SDE Mgmt Snake-bite

Guidelinesfor the Clinical Management ofSnake bites in the South-East Asia Region

Spectacled CobraSaw Scaled Viper

Common KraitCommon Krait

Russells ViperRussells Viper

Written and edited for SEAMEOTROPMED by David A Warrell with contributionsby an international panel of experts, first published as a Supplement to the Southeast

Asian Journal of Tropical Medicine & Public Health, Vol 30, Supplement 1, 1999

New Delhi2005

Guidelines

Reprint of the 1999 edition written and edited forSEAMEOTROPMED Regional Centre for Tropical Medicine,Faculty of Tropical Medicine, Mahidol University, Thailand.

for the Clinical Management ofSnake Bite in the South-East Asia Region

iiGuidelines for the Clinical Managementof Snake bite in the South-East Asia Region

World Health Organization 2005

Publications of the World Health Organization enjoy copyright protection in accordance with theprovisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction ortranslation, in part or in toto, of publications issued by the WHO Regional Office for South-EastAsia, application should be made to the Regional Office for South-East Asia, World Health House,Indraprastha Estate, New Delhi 110002, India.

The designations employed and the presentation of material in this publication do not imply theexpression of any opinion whatsoever on the part of the Secretariat of the World Health Organizationconcerning the legal status of any country, territory, city or area or of its authorities, or concerningthe delimitation of its frontiers or boundaries.

iiiGuidelines for the Clinical Management

of Snake bite in the South-East Asia Region

Contents

Preface ............................................................................................... v

1. Introduction .................................................................................. 11.1 Venomous snakes of South-East Asia ..................................................... 11.2 Snake venoms ...................................................................................... 81.3 How common are snake bites? ............................................................. 91.4 How do snake bites happen? .............................................................. 111.5 How can snake bites be avoided? ....................................................... 11

2. Symptoms and Signs of Snake Bite ............................................. 132.1 When venom has not been injected ................................................... 132.2 When venom has been injected ......................................................... 132.3 Clinical pattern of envenoming by snakes in South-East Asia ................ 142.4 Clinical syndromes of snake bite in South-East Asia ............................. 182.5 Long term complications (sequelae) of snake bite ................................ 19

3. Symptoms and Signs of Cobra-spit Ophthalmia ........................ 21

4. Management of Snake Bites in South-East Asia .......................... 234.1 First aid treatment ............................................................................... 234.2 Transport to hospital ........................................................................... 264.3 Treatment in the dispensary or hospital ............................................... 264.4 Detailed clinical assessment and species diagnosis ............................... 274.5 Investigations/laboratory tests .............................................................. 304.6 Antivenom treatment .......................................................................... 324.7 Supportive/ancillary treatment ............................................................ 404.8 Treatment of the bitten part ................................................................ 464.9 Rehabilitation ..................................................................................... 47

ivGuidelines for the Clinical Managementof Snake bite in the South-East Asia Region

5. Management of Cobra Spit Ophthalmia..................................... 49

6. Conclusions and Main Recommendations ................................. 51

7. Further Reading .......................................................................... 55

Annex1. Algorithm: Antivenom treatment of snakebite cases .................................... 61

2. Algorithm: Differentiating major asian snakespecies by clincal symdrome ....................................................................... 62

3. Antivenoms for treatment of bites by South-East Asian snakes ...................... 63

4. Measurement of Central Venous Pressure ................................................... 66

5. Measurement of intracompartmental pressure intensely swollen snake-bitten limbs .............................................................. 67

vGuidelines for the Clinical Management


Preface

The geographical area specifically covered by this publication extends from Pakistanand the rest of the Indian subcontinent in the west through to the Philippines andIndonesia in the east, excluding Tibet, China, Taiwan, Korea, Japan, the eastern islandsof Indonesia and New Guinea and Australia (Figure 1, inside of front cover).

In many parts of this region, snake bite is a familiar occupational hazard offarmers, plantation workers and others, resulting in tens of thousands of deaths eachyear and innumerable cases of chronic physical handicap. Much is now known about

Figure 1: Map of Asia showing the area specifically covered by the guidelines

viGuidelines for the Clinical Managementof Snake bite in the South-East Asia Region

the species of venomous snakes responsible for these bites, the nature of their venomsand the clinical effects of envenoming in human patients. This publication aims topass on a digest of this knowledge to medical doctors, nurses, dispensers andcommunity health workers who have the responsibility of treating victims of snakebite.

Any recommendations must be continually reconsidered in the light of newevidence and experience. Comments from readers are welcomed so that futureeditions can be updated and improved.

The guidelines are intended to provide enough practical information to allowany medicallytrained person to assess and treat a patient with snake bite at differentlevels of the health service. Recommendations are based on clinical experience and,where possible, on the results of clinical trials. The restrictions on the size of thisdocument prevented the inclusion of detailed references to the original publicationson which these recommendations were based. These can be found in the papersand reviews listed in Further Reading.

I am grateful to the panel of experts who contributed to these Guidelines but Imust take responsibility for the writing and editing of the document.

I acknowledge the exellent help provided by Miss Eunice Berry (Centre for TropicalMedicine, University of Oxford), who typed the several drafts of the manuscript, andby Ms Vimolsri Panichyanon (Assistant Programme Coordinator, SEAMEOTROPMEDNetwork) and Drs Suvanee Supavej and Parnpen Viriyavejakul (Deputy AssistantDeans for International Relations, Faculty of Tropical Medicine, Mahidol University)who, under the overall direction of Professor Sornchai Looareesuwan, wereresponsible for organising the meeting of the international panel of experts in Bangkokon 29/30 November 1998.

David A WarrellOxford, December 1998

viiGuidelines for the Clinical Management


Nepal*Bishnu Bahadur BhetwalBijalpura - 2 V.D.C.P.O. - BijalpuraDist - MahottariNepal

IndiaKirpal S ChughKothi No 601, Sector 18BChandigarh - 160 018India

Papua New GuineaDavid G LallooNuffield Dept Clinical Medicine,University of OxfordJohn Radcliffe HospitalHeadingtonOxford OX3 9DUUK

ThailandSornchai LooareesuwanSEAMEOTROPMED Regional Centrefor Tropical MedicineFaculty of Tropical Medicine

Names and Addresses of theInternational Panel of Experts

who Contributed to the Guidelines

Mahidol University420/6 Rajvithi RoadBangkok 10400Thailand

MyanmarMay-Mya-Win)Renal and Dialysing UnitsTingangyun Sanpya HospitalYangonMyanmar

Sri LankaLena SjstrmTherapeutic Antibodies LtdClinical Operations (UK)14-15 Newbury StreetLondon EC1A 7HUUK

Sri Lanka, ThailandR David G TheakstonAlistair Reid Venom Research UnitLiverpool School of Tropical MedicinePembroke PlaceLiverpool L3 5QAUK

viiiGuidelines for the Clinical Managementof Snake bite in the South-East Asia Region

Myanmar, Sri Lanka,Thailand, Viet NamDavid A WarrellCentre for Tropical MedicineUniversity of OxfordJohn Radcliffe HospitalHeadingtonOxford OX3 9DUUK

Philippines, ThailandGeorge WattDept of MedicineAFRIMS315/6 Rajvithi RoadBangkok 10400Thailand

AustraliaJulian WhiteState Toxinology ServicesPoisons Information CentreAdelaide Childrens HospitalKing William StreetNorth AdelaideSA 5006Australia

*indicates countries of clinical experiencewith snake bite patients in theSouth-East Asian region.

1Guidelines for the Clinical Management


1.1 Venomous snakes of South-East Asia

The venom apparatus (Fig 2)

Venomous snakes of medical importance have a pair of enlarged teeth, the fangs, atthe front of their upper jaw. These fangs contain a venom channel (like a hypodermicneedle) or groove, along which venom can be introduced deep into the tissues oftheir natural prey. If a human is bitten, venom is usually injected subcutaneously orintramuscularly. Spitting cobras can squeeze the venom out of the tips of their fangsproducing a fine spray directed towards the eyes of an aggressor.

Introduction

1

Compressorglandulae muscle Venom gland

Accessoryvenom gland

Secondaryvenom duct

Venom canalVenom duct

Figure 2: Venom apparatus of a saw-scaled viper (Copyright DA Warrell)

2Guidelines for the Clinical Managementof Snake bite in the South-East Asia Region

Classification

There are two important groups (families) of venomous snakes in South-East Asia Elapidae have short permanently erect fangs (Fig 3). This family includes the cobras,king cobra, kraits, coral snakes and the sea snakes. The most important species, froma medical point of view, include the following:

cobras: N naja common spectacled Indian cobra (Fig 4)(genus Naja) N oxiana North Indian or Oxus cobra (Fig 5)

N kaouthia monocellate cobra (Fig 6)N philippinensis Philippine cobraN atra Chinese cobra (Fig 7)

spitting cobras: N siamensis (Fig 8)N sumatrana (Fig 9)N sputatrix etc

king cobra: Ophiophagus hannah (Fig 10)kraits: B caeruleus common krait (Fig 11)(genus Bungarus) B candidus Malayan krait (Fig 12)

B multicinctus Chinese krait (Fig 13)B fasciatus banded krait (Fig 14)

Sea snakes (important genera include Enhydrina, Lapemis and Hydrophis)(Fig 15)

Figure 3: Short, permanently erect, fangs of atypical elapid (Thai monocellate cobra Najakaouthia) (Copyright DA Warrell)

Figure 4: Short, permanently erect, fangs ofa typical elapid (Thai monocellate cobra Naja kaouthia (Copyright DA Warrell)

Figure 5: North Indian or Oxus cobra (Najaoxiana) (Copyright DA Warrell) Viperdaehave long fangs



Figure 6: (Left) Monocellate cobra (Naja kaouthia), (Right) Detail of hood (Copyright DA Warrell)

Figure 7: Chinese cobra (Naja atra)(Copyright DA Warrell)

Figure 8(a): Indo-Chinese spitting cobra (Naja Saimensis)(Copyright DA Warrell)


Figure 8(b): (Left) Brown coloured specimen with spectacle marking on hood. (Right) Black andwhite specimen with ill-defined spectacle marking on the hood. (Copyright DA Warrell)

Figure 9: Sumatran spitting cobra(Naja sumatrana) (a) black phase(b) golden phase (Copyright DAWarrell)

Figure 10: King cobra or hamadryad (Ophiophagushannah). The famous king cobra dance in Yangon,Myanmar (Copyright DA Warrell)

Figure 11: Common krait (Bungarus caeruleus)(Copyright DA Warrell)

Figure 12: Malayan krait (Bungarus candidus)(Copyright DA Warrell)



Figure 13: Chinese krait (Bungarusmulticinctus) (Copyright DA Warrell)

Figure 14: Banded krait (Bungarus fasciatus)(Copyright DA Warrell)

Figure 15: Blue spotted sea snake (Hydrophis cyanocinctus) (Copyright DA Warrell)

Viperidae have long fangs which are normally folded up against the upper jawbut, when the snake strikes, are erected (Fig 2). There are two subgroups, the typicalvipers (Viperinae) and the pit vipers (Crotalinae). The Crotalinae have a special senseorgan, the pit organ, to detect their warm-blooded prey. This is situated between thenostril and the eye (Fig 16).

Medically important species in South-East Asia are:

typical vipers Daboia russelii Russells vipers (Fig 17)Echis carinatus saw-scaled or carpet vipersand E sochureki (Figs 18, 19)

pit vipers Calloselasma rhodostoma Malayan pit viper (Fig 20)

Hypnale hypnale hump-nosed viper (Fig 21)

green pit vipers or bamboo vipers (genus Trimeresurus)

T albolabris white-lipped greenpit viper (Fig 22)


T gramineus Indian bamboo viper

T mucrosquamatus Chinese habu (Fig 23)

T purpureomaculatus mangrove pit viper (Fig 24)

T stejnegeri Chinese bamboo viper

Figure 16: Head of a typical pit viper white-lipped green pit viper (Trimeresurus albolabris)showing the pit organ situated between the nostril and the eye (arrow head) (Copyright DA Warrell)

Figure 17(a): Russells vipers (Copyright DAWarrell) Eastern subspecies (Daboia russeliisiamensis); specimen from Myanmar

Figure 17(b): Russells vipers (Copyright DA Warrell)specimen from India

Figure 17(c): Russells vipers(Copyright DA Warrell) Easternsubspecies (Daboia russeliisiamensis); specimen from Thailand

Figure 17(d): Russells vipers (Copyright DA Warrell)specimen from Burma



Figure 17(e): Russells vipers(Copyright DA Warrell) details offangs

Figure 18: Saw-scaled viper (Echis carinatus) specimenfrom Sri Lanka (Copyright DA Warrell)

Figure 19: Northern saw-scaled viper (Echissochureki) (Copyright DA Warrell)

Figure 20: Northern saw-scaled viper (Echissochureki) (Copyright DA Warrell)

Figure 21: Hump-nosed viper (Hynpale hypnale).Specimen from Sri Lanka (Copyright DA Warrell)

Figure 22: White-lipped green pit viper(Trimeresurus albolabris) (Copyright DAWarrell)


How to identify venomous snakes

There is no simple rule for identifying adangerous venomous snake. Some harmlesssnakes have evolved to look almost identicalto venomous ones. However, some of the mostnotorious venomous snakes can be recognisedby their size, shape, colour, pattern of markings,their behaviour and the sound they make whenthey feel threatened. For example, thedefensive behaviour of the cobras is wellknown (Fig 8): they rear up, spread a hood,hiss and make repeated strikes towards theaggressor. Colouring can vary a lot. However,some patterns, like the large white, darkrimmed spots of the Russells viper (Fig 17), orthe alternating black and yellow bands of thebanded krait (Fig 14), are distinctive. Theblowing hiss of the Russells viper and the

grating rasp of the saw-scaled viper are warning and identifying sounds.

1.2 Snake venomsComposition of venom

Snake venoms contain more than 20 different constituents, mainly proteins, includingenzymes and polypeptide toxins. The following venom constituents cause importantclinical effects:

Procoagulant enzymes (Viperidae) that stimulate blood clotting but result inincoagulable blood. Venoms such as Russells viper venom contain several differentprocoagulants which activate different steps of the clotting cascade. The result isformation of fibrin in the blood stream. Most of this is immediately broken down by

Figure 23: Chinese habu (Trimeresurus microsquamatus) (Copyright DA Warrell)

Figure 24: Mangrove pit viper(Trimeresurus purpureomaculatus)(Copyright DA Warrell)



the bodys own fibrinolytic system. Eventually, and sometimes within 30 minutes ofthe bite, the levels of clotting factors have been so depleted (consumptioncoagulopathy) that the blood will not clot.

Haemorrhagins (zinc metalloproteinases) that damage the endothelial lining ofblood vessel walls causing spontaneous systemic haemorrhage.

Cytolytic or necrotic toxins - these digestive hydrolases (proteolytic enzymesand phospholipases A) polypeptide toxins and other factors increase permeabilityresulting in local swelling. They may also destroy cell membranes and tissues.

Haemolytic and myolytic phospholipases A2 - these enzymes damage cellmembranes, endothelium, skeletal muscle, nerve and red blood cells.

Pre-synaptic neurotoxins (Elapidae and some Viperidae) - these arephospholipases A2 that damage nerve endings, initially releasing acetylcholinetransmitter, then interfering with release.

Post-synaptic neurotoxins (Elapidae) - these polypeptides compete withacetylcholine for receptors in the neuromuscular junction and lead to curare-likeparalysis.

Quantity of venom injected at a bite

This is very variable, depending on the species and size of the snake, the mechanicalefficiency of the bite, whether one or two fangs penetrated the skin and whetherthere were repeated strikes. The snake may be able to control whether or not venomis injected. For whatever reason, a proportion of bites by venomous snakes do notresult in the injection of sufficient venom to cause clinical effects. About 50% of bitesby Malayan pit vipers and Russells vipers, 30% of bites by cobras and 5-10% of bitesby saw-scaled vipers do not result in any symptoms or signs of envenoming. Snakesdo not exhaust their store of venom, even after several strikes, and they are no lessvenomous after eating their prey.

Although large snakes tend to inject more venom than smaller specimens of thesame species, the venom of smaller, younger vipers may be richer in some dangerouscomponents, such as those affecting haemostasis.

1.3 How common are snake bites?It is difficult to answer this question because many snake bites and even deaths fromsnake bite are not recorded. One reason is that many snake bite victims are treatednot in hospitals but by traditional healers.

Bites by small snakes should not be ignored or dismissed. They should be takenjust as seriously as bites by large snakes of the same species.


Bangladesh a survey of 10% of the country in 1988-9 revealed 764 bites with168 deaths in one year. Cobra bites (34% of all bites) caused a case fatality of 40%.

Bhutan (no data available)

Cambodia (no data available)

India estimates in the region of 200,000 bites and 15-20,000 snake bite deathsper year, originally made in the last century, are still quoted. No reliable nationalstatistics are available. In 1981, a thousand deaths were reported in MaharashtraState. In the Burdwan district of West Bengal 29,489 people were bitten in one yearwith 1,301 deaths. It is estimated that between 35,000 and 50,000 people die ofsnake bite each year among Indias population of 980 million.

Indonesia no reliable data are available from this vast archipelago. Snake bitesand deaths are reported from some islands, eg Komodo, but fewer than 20 deathsare registered each year.

Lao DPR (no data available)

Malaysia bites are common, especially in northwest peninsular Malaysia, butthere are few deaths.

Myanmar (Burma) snake bites and snake bite deaths have been reliably reportedfrom colonial times. Russells vipers are responsible for 90% of cases. In 1991, therewere 14,000 bites with 1,000 deaths and in 1997, 8,000 bites with 500 deaths.Under-reporting is estimated at 12%. There are peaks of incidence in May and Junein urban areas and during the rice harvest in October to December in rural areas.

Nepal there are estimated to be at least 20,000 snake bites with about 200deaths in hospitals each year, mainly in the Terai region. One survey suggested asmany as 1,000 deaths per year. Among 16 fatalities recorded at one rural clinicduring a monsoon season, 15 had died on their way to seek medical care.

Pakistan there are an estimated 20,000 snake bite deaths each year

Philippines there are no reliable estimates of mortality among the many islandsof thearchipelago. Figures of 200-300 deaths each year have been suggested. Onlycobras cause fatal envenoming, their usual victims being rice farmers.

Sri Lanka epidemiological studies in Anuradhapura showed that only two-thirds of cases of fatal snake bite were being reported to the Government Agent

To remedy the deficiency in reliable snake bite data, it is strongly recommendedthat snake bites should be made a specific notifiable disease in all countries in theSouth East Asian region.



Statistical Branch. However, the Registrar General received reports of more than 800deaths from bites and stings by venomous animals and insects in the late 1970s andthe true annual incidence of snake bite fatalities may exceed 1,000.

Thailand between 1985 and 1989, the number of reported snake bite casesincreased from 3,377 to 6,038 per year, reflecting increased diligence in reportingrather than a true increase in snake bites; the number of deaths ranged from 81 to183 (average 141) per year. In 1991 there were 1,469 reported bites with five deaths,in 1992, 6,733 bites with 19 deaths and, in 1994, 8,486 bites with eight deaths.Deaths reported in hospital returns were only 11% of the number recorded by thePublic Health Authorities. In a national survey of dead snakes brought to hospital bythe people they had bitten, 70% of the snakes were venomous species, the mostcommonly brought species being Malayan pit viper (Calloselasma rhodostoma) 38%,white-lipped green pit viper (Trimeresurus albolabris) 27%, Russells viper (Daboiarusselii siamensis) 14%, Indo-Chinese spitting cobra (Naja siamensis) 10% andmonocellate cobra (N kaouthia) 7%. In an analysis of 46 fatal cases in which thesnake had been reliably identified, Malayan kraits (Bungarus candidus) and Malayanpit vipers were each responsible for 13 cases, monocellate cobras for 12 and Russellsvipers for seven deaths.

Viet Nam there are an estimated 30,000 bites per year. Among 430 rubberplantation workers bitten by Malayan pit vipers between 1993 and 1998, the casefatality was 22%, but only a minority had received antivenom treatment. Fishermenare still occasionally killed by sea snakes but rarely reach hospitals.

1.4 How do snake bites happen?In South-East Asia, snake bite is an occupational hazard of rice farmers; rubber,coffee and other plantation workers; fishermen and those who handle snakes. Mostsnake bites happen when the snake is trodden on, either in the dark or in undergrowth,by someone who is bare-footed or wearing only sandals. The snake may be pickedup, unintentionally in a handful of foliage or intentionally by someone who is tryingto show off. Some bites occur when the snake (usually a krait) comes in to the homeat night in search of its prey (other snakes, lizards, frogs, mice) and someone sleepingon the floor rolls over onto the snake in their sleep. Not all snake bites happen inrural areas. For example, in some large cities, such as Jammu in India, people whosleep in small huts (jhuggies) are frequently bitten by kraits.

1.5 How can snake bites be avoided?Snake bite is an occupational hazard that is very difficult to avoid completely. However,attention to the following recommendations might reduce the number of accidents.

Education! Know your local snakes, know the sort of places where they liketo live and hide, know at what times of year, at what times of day/night orin what kinds of weather they are most likely to be active.


Be specially vigilant about snake bites after rains, during flooding, at harvesttime and at night.

Try to wear proper shoes or boots and long trousers, especially when walkingin the dark or in undergrowth.

Use a light (torch, flashlight or lamp) when walking at night.

Avoid snakes as far as possible, including snakes performing for snakecharmers. Never handle, threaten or attack a snake and never intentionallytrap or corner a snake in an enclosed space.

If at all possible, try to avoid sleeping on the ground.

Keep young children away from areas known to be snake-infested.

Avoid or take great care handling dead snakes, or snakes that appear to bedead.

Avoid having rubble, rubbish, termite mounds or domestic animals close tohuman dwellings, as all of these attract snakes.

Frequently check houses for snakes and, if possible, avoid types of houseconstruction that will provide snakes with hiding places (e.g. thatched rooveswith open eaves, mud and straw walls with large cracks and cavities, largeunsealed spaces beneath floorboards).

To prevent sea snake bites, fishermen should avoid touching sea snakescaught in nets and on lines. The head and tail are not easily distinguishable.There is a risk of bites to bathers and those washing clothes in muddy waterof estuaries, river mouths and some coastlines.

Snake bite: an occupational disease in South East Asia

Farmers (rice)Plantation workers (rubber, coffee)HerdsmenHuntersSnake handlers (snake charmers and in snake restaurants andtraditional Chinesepharmacies)Fishermen and fish farmersSea snake catchers (for sea snake skins, leather)



2.1 When venom has not been injectedSome people who are bitten by snakes or suspect or imagine that they have beenbitten, may develop quite striking symptoms and signs, even when no venom hasbeen injected. This results from an understandable fear of the consequences of a realvenomous bite. Anxious people may overbreathe so that they develop pins andneedles of the extremities, stiffness or tetany of their hands and feet and dizziness.Others may develop vasovagal shock after the bite or suspected bite faintness andcollapse with profound slowing of the heart. Others may become highly agitated andirrational and may develop a wide range of misleading symptoms. Another source ofsymptoms and signs not caused by snake venom is first aid and traditional treatments.Constricting bands or tourniquets may cause pain, swelling and congestion. Ingestedherbal remedies may cause vomiting. Instillation of irritant plant juices into the eyesmay cause conjunctivitis. Forcible insufflation of oils into the respiratory tract maylead to aspiration pneumonia, bronchospasm, ruptured ear drums and pneumothorax.Incisions, cauterisation, immersion in scalding liquid and heating over a fire canresult in devastating injuries.

2.2 When venom has been injected

Early symptoms and signs

Following the immediate pain of mechanical penetration of the skin by the snakesfangs, there may be increasing local pain (burning, bursting, throbbing) at the site ofthe bite, local swelling that gradually extends proximally up the bitten limb andtender, painful enlargement of the regional lymph nodes draining the site of the bite(in the groin femoral or inguinal, following bites in the lower limb; at the elbow(epitrochlear) or in the axilla following bites in the upper limb). However, bites bykraits, sea snakes and Philippine cobras may be virtually painless and may cause

Symptoms andSigns of Snake Bite

2


negligible local swelling. Someone who is sleeping may not even wake up whenbitten by a krait and there may be no detectable fang marks or signs of localenvenoming.

2.3 Clinical pattern of envenoming by snakesin South-East AsiaSymptoms and signs vary according to the species of snake responsible for the biteand the amount of venom injected. Sometimes the identity of the biting snake canbe confirmed by examining the dead snake; it may be strongly suspected from thepatients description or the circumstances of the bite or from knowledge of the clinicaleffects of the venom of that species. This information will enable the doctor to choosean appropriate antivenom, anticipate the likely complications and therefore takeappropriate action. If the biting species is unknown, recognition of the emergingpattern of symptoms, signs and results of laboratory tests (the clinical syndrome),may suggest which species was responsible.

Local symptoms and signs in the bitten part

fang marks (Fig 25)

local pain

local bleeding (Fig 26)

bruising

lymphangitis

lymph node enlargement

nflammation (swelling, redness, heat)

blistering (Fig 27)

local infection, abscess formation

necrosis (Fig 28)

Figure 25: Fang marks made by Russells viper(Copyright DA Warrell)

Figure 26: Local bleeding fromfang marks made by Malayan pitviper (Copyright DA Warrell)



Figure 28: Tissue necrosis following a bite by a Malayan pit viper (Copyright DA Warrell)

Figure 27 Local swelling and blistering (a) with bruising, following a bite by a Malayan pit viper(Copyright DA Warrell), (Bottom) Local swelling and blistering (b) with early necrosis following abite by a monocellate cobra (Naja kaouthia) (Copyright DA Warrell)

Figure 28(a): Tissue necrosis following a bite by an Indochinese spitting cobra (Naja siamensis)(Copyright Sornchai Looareesuwan)

Generalised (systemic) symptoms and signs

GeneralNausea, vomiting, malaise, abdominal pain, weakness, drowsiness, prostration

Cardiovascular (Viperidae)Visual disturbances, dizziness, faintness, collapse, shock, hypotension, cardiacarrhythmias, pulmonary oedema, conjunctival oedema (Fig 29)


Bleeding and clotting disorders (Viperidae)

bleeding from recent wounds (including fang marks (Fig 26), venepuncturesetc) and from old partly-healed wounds

spontaneous systemic bleeding from gums (Fig 30), epistaxis, bleedinginto the tears, haemoptysis, haematemesis, rectal bleeding or melaena,haematuria, vaginal bleeding, bleeding into the skin (petechiae, purpura,ecchymoses) and mucosae (eg conjunctivae [Fig 31]), intracranialhaemorrhage (meningism from subarachnoid haemorrhage, lateralising signsand/or coma from cerebral haemorrhage)

Neurological (Elapidae, Russells viper)

Drowsiness, paraesthesiae, abnormalities of taste and smell, heavy eyelids, ptosis(Fig 32), external ophthalmoplegia (Fig 33), paralysis of facial muscles and othermuscles innervated by the cranial nerves, aphonia, difficulty in swallowing secretions,respiratory and generalised flaccid paralysis

Skeletal muscle breakdown (sea snakes, Russells viper)

Generalised pain, stiffness and tenderness of muscles, trismus, myoglobinuria(Fig 34), hyperkalaemia, cardiac arrest, acute renal failure

Renal (Viperidae, sea snakes)

Loin (lower back) pain, haematuria, haemoglobinuria, myoglobinuria, oliguria/anuria,symptoms and signs of uraemia (acidotic breathing, hiccups, nausea, pleuritic chestpain....)

Endocrine (acute pituitary/adrenal insufficiency) (Russells viper)

Acute phase: shock, hypoglycaemiaChronic phase (months to years after the bite): weakness, loss of secondary sexualhair, amenorrhoea, testicular atrophy, hypothyroidism etc (Fig 35)

Figure 29: Bilateral conjunctival oedema (chemosis) after a bite by a Burmese Russells viper(Copyright DA Warrell)



Figure 30: Bleeding from gingival sulci in a patient bitten by a saw-scaled viper(Copyright DA Warrell)

Figure 31: Subconjunctival haemorrhages in a patient bitten by a Burmese Russells viper(Copyright DA Warrell)

Figure 32: Bilateral ptosis (a) in a patient bitten by a common krait (Copyright DA Warrell),Bilateral ptosis (b) in a patient bitten by a Sri Lankan Russells viper (Copyright DA Warrell)


Figure 33: External ophthalmoplegia in a patientbitten by a Russells viper in Sri Lanka. Thepatient is attempting to look to his right. Theeyes are held open because of the bilateralptosis (Copyright DA Warrell)

Figure 34: Patient bitten by a Sri LankanRussells viper who began to pass darkbrown urine containing myoglobin andhaemoglobin 8 hours after the bite(Copyright DA Warrell)

Figure 35: (a) Haemorrhagic infarction of the anterior pituitary (Sheehans-like syndrome) after abite by a Burmese Russells viper, (b) Patient bitten by a Burmese Russells viper three yearspreviously, showing clinical signs of panhypopituitarism: loss of secondary sexual hair andtesticular atrophy (Copyright DA Warrell)

2.4 Clinical syndromes of snake bite in South-East Asia

Limitations of syndromic approach

The more carefully the clinical effects of snake bites are studied, the more it is realisedthat the range of activities of a particular venom is very wide. For example, someelapid venoms, such as those of Asian cobras, can cause severe local envenoming



(Fig 28), formerly thought to be an effect only of viper venoms. In Sri Lanka andSouth India, Russells viper venom causes paralytic signs (ptosis etc) (Fig 32), suggestingelapid neurotoxicity, and muscle pains and dark brown urine (Fig 34), suggesting seasnake rhabdomyolysis. Although thre may be considerable overlap of clinical featurescaused by venoms of different species of snake, a syndromic approach may still beuseful, especially when the snake has not been identified and only monospecificantivenoms are available (see Annex 1 & 2).

Syndrome 1Local envenoming (swelling etc) with bleeding/clotting disturbances = Viperidae(all species)

Syndrome 2Local envenoming (swelling etc) with bleeding/clotting disturbances, shock or renalfailure = Russells viper (and possibly saw-scaled viper Echis species in someareas)

with conjunctival oedema (chemosis) and acute pituitary insufficiency = Russellsviper, Burma

with ptosis, external ophthalmoplegia, facial paralysis etc and dark brown urine =Russells viper, Sri Lanka and South India

Syndrome 3Local envenoming (swelling etc) with paralysis = cobra or king cobra

Syndrome 4Paralysis with minimal or no local envenoming

Bite on land while sleeping, outside the Philippines = krait

in the Philippines = cobra (Naja philippinensis)

Bite in the sea = sea snake

Syndrome 5Paralysis with dark brown urine and renal failure:

Bite on land (with bleeding/clotting disturbance) = Russells viper, Sri Lanka/SouthIndia

Bite in the sea (no bleeding/clotting disturbances) = sea snake

2.5 Long term complications (sequelae) of snake biteAt the site of the bite, loss of tissue may result from sloughing or surgical dbridementof necrotic areas or amputation: chronic ulceration, infection, osteomyelitis or arthritismay persist causing severe physical disability (Fig 36). Malignant transformation mayoccur in skin ulcers after a number of years (Fig 37).


Chronic renal failure occurs afterbilateral cortical necrosis (Russellsviper bites) and chronicpanhypopituitarism or diabetesinsipidus after Russells viper bites inMyanmar and South India (Fig 35b).Chronic neurological deficit is seenin the few patients who surviveintracranial haemorrhages(Viperidae).

Figure 36: (a) and (b) Chronic physical handicap resulting from necrotic envenoming by Malayanpit vipers (Copyright DA Warrell)

Figure 37: Squamous cell carcinoma developing atthe site of a chronic skin ulcer with osteomyelitis 8years after a bite by a Malayan pit viper (CopyrightDA Warrell)



If the spat venom enters the eyes, there is immediate and persistent intense burning,stinging pain, followed by profuse watering of the eyes with production of whitishdischarge, congested conjunctivae, spasm and swelling of the eyelids, photophobiaand clouding of vision. Corneal ulceration, permanent corneal scarring and secondaryendophthalmitis are recognised complications of African spitting cobra venom buthave not been described in Asia.

Symptoms and Signs ofCobra-spit Ophthalmia

3

(Eye injuries from spitting cobras) (Fig 38)

Figure 38: Bilateral conjunctivitis in a patient who had venom spat into both eyes by an Indo-Chinese spitting cobra (Naja siamensis) (Copyright DA Warrell)



Management of SnakeBites in South-East Asia

4

The following steps or stages are often involved

Management of snake bite

First aid treatment

Transport to hospital

Rapid clinical assessment and resuscitation

Detailed clinical assessment and species diagnosis

Investigations/laboratory tests

Antivenom treatment

Observation of the response to antivenom: decision about the need for furtherdose(s) of antivenom

Supportive/ancillary treatment

Treatment of the bitten part

Rehabilitation

Treatment of chronic complications

4.1 First aid treatmentFirst aid treatment is carried out immediately or very soon after the bite, before thepatient reaches a dispensary or hospital. It can be performed by the snake bite victimhimself/herself or by anyone else who is present.


Aims of first aid

attempt to retard systemic absorption of venom

preserve life and prevent complications before the patient can receive medicalcare (at a dispensary or hospital)

control distressing or dangerous early symptoms of envenoming

arrange the transport of the patient to a place where they can receive medicalcare (4.2)

Above all, do no harm!

Unfortunately, most of the traditional, popular, available and affordable first aidmethods have proved to be useless or even frankly dangerous. These methods include:making local incisions or pricks/punctures (tattooing) at the site of the bite or in thebitten limb, attempts to suck the venom out of the wound, use of (black) snakestones, tying tight bands (tourniquets) around the limb, electric shock, topicalinstillation or application of chemicals, herbs or ice packs.

Local people may have great confidence in traditional (herbal) treatments, butthey must not be allowed to delay medical treatment or to do harm.

Most traditional first aid methods should be discouraged:They do more harm than good !

Recommended first aid methods

Reassure the victim who may be very anxious

Immobilise the bitten limb with a splint or sling (any movement or muscularcontraction increases absorption of venom into the bloodstream and lymphatics)

Consider pressure-immobilisation (Fig 39) for some elapid bites

Avoid any interference with the bite wound as this may introduce infection,increase absorption of the venom and increase local bleeding

As far as the snake is concerned do not attempt to kill it as this may be dangerous.However, if the snake has already been killed, it should be taken to the dispensary orhospital with the patient in case it can be identified. However, do not handle thesnake with your bare hands as even a severed head can bite!

The special danger of rapidly developing paralytic envenoming afterbites by some elapid snakes: use of pressure-immobilisation

Bites by cobras, king cobras, kraits or sea snakes may lead, on rare occasions, to therapid development of life-threatening respiratory paralysis. This paralysis might be



delayed by slowing down the absorption of venom from the site of the bite. Thefollowing technique is currently recommended:

Pressure immobilisation method (Fig 39). Ideally, an elasticated, stretchy, crepebandage, approximately 10 cm wide and at least 4.5 metres long should be used. Ifthat it not available, any long strips of material can be used. The bandage is boundfirmly around the entire bitten limb, starting distally around the fingers or toes andmoving proximally, to include a rigid splint. The bandage is bound as tightly as for asprained ankle, but not so tightly that the peripheral pulse (radial, posterior tibial,dorsalis pedis) is occluded or that a finger cannot easily be slipped between its layers.

Pressure immobilisation is recommended for bites by neurotoxic elapid snakes,including sea snakes but should not be used for viper bites because of the dangerof increasing the local effects of the necrotic venom.

Ideally, compression bandages should not be released until the patient is undermedical care in hospital, resuscitation facilities are available and antivenom treatmenthas been started (see Caution below).

Caution: Release of a tight tourniquet or compression bandage may resultin the dramatic development of severe systemic envenoming.

Tight (arterial) tourniquets are not recommended!

Traditional tight (arterial) tourniquets. To be effective, these had to be applied aroundthe upper part of the limb, so tightly that the peripheral pulse was occluded. Thismethod was extremely painful and very dangerous if the tourniquet was left on fortoo long (more than about 40 minutes), as the limb might be damaged by ischaemia.Many gangrenous limbs resulted!

Figure 39: Pressure immobilisation method. Recommended first-aid for bites by neurotoxicelapid snakes (by courtesy of the Australian Venom Research Unit, University of Melbourne)


Viper and cobra bites

The pressure-immobilisation method as described above will increaseintracompartmental pressure and, by localising the venom, might be expected toincrease the locally-necrotic effects of viper venoms and some cobra venoms.

Pressure bandaging is not recommended for bites by vipers and cobras whosevenoms cause local necrosis.

The use of a local compression pad applied over the wound, without pressurebandaging of the entire bitten limb, has produced promising results in Myanmar anddeserves further study.

Arterial tourniquets are not recommended

4.2 Transport to hospitalThe patient must be transported to a place where they can receive medical care(dispensary or hospital) as quickly, but as safely and comfortably as possible. Anymovement, but especially movement of the bitten limb, must be reduced to anabsolute minimum to avoid increasing the systemic absorption of venom. Any muscularcontraction will increase this spread of venom from the site of the bite. A stretcher,bicycle, cart, horse, motor vehicle, train or boat should be used, or the patient shouldbe carried.

4.3 Treatment in the dispensary or hospital

Rapid clinical assessment and resuscitation

Cardiopulmonary resuscitation may be needed, including administration of oxygenand establishment of intravenous access. Airway, respiratory movements (Breathing)and arterial pulse (Circulation) must be checked immediately. The level ofconsciousness must be assessed.

The following are examples of clinical situations in which snake bite victimsmight require urgent resuscitation:

Profound hypotension and shock resulting from direct cardiovascular effectsof the venom or secondary effects such as hypovolaemia or haemorrhagicshock.

Terminal respiratory failure from progressive neurotoxic envenoming thathas led to paralysis of the respiratory muscles.

Sudden deterioration or rapid development of severe systemic envenomingfollowing the release of a tight tourniquet or compression bandage (seeCaution above).



Cardiac arrest precipitated by hyperkalaemia resulting from skeletal musclebreakdown (rhabdomyolysis) after sea snake bite.

Late results of severe envenoming such as renal failure and septicaemiacomplicating local necrosis.

4.4 Detailed clinical assessment and species diagnosis

History

A precise history of the circumstances of the bite and the progression of local andsystemic symptoms and signs is very important. Three useful initial questions are:

In what part of your body have you been bitten?

The doctor can see immediately evidence that the patient has been bitten by asnake (eg fang marks) and the nature and extent of signs of local envenoming.

When were you bitten?

Assessment of the severity of envenoming depends on how long ago the patient wasbitten. If the patient has arrived at the hospital soon after the bite, there may be fewsymptoms and signs even though a large amount of venom may have been injected.

Where is the snake that bit you?

If the snake has been killed and brought, its correct identification can be very helpful.If it is obviously a harmless species (or not a snake at all!), the patient can be quicklyreassured and discharged from hospital.

Early clues that a patient has severe envenoming:

Snake identified as a very dangerous one

Rapid early extension of local swelling from the site of the bite

Early tender enlargement of local lymph nodes, indicating spread of venom inthe lymphatic system

Early systemic symptoms: collapse (hypotension, shock), nausea, vomiting,diarrhoea, severe headache, heaviness of the eyelids, inappropriate(pathological) drowsiness or early ptosis/ophthalmoplegia

Early spontaneous systemic bleeding

Passage of dark brown urine

Patients who become defibrinogenated or thrombocytopenic may begin to bleedfrom old, partially-healed wounds as well as bleeding persistently from the fang marks.

The patient should be asked how much urine has been passed since the bite andwhether it was a normal colour.


An important early symptom of sea snake envenoming that may develop as soonas 30 minutes after the bite is generalised pain, tenderness and stiffness of musclesand trismus.

Physical examination

This should start with careful assessment of the site of the bite and signs of localenvenoming.

Examination of the bitten part

The extent of swelling, which is usually also the extent of tenderness to palpation,should be recorded. Lymph nodes draining the limb should be palpated and overlyingecchymoses and lymphangitic lines noted.

A bitten limb may be tensely oedematous, cold, immobile and with impalpablearterial pulses. These appearances may suggest intravascular thrombosis, which isexceptionally rare after snake bite, or a compartmental syndrome, which isuncommon. If possible, intracompartmental pressure should be measured (seeAnnex 5) and the blood flow and patency of arteries and veins assessed (eg by dopplerultrasound).

Early signs of necrosis may include blistering, demarcated darkening (easilyconfused with bruising) or paleness of the skin, loss of sensation and a smell ofputrefaction (rotting flesh).

General examination

Measure the blood pressure (sitting up and lying to detect a postural drop indicativeof hypovolaemia) and heart rate. Examine the skin and mucous membranes forevidence of petechiae, purpura, ecchymoses and, in the conjunctivae, chemosis.Thoroughly examine the gingival sulci, using a torch and tongue depressor, as thesemay show the earliest evidence of spontaneous systemic bleeding. Examine the nosefor epistaxis. Abdominal tenderness may suggest gastrointestinal or retroperitonealbleeding. Loin (low back) pain and tenderness suggests acute renal ischaemia (Russellsviper bites). Intracranial haemorrhage is suggested by lateralising neurological signs,asymmetrical pupils, convulsions or impaired consciousness (in the absence ofrespiratory or circulatory failure).

Neurotoxic envenoming

To exclude early neurotoxic envenoming, ask the patient to look up and observewhether the upper lids retract fully (Fig 40). Test eye movements for evidence ofearly external ophthalmoplegia (Fig 33). Check the size and reaction of the pupils.Ask the patient to open their mouth wide and protrude their tongue; early restrictionin mouth opening may indicate trismus (sea snake envenoming) or more often paralysisof pterygoid muscles (Fig 41). 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 (Fig 42).



Bulbar and respiratory paralysis

Can the patient swallow or are secretions accumulating in the pharynx, an early signof bulbar paralysis? Ask the patient to take deep breaths in and out. Paradoxicalrespiration (abdomen expands rather than the chest on attempted inspiration)indicates that the diaphragm is still contracting but that the intercostal muscles andaccessory muscles of inspiration are paralysed. Objective measurement of ventilatorycapacity is very useful. Use a peak flow metre, spirometer (FEV1 and FVC) or ask thepatient to blow into the tube of a sphygmomanometer to record the maximumexpiratory pressure (mmHg). Remember that, provided their lungs are adequatelyventilated, patients with profound generalised flaccid paralysis from neurotoxicenvenoming are fully conscious. Because their eyes are closed and they do not moveor speak, they are commonly assumed to be unconscious. They may still be able toflex a finger or toe and so simple communication is possible.

Figure 40: Examination for ptosis,usually the earliest sign of neurotoxicenvenoming (Copyright DA Warrell)

Figure 42: Broken neck sign in a child envenomed by a cobra in Malaysia (Copyright the lateHA Reid)

Figure 41: Inability to open the mouth and protrude thetongue in a patient with neurotoxic envenoming fromthe Malayan krait (Copyright DA Warrell)


Do not assume that patients have irreversible brain damage because they areareflexic, unresponsive to painful stimuli, or have fixed dilated pupils.

Generalised rhabdomyolysis

In victims of envenoming by sea snakes and Russells vipers in Sri Lanka and SouthIndia, muscles, especially of the neck, trunk and proximal part of the limbs, maybecome tender and painful on active or passive movement and later may becomeparalysed. In sea snake bite there is pseudotrismus that can be overcome by sustainedpressure on the lower jaw. Myoglobinuria may be evident 3 hours after the bite.

Examination of pregnant women

There will be concern about fetal distress (revealed by fetal bradycardia), vaginalbleeding and threatened abortion. Monitoring of uterine contractions and fetal heartrate is useful. Lactating women who have been bitten by snakes should be encouragedto continue breast feeding.

Species diagnosis

If the dead snake has been brought, it can be identified. Otherwise, the speciesresponsible can be inferred indirectly form the patients description of the snake andthe clinical syndrome of symptoms and signs (see above and Annex 1 & 2). This isspecially important in Thailand where only monospecific antivenoms are available.

4.5 Investigations/laboratory tests

20 minute whole blood clotting test (20WBCT)

This very useful and informative bedside test requires very little skill and only onepiece of apparatus - a new, clean, dry, glass vessel (tube or bottle).

20 minute whole blood clotting test (20WBCT)

Place a few mls of freshly sampled venous blood in a small glass vessel

Leave undisturbed for 20 minutes at ambient temperature

Tip the vessel once

If the blood is still liquid (unclotted) and runs out, the patient has hypo-fibrinogenaemia (incoagulable blood) as a result of venom-inducedconsumption coagulopathy

In the South East Asian region, incoagulable blood is diagnostic of a viper biteand rules out an elapid bite

Warning! If the vessel used for the test is not made of ordinary glass, or if ithas been used before and cleaned with detergent, its wall may not stimulateclotting of the blood sample in the usual way and test will be invalid

If there is any doubt, repeat the test in duplicate, including a control (bloodfrom a healthy person)



Other tests

Haemoglobin concentration/haematocrit: a transient increase indicateshaemoconcentration resulting from a generalised increase in capillary permeability(eg in Russells viper bite). More often, there is a decrease reflecting blood loss or, inthe case of Indian and Sri Lankan Russells viper bite, intravascular haemolysis.

Platelet count: this may be decreased in victims of viper bites.

White blood cell count: an early neutrophil leucocytosis is evidence of systemicenvenoming from any species.

Blood film: fragmented red cells (helmet cell, schistocytes) are seen whenthere is microangiopathic haemolysis.

Plasma/serum may be pinkish or brownish if there is gross haemoglobinaemiaor myoglobinaemia.

Biochemical abnormalities: aminotransferases and muscle enzymes (creatinekinase, aldolase etc) will be elevated if there is severe local damage or, particularly, ifthere is generalised muscle damage (Sri Lankan and South Indian Russells viperbites, sea snake bites). Mild hepatic dysfunction is reflected in slight increases inother serum enzymes. Bilirubin is elevated following massive extravasation of blood.Creatinine, urea or blood urea nitrogen levels are raised in the renal failure of Russellsviper and saw-scaled viper bites and sea snake bites. Early hyperkalaemia may beseen following extensive rhabdomyolysis in sea snake bites. Bicarbonate will be lowin metabolic acidosis (eg enal failure).

Arterial blood gases and pH may show evidence of respiratory failure (neurotoxicenvenoming) and acidaemia (respiratory or metabolic acidosis).

Warning: arterial puncture is contraindicated in patients with haemostaticabnormalities (Viperidae)

Desaturation: arterial oxygen desaturation can be assessed non-invasively inpatients with respiratory failure or shock using a finger oximeter.

Urine examination: the urine should be tested by dipsticks for blood/haemoglobin/myoglobin. Standard dipsticks do not distinguish blood, haemoglobinand myoglobin. Haemoglobin and myoglobin can be separated by immunoassaysbut there is no easy or reliable test. Microscopy will confirm whether there areerythrocytes in the urine. Red cell casts indicate glomerular bleeding. Massiveproteinuria is an early sign of the generalised increase in capillary permeability inRussells viper envenoming.


4.6 Antivenom treatment

Antivenom is the only specific antidote to snake venom. A most important decisionin the management of a snake bite victim is whether or not to give antivenom.

What is antivenom?

Antivenom is immunoglobulin (usually the enzyme refined F(ab)2 fragment of IgG)purified from the serum or plasma of a horse or sheep that has been immunised withthe venoms of one or more species of snake. Specific antivenom, implies that theantivenom has been raised against the venom of the snake that has bitten the patientand that it can therefore be expected to contain specific antibody that will neutralisethat particular venom. Monovalent or monospecific antivenom neutralises the venomof only one species of snake. Polyvalent or polyspecific antivenom neutralises thevenoms of several different species of snakes, usually the most important species,from a medical point of view, in a particular geographical area. For example, Haffkine,Kasauli, Serum Institute of India and Bengal polyvalent anti-snake venom serum israised in horses using the venoms of t he four most important venomous snakes inIndia (Indian cobra, Naja naja; Indian krait, Bungarus caeruleus; Russells viper, Daboiarusselii; saw-scaled viper, Echis carinatus). Antibodies raised against the venom ofonespecies may have cross-neutralising activity against other venoms, usually from closelyrelated species. This is known as paraspecific activity. For example, the manufacturersof Haffkine polyvalent anti-snake venom serum claim that this antivenom alsoneutralises venoms of two Trimeresurus species.

Indications for antivenom treatment (see also Annex 1 & 2)

Antivenom treatment carries a risk of severe adverse reactions and in most countriesit is costly and may be in limited supply. It should therefore be used only in patientsin whom the benefits of antivenom treatment are considered to exceed the risks.

Indications for antivenom vary in different countries.

Inappropriate use of antivenom

In some parts of the world, antivenom is given to any patient claiming to have beenbitten by a snake, irrespective of symptoms or signs of envenoming. Sometimes thelocal community are so frightened of snake bite that they compel the doctor to giveantivenom against medical advice. These practices should be strongly discouragedas they expose patients who may not need treatment to the risks of antivenomreactions; they also waste valuable and scarce stocks of antivenom.



Indications for antivenom

Antivenom treatment is recommended if and when a patient with proven orsuspected snake develops one or more of the following signs

Systemic envenoming

Haemostatic abnormalities: spontaneous systemic bleeding (clinical),coagulopathy (20WBCT or other laboratory) or thrombocytopenia (


Contraindications to antivenom

There is no absolute contraindication to antivenom treatment, but patients whohave reacted to horse (equine) or sheep (ovine) serum in the past (for example aftertreatment with equine anti-tetanus serum, equine anti-rabies serum or equine orovine antivenom) and those with a strong history of atopic diseases (especially severeasthma) should be given antivenom only if they have signs of systemic envenoming.

Prophylaxis in high risk patients

In the absence of any prophylactic regimen that has proved effective in clinical trials,these high risk patients may be pre-treated empirically with subcutaneous epinephrine(adrenaline), intravenous antihistamines (both anti-H1, such as promethazine orchloramphenicol; and anti- H2, such as cimetidine or ranitidine) and corticosteroid.In asthmatic patients, prophylactic use of an inhaled adrenergic 2 agonist such assalbutamol may prevent bronchospasm.

Selection of antivenom

Antivenom should be given only if its stated range of specificity includes the speciesknown or thought to have been responsible for the bite. Liquid antivenoms that havebecome opaque should not be used as precipitation of protein indicates loss ofactivity and an increased risk of reactions.

Expiry dates quoted by manufacturers are often very conservative. Provided thatantivenom has been properly stored, it can be expected to retain useful activity formany months after the stated expiry date.

If the biting species is known, the ideal treatment is with a monospecific/monovalent antivenom, as this involves administration of a lower dose of antivenomprotein than with a polyspecific/ polyvalent antivenoms. Polyspecific/polyvalentantivenoms are preferred in many countries because of the difficulty in identifyingspecies responsible for bites. Polyspecific antivenoms can be just as effective asmonospecific ones, but since they contain specific antibodies against several differentvenoms, a larger dose of antivenom protein must be administered to neutralise aparticular venom.

Administration of antivenom

Epinephrine (adrenaline) should always be drawn up in readiness beforeantivenom is administered.

Antivenom should be given by the intravenous route whenever possible.

Freeze-dried (lyophilised) antivenoms are reconstituted, usually with 10 ml of sterilewater for injection per ampoule. The freeze-dried protein may be difficult to dissolve.Two methods of administration are recommended:



(1) Intravenous push injection: reconstituted freeze-dried antivenom or neatliquid antivenom is given by slow intravenous injection (not more than 2ml/minute). This method has the advantage that the doctor/nurse/dispensergiving the antivenom must remain with the patient during the time whensome early reactions may develop. It is also economical, saving the use ofintravenous fluids, giving sets, cannulae etc.

(2) Intravenous infusion: reconstituted freeze-dried or neat liquid antivenom isdiluted in approximately 5-10 ml of isotonic fluid per kg body weight (ie250-500 ml of isotonic saline or 5% dextrose in the case of an adult patient)and is infused at a constant rate over a period of about one hour.

Local administration of antivenom at the site of the bite is notrecommended!

Although this route may seem rational, it should not be used as it is extremely painful,may increase intracompartmental pressure and has not been shown to be effective.

Intramuscular injection of antivenom

Antivenoms are large molecules (F(ab )2 fragments or sometimes whole IgG) which,after intramuscular injection, are absorbed slowly via lymphatics. Bioavailability ispoor, especially after intragluteal injection and blood levels of antivenom never reachthose achieved rapidly by intravenous administration. Other disadvantages are thepain of injection of large volumes of antivenom and the risk of haematoma formationin patients with haemostatic abnormalities.

Antivenom must never be given by the intramuscular route if it could be givenintravenously.

Situations in which intramuscular administration might be considered :

at a peripheral first aid station, before a patient with obvious envenoming isput in an ambulance for a journey to hospital that may last several hours;

on an expedition exploring a remote area very far from medical care;

when intravenous access has proved impossible.

Although the risk of antivenom reactions is less with intramuscular than intravenousadministration, epinephrine (adrenaline) must be readily available. Patients must beclosely observed for at least one hour after starting intravenous antivenomadministration, so that early anaphylactic antivenom reactions can be detected andtreated early with epinephrine (adrenaline).

Under these unusual circumstances, the dose of antivenom should be dividedbetween a number of sites in the upper anterolateral region of both thighs. A maximumof 5-10 ml should be given at each site by deep intramuscular injection followed bymassage to aid absorption. Local bleeding and haematoma formation is a problem inpatients with incoagulable blood.


Finding enough muscle mass to contain such large volumes of antivenom isparticularly difficult in children.

Antivenom should never be injected into the gluteal region (upper outer quadrantof the buttock) as absorption is exceptionally slow and unreliable and there isalways the danger of sciatic nerve damage when the injection is given by aninexperienced operator.

Dose of antivenom

Snakes inject the same dose of venom into children and adults. Children musttherefore be given exactly the same dose of antivenom as adults.

Manufacturers recommendations are usually based on inappropriate animal tests inwhich venom and antivenom are incubated before being injected into the test animal.The recommended dose is often the amount of antivenom required to neutralise theaverage venom yield when captive snakes are milked of their venom. In practice, thechoice of an initial dose of antivenom is usually empirical.

Antivenom manufacturers, health institutions and medical research organisationsshould encourage and promote the proper clinical testing of antivenoms as withother therapeutic agents. This is the only reliable guide to the initial dose (andsafety) of an antivenom.

Since the neutralising power of antivenoms varies from batch to batch, the resultsof a particular clinical trial may soon become obsolete if the manufacturers changethe strength of the antivenom.

Antivenom reactions

A proportion of patients, usually more than 20%, develop a reaction either early(within a few hours) or late (5 days or more) after being given antivenom.

Early anaphylactic reactions: usually within 10-180 minutes of starting antivenom,the patient begins to itch (often over the scalp) and develops urticaria, dry cough,fever, nausea, vomiting, abdominal colic, diarrhoea and tachycardia. A minority ofthese patients may develop severe life-threatening anaphylaxis: hypotension,bronchospasm and angio-oedema. Fatal reactions have probably been under-reportedas death after snake bite is usually attributed to the venom.

In most cases, these reactions are not truly allergic. They are not IgE-mediatedtype I hypersensitivity reactions to horse or sheep proteins as there is no evidence ofspecific IgE, either by skin testing or radioallergosorbent tests (RAST). Complementactivation by IgG aggregates or residual Fc fragments or direct stimulation of mastcells or basophils by antivenom protein are more likely mechanisms for these reactions.



Pyrogenic (endotoxin) reactions usually develop 1-2 hours after treatment.Symptoms include shaking chills (rigors), fever, vasodilatation and a fall in bloodpressure. Febrile convulsions may be precipitated in children. These reactions arecaused by pyrogen contamination during the manufacturing process. They arecommonly reported.

Late (serum sickness type) reactions develop 1-12 (mean 7) days after treatment.Clinical features include fever, nausea, vomiting, diarrhoea, itching, recurrent urticaria,arthralgia, myalgia, lymphadenopathy, periarticular swellings, mononeuritis multiplex,proteinuria with immune complex nephritis and rarely encephalopathy. Patients whosuffer early reactions and are treated with antihistamines and corticosteroid are lesslikely to develop late reactions.

Treatment of early anaphylactic and pyrogenic antivenomreactions

Epinephrine (adrenaline) is given intramuscularly (into the deltoid muscle or theupper lateral thigh) in an initial dose of 0.5 mg for adults, 0.01 mg/kg body weight forchildren. Severe, life-threatening anaphylaxis can evolve very rapidly and soepinephrine (adrenaline) should be given at the very first sign of a reaction, evenwhen only a few spots of urticaria have appeared or at the start of itching, tachycardiaor restlessness. The dose can be repeated every 5-10 minutes if the patients conditionis deteriorating.

At the earliest sign of a reaction:

Antivenom administration must be temporarily suspended

Epinephrine (adrenaline) (0.1% solution, 1 in 1,000, 1 mg/ml) is the effectivetreatment for early anaphylactic and pyrogenic antivenom reactions

Additional treatment

After epinephrine (adrenaline), an anti H1 antihistamine such as chlorpheniraminemaleate (adults 10 mg, children 0.2 mg/kg by intravenous injection over a few minutes)should be given followed by intravenous hydrocortisone (adults 100 mg, children2 mg/kg body weight). The corticosteroid is unlikely to act for several hours, but mayprevent recurrent anaphylaxis.

There is increasing evidence that anti H2 antihistamines such as cimetidine orranitidine have a role in the treatment of severe anaphylaxis. Both drugs are given,diluted in 20 ml isotonic saline, by slow intravenous injection (over 2 minutes).

Doses: cimetidine adults 200 mg, children 4 mg/kg;ranitidine adults 50 mg, children 1 mg/kg.

In pyrogenic reactions the patient must also be cooled physically and withantipyretics (for example paracetamol by mouth or suppository). Intravenous fluidsshould be given to correct hypovolaemia.


Treatment of late (serum sickness) reactions

Late (serum sickness) reactions usually respond to a 5-day course of oral antihistamine.Patients who fail to respond in 24-48 hours should be given a 5-day course ofprednisolone.

Doses: Chlorpheniramine: adults 2 mg six hourly, children 0.25 mg/kg /dayin divided doses

Prednisolone: adults 5 mg six hourly, children 0.7 mg/kg/day in divided doses for5-7 days

Observation of the response to antivenom

If an adequate dose of appropriate antivenom has been administered, the followingresponses may be seen.

General: the patient feels better. Nausea, headache and generalised achesand pains may disappear very quickly. This may be partly attributable to aplacebo effect.

Spontaneous systemic bleeding (eg from the gums) usually stops within 15-30 minutes.

Blood coagulability (as measured by 20WBCT) is usually restored in 3-9hours. Bleeding from new and partly healed wounds usually stops muchsooner than this.

In shocked patients, blood pressure may increase within the first 30-60minutes and arrhythmias such as sinus bradycardia may resolve.

Neurotoxic envenoming of the post-synaptic type (cobra bites) may beginto improve as early as 30 minutes after antivenom, but usually take severalhours. Envenoming with presynaptic toxins (kraits and sea snakes) is unlikelyto respond in this way.

Active haemolysis and rhabdomyolysis may cease within a few hours andthe urine returns to its normal colour.

Recurrence of systemic envenoming

In patients envenomed by vipers, after an initial response to antivenom (cessation ofbleeding, restoration of blood coagulability), signs of systemic envenoming may recurwithin 24-48 hours.

This is attributable to:

(1) continuing absorption of venom from the depot at the site of the bite,perhaps assisted by improved blood supply following correction of shock,hypovolaemia etc, after elimination of antivenom (range of elimination half-lives: IgG 45 hours; F(ab)2 80-100 hours; Fab 12-18 hours);

(2) a redistribution of venom from the tissues into the vascular space, as theresult of antivenom treatment.

Recurrent neurotoxic envenoming after treatment of cobra bite has also beendescribed.



Criteria for repeating the initial dose of antivenom

Criteria for giving more antivenom

Persistence or recurrence of blood incoagulability after 6 hr of bleeding after1-2 hr

Deteriorating neurotoxic or cardiovascular signs after 1-2 hr

If the blood remains incoagulable (as measured by 20WBCT) six hours after theinitial dose of antivenom, the same dose should be repeated. This is based on theobservation that, if a large dose of antivenom (more than enough to neutralise thevenom procoagulant enzymes) is given initially, the time taken for the liver to restorecoagulable levels of fibrinogen and other clotting factors is 3-9 hours.

In patients who continue to bleed briskly, the dose of antivenom should berepeated within 1-2 hours.

In case of deteriorating neurotoxicity or cardiovascular signs, the initial doseof antivenom should be repeated after 1-2 hours, and full supportive treatment mustbe considered.

Conservative treatment when no antivenom is available

This will be the situation in many parts of the region, where supplies of antivenomrun out or where the bite is known to have been inflicted by a species against whosevenom there is no available specific antivenom (for example for bites by the Malayankrait (Bungarus candidus), coral snakes - genera Calliophis and Maticora), sea snakes,the mangrove/shore pit viper T purpureomaculatus and the mountain pit viper Ovophismonticola.

The following conservative measures are suggested:

Neurotoxic envenoming with respiratory paralysis: assisted ventilation. Thishas proved effective, and has been followed by complete recovery, even after beingmaintained for periods of more than one month. Manual ventilation (anaestheticbag) by relays of doctors, medical students, relatives and nurses has been effectivewhere no mechanical ventilator was available. Anticholinesterases should always betried (see below Trial of anticholinesterase, p 41).

Haemostatic abnormalities strict bed rest to avoid even minor trauma;transfusion of clotting factors and platelets; ideally, fresh frozen plasma andcryoprecipitate with platelet concentrates or, if these are not available, fresh wholeblood. Intramuscular injections should be avoided.

Shock, myocardial damage: hypovolaemia should be corrected with colloid/crystalloids, controlled by observation of the central venous pressure. Ancillary pressor


drugs (dopamine or epinephrine-adrenaline) may also be needed. Patients withhypotension associated with bradycardia should be treated with atropine.

Renal failure: conservative treatment or dialysis (see Oliguria and renal failure,page 42).

Dark brown urine (myoglobinuria or haemoglobinuria): correct hypovolaemiaand acidosis and consider a single infusion of mannitol (see Prevention of renal damagein patients with myoglobinuria or haemoglobinuria, page 45 ).

Severe local envenoming: local necrosis, intracompartmental syndromes andeven thrombosis of major vessels is more likely in patients who cannot be treatedwith antivenom. Surgical intervention may be needed but the risks of surgery in apatient with consumption coagulopathy, thrombocytopenia and enhanced fibrinolysismust be balanced against the lifethreatening complications of local envenoming.Prophylactic broad spectrum antimicrobial treatment is justified (see Bacterialinfections, page 46).

4.7 Supportive/ancillary treatmentAntivenom treatment can be expected to neutralise free circulating venom, preventprogression of envenoming and allow recovery. However, these processes take timeand the severely envenomed patient may require life support systems such as assistedventilation and renal dialysis until the severely damaged organs and tissues have hadtime to recover.

Dangers of venepuncture in patients with haemostaticabnormalities

In patients with incoagulable blood, any injection (subcutaneous, intramuscular) and,particularly venepuncture, carries a risk of persistent bleeding and haematomaformation. Arterial puncture is contraindicated in such patients.

Repeated venepuncture can be avoided by using an indwelling cannula and three-way tap system. When blood coagulability has been restored, the dead space shouldbe filled with heparinised saline, but beware! If this is not flushed out before bloodsampling, misleading results will be obtained in clotting tests, including the 20WBCT.

In patients with coagulopathy, sites of venous access and placement of intravenouscannulae or catheters should be chosen where haemostasis by external pressure ismost likely to be effective, eg the antecubital fossa. If possible, avoid jugular, subclavianand femoral vein puncture. A pressure pad must be applied at the site of anyvenepuncture.

Neurotoxic envenoming

Antivenom treatment alone cannot be relied upon to save the life of a patient withbulbar and respiratory paralysis.



Death may result from aspiration, airway obstruction or respiratory failure. Aclear airway must be maintained. Once there is loss of gag reflex and pooling ofsecretions in the pharynx, failure of the cough reflex or respiratory distress, a cuffedendotracheal tube should be inserted. If this is impossible for any reason, atracheostomy should be performed and a snugly-fitting or cuffed tracheostomy tubeinserted.

Although artificial ventilation was first suggested for neurotoxic envenoming 125years ago, patients continue to die of asphyxiation because some doctors believethat antivenom is sufficient treatment.

Anticholinesterase drugs have a variable, but potentially very useful effect inpatients with neurotoxic envenoming, especially those bitten by cobras.

A trial of anticholinesterase (eg Tensilon test) should be performed in everypatient with neurotoxic envenoming, as it would be in any patient with suspectedmyasthenia gravis.

Trial of anticholinesterase

Anticholinesterase (eg Tensilon/edrophonium) test

Baseline observations

Give atropine intravenously

Give anticholinesterase drug

Observe effect

If positive, institute regular atropine and (long acting) anticholinesterase

Ideally, a short acting anticholinesterase, such as edrophonium (Tensilon), shouldbe used. Baseline observations or measurements are made against which to assessthe effectiveness of the anticholinesterase. Atropine sulphate (adults 0.6 mg, children50 g/kg body weight) is given by intravenous injection (to prevent the undesirablemuscarinic effects of acetylcholine such as increased secretions, sweating, bradycardiaand colic) followed immediately by edrophonium chloride (adults 10 mg, children0.25 mg/kg body weight) given intravenously over 3 or 4 minutes. The patient isobserved over the next 10-20 minutes for signs of improved neuromusculartransmission. Ptosis may disappear (Fig 43) and ventilatory capacity (peak flow, FEV1or maximum expiratory pressure) may improve.

If edrophonium chloride is not available, any other anticholinesterases(neostigmine Prostigmine, distigmine, pyridostigmine, ambenomium) can be usedfor this assessment but a longer period of observation will be needed (up to 1 hour).

Patients who respond convincingly can be maintained on a longer-actinganticholinesterase such as neostigmine methylsulphate combined with atropine.


Hypotension and shock

Snake bite: causes of hypotension and shock

(1) Anaphylaxis (2) Antivenom reactionVasodilatation Respiratory failureCardiotoxicity Acute pituitary adrenal insufficiencyHypovolaemia Septicaemia

This is usually the result of hypovolaemia (from loss of circulating volume into theswollen limb, or internal/external haemorrhage), venom-induced vasodilatation ordirect myocardial effects with or without arrhythmias. Ideally, treatment with plasmaexpanders (colloids or crystalloid) should be controlled by observation of the centralvenous pressure (jugular venous pressure or direct measurement of pressure in thesuperior vena cava via a catheter connected to a saline manometer, see Annex 4).Excessive volume replacement may cause pulmonaryoedema when plasmaextravasated in the bitten limb and elsewhere is reabsorbed into the circulation.

In patients with evidence of a generalised increase in capillary permeability, aselective vasoconstrictor such as dopamine may be given by intravenous infusion,preferably into a central vein (starting dose 2.5-5 g/kg/minute).

In victims of Russells viper bites in Myanmar and South India, acute pituitaryadrenal insufficiency resulting from haemorrhagic infarction of the anterior pituitarymay contribute to shock. Hydrocortisone is effective in these cases.

Oliguria and renal failure

Detection of renal failure

Dwindling or no urine output

Rising blood urea/creatinine concentrations

Clinical uraemia syndrome

nausea, vomiting, hiccups, fetor, drowsiness, confusion, coma, flapping tremor,muscle twitching, convulsions, pericardial friction rub, signs of fluid overload

Figure 43: (a) before and (b) after intravenous atropine followed by intravenous edrophoniumchloride in a patient envenomed by a Malayan krait (Bungarus candidus) (Copyright DA Warrell)



In patients with any of these features, the following should be monitored

pulse rate

blood pressure, lying and sitting, to detect postural hypotension

respiratory rate

temperature

height of jugular venous pulse

auscultation of lung bases for crepitations

Oliguric phase of renal failure

Most, but not all, patients with acute renal failure are oliguric, defined as a urineoutput of less than 400 ml/day or less than 20 ml/hour. Conservative managementmay tide the patient over, avoiding the need for dialysis. If the patient is hypovolaemic,indicated by supine or postural hypotension, empty neck veins, sunken eyeballs, lossof skin turgor and dryness of mucosae, proceed as follows:

(1) Establish intravenous access

(2) Insert a urethral catheter (full sterile precautions!)

(3) Determine the central venous pressure. This can be achieved either byobserving the vertical height of the jugular venous pulsation above the sternalangle with the patient propped up on pillows at 45o; or by directmeasurement of central venous (superior vena caval) pressure through along catheter preferably inserted at the antecubital fossa (see Annex 4). Thecatheter is connected to a saline manometer, the 0 point of which must beplaced at the same level as the right atrium (that is, at the sternal anglewhen the patient is propped up at 45o). In someone who is obviously volume-depleted, resuscitation should start immediately, and not be delayed until acentral venous line has been inserted.

(4) Fluid challenge: depending on the initial state of hydration/dehydration,an adult patient can be given two litres of isotonic saline over one hour or,until the jugular venous pressure/central venous pressure has risen to 8-10cm above the sternal angle (with the patient propped up at 45o). The patientmust be closely observed while this is being done. The fluid challenge mustbe stopped immediately if pulmonary oedema develops. If the urine outputdoes not improve, try furosamide challenge.

(5) Furosamide (frusemide) challenge: 100 mg of furosamide is injected slowly(4-5 mg/minute). If this does not induce a urine output of 40 ml/hour, givea second dose of furosamide, 200 mg. If urine output does not improve, trymannitol challenge.

(6) Mannitol challenge: 200 ml of 20% mannitol may be infused intravenouslyover 20 minutes but this must not be repeated as there is a danger ofinducing dangerous fluid and electrolyte imbalance. An improvement inurine output to more than 40 ml/hr or more than 1 litre/day is consideredsatisfactory.

(7) Conservative management: If the urine output does not improve, despitethese challenges, no further diuretics should be given and fluid intake should


be restricted to a total of the previous days output plus insensible losses(500-1000 ml/day). If possible, the patient should be referred to a renalunit. The diet should be bland, high in calories (1700/day), low in protein(less than 40g/day), low in potassium (avoid fruit, fruit juices and potassium-containing drugs) and low in salt. Infections will cause tissue breakdownand increase urea levels. They should be prevented or treated promptlywith non-nephrotoxic antibiotics (ie avoid aminoglycosides such asgentamicin).

(8) Biochemical monitoring: Serum potassium, urea, creatinine and, if possible,pH, bicarbonate, calcium and phosphate should be monitored frequently.If this is not possible the electrocardiogram (ECG) should be examined forevidence of hyperkalaemia, especially following bites by sea snakes, or SriLankan or South Indian Russells vipers or if the patient is passing darkbrown urine, indicating rhabdomyolysis or intravascular haemolysis.

ECG evidence of hyperkalaemia: tall peaked T waves, prolonged P-Rinterval, absent P waves, wide QRS complexes.

Emergency treatment of hyperkalaemia(serum potassium >6.5 mmol/l or ECG changes)

give 10 ml of 10% calcium gluconate intravenously over 2 minutes(with ECG monitoring if possible) repeated up to three times

give 50 ml of 50% dextrose with 10 units of soluble insulin intravenously

sodium bicarbonate (40 ml of 8.4%) by slow intravenous infusion anda 2 agonist aerosol by inhaler (eg salbutamol Ventolin 5-10 mg)may also be used

These emergency treatments will control hyperkalaemia for 3-6 hoursonly. If the patient is hypotensive and profoundly acidotic (deep sighingKussmaul respirations, very low plasma bicarbonate concentration or verylow pH - 6 mg/dl (500 mol/l)urea >200 mg/dl (400 mmol/l)potassium >7 mmol/l (or hyperkalaemic ECG changes)symptomatic acidosis



Prevention of renal damage in patients with myoglobinuria orhaemoglobinuria

To minimise the risk of renal damage from excretedmyoglobin and/or haemoglobin:

correct hypovolaemia (see above) and maintain saline diuresis (if possible)

correct severe acidosis with bicarbonate (see above)

give a single infusion of mannitol (200 ml of 20% solution over 20 minutes)

Diuretic phase of renal failure

Urine output increases following the period of anuria. The patient may becomepolyuric and volume depleted so that salt and water must be carefully replaced.Hypokalaemia may develop, in which case a diet rich in potassium (fruit and fruitjuices) is recommended.

Renal recovery phase

The diuretic phase may last for months after Russells viper bite. In Myanmar andSouth India, hypopituitarism may complicate recovery of Russells viper bite victims.Corticosteroid, fluid and electrolyte replacement may be needed in these patients.

Persisting renal dysfunction

In Myanmar, persistent tubular degenerative changes were observed in Russells viperbite victims who showed continuing albuminuria, hypertension and nocturia for upto 11 months after the bite, despite apparent recovery in renal function. In India, 20-25% of patients referred to renal units with acute renal failure following Russellsviper bite suffered oliguria for more than 4 weeks suggesting the possibility of bilateralrenal cortical necrosis. This can be confirmed by

SDE Mgmt Snake-bite

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