormerod LD, Prentice CR. Necrosis,
623-624. haemorrhage and complement depletion
following bites by the spitting cobra (Naja
nigricollis). Q J Med. 1976 Jan; 45(177):1
Warrell DA. The global problem of 22.
snakebite: its prevention and treatment. In:
Gopalakrishnakone P, Tan CK, editions. Warrell DA, Davidson NMcD, Greenwood BM,
Recent Advances in Toxinology Research. Ormerod LD, Pope HM, Watkins BJ et al.
Singapore: National University of Singapore Poisoning by bites of the saw-scaled or carpet
Press;1992. p. 121-53. viper (Echiscarinatus) in Nigeria. Q J Med. 1977
Jan; 46(181): 33-62.

Warrell DA, Looareesuwan S, White NJ,


Warrell DA. Sea snakebites in the Asia-
Theakston RD, Warrell MJ, Kosakarn W,et al.
Pacific region. In Gopalkrishnakone P,
Severe neurotoxic envenoming by the
editions. Sea Snake Toxinology.
Malayan krait Bungarus candidus (Linnaeus):
Singapore; Singapore University Press:
response to antivenom and
1994. p. 1-36.
anticholinesterase. BMJ 286: 678-80.

Warrell DA, Looareesuwan S, Theakston RD,


Warrell DA. Clinical toxicology of
Phillips RE, Chanthavanich P, Viravan C, et al.
snakebite in Asia. In: Meier J, White J,
Randomised comparative trial of three
editions. Clinical Toxicology of Animal
monospecific antivenoms for bites by the
Venoms and Poisons. Boca Ranton: CRC
Malayan pit viper (Calloselasma rhodostoma)
Press; 1995.p. 493-594.
in southern Thailand: clinical and laboratory
correlations. Am J Trop Med Hyg. 1986 Nov;
Warrell DA. Geographical and intraspecies 35(6): 1235-47.
variation in the clinical manifestations of
envenoming by snakes. In Thorpe RS, Warrell DA, Looareesuwan S, Stimson AF.
Wster W, Malhotra A, editors: Venomous Rediscovery and redefinition of Malcolm
snakes: Ecology, evolution and snakebite. Smith's Trimeresurus kanburiensis in
Oxford:Clarendon Press;1997.p.189-203. Thailand, with a report of envenoming. Trans
R Soc Trop Med Hyg. 1992;86:95-9.

Warrell DA. Researching nature's venoms Warrell DA, Hudson BJ, Lalloo DG, Trevett
and poisons. Trans R Soc Trop Med Hyg. AJ, Whitehead P, Bamler PR, et al. The
2009 Sep;103(9):860-6. emerging syndrome of envenoming by the
New Guinea small-eyed snake Micropechis
ikaheka. Quart J Med.1996 Jul;
89(7):523-30.

182 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Warrell DA, Gutirrez JM, Calvete JJ, Weinstein SA, Warrell DA, White J, Keyler DE.
Williams D. New approaches & (2011). Venomous bites from non-
technologies of venomics to meet venomous snakes: A critical analysis of risk and
the challenge of human envenoming management of colubrid snakebites,
by snakebites in India. Indian J Med London: Elsevier; 2011. 364 p.
Res. 2013;138:38-59.

Watt G, Theakston RD, Hayes CG, Weinstein SA, White J, Westerstrm A, Warrell
Yambao ML, Sangalang R, Ranoa CP, et DA. Anecdote vs. Substantiated Fact: The
al. Positive response to edrophonium in Problem of Unverified Reports in the
patients with neurotoxic envenoming Toxinological and Herpetological Literature
by cobras (Naja naja philippinensis): a Describing Non-front-fanged Colubroid
placebo-controlled study. New Engl J (Colubrid) Snakebites. Herpetological Review.
Med. 1986;315(23): 1444-8. 2013 March;44(1), 239.

Watt G, Padre LP, Tuazon ML, Theakston


RD, Laughlin LW. Tourniquet application Whitaker R. Snakebite in India today. Neurol
after cobra bite: delay in the onset of India.2015; 63(3) : 300-3.
neurotoxicity and the dangers of sudden
release. Am J Trop Med & Hyg.1988;38:
618-22. Whitaker R, Martin G. Diversity and distribution
of the medically important snakes of India.
Watt G, Meade BD, Theakston RD, Padre LP, Clinical Toxinology in Asia pacific and Africa.
Tuazon ML, Calubaquib C, et al. Comparison 2015 January 2015; 2:115-36.
of tensilon and antivenom for the treatment
of cobra-bite paralysis. Trans Roy Soc Trop
Med Hyg. 1989; 83: 570-3. Williams DJ, Jensen SD, Nimorakiotakis B, Mller
R, Winkel KD. Antivenom use, premedication
Watt G, Theakston RD. Seasnake bites in a and early adverse reactions in the management
freshwater lake. Am J Trop Med Hyg. of snakebites in rural Papua New Guinea.
1985;34(4):770-3. Toxicon. 2007; 49(6):780-92.

Weinstein SA, Griffin R, Ismail AK. Non-


front-fanged colubroid ("colubrid") Williams DJ, Jensen SD, OShea M. Snakebite
snakebites: three cases of local management in Cambodia: towards improved
envenoming by the mangrove or ringed prevention, clinical treatment and rehabilitation.
cat-eyed snake (Boiga dendrophila; Manila: WHO WPRO. 2009.
Colubridae, Colubrinae), the Western
beaked snake
(Rhamphiophis oxyrhynchus; Williams D, Gutirrez JM, Harrison R, Warrell
Lamprophiidae, Psammophinae) and the DA, White J, Winkel KD, et al. The Global
rain forest cat-eyed snake (Leptodeira Snakebite Initiative: an antidote for snakebite.
frenata; Dipsadidae). Clin Toxicol (Phila). Lancet.2010 Jan 2; 375(9708): 8991.
2014;52(4):277-82.

Weinstein SA, Smith TL, Kardong Williams SS, Wijesinghe CA, Jayamanne SF,
KV.Reptile venom glands: Form, function, Buckley NA, Dawson AH, Lalloo DG, et al.
and future, In Mackessy SP, editor: Delayed psychological morbidity associated
Handbook of venoms and toxins of with snakebite envenoming. PLoS Negl Trop
reptiles. Boca Raton : CRC Press; 2009. P. Dis. 2011 August 2; 5(8):e1255.
65-91.

ManageMent of snakebites
in south-east asia
183
Win-Aung, Tin-Tun, Khin-Maung-Maung, Zakariah A. Presentation on variability
Aye-Kyaw, Hla-Pe, Tin-Nu-Swe, et al. of polyvalent ASV efficacy- Clinical
Clinical trial of intramuscular anti-snake Experience at Christian Medical
venom administration as a first aid College, Vellore 3rd national
measure in the field in the management of conference on Tropical Medicine and
Russells viper bite patients. Southeast Toxicology in Bangladesh. Dhaka (Bd) ;
Asian J Trop Med Public Health. 1996 Sep; December 2014. Available from: http://
27(3):494-7. medicinesomc.com/wp-content/
uploads/2015/01/Variability-of-
Polyvalent-ASV-efficacy-Clinical-
Wongtongkam N, Wilde H, Sitthi-Amorn C,
experience-of-Christian-Medical-
Ratanabanangkoon K. A study of 225
College-Vellore.pptx
Malayan pit viper bites in Thailand. Mil
Med. 2005 Apr;170(4):342-8.

World Health Organization. Progress in the


characterization of venoms and
standardization of antivenoms.
Geneva :WHO Press; 1981.Report No. 58.

World Health Organization. Rabies and


envenomings. A neglected public health
issue. Report of a Consultative Meeting.
Geneva, 10 January 2007. 32 p.

World Health Organization. WHO guidelines


for the production, control and regulation of
snake antivenom immunoglobulins and
Venomous snakes distribution and species risk
categories [internet] Geneva: WHO Press;2008.
Available from http://www.who.int/
bloodproducts/snake_antivenoms/
snakeantivenomguideline.pdf?ua=1.

Wster W, Warrell DA, Cox MJ, Jaintakune P,


Narhitabhata. Redescription of Naja siamensis
(Serpentes: Elapidae), a widely overlooked
spitting cobra from South-East Asia:
geographic variation, medical importance and
designation of neotype. J Zool Lond.1997;
243(4): 771-88.

184 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Annexes

Annexes 185
186 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Algorithm: Diagnosis of snakebite
1 annex

cases based on clinical data as a


basis for antivenom treatment
Algorithms should be created based on local data so that they can be relevant for local
use. The example below is intended for use in Sri Lanka (Ariaratnam et al., 2009).

Patient presents with a history of


snakebite BUT no dead snake and little/no
description of the snake

Non clothing blood/


YES YES
Neurotoxic signs Marked local swelling spontaneous
systemic bleeding

YES NO YES

Non clothing blood/


spontaneous Neurotoxic signs Neurotoxic signs
systemic bleeding
NO YES YES NO

Early Acute Bitten on land


blistering/ Renal sleeping on Bitten in Acute Renal
necrosis Failure floor of house sea Failure

YES NO

Cobra Russells Krait Sea Snake Hump Nosed Saw Scaled


bite Viper bite bite bite Viper bite Viper bite

Figure 89a. Algorithm for diagnosis of the snake responsible for a bite in Sri Lanka (Ariaratnam et al., 2009)

Annexes 187
2 annex
Algorithm: Differentiating major Asian
snake species by clinical syndrome
These should be created based on local data so that they can be relevant for local use. The
example below is intended for use in Sri Lanka (Ariaratnam et al., 2009).

VIPERIDAE
Daboia russelii Echis carinatus

Trimeresurus trigonocephalus Hypnale hypnale

188 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
elapidae
Naja naja

Bungarus caeruleus Bungarus ceylonicus

elapidae
Hydrophis cyanocinctus

Figure 89b: Syndromic approach to snakebite management in Sri Lanka: venomous snakes of Sri Lanka (Ariaratnam et al., 2009)

Annexes 189
Clinical spectrum of syndromes of snakebites, Sri Lanka
Species No. Local effects Coagulopathy Neurotoxicity Renal toxicity Myotoxicity
(%) (%) (%) (%) (%)

Russells viper 319 96 76 59 19 24

Hump-nosed viper 302 91 39 - 10 -

Common krait 88 9 - 95 - -

Cobra 45 91 - 80 - -

Sensitivity and specificity of clinical syndromes as a screening test in


identifying snakebites, Sri Lanka

Snake Sensitivity (%) Specificity (%)

Russells viper 14 100

Cobra 78 96

Common krait 66 100

Hump-nosed viper 10 97

190 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Antivenoms for treatment of bites
3 annex

by South-East Asian snakes


Antivenoms for treatment of bites by South-East Asian snakes (listed by country
of manufacture). Recommended doses are those quoted by the manufacturers.
For recommended initial doses of some of these antivenoms, according to the
species of snake responsible for envenoming, based on clinical experience, are
given in Table 1

A. Australia Agkistrodon acutus antivenin (purified)


Bio CSL Commonwealth Serum (= Deinagkistrodon acutus, found in North
Laboratories Viet Nam).
45 Poplar Rd Recommended initial dose: 8000 IU (= 4
Parkville, Victoria 3052, Australia ampoules)
Phone: +61 3 9389 1911
Fax: +61 3 9389 1434 Agkistrodon halys (= Gloydius
customerservice@csl.com.au brevicaudus) antivenin (purified) (said to be
Phone: +61 39389 1204 active against venoms of Protobothrops/
Black snake (Pseudechis spp.), brown Trimeresurus mucrosquamatus and
snake (Pseudonaja spp.), death adder Viridovipera/Trimeresurus stejnegeri).
(Acanthophis spp.), polyvalent, sea snake Recommended initial dose: 6000 IU
antivenoms. (= 1 ampoule)
Recommended initial dose: 1-3 vials
Bungarus multicinctus antivenin (purified)
B. China (said to be effective against the venom of
Shanghai Institute of Biological Products, Ophiophagus hannah).
Ministry of Health, 1262 Yan An Road (W), Recommended initial dose; for bites by
Shanghai 200052, China both species 10 000 IU (= 1.25 ampoules)
Tel + 8621-62803189;
Fax +8621-62801807. Naja naja antivenom (purified)
Contact: Ms Minzhi Lu, Manager, (= Naja atra).
International Affairs & Trade Department Recommended initial dose: 2000 IU
(Tel +8621-62805234) (= 2 ampoules)
(liquid antivenoms, 10-15 ml/ampoule)

Annexes 191
C. India 3. Bengal Chemicals and
Polyvalent antivenoms raised in equines Pharmaceuticals Ltd,
against venoms of Bungarus caeruleus, 6 Ganesh Chunder Avenue 700013
Naja naja, Daboia russelii, Echis carinatus Kolkota
collected in Mamallapuram, Tamil Nadu Tel: +91-33-2237-1525
but more recently also from other areas Fax:+91-33-2225-7697
(to be confirmed). Antivenoms are (currently stopped production)
lyophilised (reconstituted to 10ml per vial)
or liquid. 4. King Institute, Chennai (in 2016,
announced resumption of production
Recommended initial dosage for all these after a 15 year break)
antivenoms is:
Bungarus caeruleus: 10-20 vials Private sector
Naja naja: 10-20 vials
Daboia/Vipera russelli: 10 vials 1. Serum Institute of India
Echis carinatus: 5 vials (10 vials for E. c. 212/2, Hadapsar
sochureki in N and NW India) Off Soli Poonawalla Road 411028 Pune
Tel:+91-20-26993900
Note: venoms of other species (including Fax:+91-20-26993921
hump-nosed pit-viper Hypnale hypnale (reduced/stopped production)
SW India and Sri Lanka, and all other
pit-vipers) are not covered by Indian 2. VINS Bioproducts Ltd
polyvalent antivenoms, nor are venoms by 806,Essjay House,
Naja, Daboia or Echis species, sea snakes Road Nr 3, Banjara Hills 500034
or other species occurring outside India. Hyderabad Tel:+91-40-23354550,
Fax:+91-40-23350410 Cobra
Annual production estimates of Antivenin, Russells Antivenin, Anti
number of 10 ml vials of polyvalent snake Venom Polyvalent
antivenom (ASV) (2015-16) are given in (production 2015-16: 1 000 000 vials)
parentheses.
3. Biological E. (Evans) Limited 18/1 and
Public sector 3, Azamabad 500020 Hyderabad
1. Central Research Institute, Kasauli Tel:+91-40-30213999,
173204 Kasauli (H.P.) Fax:+91-40-27615309
Tel:+91-1-792-72114 E-mail info@biologicale.co.in
Fax:+91-1-792-72049 (production 2015-16: 500 000 vials of
(reduced/stopped production)] liquid antivenom only)

2. Haffkine Institute 4. Bharat Serum and Vaccine


Haffkine Bio-Pharmaceutical Acharya Plot No. K-27, Anand Nagar, Additional
Donde Marg, M.I.D.C. Ambernath (East)
Parel -400012 Mumbai Tel:+91-251-2621 645,
Tel:+91-22-412-9320, Fax:+91-251-2621 089
Fax:+91-22-416-8578 Snake Venom Antiserum I.P.
(production 2015-16: 400 000 vials) (production 2015-16: 800,00)
(supplying Maharashtra State)

192 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
5. Mediclone Biotech Pvt. Ltd., 36/37 E. Iran
Millenium House, M.K.Srinivasan Nagar State Serum & Vaccine Institute,
Main road, Perungudi, Chennai Razi Hessarek, bP 656, Teheran
Tel +91-44-24963845 (liquid antivenoms, 10 ml/ampoule)
Fax +91-44-24963846 (Tel +98 2221 2005)
(production 2015-16: 40 000 vials) Polyvalent snake antivenom (equine)
(reducing production) (said to neutralize the venoms of two
South-East
6. Premium Serum and Vaccines Asian species - Naja oxiana and Echis
Narayangaon carinatus (probably E sochureki), Vipera
406, B Wing, Highway Rose Co-op. lebetina (= Macrovipera lebetina) and
Housing Society, Pseudocerastes persicus
92 Dixit Road Extensions, Recommended initial dose: ?
Vile Parle (East), Mumbai 400057,
Maharashtra, F. Japan
Farm and manufacturing facility Japan Snake Institute
S.No 354-1,354-2A/1 At and post Nihon Hebizoku Gakujutsu Kenkyujo
Narayangaon, near Champagne India, 3318 Yunoiri Yabuzuka
Tal- Junnar, Dist- Pune-410504, Yabuzukahonmachi Nittagun
Maharashtra, Gunmaken 379-2301
E-mail sales@premiumserums.com Tel 0277 785193 Fax 0277 785520
premiumserums@gmail.com Snake-c@sunfield.ne.jp
website: www.premiumserums.com www.sunfield.ne.jp/~snake-c/
Polyvalent Snake Venom Antiserum
both in Lyophilized or liquid form Yamakagashi (Rhabdophis tigrinus)
(production 2015-16: 600 000 vials) antivenom (also effective against red-
Venom sources Maharashtra and Uttar necked keelback R. subminiatus venom)
Pradesh in addition to Irula Society in
Tamilnadu. G. Myanmar (Burma)
Myanmar Pharmaceutical Factory, Insein,
D. Indonesia Yangon (production capacity 100 000
PT Bio Farma (persero) vials/year)
Jl Pasteur no 28 Bandung - 40161 (lyophilized and liquid equine F(ab)2
Tel. +62 22033375 antivenoms, 10 ml/ampoule)
Fax +62 222041306 Viper antivenom (V. russelli = Daboia
Website: www.biofarma.co.id siamensis)
Email : mail@biofarma.co.id Cobra antivenom (N. kaouthia)
Recommended initial dose: 2 x 5 ml vials Recommended initial dose: 8 vials for
(maximum 80-100 ml) D. siamensis, 4 vials for N. kaouthia
Liquid antivenom A new ovine D. siamensis antivenom is
now in production (Dr Aung Zaw, personal
Biosave (polyvalent Anti-Snake Venom communication).
Sera, Equine) serum anti bisa ular
polivalen (kuda) Naja sputatrix-cobra, H. Pakistan
Bungarus fasciatus - banded krait, National Institute of Health,
Agkistrodon rhodostoma Malayan Biological Production Division, Islamabad
pit viper Tel +9251- 240946;
Fax +9251-20797; Telex 5811-NAIB-PK

Annexes 193
(no recent information available) D. russelii, E. carinatus, H. hypnale, and
Dr. Birjees Mazher Kazi, Executive Director N. naja. It showed satisfactory preclinical
National Institute of Health, Islamabad potency and will be subjected to clinical
Tel: (051) 9255117 trials in Sri Lanka. Antivenom against
Fax: (051) 9255099, 9255125 B. caeruleus is also being developed, to
Email: edoffice@isb.apollo. provide cover against all five medically
net.pk webmaster@nih.org.pk important snakes.
Contact: Shahid Akhtar
(liquid and lyophilized antivenoms, L. Thailand
10 ml/ampoule) The Thai Red Cross Society (production
Polyvalent anti-snake venom serum capacity 75 000 82 000 vials/year)
(B. caeruleus, E. carinatus, N. naja, Queen Saovabha Memorial Institute,
V. lebetina (=Macrovipera lebetina), 1871 Rama VI Road, Bangkok 10330
V. russelli (= Daboia russelii) Tel +662-2520161-4;
Recommended initial dose: 5 vials for Echis Fax +662-2540212;
carinatus, 10 vials for other species. Telex 82535 THRESCO TH)
(freeze-dried monovalent antivenoms, 10
J. Taiwan ml/ampoule)
National Institute of Preventive Medicine,
161 Kun-Yang Street, Nan-Kang, 1. Cobra antivenom (Naja kaouthia):
Taipei, ROC 11513 recommended dose 100 ml*
Tel +8862-7859215; 2. King cobra antivenin (Ophiophagus
Fax +8862-7853944. hannah): 50 ml*
Contact: Dr Gong-Ren Wang, Director 4. Russells viper antivenin (Daboia
(lyophilised antivenoms, 10 ml/ampoule) siamensis): 30 ml*
Bungarus multicinctus and N atra bivalent 5. Malayan pit viper antivenin
antivenom (Calloselasma rhodostoma): 30 ml*
Trimeresurus mucrosquamatus 6. Green pit viper antivenin (Cryptelytrops
(= Protobothrops mucrosquamatus) and Trimeresurus albolabris): 30 ml*
Trimeresurus grammineus (= Viridovipera 7. Malayan Krait Antivenin (Bungarus
stejnegeri) bivalent antivenom candidus): 50 ml*
Recommended initial dose: 5 vials (freeze-dried polyvalent antivenoms, 10
Agkistrodon acutus (= Deinagkistrodon ml/ampoule)
acutus) antivenom Neuro polyvalent (raised against 1-3
Recommended initial dose: ? and 7): 20 ml* for all species

K. Sri Lanka Haemato polyvalent (raised against 4-6):


A new polyspecific, freeze-dried whole 20 ml* for all species
IgG antivenom, manufactured by caprylic
acid precipitation, has been developed *Recommended doses according to
through a collaboration between approved registration dossiers from
Instituto Clodomiro Picado (University Thai FDA (Professor Sumana Khomvilai,
of Costa Rica), Animal Venom Research personal communcation 21-07-2016).
International (AVRI), USA, and University These differ from suggested initial doses
of Peradeniya. The antivenom has been quoted in Table 1, based on clinical
raised against venoms from Sri Lankan experience.

194 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Pressure-immobilization and pressure
4 annex

Pressure-immobilization methods A rubber and/or folded material pad


Bites by cobras, king cobras, kraits, approximately 5 cm square and 2-3 cm
Australasian elapids or sea snakes may thick is placed directly over the bite site
lead, on rare occasions, to the rapid anywhere on the body and bound in place
development of life-threatening respiratory with a non-elastic bandage at a pressure
paralysis. This paralysis might be delayed of at least 70 mmHg.
by slowing down the absorption of venom
from the site of the bite. The following Pressure-bandage plus immobilization
techniques are currently recommended: Sutherland et al., 1979; Sutherland and
Tibballs, 2001) (Fig 91).
Pressure-pad plus immobilization
(Anker et al.,1982; Tun-Pe et al., 1995) Ideally, an elasticated bandage,
(Fig 90) approximately 10 15 cm wide and at least

pad of rubber or cloth approx. 6 x 6 x 3 cm applied directly over bite site


secured tightly with inelastic bandage at approx 70 mmHg pressure

Figure 90: Pressure-pad immobilization method (Copyright Dr David J Williams)

Annexes 195
4.5 metres long should be used (Canale et a rigid splint. The bandage is bound firmly
al., 2009). If that it not available, any long (at a pressure of 50-70 mmHg), but not
strips of material can be used. The bandage so tightly that the peripheral pulse (radial,
is bound firmly around the entire bitten posterior tibial, dorsalis pedis) is occluded
limb, starting distally around the fingers or that the patient develops severe
or toes and moving proximally, to include (ischaemic) pain in the limb.

Sutherlands Pressure bandage -immobilisation: Elastic (not crepe) bandages 10 cm wide x 3.5 - 4.5 m long
Figure 91: Pressure-bandage immobilization: left lower limb; right - upper limb (Copyright Dr David J Williams)

196 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Measurement of central venous pressure
5 annex

In seriously ill patients with shock or renal


failure in whom clinical assessment of
the jugular venous pressure is difficult or
considered inaccurate, a central venous
catheter should be inserted percutaneously.
In those with no haemostatic problems, a
catheter may be inserted into the jugular or
subclavian vein provided adequate facilities
for a sterile procedure and subsequent
nursing are available. However, patients
who have been bitten by vipers may have
obvious haemostatic problems or may
develop coagulopathy. In these cases, the [a]
antecubital approach is by far the safest
as haemostasis can be achieved by local
pressure. A long catheter (at least 50-70
cm for an adult) is required (Fig 92a). The
catheter is connected via a three-way tap
and pressure tubing to a manometer. The
whole system is filled with sterile isotonic
saline. Before readings can be taken, the
zero on the manometer must be aligned as
accurately as possible with the horizontal
plane of the left atrium. A simple spiritlevel
(eg a 20 ml glass ampoule with bubble,
taped to a ruler) can be used to locate
the manometer zero at the same height
as an appropriate chest-wall landmark,
such as the midaxillary line, in the supine
[b]
patient (Fig 92b) or the sternal angle in a
patient sitting up at 45. There should be Figures 92: Central venous pressure monitoring in patients with shock: (a) 70 cm
long catheter inserted into an antecubital vein (Seldinger percutaneous guidewire
strict attention to asepsis. Infection and technique) and advanced until its tip was in the superior vena cava. An extension
thrombosis are potential complications; tube connects with a simple saline manometer whose zero point is at the level of
the mid-axillary line; (b) Adjusting the zero point of the central venous pressure
especially if the catheter remains in place manometer to the midaxillary line, using a home-made ruler-plus-glass-ampoule
for a long time. spirit level (Copyright DA Warrell)

Annexes 197
6 annex
Measurement of intracompartmental pressure
Measurement of intracompartmental way tap, the system is connected, through
pressure in tensely swollen snake- a side arm to a blood pressure transducer
bitten limbs or saline or mercury manometer (Fig 93a).
To confirm a clinical suspicion of The system is filled with sterile isotonic
intracompartmental syndrome the saline. If a syringe-type infusion pump
pressure inside the particular compartment and arterial blood pressure transducer
should be measured directly (Matsen with monitor is used, the pressure can
1980; Mars and Hadley 1998; Mars et al., be measured continuously at a very slow
1991). rate of infusion (eg 0.7 ml/day). If a saline
or mercury manometer is used, a much
The threshold pressure required to higher rate of infusion is required to
initiate the flow of liquid into the fascial initiate flow into the compartment. These
compartment is a measure of the tissue systems are not suitable for continuous
pressure inside that compartment. With intracompartmental pressure monitoring.
full sterile precautions and after infiltrating Alternatively, the simple but expensive
local anaesthetic, a 21 or 22 gauge Stryker pressure monitor can be used
cannula, approximately 3-4 cm long, is (Fig 93b).
inserted into the compartment through
or around an introducing 20 or 21 gauge Whatever system is employed, the zero
needle. The cannula is connected through point in the pressure measuring device
narrow pressure tubing to a syringe or low must be aligned to the level at which the
speed infusion pump. Through a three- cannula enters the fascial compartment.

[a] [b]
Figures 93: Measurement of intracompartmental pressure to exclude compartment syndrome in a snakebite victim: (a) infusion pump, saline
manometer system in use for measuring the tissue pressure inside the anterior tibial compartment; (b) Stryker pressure monitor in use for
measurement of intracompartmental pressure (Copyright DA Warrell)

198 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
List of Contributors
7 annex

Professor Mohammad Abul Faiz VINS Bioproducts Ld


Former Director General of Health Services Hyderabad, India
& Professor of Medicine
Dhaka, Bangladesh Dr A.K. Gadpayle
Consultant Physician
Dr Md. Taufiqui Islam Department of Medicine
Civil Surgeon Dr R.M.L Hospital
Kurigram New Delhi, India
Bangladesh
Dr Anand Zachariah
Mr Nechen Dorji Professor and Head, Department of
Health Assistant Medicine
Trongsa Hospital Medicine Unit 1
Thimphu, Bhutan Christian Medical College,
Vellore, India
Dr Shiv Lal
Senior Advisor (Public Health) Dr Tri Maharani
National Institute of Health and Family Head of Emergency department Lung
Welfare Hospital Dungus
Ministry of Health and Family Welfare Madiun, Indonesia
New Delhi, India
Mrs Ipah Epalia
Dr Mradul Kumar Daga Senior Representative
Professor of Medicine Bio Farma
Maulana Azad Medical College Bandung, Indonesia
New Delhi, India
Dr Fathimath Zuwaida
Mr Ajit Nair Medical Officer
Director Indira Gandhi Memorial Hospital
VINS Bioproducts Ld Male, Maldives
Hyderabad, India
Dr Aung Zaw
Mr D.G. Kulkarni Deputy General Manager / Programme
Vice President Technical Manager

Annexes 199
Myanmar pharmaceutical Industry Professor Christeine Ariaranee
Ministry of Industry Gnanathasan
Yangon, Myanmar Professor in Medicine,
Faculty of Medicine,
Professor Khin Thida Thwin University of Colombo
Programme Manager, Colombo, Sri Lanka
WHO Snakebite Control Project, Myanmar
Professor and Head of Department Dr H.M.K. Wickramanayake
Department of Renal Medicine, Director
University of Medicine (I) Primary Care Services, Ministry of
500 Beded Yangon Speciality Hospital Healthcare & Nutrition
Yangon, Myanmar Colombo, Sri Lanka

Dr Khin Saw Than Dr Suchai Suteparuk


Associate Professor Expert Toxinologist
Yangon General Hospital WHO Collaborating Centre for Venomous
Yangon, Myanmar Snake Toxicology and Research
Queen Saovabha Memorial Institute
Dr Maung Maung Thai Red Cross Society
General Manager Bangkok, Thailand
Myanmar Pharmaceutical Factory
Yangon, Myanmar Professor Dr Sumana Khomvilai
Deputy Technical Director and Deputy
Mr Naing Linn Director in Administrative Affairs
Manager WHO Collaborating Centre for Venomous
Myanmar PharmaceuticalFactory Snake Toxicology and Research
Yangon, Myanmar Queen Saovabha Memorial Institute
Thai Red Cross Society
Dr Sanjib Kumar Sharma Bangkok, Thailand
Professor, Department of Internal Medicine
B P Koirala Institute of Health Sciences Prof Dr Visith Sitprija
Dharan, Nepal Director
Queen Saovabha Memorial Institute
Dr Chhabi Lal Thapa The Thai Red Cross Society,
Medical Superintendent Bangkok, Thailand
Sindhuli Hospital
Nepal Professor David Warrell
Emeritus Professor of Tropical Medicine
Dr Bhola Ram Shrestha Nuffield Department of Clinical Medicine
Senior Consultant Medical Generalist University of Oxford
Bharatpur Hospital, Nepal John Radcliffe Hospital
Oxford,United Kingdom
Professor H Janaka de Silva
Senior Professor of Medicine Fan Hui Wen
Faculty of Medicine, University of Kelaniya Instituto Butantan
Colombo, Sri Lanka Sau Paulo, Brazil

200 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES
Dr Simon D. Jensen Dr Aparna Singh Shah
Consultant Emergency Physician Regional Adviser
Nambour General Hospital Health Laboratory Services
Queensland, Australia and Blood Safety
WHO SEARO
Dr Rajesh Bhatia New Delhi, India
Former Director Communicable Diseases
WHO SEARO Dwi Adi Maryandi
New Delhi, India Junior Public Health Professional
Health Laboratory Services
Dr Lin Aung and Blood Safety
Coordinator Emerging Diseases WHO SEARO
WHO SEARO, New Delhi, India New Delhi, India

Annexes 201
VENOMOUS SNAKES OF THE searo REGION,
THEIR VENOMS, AND THE PATHOPHYSIOLOGY...
203
Snakebites are well-known medical emergencies in many parts of the world, especially
in rural areas. Agricultural workers and children are the most affected. The incidence
of snakebite mortality is particularly high in South-East Asia. Rational use of snake
anti-venom can substantially reduce mortality and morbidity due to snakebites.
These guidelines are a revised and updated version of Regional Guidelines for the
Management of snakebites published by the WHO Regional Office in South-East Asia
in 2011. These guidelines aim to promote the rational management of snakebite cases
in various health facilities where trained health functionaries and quality snake anti-
venom are available.

ISBN: 978-92-9022-530-0

World Health House


Indraprastha Estate,
Mahatma Gandhi Marg,
New Delhi-110002, India
Website: www.searo.who.int

204 GUIDELINES FOR THE


MANAGEMENT OF SNAKEBITES