Tetanus in Indian ICU: Is it still a common

problem?

Tetanus is a preventable infectious disease with high mortality.

Tetanus is a disease which affects people all over world. There are
very few cases of tetanus in developed world. In US only 33 cases
were reported in 1999. In developing countries it remains a major
public health problem. There is no systematic collection of data
available from India. In a recent stud y b y Anuradha, 217 cases of
tetanus were reported over three years with mortality rate of 38% 1 .
Such a high number of tetanus assumes much more significance in
light of ver y limited ICU resources in India. In our institution, over a
period of two years and four months (September 2004 – December
2006) 528 patients were admitted in medical ICU out of which 34
(6.43%) were of tetanus. This number of patients put tremendous
pressure on alread y limited resources of ICU.

Treatment of tetanus has undergone little pharmacological change

since early 20th century. Tetanus has traditionally been treated with
heavy sedation and supportive treatment in quite, dark room to
minimize external stimulation. This treatment is still prevalent in
those parts of world where mechanical ventilator y support is not
readily available. These areas comprise of majority of developing
world including a significant portion of India.

A significant reduction in mortality due to tetanus was observed after

introduction of muscle relaxants, mechanical ventilation and
intensive care in routine management of tetanus. Mortality
decreased from 43 to 15% in a stud y b y Trujillo, analyzing 641 cases
of tetanus managed by such intensive care 2 . In a similar stud y by
Udwadia, anal yzing 150 cases of tetanus, reported that intensive
care, proper nutrition, earl y tracheostom y and ventilator support in
severe tetanus were chiefly responsible for an overall reduction in
mortality from 30 to 12% while the mortality in severe tetanus was
reduced from 70 to 23% 3 . Both studies reported cardiac abnormality
due to autonomic d ysfunction as major cause of mortality, instead of
respirator y failure which has been predominant cause of mortality
prior to use of intensive care practices in management of tetanus.

The aspects which should be considered while managing a patient

with tetanus are:
1. Early diagnosis
2. Specific treatment, which includes wound management,
antibiotic therap y, neutralization of unbound toxin, control of
muscle spasms, management of autonomic instability,
3. Prevention of early complications
4. Supportive treatment

Early diagnosis
The diagnosis of tetanus is primaril y clinical with laboratory
investigations being virtually of no use. History of injur y, or presence
of a wound aids in strengthening the diagnosis. Clinical diagnosis
requires high index of suspicion especially in areas with lower
incidence of disease.

Tetanus follows an injur y with a median incubation period of 7

days; 15% of cases occur with in 3 da ys and 10% after 14 days. In
15 to 30% of patients, where the portal of entry is not evident, a
careful search for signs of parentral drug abuse, otitis media,
instrumentation like septic abortion, injections or minor surgical
procedures should be inquired.
The first symptoms of tetanus is due to rigidity of muscles
supplied by cranial nerves, trismus being the most common
presentation, followed by risus sardonicus and neck stiffness.
Patients complain of d ysphagia and stiffness in the jaw, abdomen, or
back. Generalized rigidity of facial muscles causes the characteristic
expression of risus sardonicus. Reflex spasms develop within 1 to 4
days of the first symptoms. Spasm may be precipitated b y minimal
stimuli such as noise, light, or touch and last from seconds to
minutes. In severe tetanus respiration may be compromised because
of generalized spasms. In very severe tetanus autonomic
d ysfunction predominates.

Spatula test is a practical simple bedside test for early diagnosis

of tetanus. A positive test result (reflex spasm of the masseters on
touching the posterior phar yngeal wall) was seen in 359 (94%) of
380 patients with tetanus and in no patient without tetanus. The test
performed on presentation had a high specificity (100%) and
sensitivity (94%) for diagnosing tetanus 4 .

Differential diagnosis of tetanus includes a number of

conditions that can simulate one or more of the clinical findings of
tetanus. Early symptoms of tetanus may be mimicked b y either
strychnine poisoning or a dystonic reaction to phenothiazines.
Phenothiazine reactions can cause trismus, but the associated
tremors, athetoid movements, and torticollis should make one
suspect this drug reaction. Trismus tends to appear late, and
s ymptoms and signs develop much more rapidly in strychnine
poisoning than in tetanus. Most common local condition that results
in trismus is an alveolar abscess. Purulent meningitis can be
excluded by examination of the cerebrospinal fluid. Encephalitis is
occasionall y associated with trismus and muscular spasms, but the
patient’s sensorium is usuall y clouded.

Specific treatment
In cases of tetanus, life-threatening respiratory and cardiovascular
complications can present with troubling rapidity following the initial
diagnosis and admission to the intensive care unit is recommended
for these patients.

No specific drug has been discovered which can counteract the toxin
once it is bound to nervous tissue.

The objectives of management of tetanus are:

(1) To provide supportive care until the tetanospasmin that is fixed
in tissue has been metabolized
(2) To neutralize circulating toxin; and
(3) To remove the source of tetanospasmin.

Tetanus immunoglobulin neutralizes circulating tetanospasmin and

toxin in wound. Even though tetanus immunoglobulin does not
ameliorate the clinical symptoms of tetanus, it significantly reduces
mortality. Although the optimal dose of tetanus immunoglobulin is
unknown; the usual dose of equine preparation is 500-1000 IU/kg
given intravenously or intramuscularl y. The dose of Human tetanus
immunoglobulin is 5000-8000 IU intramuscularl y. It should be given
before wound debridement, because exotoxin may be released
during wound manipulation. Repeated doses of tetanus
immunoglobulin are unnecessary, because the half life of anti toxin
is 28 days 5 . In an attempt to inactivate the toxin bound to nervous
tissue, antitoxin has been administered intrathecally. But further
studies failed to support their use.

Debridement of a wound is important to eradicate spores and

change conditions for germination, thereby preventing further
elaboration and absorption of the neurotoxin. This is most effective
after the injury but unfortunatel y most wounds implicated in tetanus
are so trivial that it is either ignored or treated with home remedies.
Linear wounds with sharp edges that are well vascularised and not
obviously infected are usuall y non-tetanus prone. All other wounds,
that have resulted from blunt trauma, bites and are obviously
contaminated, are considered potentially predisposed. Wound
debridement is of no value after the disease has been established
and that antibiotics are of no value after debridement, still ensuring
that no further toxin is produced at wound level may be preferable.

Antibiotics are of questionable utility but are traditionall y

administered. Penicillin, which is effective against almost all
clostridial infections, has been drug of choice for many decades. But
it is no longer recommended as it antagonizes GABA and potentiate
effects of tetanospasmin. Metronidazole, a bactericidal against
anaerobes, is preferred agent now . A randomized trial by Salim
proved metronidazole to be more effective along with significantl y
lower mortality rates in comparision to penicillin 6 . Metronidazole is
given in a dose of 500 mg intravenousl y 8 hourly for 10 days.

The optimal approach to a tetanic patient with respiratory

compromise lies in early intervention with airway and spasm
control. Intubation of the trachea should be carried out when
maintenance of the airway is in doubt. As the presence of the
endotracheal tube is in itself a strong stimulus for spasms, some
authors recommend that a tracheotom y be performed immediatel y 7 .
Tracheostom y should be carried out with in 24hr of diagnosis in all
patients predicted to develop moderate and severe tetanus.

Ablett has classified tetanus according its se verity 8 :

Grade I Mild: Mild to moderate trismus; general spasticity; no
respirator y embarrassment; no spasms; little or no dysphagia
Grade II Moderate: Moderate trismus; well-marked rigidity; mild to
moderate but short spasms; moderate respiratory embarrassment
with an increased respirator y rate greater than 30, mild d ysphagia
Grade III Severe: Severe trismus; generalized spasticity; reflex
prolonged spasms; respiratory rate greater than 40; apnoeic spells,
severe dysphagia; tachycardia > 120.
Grade IV Very severe: Grade III and violent autonomic disturbances
involving the cardiovascular system. Severe hypertension and
tach ycardia alternating with relative hypotension and bradycardia,
either of which may be persistent

Spasms in tetanus are potentiall y life threatening, for they impair

respirator y function, produce exhaustion and often lead to aspiration
of gastric contents. Control of tetatnic spasms should be carried out
simultaneousl y as measures are being taken for airwa y control.
Tetanospasmin prevents neurotransmitter release at inhibitor y
interneurons, and terap y of tetanus is aimed at restoring normal
inhibition. Benzodiazepines have been traditionall y used for control
of spasms. Diazepam is usuall y the first drug to be used in the initial
phase of the illness. The average dose used as an adjunct to muscle
relaxants is 10-30 mg 6-8 hrl y, and is usuall y the starting dose even
when used solely. However, the large intravenous doses of
diazepam required in tetanus may result in metabolic acidosis
secondar y to prop ylene glycol vehicle. Thus, the water soluble
agent, midazolam, is the preferred agent for producing muscle
relaxation in patients with tetanus.[5] Propofol has been
successfull y used in a dose of 3.5 – 4.5 mg/kg/hr after a loading
dose of 50mg. Propofol has advantages in terms of reduction in
muscle rigidity and rapid recovery, but suspected contribution to
cardiovascular instability during autonomic dysfunction and high
cost has precluded routine use 9 .

Neuromuscular blocking agents are used when sedatives are

inadequate to prevent and control spasms. Vecuronium is drug of
choice because of minimal cardiovascular side effects.
Pancuronium is avoided because of its hypotensive action, while
Rocuronium is much expensive. At racuronium and
Cisatracuronium can be used in severe hepatic and renal disease.
Use of steroids concomitantl y with these neuromascular blockers is
strongly discouraged because of high risk of m yopath y. Intathecal
baclofen therapy has been proved to be efficacious in management
of tetanus in a number of series although largest series is of 14
cases only. Baclofen has relatively narrow therapeutic range and its
administration requires surgical expertise which is not easily
available.

Autonomic dysfunction is diagnosed in most cases b y presence of

spontaneous fluctuations in blood pressure and heart rate, in
absence of an y external stimulus and spasms, in patients on
adequate sedation. Prompt recognition and treatment of autonomic
d ysfunction are important in reducing the mortality. Drugs have been
used with the aim to produce adrenergic blockade or to prevent
release of catecholamines and thereby suppress autonomic
h yperactivity 1 0 .
Labetolol has been frequentl y used to treat adrenergic overactivity
for it produces dual adrenergic blockade, although the β-blocking
effect is more significant. However, concerns about unopossed
release of catecholamines cauing m yocardial damage and cardiac
arrest were raised.

Suppression of catecholemines release has been recognized as

the more effective method of controlling dysautonomia in tetanus.
Morphine acts centrally to reduce sympathetic tone in the heart and
vascular system resulting in brad ycardia and hypotension. It has
excellent sedative properties and minimal effect on cardiovascular
performance. It reduces mean arterial pressure, heart rate and
s ystemic vascular resistance while having minimal effect on the
cardiac output 11 . But tolerance develops rapidl y and it has minimal
effect instability occurring with spasms and stimulation. Clonidine, a
centrall y acting sympathol ytic, has also been used with mixed
resuts.

Magnesium blocks neuromuscular transmission and also controls

d ysautonomia. Magnesium competes with calcium at presynaptic
junction and inhibits release of acetylcholine, resulting in
neuromuscular blockade. Magnesium spares respirator y muscles
making its profile more favourable 1 2 . The fact that magnesium can
control spasms and dysautonomia while patients remain conscious
and co-operative and mobilized is a tremendous advantage. This
enables simplified nursing care, which should contribute significantly
to a better outcome. Parameter which are to be observed are
oliguria <30 ml/hr, absence of deep tendon reflexes and respirator y
rate < 11/min. Magnesium bolus of 5 mg is given over 20 min
followed by dose titration to control muscle spasms and rigidity,
which may be as higher as 4-5 gm/ hr. Magnesium therapy seems to
be better than conventional tetanus therapy in a number of wa ys.
Magnesium controls spasms without other drug supplementation
except in a ver y severe disease and is non sedative 1 3 . It is a
feasible regimen in developing world and is recommended as
firstline therap y in tetanus management.

Finall y, supportive treatment in the form of good critical care and

expert nursing care pla y a vital role in reducing complications and
preventing death. These measures include ensuring patent airwa ys
and tracheostom y care; maintaining adequate tissue oxygenation
and mechanical ventilation if required; expert chest physiotherap y
especiall y in between spasms; fluid, electrolyte and acid-base
balance; prevention, early detection and control of infection and
sepsis; supportive nutrition; detection and treatment of
h yperp yrexia.
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