This study evaluated factors affecting the severity of bite site of the vascular structure.6,7 The major hemorrhagin of this
necrosis and systemic symptoms resulting from envenoma- venom is a glycoprotein termed rhodostoxin. It is reported to be
tion among patients bitten by Malayan pit vipers (Cal- responsible for local necrosis through activation of tissue tumor
loselasma rhodostoma) in Thailand. We studied 145 victims necrosis factor-␣.8 However, the role of hemorrhagic metallopro-
plete blood counts, and VCT. Electrolyte levels and renal func-
tion parameters were evaluated where indicated. Data were col-
lected at admission, 2 and 12 hours later, and daily thereafter.
This information was compiled with the SSS level.13 Statistical
analyses used the 2 test or Student’s t test.
Results
The prospective study collected a total of 145 MPV bite victims
from six provinces (Fig. 3). The victims came from the southern
region, which included Trang (33.79%), Nakhon Si Thammarat
(22.07%), Prachuap Khiri Khan (17.93%), Surat Thani (15.06%),
TABLE I
MODIFIED SSS
Criteria Level
Pulmonary system
No symptom/sign 0
Minimal dyspnea, chest tightness, mild or vague systemic discomfort, or respirations of 20–25 breaths/minute 1
Moderate dyspnea (tachypnea, 26–40 breaths/minute; use of accessory muscle) 2
Cyanosis, air hunger, extreme tachypnea, or respiratory insufficiency/failure 3
Cardiovascular system
No symptom/sign 0
Tachycardia (100–125 beats/minute), palpitations, generalized weakness, benign dysrhythmia, or hypertension 1
necrosis (scores of 2–3) that required surgical debridement. came to the hospital comatose and with severe coagulopathy
There was no need for amputation in either group. The severity (VCT of ⬎30 minutes and hematuria). He had been bitten by a
of tissue necrosis was significantly influenced by the quality and MPV 3 days previously and had been treated by a traditional
timing of treatment rendered (p ⬍ 0.05). However, two victims healer with herbal remedies and local potions. He was moribund
required surgical decompression because of swelling and circu- and had moderately severe tissue necrosis (score of 2) at the bite
latory impairment; bite sites were a finger or toe, locations with- site. The patient was intubated and given 30 mL of antivenin,
out abundant soft tissue space, causing the compartment syn- and his VCT returned to normal after 6 hours. However, he had
drome (scores of 2–3). developed intracranial hemorrhage and never regained con-
Systemic manifestations involved the central nervous, cardio- sciousness. The second fatality was a 72-year-old man. He was
vascular, pulmonary, gastrointestinal, and hematologic sys- admitted to the hospital 1 hour after having been bitten by a
tems. An overall analysis of SSS values revealed 0.80 to 1.00 MPV. On the first day of admission, he had pain at the bite site
involving the central nervous system, 0.40 to 0.90 the pulmo- and was very apprehensive but had no abnormal systemic
nary system, 0.03 to 0.17 the gastrointestinal system, 0.45 to symptoms and no coagulopathy (VCT of 10 minutes). On the
0.83 the cardiovascular system, 1.69 to 1.84 the hematologic morning of his second hospital day, the patient developed bleed-
system, and 1.01 to 1.17 bite site reactions. The highest scores ing from his gums and had a VCT of ⬎30 minutes. There was no
appeared 12 hours after hospitalization (Fig. 7). No patients antivenin available at that time. In the afternoon, the patient
developed septicemia but two subjects had the disseminated went into shock, lost consciousness, and developed hematuria,
intravascular coagulation syndrome and died as a result of hematemesis, and thrombocytopenia. He remained deeply un-
intracranial hemorrhage. The first patient, a 60-year-old man, conscious and required vasopressors. During the afternoon of
were still ⬎30 minutes 12 hours later. The patients were given
an additional three to five vials, which rapidly normalized the
VCT in all cases.
Discussion
Our prospective and retrospective studies revealed some de-
gree of bite site tissue injury for almost all victims. None of the
patients required amputations, which indicates that even severe
tissue necrosis of level 3 (by SSS) usually resolves in 2 to 3
weeks. Resolution can occasionally take 2 to 3 months, and for
some victims the limb may remain permanently swollen because
of vascular and/or lymphatic damage.16
Species-specific antivenin neutralizes circulating venom and
reverses systemic symptoms. Local bite site necrosis, however,
responds poorly (if at all) to antivenin administration.17 This is
Fig. 3. Map of Thailand, showing the 10 provincial locations. partly attributable to the fact that tissue injury occurs rapidly
and may be well established by the time the patient arrives at a
hospital. Severe tissue necrosis was found in 2 (1.4%) of 145
cases in our prospective study and required surgical debride-
ment. Both subjects appeared with a delay of 4 to 5 hours. They
did receive 15 vials (150 mL) of antivenin after arrival at the
hospital, but there was still progression of local necrosis. An
additional four patients with tissue necrosis, who did not receive
antivenin, had first been treated by traditional healers. The
patients required surgical wound debridement. There were no
cases of severe tissue necrosis in the retrospectively studied
group. This finding is surprising and needs an explanation.
Prachuap Khiri Khan provincial hospital, the site of the retro-
Fig. 4. Distribution of snakebite victims among the 10 provincial hospitals, in spective study, is located in a relatively prosperous region with
the prospective study. good road infrastructure, a higher level of education, and good
access to medical centers. It is likely that patients in this region
reported more rapidly for medical care, rather than visiting
the second day, after it was decided that his case was hopeless, traditional healers. This may be one explanation for less tissue
the patient was taken home to die. injury and better outcomes. Only 61 (25%) patients in this group
Among victims with coagulopathy, 52.48% and 35.44% in the received antivenin.
prospective and retrospective groups, respectively, had severe Traditionally, patients bitten by venomous snakes in Thai-
abnormal coagulopathy (VCT of ⬎30 minutes). The mean VCT land applied tourniquets to the bite site in an attempt to delay
was ⬎21 minutes on the first day and gradually decreased to absorption of venom into the circulation. This is no longer rec-
normal by day 5 after treatment with antivenin. Most patients ommended, because it was found to be dangerous.12 A previous
who had VCTs of ⬎30 minutes and who received antivenin study of patients bitten by MPVs in Thailand showed that tour-
(three to five vials) showed improvement in the VCT 6 to 12 niquets applied by patients failed to inhibit the spread of venom
hours later, with return to normal 2 days later. In the prospec- into the general circulation.12,18,19 Another study reported gan-
tive study, 25 of 145 victims did receive antivenin but their VCTs grene after tourniquet application.14 Data concerning bite vic-
TABLE II
VARIOUS FACTORS AFFECTING TISSUE NECROSIS
was five vials, which is in accordance with the manufacturer’s the retrospective study. There were no amputations among our
recommendations. We identified only two patients who received patients, compared with 2.2% reported by Warrell et al.14 However,
antivenin and developed mild to moderate serum sickness 27 (18.6%) of 145 subjects had permanently swollen limbs be-
(1.8%). There were no cases of anaphylaxis among a total of 111 cause of vascular and/or lymphatic damage. The improved out-
subjects who received purified, pepsin-digested antivenin of comes in our two groups are most likely attributable to better
equine origin, demonstrating again the relative safety of puri- public education and road infrastructure and expanded health
fied, pepsin-digested, snake antivenin. care facilities in rural areas. There was also considerable improve-
The severity of tissue necrosis in our two groups was decreased ment in the quality of the antivenin used. Warrell et al.14 demon-
compared with previous studies reported more than a decade ago. strated that at least one batch of C. rhodostoma antivenin, manu-
Those studies found significant necrosis requiring surgical de- factured in Thailand before 1986, was of poor efficacy. Traditional
bridement and even amputation in 10.9% of cases (5 of 46 vic- healers, who may cause delays in treatment and increase the risk
tims).14 We identified only 8 cases (5.5%) among 145 patients in of wound infection, appear to play a lesser role in caring for snake-
the prospective group and one case (1.25%) among 80 patients in bite victims today.
The MPV (C. rhodostoma) is prevalent through most of south- 8. Moura-da-Silva AM, Laing GD, Paine MJI, et al: Processing of pro-tumor necrosis
factor-␣ by venom metalloproteinases: a hypothesis explaining local tissue dam-
east Asia. It is a dangerous snake, because its coloration makes
age following snake bite. Eur J Immunol 1996; 26: 2000 –5.
it difficult to spot in its natural environment. It often bites 9. Navdaev A, Clemetson JM, Polgar J, et al: Aggretin, a heterodimeric C-type lectin
without warning and is an occupational hazard for rubber plan- from Calloselasma rhodostoma (Malayan pit viper), stimulates platelets by bind-
tation workers and the military operating in the field. This snake ing to ␣21 integrin and glycoprotein Ib, activating Syk and phospholipase C␥2,
is both tissue toxic and hematotoxic, and deaths resulting from but does not involve the glycoprotein VI/Fc receptor ␥ chain collagen receptor.
coagulopathy and disseminated intravascular consumption J Biol Chem 2001; 276: 20882–9.
have been reported. Purified, pepsin-digested, species-specific 10. Sanders WE, Read MS, Reddick RL, Garrris JB, Brinkhous KM: Thrombotic
thrombocytopenia with von Willebrand factor deficiency induced by botrocetin:
antivenin is manufactured in Thailand. It is active against co- an animal model. Lab Invest 1988; 59: 443–52.
agulopathy and systemic symptoms but appears to do little to 11. Wang R, Kini RM, Chung MCM: Rhodocetin, a novel platelet aggregation inhibitor
counteract local tissue necrosis, which is usually well estab- from the venom of Calloselasma rhodostoma (Malayan pit viper): synergistic and
lished by the time victims present for treatment. noncovalent interaction between its subunits. Biochemistry 1999; 38: 7584 –93.
Dr. Perlin presents the John D. Chase Award for Physician Executive Excellence
to Dr. Michael J. Kussman-VA (BG, MC, USA (Ret.))