A Brief Guide to Snake Envenomations in Malaysia and Antivenom Therapy

Prof Tan Nget Hong (PhD, University of Chicago)a, Dr Tan Choo Hock (MBBS, University of Malaya) b, Leong Poh Kuan (BBMedSc, University Malaya)b Venom and Toxin Research Group Department of Molecular Medicine, Faculty of Medicine, University of Malaya; bDepartment of Pharmacology, Faculty of Medicine, University of Malaya

1. Introduction
Venomous snakebite leading to envenomation syndrome is a classifiable disease indexed by the
WHO International Classification of Disease (ICD-10), and appropriately categorized as a Neglected Tropical Disease (WHO, 2009) that constitues a serious public health problem in the tropics (Chippaux, 1998; Kasturiratne et al., 2008). The severity of the issue unfortunately has been neglected systemically (Gutirrez et al., 2006; Alirol et al., 2010), partly due to under-reporting and inconsistent epidemiological studies that includes Malaysia. Earlier reports (year 1958 to 1980) estimated as

many as 55000 cases of snakebites admitted to the hospitals in Malaysia, with majority of the bite cases came from northern states of Peninsular Malaya where agricultural activities were common. While the mortality rate of snakebite in Malaysia is only 0.3 per 100000 population (this figure appears though to be underestimated), complications like crippling deformity caused by the necrotizing effect of some venoms, and psychological trauma, are among features of prolonged morbidity that add to the human suffering, and significantly jeopardize the victims quality of life. A survey at General Hospital Kuala Lumpur (1999-2003) alone indicated that snakebite affected not only rural places but also suburban areas neighboring cities like Kuala Lumpur. It reflected the fact that rapid and intense urbanization increased the chances of snake encounter as more humans were encroaching into their habitats. In view of the global experience and the development trend in our country, precautions and clinical guidelines need to be addressed despite the fact that a more systematic and updated epidemiological study is yet unavailable.

2. Venomous Snakes of Malaysia

In Malaysia and the coastal waters of the region, there are at least 18 different species of venomous front-fanged land snakes and more than 22 different species of sea snakes. These venomous snakes belong to the following 2 families (3 subfamilies):

Table 1: Medically important venomous snakes in Malaysia

Family Viperidae Subfamily Crotalinae Genus - Calloselasma Common names - Malayan pit viper (ular kapak bodoh) Cryptelytrops - Asian lance-headed pit Tropidolaemus viper(ular kapak) Parias Naja - Cobra (ular senduk) Bungarus - Krait (ular katang) Ophiophagus - King cobra (ular tedung selar) - Coral* snake (ular karang*) Calliophis/ Maticora - Sea snake (ular laut) Main habitat - Land - Tree

Elapidae

Elapinae

- Land *the name coral/karang does not indicate its habitat - Seas and coastal region

Hydrophiinae - Laticauda - Enhydrina - Kerilia - Hydrophis - Thalassophis - Pelamis - Kolpophis - Aipysurus

Only a few of the Malaysian venomous snakes can be regarded as of medical importance. Epidemiological studies showed that in Malaysia, bites were mainly due to four species of land snakes: Calloselasma rhodostoma (Malayan pit viper), Naja (Asian common cobra, there are two species: Naja sumatrana (equatorial spitting cobra) and Naja kaouthia (monocellate cobra), Cryptelytrops purpureomaculatus (mangrove pit viper) and Tropidolaemus wagleri (Waglers pit viper). Other venomous snakes indigenous to Malaysia that are potentially dangerous to human include Bungarus candidus (Malayan krait), Bungarus fasciatus (banded krait), Bungarus flaviceps (red-headed krait), Ophiophagus hannah (king cobra), Parias sumatranus (Sumatran pit viper) and the sea snakes. The species Cryptelytrops purpureomaculatus, Parais sumatranus and Tropidolaemus wagleri (Waglers pit viper) belong to the Trimeresurus complex (Asian lance-headed pit vipers). There are more than 7 different species of Asian lance-headed pit vipers in Malaysia. Refer to Figure 1 (a-f: Elapidae; g-j: Viperidae; typical features for quick

identification were given in parentheses but remember variations do exist) for pictures of some medically important snakes in Malaysia, or contact the authors.

Figure 1 a: Naja sumatrana (white bands on neck); b: Naja kauthia (oval mark on hood); Bungarus flaviceps (red-headed, red-tailed, body and belly black); d: Bungarus candidus (alternate dark bluish and yellowish white bands); e: Bungarus faciatus (alternate black and yellow bands); f: Enhydrina eschistosa (dark grey back, whitish sides);

Figure 1. g: Calloselasma rhodostoma (large scale over the head, stout, light brownish body with dark brown saddles); h: Cryptelyptrops purpureomaculatus (olive to dark purplish brown; a white line may present along each side); i: Cryptelyptrops albolabris (green above, pale green or white below the eyes including lips); j: Tropidolaemus wagleri (green body with darkbordered scales; multiple green-yellow crossbars on the back). Table 2 shows statistics of snakebites in West Malaysia, 1965-1971, based on data from 28 hospitals. Some recent reports, however, suggested that cobra bites are more prevalent that bites by other snakes (Tan et al., 1990; Jamaiah et al., 2004; 2006).

Table 2: Snakebites in West Malaysia

Snake Species Malayan pit viper (Calloselasma rhodostoma) Sea snake Asian common cobra (Naja) Asian lance-headed viper (Trimeresurus) King cobra (Ophiophagus hannah) Krait (Bungarus) Unidentified Non-venomous Total Cases 1136 158 112 25 6 1 3765 184 Fatal Cases 4 5 3 0 0 0 6 0

Report from monthly statistics of 28 hospitals throughout Malaysia, 1965-1971.

3. Biochemical composition of Snake Venoms

Snake venom contains mainly proteins (70-90%) and small amounts of metals, amino acids, peptides, nucleotides, carbohydrates, lipids and biogenic amines. The protein components include enzymes and non-enzymatic proteins/polypeptides and are usually the main toxic compounds. The main toxic principles in the venoms of elapid snakes (cobra, krait and sea snakes) include polypeptide neurotoxins, polypeptide cardiotoxins and phospholipases A that may exhibit presynaptic neurotoxicity or myotoxicity. The main toxic principles of crotalid (pit viper) snake venoms are thrombin-like enzymes, hemorrhagic proteases and platelet-aggregation inducers.

4. Elapid (cobras, kraits and sea snakes) Envenoming

Elapid venoms generally produce neurotoxicity and cardiotoxicity. The earliest symptom of systemic elapid envenoming is a feeling of drowsiness or intoxication, which starts from 15 min to 5 hr after cobra bites. Neurotoxicity manifested as progressive descending flaccid paralysis often begin with bilateral ptosis (difficulty in opening the eyes:
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eyelids may remain completely closed though the patient usually remains conscious until respiratory failure is advanced where hypoxia compromises consciousness), ophthalmoplegia, facial muscle paralysis (with difficulty in opening the mouth, moving the lips) and bulbar palsy (with aphonia, dysphagia, difficulty in protruding the tongue beyond incisors) within 1 to 4 hrs. Broken-neck sign is a telltale sign that should be elicited as part of routine clinical examination, especially in pediatric, delirious or semi-conscious patients. Fixed, dilated pupils, limb weakness, loss of tone and deep tendon reflexes are other important signs. However, once the paralysis involves the diaphragm and intercostals muscles, respiratory failure sets in even as fast as 30 minutes within the bite. Mechanical ventilation hence should be on standby in any case suspected of venomous snakebite. Cardiotoxicity is caused by polypeptide cardiotoxin that affects both excitable and nonexcitable cells, causing irreversible depolarization of the cell membrane and consequently impairing the structure and function of various cells, thus contributing to muscle paralysis postsynaptically; and cardiac complications e.g. arrhythmias leading to circulatory failure and systolic arrest. Electrocardiogram (ECG) monitoring and perhaps cardiac enzymes test are therefore valuable in monitoring the victims clinical progress. Cobra (Naja sp.) venoms cause extensive local necrosis of the bitten limb, while krait and sea snake bites do not usually cause local envenoming and can be virtually painless hence the possibility of late discovery and delayed treatment. Although it may not be fatal, local tissue destruction should receive early attention and surgical intervention if indicated, in order to salvage the limb function as much as possible. In addition, the equatorial spitting cobra is also potentially responsible for cobra-spit ophthalmia (with corneal ulceration and scarring, secondary endophthalmitis) from its venom spat onto victims eyes. Sea snake venoms contain both polypeptide neurotoxin (homologous to elapid neurotoxin) and myotoxin, which is usually a basic phospholipase A2. The venoms cause respiratory failure (neurotoxic effect) and myonecrosis (myotoxic effect), leading to rhabdomyolysis, myoglobinuria and acute kidney injury. Generalized muscle pain/tenderness and stiffness, trimus; and dark-brown urine are suggestive clinical features. Urine output and renal function in these patients deserve close monitoring in anticipation of renal failure.

Figure 2 a: ptosis, an early sign of neurotoxic envenoming; b: broken-neck sign in a child envenomed by cobra in Malaysia (copyright the late Dr HA Reid); c: tissue necrosis complicating a cobra bite.

5. Pit Viper Envenoming

The venom of pit vipers invariably causes edema, pain, blistering, hemorrhage and necrosis at the bite sites, sometimes extending to the whole limb. Tender regional lymphadenopathy is not uncommon as the venom is absorbed and distributed. Coagulopathy is the hallmark of systemic envenoming by pit vipers, leading to spontaneous systemic hemorrhage. In Malayan pit viper bite, the clotting defect is primarily due to thrombocytopenia, aggravated by defibrinogenation syndrome. The commonest and earliest evidence of spontaneous systemic hemorrhage is gingival bleeding. Persistent bleeding from the bite wound, blood-stained tears, petechiae, purpura, ecchymoses, hemoptysis, hematemesis, epistaxis, and bleeding from other body orifices are suggestive of hemostatic disturbances. Severe complications e.g. intra- or retroperitoneal and intracranial hemorrhage, cardiac ischemia and hypovolemic shock are all fatal sequelae but may develop slowy, hence the rationale for the victims coagulation profiles to be monitored closely from the beginning even if antivenom has been given and patients appear generally well. Where possible, blood product transfusion should be on standby in all cases. b Figure 3. Left: Ecchymosis; Right: edema (usually followed by extensive tissue sloughing and necrosis).

6. Death Times
Generally speaking, deaths are most rapid following elapid bites and most protracted following pit viper bites: Snake species King cobra (Ophiophagus hannah) Cobra (Naja) Malayan pit viper (Calloselasma rhodostoma) Mangrove pit viper (Cryptelytrops purpureomaculatus Average Death time (hr) -8.4 64.6 -Death time (hr) Range few min- 6 - 60 5-240 12

The estimation of death times does not imply the allowance for delaying medical treatment, but rather highlight the urgency to initiate indicated treatment as soon as possible, and to thoroughly monitor the clinical progress of the patients.

7. First-Aid Measure in Snake Envenoming

1. Do not panic! Keep calm, reassure the individual as complete recovery is the rule. 2. Lie the patient down to ensure minimum activity. Keep the bitten part at rest, immobilize the bitten limb with a splint or a sling musculature contraction may increase the absorption and dissemination of venom through bloodstream and lymphatics. 3. Consider pressure immobilization with compression bandage (using a broad, elastic, stretchable crepe bandage) bound as tightly as for a sprained ankle, without compromising the distal pulses. Only recommended for non-locally necrotizing neurotoxic snakebite (king cobra, kraits, coral snakes and maybe sea snakes), otherwise might cause more severe local tissue destruction and increased intracompartmental pressure. 4. Avoid any interference with the bite wound to prevent hastening venom absorption, worsening local bleeding or introducing infection. Washing or wiping the wound is controversial (in addition, traces of snake oral secretion on the wound may be of value for diagnostics in future). Do not attempt to cut the wound and suck out the venom. 5. Arterial tourniquets (and any tight ligature applied around the bitten limb) are not recommended as this can lead to limb ischemia and gangrene; and worse still, when
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released there may be a dramatic increase of the venom dissemination systemically via hyperemic response. 6. All patients with snake bites must be as soon as possible brought to the hospital for treatment with absolute minimum movement of the body especially the bitten limb. Where vehicles are not available, the victim should be carried using a stretcher. 7. Do not attempt to catch or kill the biting snake. However, if the snake has been killed, bring it to the hospital for identification but never allow handling of the snake barehanded as even a severed head can bite with reflex!

8. Diagnosis and Early Assessment of Snakebite Envenomation:

Two major questions when a snakebite victim presents at a healthcare centre are: the identity of the snake inflicting the bite (diagnosis), and the severity of envenoming (early assessment): a. Diagnosis of the biting species: This can be ascertained by i) Identification of the snake if the patient brings the snake to the hospital. ii) Immunodiagnosis: this is costly and can be performed only in a well-equipped laboratory. Presently not available in Malaysian hospitals. The facilities are available at the Venom and Toxin Research Group at Faculty of Medicine, University of Malaya. iii) Clinical observation and inquiring circumstances of bite: Systemic pit viper envenoming (bites by Malayan pit viper (Calloselasma rhodostoma) and the Asian lance-headed pit vipers (Trimeresurus complex) is characterized by non-clotting blood and other hemorrhagic syndrome accompanied by rapid local swelling after the bite. Systemic elapid envenoming (due to cobras and kraits) is characterized by neurotoxic effects including ptosis, bulbar palsy, respiratory paresis and sometime cardiac effects. Systemic sea snake envenoming is characterized by myotoxic effects such as myalgia, paresis, myoglobinuria, hyperkalaemia. Note: NOT all snakes are venomous for confirmed non-venomous bite, manage as puncture wound. b. Early assessment of the severity of snakebite envenoming can generally be made by observing the extent of local envenoming effects and initial laboratory investigations.

In dry bite cases, venom was not injected although bite was inflicted by a venomous species. Local signs and laboratory investigations usually are unremarkable. As with a puncture wound, inflammation and potential infection should be managed accordingly. In mildly envenomed cases, there are minimal local signs, with swelling in the immediate vicinity of the wound, no oozing blood from bite site, and no significant systemic manifestations. Laboratory investigations reveal no abnormalities. In severe cases, there is swelling, usually massive and rapidly extending, accompanied by greater pain. Early tender lymphadenopathy indicates fast venom systemic spread. Early systemic features include nausea, vomiting, diarrhea, drowsiness, heavy eyelids, bleeding from gum or venepuncture and bite site, myalgia, passing brown urine, oliguria and abnormal laboratory results (e.g. prolonged clotting time, or 20 min whole blood clotting). In these patients, close monitoring is warranted and antivenom is usually indicated.

9. Management Principles in Snake Envenomation

9.1 General management of snakebite: General management of snakebite envenoming includes first-aid and the following measures: Adequate reassurance; Immobilization particularly the bitten limb. Venous access precaution needs to be exercised in patients with coagulopathy. All bitten patients, even without local or systemic features, should be admitted to hospital for observation of at least 24 hours. 9.2 Antivenom Therapy Antivenom is the only specific treatment for snake envenomation that is of proven value. Early (anaphylactic), pyrogenic and late (serum sickness) reactions can occur following antivenom treatment. Incidence of early reactions following antivenom administration ranges from 3 to 5%. About 40% of these reactions involve severe systemic anaphylaxis (bronchospasm, hypotension or angioneurotic edema), though few fatal cases have been reported. Most authorities have recommended that antivenom should be diluted in isotonic fluid and given by slow intravenous infusion. Prophylactic regimen e.g. adrenaline, antihistamines and corticosteroids has been practiced in many places empirically especially
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for high risk patients. In asthmatic patients, prophylactic use of an inhalational adrenergic 2 agonist e.g. salbutamol has the rationale to prevent bronchospasm. Certainly, resuscitation facility should be made available prior to the use of antivenom.

Antivenoms Suppliers 9.2.1. Thailand antivenoms The main antivenoms producer in Thailand is Queen Saovabha Memorial Institute (QSMI), Bangkok, Thailand. (Tel: 02-2520162, email info@saovabha.com, 1871, Rama IV Road, Bangkok 10330). Due to the geographical proximity of Thailand and Malaysia, many venomous snakes in Thailand are similar or closely related to the venomous snakes in Malaysia, and hence antivenoms produced by QSMI could effectively neutralize venoms from many species of Malaysia venomous snakes. By adopting an evidence-based approach, the efficacy of Thai antivenoms in neutralizing local (Malaysian) snake venoms has been researched in the laboratory (of University of Malaya) for their potential therapeutic use in Malaysia (see below and Table 3 for types of antivenoms and their efficacies). QSMI Monovalent antivenoms: Monovalent Thai cobra antivenom: effective against the two species of cobra in Malaysia (Naja sumatrana and Naja kaouthia), as well as king cobra (Ophiophagus hannah); Monovalent king cobra antivenom: effective against king cobra (Ophiophagus hannah), efficacy against Malaysian cobra venoms has not been examined; Monovalent banded krait antivenom: effective against Malaysian banded krait (Bungarus fasciatus) but not other kraits; Monovalent Malayan pit viper antivenom: effective against Malayan pit viper (Calloselasma rhodostoma) but not against Asian lance-headed viper (Trimeresurus complex) Monovalent green pit viper antivenom: effective against Asian lance-headed viper (Trimeresurus complex) in general but not against Malayan pit viper Monovalent Russells viper antivenom: there is no Russells viper (Daboia russelli) in Malaysia

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QSMI polyvalent antivenoms Recently, QSMI produced two new polyvalent antivenoms: Neuro polyvalent antivenom for treatment of elapid (cobra/krait) bites, and Hemato polyvalent antivenom for treatment of viper/pit viper bites Neuro Polyvalent Snake Antivenom This polyvalent antivenom is raised against venoms of Thai cobra (Naja kaouthia) king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus) and Malayan krait (Bungarus candidus). Preclinical tests in our laboratory indicated that the polyvalent antivenom could effectively neutralize all cobras and kraits of Malaysia origin, and is more effective against cobra venoms compare to the monovalent Thai cobra antivenom produced by the same institute. (see Table 3 below) Table 3: Neutralizaiton capactigy of venoms from Malaysia venomous snakes by the Neuro polyvalent snake antivenom Venomous snake Neutralization capacity Neutralization capacity of Neuro polyvalent of Monovalent Thai antivenom cobra antivenom 1.84 mg/mL 0.92 mg/mL 0.55 mg/mL 8.19 mg/mL 1.38 mg/mL 0.73 mg/mL 1.47 mg/mL 0.55 mg/mL 2.46 mg/mL Not effective Not effective Not effective

Equatorial spitting cobra (Naja sumatrana) Monocellate cobra (Naja kaouthia) King cobra (Ophiophagus hannah) Banded krait (Bungarus fasciatus) Malayan krait (Bungarus candidus) Red headed krait (Bungarus flaviceps)

All the venoms tested are from snakes captured in Malaysia. Neutralization capacity is defined as the amount of venom neutralized by 1 mL of reconstituted antivenom. The antivenom was reconstituted according to manufacturers recommendation: 10 mL of sterile water was added to each vial of antivenom.

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Hemato Polyvalent Snake Antivenom: This polyvalent antivenom is raised against venoms of Malayan pit viper (Calloselasma rhodostoma), White-lipped pit viper (Cryptelytrops albolabris) and Russells viper (Daboia russelli). Preclinical tests in our laboratory showed that the Hemato polyvalent snake antivenom could effectively neutralize venoms of: (a) Malayan pit viper (Calloselasma rhodostoma), neutralization capacity of 7.2 mg/mL. This is more potent that the monovalent Malayan pit viper antivenom produced by the same institute (neutralization capacity 3.2 mg/mL) (b) Mangrove pit viper (Cryptelytrops purpureomaculatus), neutralization capacity of 4.2 mg/mL; (c) White-lipped pit viper (Cryptelytrops albolabris), neutralization capacity of 3.64 mg/mL. It is likely that the Hemato polyvalent antivenom can neutralize venoms of other species of pit vipers belonging to the Trimeresurus complex (Asian lance-headed vipers), as our early work demonstrated extensive cross-neutralization of antivenom against species of Trimeresurus complex (Tan et al 1994).

9.2.2 Australian CSL antivenom against sea snake The Commonwealth Serum Laboratories from Parkville, Victoria, Australia produced antivenom against sea snake. The sea snake antivenom is effective against sea snake envenomation in Malaysia. Antivenoms raised against cobra or krait venoms may be able to neutralize sea snake venom, as they possess common (similar) venom toxins. The efficacy of cobra or krait antivenoms against sea snake envenomation, however, has not been investigated.

9.2.3 Indonesia polyvalent antivenom serum The Perum Bio Farma (Pasteur Institute) of Indonesia produced a polyvalent antivenom serum. The antivenom (in liquid form) was raised against venoms from three venomous snakes: Malayan pit viper (Calloselasma rhodostoma), Banded krait (Bungarus fasciatus) and Javan spitting cobra (Naja sputatrix). The efficacy of this polyvalent antivenom against envenomations by Malaysian venomous has not been investigated. However, it is possible that this antivenom could neutralize venoms of Malayan pit viper, cobra and Banded krait from Malaysia. However, the antivenom is likely to be ineffective against venom of Malayan krait (Bungarus candidus) and Asian lance-headed viper (Trimeresurus complex). The
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contact address of Perum Bio Farma is Jl Pasteur 28, PO Box 1136, Bandung 40161. (Tel +6222-83755).

9.2.4 India Polyvalent Antivenoms There are several antivenoms manufactuers in India, most of them produced polyvalent antivenom raised agains the Big Four of India venomous snakes: Indian cobra ( Naja naja), Indian krait (Bungarus caeruleus), Russells viper (Daboia russelli) and saw-scaled viper (Echis carinatus). Followings are results of the preclinical assessment of the efficacy of Indian polyvalent antivenom (against Malaysian snake venoms) produced by two different manufacturers: Vins Bioproducts Ltd (Hyderabad, India) and Bharat Serums and Vaccines Limited (Mumbai, India). The polyvalent antivenom produced by Vins is termed Snake Venom Antiserum I.P. whereas the antivenom produced by Bharat is termed Anti Snake Venom Serum, or ASVS. Vins Snake Venom Antiserum I.P. Vins polyvalent antivenom is weakly to moderately effective against venoms of Malaysia cobras (neutralization capacity 0.22 mg/mL and 1.18 mg/mL, respectively, against Naja kaouthia and Naja sumatrana venom), weakly effective against king cobra (O. hannah, 0.22 mg/mL) and Malayan krait (B. candidus 0.22 mg/mL). It is not effective against another common krait in Malaysia: Banded krait (B. fasciatus). It is not effective against Malayan pit viper (Calloselasma rhodostoma) and Asian lance-headed viper (Trimeresurus complex) Bharat ASVS The Bharats ASVS is only weakly effective against venom of the Equatorial spitting cobra ( N. sumatrana, neutralization potency 0.31 mg/mL) and Malayan krait (B. candidus, neutralization potency 0.14 mg/mL). It is not effective against other Malaysian elapid venoms or pit viper venoms. Note: the fact that both Vins and Bharat polyvalent antivenoms were not effective against Malaysian pit viper venoms is not surprising as the Indian polyvalent antivenoms were raised against venoms from Russells viper and saw-scaled viper, both from the subfamily Viperidae (true viper or Old World viper), whereas the Malaysian pit vipers (Malayan pit viper and Asia lance-headed vipers) belong to a different (evolutionary distant) subfamily, Crotalinae (pit viper). The toxinology of venoms from Viperidae snakes is significantly different from that of venoms from Crotalinae snakes.

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RECOMMENDATIONS RE USAGE OF ANTIVENOMS IN TREATMENT OF SNAKE BITES IN MALAYSIA

In Malaysia, particularly in the rural areas, species diagnosis is usually not possible. Hence there is a need to have a polyvalent antivenom that can be used to for treatment of all snake bites with systemic envenoming. Unfortunately, to date there is no such cure all antivenom available. The Indian polyvalent antivenom will not be effective against Malaysian pit viper bites. It may be moderately effective in neutralization of cobra venom but unlikely to be of use in krait bites. The efficacy of Indonesia polyvalent antivenom against Malaysian snake venoms has not been investigated, however, it is highly unlikely to be effective against venoms of the Malayan krait, red-headed krait and pit viper of the Trimeresurus complex (eg, the Cryptelytrops). At the moment, the two Thai QSMI polyvalent antivenoms appear to be the most suitable for treatment of systemic envenomations in Malaysia. It is easy to distinguish between elapid (krait and cobra) bites and pit viper bites clinicallythe former is mainly neurotoxic, whereas the latter hemorrhagic. Neuro polyvalent antivenom can neutralize venoms from all Malaysian cobras and kraits, whereas Hemato polyvalent antivenom can neutralize venoms from all Malaysian pit vipers; except the Waglers pit viper, Tropidolaemus wagleri . At the moment, there is no antivenom available to neutralize the venom of Wagler s pit viper.

9.3 Supportive/ Ancillary Treatment a. If there is danger of respiratory paralysis, intubate or ventilate via tracheostomy. Mechanical ventilation is recommended for patients with respiratory paralysis. b. Treatment of local lesion: Massive tissue sloughing and necrosis, intracompartmental syndrome, suppurative complications etc may need surgical intervention, however the risks of surgery in a patient with hemostatic disturbances must be balanced against the life-threatening complications of local envenoming. c. Treatment of shock; correction of fluid imbalance (venous access is vital but topmost care is needed for patients with hemostatic disturbances). d. Renal replacement therapy (peritoneal dialysis in acute setting) if indicated.
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e. Anticholinesterases e.g. edrophonium can partly overcome blockade by postsynaptic neurotoxins. f. Tetanus prophylaxis: A booster of tetanus toxoid is recommended for all snakebite patients in the absence of coagulopathy. g. Antibiotic use if indicated for infected wound.

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Literatures on Malaysian venomous snakes and clinical observations and treatment of snakebites in Malaysia: Alirol, E., Sharma, S.K., Bawaskar, H.S., Kuch, U., Chappuis, F., 2010. Snake bite in South Asia: a review. PLoS Negl Trop Dis. 4, e603. Chippaux, JP and Goyffon, M., 1998. Venoms, antivenoms and immunotherapy. Toxicon. 36, 823-846. Gutirrez, J.M., Theakston, R.D.G., Warrell, D.A., 2006. Confronting the Neglected Problem of Snake Bite Envenoming: The Need for a Global Partnership. PLoS Med. 3, e150. Harrison, R.A., Hargraves, A., Wagstaff, S.C., Faragher, B., Lalloo, D.G. 2009., Snake envenoming: a disease of poverty. PLoS Negl Trop Dis. 3, e569. Jamaiah, I., Rohela, M., Roshalina, R. and Undan, R.C. (2004) Prevalence of snake bites in Kangar District Hospital, Perlis, West Malaysia: A retrospective study (Jan 1999-Dec 2000). Southeast Asian J Trop Med Public Health, 35: 962-965. Jamaiah, I., Rohela, M., Ng, T.K., Chng, K.B.H., Teh, Y.S., Nurulhuda, A.L. and Suhaili, N. (2006) Retrospective prevalence of snaket bites from hospital Kuala Lumpur (HKL), Southeast Asian J. Trop. Med. Public Health, 37:200-206. Kasturiratne, A., Wickremasinghe, A.R., de Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna R., Savioli, L., Lalloo, D.G., de Silva, H.J. (2008) Estimation of the global burden of snakebite. PLoS Med 5(11): e218. doi:10.1371/journal.pmed.0050218 Lim, B.L. (1982) Poisonous Snakes of Peninsular Malaysia. 2nd Ed. Malayan Nature Society, Kuala Lumpur, 72pp. Mitrakul, C. (1973). Effects of green pit viper venoms on blood coagulation, platelets and the fibrinolytic enzyme systems: studies in vivo and in vitro. Am. J. clin. Pathol. 60, 654-662. Reid, H.A., Lim, K.J. (1957). Sea-snake bite. Br. Med. J. 2, 1266-1272. Reid, H.A., Chan, K.E. and Thean, P.C. (1963). Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite. Lancet, i, 621-626. Reid, H.A., Thean, P.C., Chan, K.E. and Baharom, A.R. (1963). Clinical effects of bites by Malayan viper. Lancet i, 617-621. Reid, H.A. (1964). Cobra bites. Br. Med. J. 2, 540-545. Reid, H.A. (1968) Symptomatology, pathology and treatment of land snake bites in India and Southeast Asia. In: Venomous Animals and Their Venoms. Vol.1. (Buckely, E.D., Bucheri, W., and Deulofeu, V. Eds.), Academic Press, New York. Pp. 611-642. Reid, H.A., Theakston, R.D.S. (1983). The management of snake bite. Bull. W.H.O., 61, 885-895. Tan, K.K., Choo, K.E., Ariffin, W.A. (1990) Snake bite in Kelantanese children: A five year experience. Toxicon, 28:225-230. Tan, N.H. (1991) The biochemistry of venoms of some venomous snakes of Malaysia. A Review. Tropical Biomedicine 8, 91-103.
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