a2 snakebite management in asia and africa

Snakebite Management in Asia & Africa AA gguuiiddee ttoo ssnnaakkeebbiittee iinn tthhee kkeeyy aarreeaass ffoorr mmoorrttaalliittyy && mmoorrbbiiddiittyy

AA22

2

Guidelines produced by:

Pakistan Medical Research Council

Endorsed by:

Pakistan Medical Association

World Health Organization Pakistan Country Office

3

Indian Journal of Emergency Pediatrics

National Program for Family Planning and Primary Health Care

4

FFoorrwwaarrdd

Snakebite remains a medical condition of the rural poor in developing

countries and yet ironically, western developed countries largely produce

textbooks and guidelines for treatment of snakebite. These developed country

guidelines are probably effective in a developed country infrastructure with

access to advanced facilities but developing countries are different. Solutions

proposed must be practical, preferably low cost and should be based on

extensive experience of developing country facilities.

As a result of this PMRC has embarked on a programme to develop a set of

guidelines for snakebite management for the two key areas of mortality, Asia

and Africa. The guidelines are based on extensive study of the problem and

needs of developing countries. Recommendations are practical and

applicable in the most basic medical facilities.

The core intention of the guidelines are to enable doctors in basic facilities

manage snakebite effectively and determine when the patient can be treated

locally and when and under what conditions they should be referred to better

equipped hospitals. Referral of patients is a reality in developing countries and

yet there have been few guides that assist in how this can be most effectively

managed.

We hope that these guidelines will be widely disseminated which is why we

have made them freely available for doctors to download and use within their

own facilities. We hope that Health Departments will assist in circulating the

guidelines to all doctors in snakebite prone areas.

5

IInnttrroodduuccttiioonn

Snakebite has remained an enduring medical problem for many decades and

little progress has been made in reducing mortality. Globally, approximately

50,000 – 60,000 people die each year as a result of snakebite and more are

left permanently impaired. The vast majority are rural agricultural workers

engaged in subsistence farming.

Over 90% of these fatalities occur in two continents i.e. Africa and Asia. The

influence of Western textbooks on the medical education of these continents

is high and as a result doctor confidence and capability in managing snakebite

is sub optimal as guidelines are not continent specific or appropriate for the

developing world. Ironically however, much of appropriate snakebite

treatment is common to all areas.

Too little attention to providing guidelines for physicians has been given by

snakebite experts, despite this being regularly identified as an area of concern

for many decades. This text is intended to guide doctors in how to deal with

snakebite in both Asia and Africa.

Much of snakebite treatment is not based on clinical trials as very few have

been carried out by experts in the last four decades, funds have been

deployed on conferences and ‘planning’ meetings’! The argument propounded

by many experts that guidelines should not be published until trial data is

available is both unhelpful and unrealistic. ‘Evidence based medicine’ has

now become the battle cry of those who have delivered little in many decades

and wish to inhibit any potential progress.

Doctors are treating snakebite daily and guidelines are urgently required.

Victims require our help today and cannot be told that treatment will have to

wait for trial data, particularly when we have already been waiting for several

decades.

6

These guidelines are based on practical experience of all levels of medical

care in developing countries, mainly in the Government Hospital sector where

the majority of snakebites are treated. The guidelines include very practical

approaches and improvised solutions that are based on the real environment

in which snakebite is treated. Western approaches, based on western hospital

profiles or western originated ‘international training courses’ have been shown

to fail to prepare developed world doctors from providing assistance in

developing countries.

No guidelines, including these, are perfect. As doctors use these guidelines to

treat victims their observations and innovations will lead to further progress in

both understanding and treatment of snakebite. Progress in treatment is

essential if victims are to be best served by the medical facilities that cater to

them.

The guidelines are comprehensive and are targeted at doctors and health

officials who administrate health in developing countries. Recommendations

concerning how to for prepare for snakebite in natural disasters and how to

equip basic health facilities to deal with snakebite are key areas for

administrators. If health officials are not familiar with the key drug

requirements to deal with snakebite doctors will not be properly equipped.

These guidelines present an open and clear indication of some of the key

controversies within snakebite management, such as the use of swelling as

an indication for administering anti venom.

Where the principles contained within these guidelines have been

implemented, direct improvements in treatment, reduced mortality and more

efficient use of anti venom has been the result.

7

Snakebite is not the source for television programmes or conferences, it is a

terrible malady of the rural agricultural worker and it is entirely manageable in

even the most basic settings if practical guidelines are made available and

subject to a cascade process.

It is hoped that these guidelines can contribute to that process.

Ian D Simpson Snakebite Adviser: Pakistan Medical Research Council. Editorial Advisory Board: Pakistan Journal of Medical Research. Snakebite Adviser: KFBG China Programme. Government Snakebite Task Forces Tamil Nadu, India, West Bengal, India. Editorial Advisory Board: Indian Journal of Emergency Pediatrics. Email ID: [email protected]

mailto:[email protected]

8

CCoonntteennttss

11..00 SSnnaakkeess ooff MMeeddiiccaall SSiiggnniiffiiccaannccee 1144

11..11 IInnttrroodduuccttiioonn 1144

11..22 SSnnaakkeess ooff MMeeddiiccaall SSiiggnniiffiiccaannccee 1144

11..33 SSoouutthh AAssiiaa 1166

11..44 AAssiiaa CCeennttrraall,, SSoouutthh EEaasstt aanndd EEaasstt 2200

11..55 WWeesstt AAssiiaa 2222

11..66 AAffrriiccaa SSoouutthh ZZoonnee 2244

11..77 AAffrriiccaa WWeesstt ZZoonnee 2277

11..88 AAffrriiccaa NNoorrtthh EEaasstt ZZoonnee 2288

11..99 AAffrriiccaa PPrrooggrreessssiivvee WWeeaakknneessss SSppeecciieess 3333

22..00 SSnnaakkeebbiittee FFiirrsstt AAiidd 3355


22..22 IInnaapppprroopprriiaattee FFiirrsstt AAiidd 3355

22..33 TTiigghhtt TToouurrnniiqquueettss 3355

22..44 CCuuttttiinngg aanndd SSuuccttiioonn 3377

22..55 PPrreessssuurree IImmmmoobbiilliissaattiioonn MMeetthhoodd ((PPIIMM)) 3388

22..66 OOtthheerr PPrreessssuurree TTeecchhnniiqquueess 4400

22..77 EElleeccttrriicciittyy aanndd IIccee 4411

22..88 WWaasshhiinngg tthhee WWoouunndd 4422

22..99 TTrraaddiittiioonnaall RReemmeeddiieess 4422

22..1100 TTrraaddiittiioonnaall RReemmeeddiieess:: SSnnaakkee SSttoonneess 4455

22..1111 TTrraaddiittiioonnaall RReemmeeddiieess:: SSccaarriiffiiccaattiioonn 4466

22..1122 RReeccoommmmeennddeedd FFiirrsstt AAiidd 4477

33..00 PPaattiieenntt AArrrriivvaall 4499


33..22 AAssyymmppttoommaattiicc AArrrriivvaall 4499

33..33 SSyymmppttoommaattiicc ppaattiieennttss 4499

33..44 KKeeyy IInntteerrvveennttiioonnss 5500

33..55 NNoonn--CCrriittiiccaall AArrrriivvaall 5511

9

44..00 PPaattiieenntt DDiiaalloogguuee 5533


44..22 TTiimmee ooff tthhee BBiittee 5533

44..33 SSnnaakkee SSeeeenn aanndd//oorr KKiilllleedd 5533

44..44 AAllllooppaatthhiicc TTrreeaattmmeenntt BBeeffoorree HHoossppiittaall 5533

44..55 TTrraaddiittiioonnaall TTrreeaattmmeennttss BBeeffoorree HHoossppiittaall 5533

44..66 AAccttiivviittyy aatt TTiimmee ooff BBiittee 5544

55..00 DDiiaaggnnoossiiss:: SSiiggnnss aanndd SSyymmppttoommss ooff EEnnvveennoommiinngg 5566


55..22 BBlleeeeddiinngg 5566

55..33 PPrrooggrreessssiivvee WWeeaakknneessss 5577

55..44 PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg 5577

66..00 DDiiaaggnnoossiiss ooff EEnnvveennoommiinngg 5588


66..22 VViissiibbllee CCrriitteerriiaa 5588

66..33 SSiimmppllee DDiiaaggnnoossttiicc MMeetthhooddss 6600

66..44 TTeecchhnniiccaall DDiiaaggnnoossttiicc MMeetthhooddss 6611

66..55 BBiittee mmaarrkkss 6622

77..00 AAnnttii SSnnaakkee VVeennoomm 6633


77..22 LLyyoopphhiilliisseedd AASSVV VVss LLiiqquuiidd 6633

77..33 MMoonnoovvaalleenntt VVss PPoollyyvvaalleenntt AASSVV 6633

77..44 WWhhaatt CCaann AASSVV DDoo aanndd NNoott DDoo 6655

77..55 SSwweelllliinngg aanndd AASSVV 6666

77..66 AASSVV SSaaffeettyy 6666

10

88..00 CCrriitteerriiaa ffoorr AAddmmiinniisstteerriinngg AASSVV 6677


88..22 BBlleeeeddiinngg 6677

88..33 PPrrooggrreessssiivvee WWeeaakknneessss 6677

88..44 TThhee ccaassee ffoorr SSwweelllliinngg aanndd LLooccaall ddaammaaggee 6688

88..55 PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg 6688

88..66 HHooww ttoo AAddmmiinniisstteerr AASSVV 6699

88..77 AASSVV AAddmmiinniissttrraattiioonn PPeerriioodd 6699

99..00 AASSVV DDoossaaggee 7700


99..22 IInniittiiaall DDoossiinngg EExxcceeppttiioonnss 7700

99..33 MMaaxxiimmuumm DDoosseess 7711

99..44 LLaattee AAddmmiinniissttrraattiioonn ooff AASSVV 7711

99..55 AASSVV && PPrreeggnnaannccyy 7722

99..66 PPaaeeddiiaattrriicc AASSVV DDoossiinngg 7733

99..77 RReeppeeaatt BBiitteess 7733

99..88 SSoouutthh AAssiiaa AASSVVss 7755

99..99 AAssiiaa CCeennttrraall,, SSoouutthh EEaasstt aanndd EEaasstt AASSVVss 7766

99..1111 WWeesstt AAssiiaa AASSVVss 8811

99..1122 RReeppeeaatt AASSVV DDoosseess 8833

99..1133 RReeppeeaatt AASSVV DDoosseess:: BBlleeeeddiinngg 8833

99..1144 RReeppeeaatt AASSVV DDoosseess:: PPrrooggrreessssiivvee WWeeaakknneessss 8833

99..1155 RReeppeeaatt AASSVV DDoosseess:: PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg 8844

99..1166 SSiiggnnss ooff RReeccoovveerryy 8844

1100..00 AAddvveerrssee AAnnttii SSnnaakkee VVeennoomm RReeaaccttiioonnss 8855


1100..22 MMeecchhaanniissmm ooff tthhee RReeaaccttiioonn 8855

1100..33 PPrreeddiiccttiioonn ooff AAddvveerrssee RReeaaccttiioonnss 8855

1100..44 PPrreevveennttiinngg AAddvveerrssee RReeaaccttiioonnss 8866

1100..55 TTrreeaattmmeenntt ooff AAddvveerrssee RReeaaccttiioonnss 8877

1100..66 AASSVV RReeaaccttiioonn SSuuppppoorrtt DDrruuggss 8888

11

1111..00 NNeeuurroottooxxiicc EEnnvveennoommaattiioonn aanndd AAnnttiicchhoolliinneesstteerraassee DDrruuggss 9900


1111..22 AAnnttiicchhoolliinneesstteerraassee DDrruuggss 9900

1111..33 TThhee TTeesstt 9911

1111..44 AAnnttiicchhoolliinneesstteerraassee DDrruuggss:: TTeessttss aanndd DDoosseess 9911

1122..00 AAiirrwwaayy SSuuppppoorrtt IItteemmss 9933


1122..22 DDeevveellooppiinngg WWoorrlldd AAiirrwwaayy MMaannaaggeemmeenntt CCoonntteexxtt 9933

1122..33 IImmpprroovviisseedd DDeevviicceess 9944

1122..44 BBrriiddggiinngg DDeevviicceess 9955

1122..55 IIddeeaall SSoolluuttiioonn 9977

1133..00 HHaaeemmoottooxxiicc EEnnvveennoommaattiioonn,, BBlloooodd PPrroodduuccttss aanndd RReennaall FFaaiilluurree 9988


1133..22 AAnnttiiccooaagguullaannttss 9999

1133..33 CCooaagguullaannttss 9999

1133..44 LLoonnggeerr TTeerrmm IIssssuueess 9999

1133..55 RReennaall FFaaiilluurree 110000

1144..00 PPaaiinn,, WWoouunndd MMaannaaggeemmeenntt aanndd tthhee SSuurrggiiccaall AAssppeeccttss ooff SSnnaakkeebbiittee 110022

1144..11 PPaaiinn aanndd WWoouunndd MMaannaaggeemmeenntt 110022

1144..22 AAnnttiibbiioottiiccss 110022

1144..33 SSnnaakkee VVeennoomm OOpphhtthhaallmmiiaa 110033

1144..44 SSuurrggeerryy aanndd SSnnaakkeebbiittee 110033

1144..55 SSnnaakkeebbiittee && LLiiffee TThhrreeaatteenniinngg

CCoonnddiittiioonnss RReeqquuiirriinngg SSuurrggeerryy 110033

1144..66 DDeebbrriiddeemmeenntt ooff NNeeccrroottiicc TTiissssuuee 110044

1144..77 CCoommppaarrttmmeenntt SSyynnddrroommee 110044

12

1155..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt iinn BBaassiicc oorr PPrriimmaarryy CCaarree FFaacciilliittiieess 110066


1155..22 PPaattiieenntt AArrrriivvaall && AAsssseessssmmeenntt 110066

1155..33 EEnnvveennoommaattiioonn:: HHaaeemmoottooxxiicc 110066

1155..44 RReeffeerrrraall CCrriitteerriiaa 110077

1155..55 EEnnvveennoommaattiioonn:: NNeeuurroottooxxiicc 110077

1155..66 RReeffeerrrraall CCrriitteerriiaa 110088

1155..77 CCoonnddiittiioonnss aanndd EEqquuiippmmeenntt ffoorr NNeeuurroottooxxiicc RReeffeerrrraall 110088

1166..00 EEqquuiippppiinngg aa BBaassiicc HHoossppiittaall ffoorr EEffffeeccttiivvee SSnnaakkeebbiittee MMaannaaggeemmeenntt 111100


1166..22 AAssssuummppttiioonnss 111100

1166..33 AAnnttii SSnnaakkee vveennoomm 111111

1166..44 OOtthheerr SSuuppppoorrtt DDrruuggss 111122

1166..55 SSuuppppoorrtt EEqquuiippmmeenntt 111133

1177..00 SSnnaakkeebbiittee:: RRiisskk AAccttiivviittiieess aanndd PPrreevveennttiioonn 111144


1177..22 PPrreevveennttiioonn MMyytthhss 111144

1177..33 TThhee DDooccttoorr’’ss RRoollee 111155

1188..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt WWhheenn AASSVV iiss UUnnaavvaaiillaabbllee 111177


1188..22 GGuuiiddiinngg PPrriinncciipplleess 111177

1188..33 AAccttiioonnss ffoorr tthhee PPhhyyssiicciiaann 111188

1199..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt iinn NNaattuurraall DDiissaasstteerrss 112200


1199..22 LLiikkeellyy CCoonnddiittiioonnss aanndd IImmppaacctt 112200

1199..33 DDooccttoorrss aanndd mmeeddiiccaall AAuutthhoorriittyy RReessppoonnssee 112211

13

2200..00 PPrreesseerrvviinngg aanndd IIddeennttiiffyyiinngg SSnnaakkee SSppeecciimmeennss 112266


2200..22 MMeetthhoodd ooff PPrreesseerrvvaattiioonn 112266

2200..33 TTaakkiinngg SSnnaakkee PPhhoottooss ffoorr IIddeennttiiffiiccaattiioonn 112266

2200..44 RReeffeerrrraall ttoo aann EExxppeerrtt 112277

2211..00 SSnnaakkeebbiittee EEppiiddeemmiioollooggyy 112299


2211..22 RReecceenntt EEppiiddeemmiioollooggyy SSttuuddiieess 112299

2211..33 AA PPrraaccttiiccaall AApppprrooaacchh ttoo tthhee AAffrriiccaa AAssiiaa RReeggiioonn 113300

2211..44 TThhee DDooccttoorr’’ss RRoollee 113322

2222..00 PPhhoottooggrraapphhiicc CCrreeddiittss 113333 2233..00 GGeenneerraall AAuutthhoorr AAcckknnoowwlleeddggeemmeennttss 113344 2244..00 RReeffeerreenncceess 113355

14

11..00 SSnnaakkeess ooff MMeeddiiccaall SSiiggnniiffiiccaannccee

11..11 IInnttrroodduuccttiioonn

Despite living in the ‘Nat Geo’ age where the assumption prevails that we

know most of what we need to know about venomous species, the truth is

very different. In many areas there are a number of species of unknown

medical significance. In some areas, uninformed myths such as the ‘Big Four’

in India, based on virtually no compelling evidence dominate thinking and

generate misleading data. Partly this is due to a paucity of useful data

produced by herpetologists who generate theories based on singular

conversations with doctors. The result is that dangerous species can be

underestimated due to poor identification and assumption.

11..22 SSnnaakkeess ooff MMeeddiiccaall SSiiggnniiffiiccaannccee

The snakes of medical importance model is the most useful method of

classifying venomous species in any given area based on potential to cause

death or serious injury frequently or infrequently. This model is not concerned

with precise numbers of deaths, which is unknown in virtually every country,

but the snake’s capability.

The classes are defined as follows:

Class I: Commonly cause death or serious disability

Class II: Uncommonly cause bites but are recorded to cause serious effects

(death or local necrosis)

Class III: Commonly cause bites but serious effects are very uncommon.

In many countries there are snake species, which are known to be venomous

or are suspected of being venomous but their level of threat to humans is not

clear. This model allows physicians to carry out studies and determine which

species fit into the model categories. For example, many of the pit viper family

in Asia and South Asia have not been classified into the model based on

15

definitive capability. The model will enable physicians to determine the threat

posed by each species. The model also enables producers of ASV to

determine whether new species need adding to the current polyvalent mixes

based on objective data.

Each of the major regions of Asia, the Middle East and Africa has been

detailed below and the following data provided.

1. Species for each region have been identified,

2. A preliminary assessment of Class of Medical significance,

3. The primary venom action of the species i.e. B = Bleeding, PPS =

Painful Progressive Swelling and PW = Progressive Weakness.

4. Whether the species is definitively covered with an ASV, not

necessarily produced within that region.

Section 20 contains guidance on preserving dead snake specimens brought

to the hospital and who doctors can send photographs of unknown species for

identification by an expert.

16

11..33 SSoouutthh AAssiiaa

Class

ASV Coverage

Non ASV Coverage

I

Naja naja PW

Naja kaouthia PW 2

Daboia russelii B

Echis carinatus B

Echis sochureki B

II

Naja oxiana PW

Bungarus caeruleus PW

Bungarus fasciatus PW

Ophiophagus hannah PW

Macrovipera lebetina PPS

Cryptelytrops albolabris PPS

Hypnale hypnale B

Hypnale nepa B

Eristicophis macmahoni PPS/PW?

Bungarus sindanus sindanus PW

Bungarus sindanus walli PW

Bungarus lividus PW

Bungarus niger PW

India, Bangladesh, Pakistan, Sri Lanka, Nepal

Note 1. A number of pit vipers are found in the region including the Trimeresurus sp which are believed to be medically significant but no reliable reports are available. This would be a fruitful area of research. Note 2. Indian and Pakistan ASV do not specifically include N. oxiana N. kaouthia or Bungarus fasciatus venom and thus has questionable efficacy against these species.

17

Fig 1.3.1 South Asia PW Cobras Top Row Naja naja (India), N. naja (Sri Lanka), N. kaouthia, Paternless N.naja (Pakistan) Bottom Row. Naja naja (India), N.oxiana (Pakistan), Ophiophagus hannah (India)

18

Fig 1.3.2 South Asia PW Kraits Top. Bungarus caeruleus (India). Middle Row. Bungarus caeruleus (Pakistan) Bottom Row. Bungarus sindanus sindanus (India), B. fasciatus (India)

19

Fig 1.3.3. South Asia Bleeding Top Row. Daboia russelii (Sri Lanka), D. russelii (India). Middle Row. Echis carinatus (India), Echis sochureki (Pakistan). Bottom Row. Hypnale hynale (India), H. hypnale (Sri Lanka)

20

11..44 AAssiiaa CCeennttrraall,, SSoouutthh EEaasstt aanndd EEaasstt

Class

ASV Coverage

Non ASV Coverage

I

Daboia siamensis B

Callesolasma rhodostoma B

Naja kaouthia PW

II

Bungarus fasciatus PW

Bungarus multicinctus PW

Bungarus candidus PW

Gloydius brevicaudus PW

Naja atra PPS

Naja sputatrix PPS

Naja philippinensis PW

Ophiophagus hannah PW

Agkistrodon halys B

Deinagkistrodon acutus B

Macrovipera lebetina PPS/B

Protobothrops flavoviridis PPS

Cryptelytrops albolabris PPS

Vipera berus PPS

Oxyuranus scutellatus canni PW/B

Acanthophis antarcticus/praelongus

PW

Pseudechis australis B

Pseudechis papaunus B/PW

Naja sumatrana PW

Naja siamensis N

Note 1. A variety of pit vipers Protobothrops, Cryptelytrops and Viridovipera are also found in the region. Some cause a large number of bites but mortality is low and few ASVs are available.

21

Fig 1.4.1 Central, South East and East Asia Major Species. Deinagkistrodon acutus, Callesolasma rhodostoma, Naja kaouthia, Oxyuranus scutellatus

22

Fig 1.4.2 Central, South East and East Asia Progressive Weakness: Kraits. Top Row. Bungarus candidus, B. fasciatus. Bottom. Bungarus multicinctus, B. flaviceps

23

11..55 WWeesstt AAssiiaa

Class

ASV Coverage

Non ASV Coverage

I

Cerastes cerastes PPS/B

Echis coloratus B

Echis multisquamatus B

Echis sochureki B

Echis pyramidium PPS/B

Vipera palaestinae PPS

II

Cerastes gasperettii PPS/B?

Pseudocerastes persicus PPS

Cerastes vipera PPS/B

Macrovipera lebetina PPS/B

Bitis arietans PPS

Naja haje PW

Naja oxiana PW

Walterinnesia aegyptia PPS/PW?

Vipera ammodytes PPS/B

Vipera albicornuta PPS/B

Eristicophis macmahoni PPS/PW?

Armenia, Azerbaijan, Bahrain, Cyprus, Georgia, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Saudi Arabia, Syria, Turkey, U.A.E., Yemen.

24

Fig 1.5.1 West Asia Painful Progressive Swelling and Bleeding

Top Row. Echis sochureki, Vipera palaestinae. Middle Row. Echis coloratus, Echis pyramidum. Bottom Row. Macrovipera lebetina, Cerastes cerastes

25

11..66 AAffrriiccaa:: SSoouutthh ZZoonnee

Class

ASV Coverage

Non ASV Coverage

I

Bitis arietans PPS

Naja nigricollis PPS

N. mossambica PPS

II

B. gabonica PPS/B

B. nasicornis PPS/B

N. pallida PPS

Naja melanoleuca PW

Naja annulifera PW

Naja nivea PW

Dendroaspis polylepsis PW

Dendroaspis jamesoni PW

Dendroaspis augusticeps PW

Hemachatus haemachatus PPS PW

Dispholidus typus B

N. nigricincta PPS

N. ashei PPS

Angola Burundi Botswana Congo D.R.C Gabon Kenya Lesotho Malawi

Mozambique Namibia Rwanda South Africa Swaziland Tanzania Uganda

Zambia Zimbabwe

Note 1. Atheris bush vipers cause a small number of bites and one or two are capable

of lethal envenoming e.g. Atheris squamiger. No specific ASV is available. Twig snakes

Thelotornis sp occur in the region, bites are rare and there is no ASV.

26

Fig 1.6.1 Southern Zone Painful Progressive Swelling: Cobras Top Row. Naja nigricollis, N. mossambica. Bottom Row. N. pallida, N. ashei

27

Fig 1.6.2 Southern Zone Painful Progressive Swelling: Vipers Top. Bitis arietans, Middle Bitis gabonica, Bottom. Bitis nasicornis

28

11..77 AAffrriiccaa:: WWeesstt ZZoonnee

Class

ASV Coverage

Non ASV Coverage

I

Bitis arietans PPS

Naja nigricollis PPS

Echis ocellatus B

E. leucogaster B

II

B. gabonica PPS/B

B. nasicornis PPS/B

B. rhinoceros PPS/B

N. katiensis PPS

Dendroaspis viridis PW

Dispholidus typus B

Benin, Burkina Faso, Cameroon, Cape Verde, C.A R., Chad, Cote d’Ivoire, Gambia, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Mauritania, Niger Nigeria, Senegal, Sierra Leone, Togo, Western Sahara. Note 1. Atheris bush vipers cause a small number of bites and one or two are capable of lethal envenoming e.g. Atheris squamiger. No specific ASV is available.

29

Fig 1.7.1 Western Zone Painful Progressive Swelling and Bleeding: Vipers Top Row Bitis gabonica, B. nasicornis, B. rhinoceros Bottom Row. Bitis arietans, Echis ocellatus

30

11..88 AAffrriiccaa:: NNoorrtthh EEaasstt ZZoonnee

Class

ASV Coverage

Non ASV Coverage

I

Naja nigricollis PW

E. pyramidum B

E. ocellatus B

Echis coloratus B

Echis leucogaster B

II

N. pallida PPS

N. nubiae PPS

Naja haje PW

Naja melanoleuca PW

Echis multisquamatus B

Cerastes cerastes PPS/B

Dendroaspis polylepsis PW

Dispholidus typus B

N. ashei PPS

Algeria, Djibouti, Egypt, Eritrea, Ethiopia, Libya, Morocco, Sudan, Somalia, Tunisia.

31

Fig 1.8.1 North Eastern Zone Painful Progressive Swelling: Cobras Top Row. Naja nigricollis, Naja nubiae. Bottom Row. Naja pallida, Naja ashei

32

Fig 1.8.2 North Eastern Zone Painful Progressive Swelling and Bleeding: Vipers Top Row. Echis pyramidum. Middle Row. Echis ocellatus, Cerastes vipera. Bottom Row. Cerastes cerastes

33

11..99 AAllll AAffrriiccaa PPrrooggrreessssiivvee WWeeaakknneessss SSppeecciieess

Fig 1.9.1 Progressive Weakness: The mambas

Top Row. Dendroaspis polylepsis, D. augusticeps .Bottom Row. D. viridis, D. jamesoni

34

Fig 1.9.2. Progressive Weakness: The cobras

Top Row. Naja haje, N.annulifera. Bottom Row. Naja nivea, Hemachatus haemachatus,

N. melanoleuca

35

22..00 SSnnaakkeebbiittee FFiirrsstt AAiidd


Snakebite first aid remains a critical part of snakebite management and yet a

lack of clarity and attention to the evidence has resulted in little positive

progress (Simpson, 2008). Historical and newer methods continue to hold

sway when evidence has either rejected them or shown they have little merit.

Untrained personnel usually apply first aid in the immediate aftermath of

snakebite. It is essential therefore that first aid advice is clear, simple to apply

and provide the maximum benefit and least time delay.

22..22 IInnaapppprroopprriiaattee FFiirrsstt AAiidd MMeetthhooddss

22..33 TTiigghhtt TToouurrnniiqquueettss

The most enduring method of snakebite first aid is the tight ligature or

tourniquet and was recorded from ancient times (Rosner, 1974; Knoefel,

1988). The use of tight tourniquets made of rope, a rubber band, a belt, string

or cloth have been traditionally used to stop venom flow into the body

following snakebite (Bharati, 2000). Some recent publications have also

argued for its potential effectiveness (Stewart 1981) and yet others for it’s

limited effectiveness against certain species such as elapids (Christensen

1969). Klenerman’s work showed that tourniquets, if applied correctly,

reduced blood flow to approximately 1% (Klenerman, 1977a).

However if the tourniquet is applied correctly, are there any problems with its

use? Many authors have argued that correct application of a tourniquet

carries significant risks for the patient.

Necrotic and Ischaemic Risks

A major risk factor is the potential for increased necrotic damage, both as a

result of the venom and because of the risk of ischaemia, if the tourniquet

remains in place for longer than 40 minutes (Pugh, 1987; Warrell, 1999).

Some investigators have argued that in some species the risk of necrosis is

low, however this relates to species such as the Philippine cobra (Naja

36

philippinensis), which has the least necrotic of any Naja venom and kraits

(Watt, 1988). Most of the cobras and the vipers have highly necrotic venom.

The risk of ischaemia leading to irreversible gangrene is undisputed.

Risks on Release

A further risk identified, is when the tourniquet is released (Watt, 1988).

Massive and sudden binding of the venom to neuromuscular junctions can be

lethal in cases of neurotoxic envenoming such as by cobras or kraits.

Haemostatic Risks

In the case of anti-haemostatic bites, such as the Russell’s and saw-scaled

vipers, pro-coagulant venom activity causes clotting distal to the tourniquet.

When the tourniquet is released, these clots may be carried by the venous

return to the heart and lungs and cause pulmonary embolism.

Research has also shown that once a tourniquet is removed, the fibrinolytic

system is raised for approximately 15 minutes after removal. There is thus the

risk that coagulation tests will be compromised during this period and a false

indication of coagulopathy may result (Klenerman, 1977b). In addition to

ischaemia, it has been pointed out that the release of toxic metabolites upon

release of the tourniquet presents a danger (Trevett, 1993).

Effectiveness Risks

There has been some debate about whether tourniquets do reduce venom

spread in practice. Many authors have concluded that the tourniquets actually

used in developing countries are ineffective, as they do not reduce systemic

absorption of venom (Khin Ohn Lim, 1984; Tun Pe, 1987; Amaral, 1998; Ho.,

1986). However, they consider tourniquets as a single entity and do not

distinguish between the different ways in which tourniquets are applied.

In most developing countries, the vast majority of tourniquets are applied

below the knee or elbow because that is where most bites are inflicted.

However, arterial occlusion in the lower portion of the limb is nearly

impossible to achieve because the structure, which allows an inter-osseous

37

venous drainage, cannot be completely inhibited by compression. Upper limb

tourniquets are considerably more effective although painful and require

frequent release, which will necessarily negate the effectiveness of preventing

venom absorption over time. Most of the debate about efficacy/practicability is

explained by the fact that most tourniquets are incorrectly tied around the

lower part of the limb. Some authors have argued that this is because non-

experts simply cannot apply a tourniquet effectively (Ismail, 1983).

Finally, psychologically, victims with ligatures tend to believe the venom flow

has been inhibited. There is a further danger that this confidence in the power

of the ligature will lead them to seek medical attention with less urgency.

Conclusions

What then are our conclusions regarding tourniquet use?

• Most tourniquets tied by lay people are ineffective as they are tied on

the wrong portion of the limb and tied too loosely.

• Tourniquets should not be applied if there is a danger of necrotic

venom activity i.e. virtually all cobras and vipers.

• There are great dangers of ischaemia, if you do manage to tie the

tourniquet correctly and if it is left in place for greater than 40 minutes

• There are significant medical risks when the tourniquet is released if

you do tie the tourniquet correctly,

• Very few bite victims are sure which kind of snake has bitten them

making it implausible to restrict the use tourniquets to people who

correctly identify the snake and are familiar with its venom action. Even

in those bitten by non-necrotic species, tourniquets in themselves still

carry the risk of ischaemia.

22..44 CCuuttttiinngg aanndd SSuuccttiioonn

Cutting the wound and the use of suction or suction devices remains

controversial. However, the large number of viper bites globally, with the anti-

haemostatic effect of the venom, makes cutting the wound highly hazardous

as well as increasing the probability of infection. However, inexplicably this

method still has advocates, justified on the basis that it may work (Stewart,

38

1981). Consumption coagulopathy renders the victim’s blood incoagulable

and cutting the wound leads to potentially serious bleeding.

Suction devices came to be viewed as a valuable tool for first aid treatment for

snakebite in the United States. Some authors advocated them on the basis

that they did no harm (Christensen, 1969). Rather than sucking venom from

the wound by mouth, a device was developed that created approximately 1

atmosphere of suction pressure. It was recommended that it should be

applied within 3 minutes of the bite. As with electrical shock, this method was

initially promoted with little research to support it. Research evidence casts a

very different light on the subject.

Studies have shown that suction devices increase the risk of tissue necrosis

(Bush et al, 2000; Gelert et al, 1992; Bharati, 2000), do not extract significant

amounts of venom from the wound (Alberts 2004; Hardy, 1992) and may

reduce the level of normal oozing from the wound and thus increase the level

of envenomation (Bush et al, 2000). This device is totally impracticable for use

in developing countries. Its cost alone and the need for it to be carried by the

potential victim render it useless.

22..55 PPrreessssuurree IImmmmoobbiilliissaattiioonn MMeetthhoodd ((PPIIMM))

The Pressure Immobilisation Technique (PIM) remains popular largely

because advocates learn the technique from general textbooks without

examining the primary evidence (Warrell, 1995;Warrell, 1999; Warrell, 2003;

Warrell, 2007). Many of those who recommend this technique would be

shocked if they examined the flimsy nature of the evidence on which this

technique is based (Nishioka, 2000).

The method was proposed in 1979, after a statistically insignificant trial was

carried out on 25 monkeys, only 11 of which were reported on and on which

only 3 had the PIM technique carried out. The reason why 14 monkeys were

excluded from the trial was never adequately explained (Sutherland, 1979).

39

The method proposed that a firm crepe bandage should be applied to the limb

at a pressure of 55mm of mercury, with an accompanying splint (Sutherland,

1979).

Further small-scale studies involving one or two subjects were also carried

out, which represent the basis for the statement that PIM has been ‘proved

both experimentally and clinically’ often referred to by proponents (Sutherland,

1981; Sutherland and Coulter, 1981; Oxer, 1982; Sutherland, 1995; Winkel

and Hawdon, 1999; Grenard, 2000). The method is described as having a

‘good experimental base’ and ‘present experimental and clinical evidence is

strongly in favour’ (Sutherland, 1983; White 1991).

On the basis of these experiments, the Australian National Health and

Medical Research Council (NHMRC) adopted PIM with unwise haste although

many experts from a number of countries expressed doubts as to the merits

of the technique (Edmondson, 1979; Anker and Straffon, 1982; Fisher, 1982;

Russell, 1982; Currie, 1992; Blaylock, 1994; Blaylock, 1995; Gray, 2003).

A number of case studies were produced which appeared to confirm the

method, including one that claimed that PIM actually reduced the requirement

for ASV but these were inconclusive (Murrell, 1981; Pearn et al, 1981;

Balmain and McClelland, 1982; Simes, 2002). Animal model studies appeared

to show effectiveness but again were inconclusive (Burgess et al, 1992; Bush

et al, 2004; German et al, 2005).

Other case studies showed that trained individuals who applied the technique

rapidly after a bite underwent systemic symptoms in any case (Maiden and

White, 2006).

Other research work demonstrated that this technique had very narrow

ranges of pressure to be applied; 40-70mm of mercury in the upper limb and

55-70mm of mercury in the lower limb; immobilisation had to be total and

walking for more than 10 minutes caused the bandage to be ineffective

(Howarth et al, 1994).

40

Work examining the capability of people to effectively apply the bandages

within the correct pressure range established that both medical personnel and

lay people were unable to achieve success even after basic training (Norris et

al, 2005). Extensive training given specifically to aid retention of the technique

also failed to equip lay people to retain the technique (Simpson et al, 2008).

Victims who have the technique properly applied can travel in an Australian

ambulance on Australian roads for only 5 minutes before the technique

became ineffective (Global Snakebite Initiative, 2008). The bandage that the

victim must be carrying should not be crepe but an elasticized sports

bandage, which presumably the poor rural worker will carry in their Nike

sports bag with their energy drink! (Global Snakebite Initiative, 2008).

The fact that the original PIM study would not pass peer review today has also

been noted (Rogers and Winkel, 2005). There is often confusion as to

whether to bandage the limb proximally or distally and even to which types of

bites it should be administered by the same author (Sutherland, 1994;

Warrell, 1995; Warrell, 1999; Warrell, 2003; Warrell, 2005a; Warrell, 2005b;

Warrell, 2006; Warrell, 2010).

Due to the lack of any beneficial evidence, the poor nature of the original

evidence, the difficulty in applying the technique, the utter confusion as to

which type of bites it should apply to and the impracticality of millions of

developing world rural workers carrying splints and crepe bandages, PIM is

NOT recommended for use in developing countries (Simpson et al, 2008).

Sutherland himself stated that to be effective a first aid technique needed to

be “Easily reproduced by inexperienced personnel” (Sutherland, 1983). PIM

does not pass the test and should NOT be used in developing countries.

22..66 OOtthheerr PPrreessssuurree TTeecchhnniiqquueess

Some initial research was carried out that has suggested that a ‘Pressure Pad

or Monash Technique’ may have some benefit in slowing the movement of

venom following envenomation (Anker et al, 1982;Tun Pe et al, 1995; Tun Pe

41

et al, 2000). In this approach, a hard pad of rubber or cloth is applied directly

to the wound.

In one study, it was suggested that the Monash technique out-performed both

the use of air splints and PIM to apply pressure and retard venom flow

although the originators of the PIM technique lost no time in decrying the

research (Duncan et al, 1982; Anker, 1983). Why this method was not more

enthusiastically pursued was certainly asked (Pantanowitza, 1997) but never

followed up.

This method should be subjected to further research to assess its efficacy.

This method may have particular relevance to the Armed Forces who carry

shell dressings as part of their normal equipment, and would thus be ideally

equipped to apply effective first aid in difficult geographic settings where the

need is great.

22..77 EElleeccttrriicciittyy aanndd IIccee

The use of electric shock to de-nature venom held popular appeal mainly in

the United States. It was based on a letter to the Lancet, not on a clinical trial,

which claimed that the application of an electric shock rendered venom

ineffective (Guderian et al, 1986). The method received some initial support

mainly in the form of letters and not scientific studies (Kroegal et al, 1986;

McPartland and Foster, 1988; Bucknall, 1991).

Properly constructed studies however showed that:

1. Venom was not denatured by electrical shock (Davis et al, 1992)

2. No beneficial effect was noted from the use of electricity in snakebite

(Russell, 1987; Russell, 1987a; Snyder et al, 1987; Dart and

Gustafson, 1991; Hardy, 1992)

Electrical therapy has no role in snakebite first aid.

42

During the 1950’s the use of ice and cold to slow the movement of venom by

constricting capillaries was proposed (Stahnke, 1953, Glass, 1981). Further

research showed this method was ineffective and indeed risked increasing

necrotic damage.

22..88 WWaasshhiinngg tthhee WWoouunndd

Snake bite victims or bystanders frequently want to wash the wound after

snakebite. Reasons for this include the removal of any venom on the skin that

might be subsequently absorbed and/or the view that somehow infection may

be transmitted via the venom.

The key point to remember is that the priority is to avoid anything that

increases the systemic absorption of venom via the lymph. Key influences on

lymph flow are:

• Breathing

• Muscular contraction

• Elevating the part

• A stroking massage towards the heart which stretches the skin

Washing the wound requires rubbing of the skin, which will inevitably involve

massaging the tissue, thereby causing more venom to be absorbed. This

should not be done as the action of washing increases the flow of venom into

the system by stimulating the lymphatic system (Gray, 2003).

22..99 TTrraaddiittiioonnaall RReemmeeddiieess

Introduction

Traditional remedies are usually concerned with curing snakebite in its totality.

Traditional healers and Ayurvedic medicine for example, offer a full treatment

philosophy, which they believe ‘cures’ snakebite.

There is a key aspect to the mathematics of snakebite that must be

understood to place traditional medicine in context. In the case of 100

43

snakebites, 70 are likely to result from a non-venomous species. The

remaining 30 bites will result from a venomous species. However,

approximately 50% of bites from venomous species result in a dry bite where

no venom is injected. It is thus likely that in the case of 100 snakebites, 85

victims will have nothing wrong with them and not require any treatment.

This is the mathematics that shows how traditional treatments APPEAR to

‘cure’ snakebite.

Once the traditional healer realises that the victim has been truly envenomed

then the victim is eventually sent to hospital. It is worth remembering that the

traditional healer has the least interest in treating an envenomed victim as

victims that die under traditional treatment reduce confidence in the healer.

One or two specific traditional treatments need examination.

44

Fig 2.1 Traditional Treatments

Top Row. Scarification of Echis ocellatus bite (Ghana). Middle Row. Use of Snake

Stone (India). Bottom Row. Application of Neem leaves (India)

45

22..1100 TTrraaddiittiioonnaall MMeeddiicciinnee;; SSppeecciiffiicc TTrreeaattmmeenntt:: SSnnaakkee SSttoonneess

The use of Black Snake Stones to attempt to cure snakebite is common in

some developing countries. Interestingly when visiting an allopathic Primary

Healthcare Centre that feeds a major medical college in India in 2006, one of

the authors was shown a black snakestone that was used as the primary

means of care before sending the victim to the tertiary Medical College.

A justification for the Stones can be found in a small book produced by the

Reverend Father Antoninus of Little Flower Dispensary in Calicut, Kerala.

Interestingly the first aid section of the book advises the use of a tourniquet

but not tied too tightly, presumably to retard venom movement. The book

further recommends washing the wound with salt water for 2-3 minutes to

wash away the polluted blood after cutting the wound.

The book’s recommendation is that the above two processes will be enough

in the ordinary case.

The book further recommends that the doctor consulted to treat snakebite,

should be selected on the basis of whether they use Snake Stones or not.

The method for the use of the stone is as follows. When the patient arrives at

a location, the wound should be cut in one or two places, washed with water

and the stone applied. The stone would adhere to the wound and begin

absorbing venom. Although one stone is regarded as sufficient, the use of

more than one stone is regarded as being better. Once the stone has

absorbed the venom it will drop from the body as frequently as once or twice

per hour. In any event, if the stone has been in place for 24 hours it should be

removed and placed in a glass of pure, unboiled cow's milk.

Father Antoninus describes how pain at the site of the Snake Stone may

increase due to its action in drawing venom away from the head and the heart

towards the limb where the stone is applied. This pain is regarded as a good

thing.

46

There is only one research study on snake stone effectiveness (Chippaux

2006), which concluded that there was no reduction in systemic envenoming

with the use of the snakestone. Research therefore has invalidated this

enduring remedy.

It is best to leave the last word on Snake Stones to Father Antoninus himself

when he perceptibly observes: “ One who has been bitten by a Cobra feels

hardly any difficulty after the application of the Stones, so much so that

ordinarily one would wonder if one had been bitten by a snake at all”: Quite

so! (Antoninus Fr)

22..1111 TTrraaddiittiioonnaall MMeeddiicciinnee SSppeecciiffiicc TTrreeaattmmeenntt:: SSccaarriiffiiccaattiioonn

In Africa and other countries scarification is a common traditional treatment for

snakebite. Cuts are administered to ‘help’ remove the venom from the

envenomed victim. In common with generalised cutting this activity is

dangerous, as it will encourage bleeding and is ineffective.

47

22..1122 TThhee RReeccoommmmeennddeedd FFiirrsstt AAiidd MMeetthhoodd:: DDoo iitt RR..II..GG..HH..TT

Useful first aid recommendations have to be based on:

1. What is effective i.e. what works!

2. What can be easily remembered and applied

The first aid that’s currently recommended to be administered by self or the

community volunteer is based around the mnemonic:

“Do it R.I.G.H.T.”

The letters in the mnemonic stands for:

þ R. = Reassure the patient. 70% of all snakebites are from non- venomous species. Only 50% of bites by venomous

species actually envenomate the patient

þ I. = Immobilise in the same way as a fractured limb. Use bandages or cloth to hold the splints, not to block the

blood supply or apply pressure (Fig X). Do not apply any

compression in the form of tight ligatures, they don’t

work and can be dangerous!

þ G. H. = Get to Hospital Immediately. Traditional remedies have NO PROVEN benefit in treating snakebite.

þ T= Tell the doctor of any systemic symptoms such as ptosis that manifest on the way to hospital.

This method will get the victim to the hospital quickly, without recourse to

traditional medical approaches, which can dangerously delay effective

treatment and will supply the doctor with the best possible information on

arrival (Simpson, 2007).

48

The snake, if killed should be carefully taken to the hospital for identification

by the doctor. No time should be wasted in attempting to kill or capture the

snake. This solely wastes time and can lead to other victims.

Fig 2.2. Do it R.I.G.H.T. First Aid Method Immobilization

49

33..00 PPaattiieenntt AArrrriivvaall


Patients with snakebite arrive at the medical facility in a variety of conditions.

33..22 AAssyymmppttoommaattiicc AArrrriivvaall

Many will appear to be asymptomatic as:

1. The bite is from a non venomous species (approximately 70% of

snakebites are from non venomous species

2. The bite is from a venomous species but has not injected enough

venom to cause symptoms or has injected none at all (dry bites)

3. The venom is of a sufficiently high level to cause symptoms but is now

progressing through the tissue without causing swelling to indicate its

presence. Envenomation can take many hours to present signs and

symptoms.

4. The victim may be envenomed but no visible signs or immediately

detectable symptoms are visible (The victim may have incoagulable

blood or bleeding or renal failure may be underway but not visible)

33..33 SSyymmppttoommaattiicc PPaattiieennttss

The victim may have very visible symptoms:

1. Visible signs of neurological impairment such as ptosis, muscular

weakness, respiratory distress or respiratory arrest

2. Visible bleeding such as continuous bleeding from the bite site,

haematuria, haemoptysis, bleeding from the gums, epistaxis or

ecchymoses.

3. Swelling or necrosis commencing at the bite site. If the patient has

delayed hospital arrival then these symptoms may be severe

4. Unconsciousness either with or without respiratory arrest

5. Distress is a common feature of snakebite. The common myth that

many patients die from ’fear’ due to the bite can be discounted.

Patients dieing of fear due to the bite is commonly stated but usually

50

results from a lack of effective treatment. Death due to fright is a

convenient reason to account for inadequate treatment.

33..44 KKeeyy IInntteerrvveennttiioonnss

Critical arrival

If a patient arrives with life threatening symptoms such as:

• Respiratory arrest

• Cardiac arrest

• Hypotension

emergency measures, the ABCs must be implemented first.

Patients should be intubated if possible or provided with airway support (See

page 83) and ventilated with a resuscitation bag.

In the case of respiratory arrest it is vital to establish from the individuals’

accompanying the victim on the journey to the hospital when the respiratory

impairment commenced. The time will give the physician critical information

concerning the likelihood of a successful patient revival. Many victims

undertake long journeys to hospital and even if a resuscitation bag is used the

efforts are often ineffective due to flaccid paralysis, without support factors

such as nasopharyngeal airways, laryngeal mask airways or endotracheal

intubation.

If the victim underwent respiratory failure shortly before reaching the hospital,

it is likely that a full recovery will be possible. This factor should be

communicated to staff responsible for mechanical ventilation of the patient.

Often a key decision is whether to continue with mechanical ventilation with a

patient who is non responsive for several hours on the ventilator. Patients with

neurological envenomation may require many hours or days on a ventilator to

achieve recovery, particularly in the case of pre synaptic envenoming. The

reality is that in many developing countries ventilators are unavailable in most

hospitals and even where present are in short supply. There is thus a

51

tendency to ventilate patients for a short period, achieve no response and

then discontinue ventilation due to ‘sepsis’ or some other ‘cause’ of death.

In the case of pre synaptic envenoming this is disastrous! It is vital that the

physician who initially receives the patient fully investigates the timeline of

respiratory arrest and informs ventilation staff of the likely outcome. In reality,

a patient that underwent respiratory arrest some distance from the hospital

will not survive unless good airway support with a resuscitation bag and

airway maintenance tools was provided in the interim period.

33..55 NNoonn--CCrriittiiccaall AArrrriivvaall

20-Minute Whole Blood Clotting Test

When the patient arrives, snakebite is suspected and if the critical phase has

been managed, the first initial step is to determine current coagulation status.

This can be carried out simply at the bedside while further investigations and

questioning of the patient is taking place. It can be carried out in even the

most basic setting without recourse to a laboratory or specialist staff. It is

essential that the test tube is GLASS and not plastic. The use of plastic

syringes, placed upside down on their base should not be continued. Plastic is

an unreliable trigger of the contact-clotting cascade.

Items Required

1. A supply of New, Clean, Glass and Dry test tubes

2. A syringe and needle.

Method

A few mLs of fresh venous blood is placed into the test tube and left

undisturbed for 20 minutes. At that time the tube is gently tilted to 45 degrees

and the status of the blood examined.

Results Interpretation

1. If the blood is solid i.e. has clotted the patient has passed the

coagulation test and no ASV is required at this stage. The patient is re-

52

tested every 30 minutes for the first three hours and then hourly after

that for 24 hours.

2. If the blood is still liquid and runny, the patient has failed the

coagulation test and consumption coagulopathy is present. ASV is now

indicated. The 20WBCT should be repeated 6 hours after ASV

administration is complete to assess any requirement for further ASV.

53

44..00 PPaattiieenntt DDiiaalloogguuee


The victim and/or bystanders present when the bite took place must be

questioned to determine the following:

44..22 WWhhaatt wwaass tthhee ttiimmee ooff tthhee bbiittee??

This information is crucial to understanding the progress of any current or

potential envenomation. A bite with no symptoms that occurred over 24 hours

before is unlikely to develop into an envenomation. A bite that has current

signs and symptoms that is over 24 hours old is unlikely to have a significant

amount of residual unattached venom that is capable of neutralisation with

ASV, it is therefore likely to be more difficult to treat and potentially therefore,

more serious.

44..33 WWaass tthhee ssnnaakkee sseeeenn aanndd//oorr kkiilllleedd??

If so, the description should be noted and identification carried out. It is useful

to have available pictures of the common snakes in the locality.

44..44 HHaavvee aannyy aallllooppaatthhiicc ttrreeaattmmeennttss bbeeeenn ttaakkeenn bbeeffoorree aarrrriivvaall

aatt tthhee pprreesseenntt mmeeddiiccaall ffaacciilliittyy??

In many areas of developing countries, smaller medical facilities are often

visited before arrival at a larger hospital. These smaller facilities may have

already administered a small quantity of ASV before transferring the patient.

44..55 HHaavvee aannyy ttrraaddiittiioonnaall ttrreeaattmmeennttss bbeeeenn ttaakkeenn bbeeffoorree aarrrriivvaall??

Traditional treatments can cause problems, in addition to the time taken to

administer them. For example, the ingestion of herbal or other products can

generate symptoms that confuse the diagnosis. In some areas the ingestion

of clarified butter or ‘ghee’ is a common remedy use to induce vomiting. The

rationale is that venom is thus vomited from the body. The victim’s vomiting

may be entirely unrelated to envenomation.

54

Chilli is ingested to counteract the venom, which can result in abdominal pain

in the victim. In areas where abdominal pain may be indicative of

envenomation e.g. krait areas, this can mislead the doctor.

44..66 WWhhaatt aaccttiivviittyy wwaass tthhee vviiccttiimm ccaarrrryyiinngg oouutt aatt tthhee ttiimmee ooff tthhee

bbiittee??

There are two principal reasons why this is a critical question:

a) Confirmation of Snakebite/ Species

There will be many occasions when victims are not sure whether

they have been bitten by a snake or not. They may have

experienced a pricking pain while carrying out an activity but they

may not be able to confirm that a snake was responsible. The

wound may have resulted from a thorn, scorpion, centipede or other

insect. In these cases ASV is clearly not required.

Certain activities can help determine if a snake was likely involved.

Grass cutting is a high bite risk activity and this may be good

evidence that a snake was involved. Feeding chickens or other

animals with grain can also indicate snakebite. Grain will attract rats

and when feeding of the animal is taking place it is possible that a

snake may be present to predate on the rats.

In some cases the activity can cast light on the likely species.

Victims that are bitten by a cobra, in South Asia, will exhibit

neurotoxic features if envenomed. If the victim was walking through

the fields during the day, then neurotoxic symptoms are highly likely

to result from a cobra as kraits are strictly nocturnal. However, if the

victim is clearing rubbish in a shed or repairing bunding at the edge

of rice fields, then it is possible that they have disturbed a krait

sleeping during the day.

55

b) Bite Activities and Prevention Advice

The prevention section (Page 99) gives details on the advice

that doctors can give the local community as to how to reduce

their risk of snakebite. The raw data for this exercise comes

during this questioning phase. Determine as accurately as

possible what precise activity the victim was performing when

the bite occurred and note this on the patient record. Once the

activities that constitute the majority of bites are identified,

strategies to make potential victims aware can be developed.

56

55..00 DDiiaaggnnoossiiss:: SSiiggnnss aanndd SSyymmppttoommss ooff EEnnvveennoommiinngg


The signs and symptoms of snakebite follow the three main categories of

envenoming i.e. Bleeding, Progressive Weakness and Painful Progressive

Swelling (Blaylock, 2005). Most species exhibit a number of different

symptoms but it is useful to categorise the species according to these criteria.

It must be remembered that the following are SIGNs and SYMPTOMs of an

envenomation at some point in time, not necessarily current, which may be

detected. They are NOT in themselves criteria for administering ASV. That is

specifically dealt with in Section 8.

55..22 BBlleeeeddiinngg

1. Consumption coagulopathy.

2. Visible systemic bleeding from the action of haemorrhagins e.g.

gingival bleeding, epistaxis, haemoptysis, continuous bleeding from the

bite site, bleeding from pre existing conditions e.g. haemorrhoids,

bleeding from freshly healed wounds.

3. Renal failure e.g. declining or no urine output, deteriorating renal signs

such as rising serum creatinine, urea or potassium. Some species e.g.

Russell’s viper (Daboia sp) frequently cause renal failure whereas

other species such as saw scale vipers (Echis sp) do not (Simpson,

2007).

4. Myoglobinuria i.e. darkening of the urine, complaints of low back pain.

5. Swelling or necrosis may be evident although this is by no means

certain; many cases of bites from species causing bleeding will not

cause these symptoms.

6. Longer term sequelae e.g. pituitary insufficiency with Russell’s viper

(Daboia sp)

57

55..33 PPrrooggrreessssiivvee WWeeaakknneessss

1. Descending paralysis

2. Weakness and paralysis of muscles enervated by the cranial nerves

e.g. ptosis, opthalmoplegia, diplopia, numbness of the lips, weakness

of the neck muscles, difficulty speaking, pooling of secretions

3. Tripod stance to assist breathing, paradoxical respiration, shortness of

breath and respiratory arrest

4. Peripheral muscle weakness e.g. unsteady gait, weakness of grip

5. Excessive sweating

6. Fasiculations i.e. mambas

7. Metallic taste in the mouth e.g. mambas

8. Possible loss of taste and smell

55..44 PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg

1. Significant painful swelling potentially involving the whole limb and

extending onto the trunk.

2. Blistering at and around the bite site.

3. Necrosis which often has a rancid smell

4. Ecchymoses due to venom action destroying blood vessel wall

5. Rarely skip lesions

6. Limb swollen and the skin taut and shiny

58

66..00 DDiiaaggnnoossiiss ooff EEnnvveennoommaattiioonn


The diagnosis of envenoming is a straightforward matter of applying one or

more of three major categories of technique. Some of these techniques can

be carried out in the simplest of medical facilities and therefore provide the

capability of treating snakebite in peripheral centers.

Others are impractical in many developing world settings as the test

equipment is unavailable (Isbister et al, 2006)

These techniques are split into three categories:

1. Visible

2. Simple Diagnostic

3. Technical Diagnostic

Examples of each of the techniques are:

66..22 VViissiibbllee CCrriitteerriiaa

A. Bleeding I. Gingival bleeding

II. Haemoptysis

III. Haematuria

IV. Ecchymoses

V. Lateral neurological signs,

59

Fig 5.1 Signs of Haemotoxic Envenomation

Top Row. Gingival Bleeding, Ecchymoses on the Trunk Bottom Row. Lateralising Neurological Signs of Intracranial Bleeding, Bleeding from a

Pre Existing Condition i.e. Prolapsed Piles.

B. Progressive Weakness I. Descending paralysis commencing with cranial nerve impairment e.g.

ptosis, opthalmoplegia

II. Numbness of lips and difficulty speaking and swallowing, pooling of

secretions

III. Weakness in the neck muscles, inability to lift or support the head

IV. Difficulty breathing

V. Fasiculations

60

C. Painful Progressive Swelling I. Rapidly developing swelling and oedema crossing joints

II. Blistering of the limb commencing at the bite site

III. Severe pain in the limb commencing at the bite site

Fig 5.2 Local damage from Envenoming

Top Row. Blistering from Echis sochureki bite, Necrosis from Echis ocellatus bite

Bottom Row. Swelling from Hypnale hypnale bite, Post necrosis from Naja atra bite.

66..33 SSiimmppllee DDiiaaggnnoossttiicc MMeetthhooddss

A. Bleeding I. The simplest test of coagulopathy is the 20 Minute Whole Blood

Clotting Test (20WBCT) (Ho et al, 1986; Sano-Martins, 1994;

Simpson, 2007).

61

B. Progressive Weakness I. Single breath count

II. Length of time upward gaze can be maintained

III. Basic Grip Tests

C. Painful Progressive Swelling I. Simple measurement and recording of the circumference of the limb

over fixed time periods

II. Simple measurement and recording of the extent and spread of the

swelling or necrosis over fixed time periods

66..44 TTeecchhnniiccaall DDiiaaggnnoossttiicc MMeetthhooddss

A. Bleeding I. Renal impairment – Serum creatinine, urea, potassium

II. Occult bleeding – haemoglobin, PCV, platelets,

B. Progressive Weakness I. Single breath count

II. FEV

III. Grip Tests with Equipment

C. Painful Progressive Swelling I. Saline manometer or Stryker measurement of intracompartmental

pressure.

62

66..55 BBiittee MMaarrkkss

There is much attention given to bite marks in diagnosing venomous

snakebite, particularly forensic medicine specialists (Modi, 1988; Pillay, 2005).

They recommend a study of the bite mark to determine whether the snake is

in fact venomous or non-venomous. Unfortunately this is nonsense and

should be ignored. Venomous species often have more than one set of fangs

in case of breakage when feeding and thus can give multiple puncture marks.

Many non-venomous species have two enlarged front teeth and this can

appear as two single puncture marks.

63

77..00 AAnnttii SSnnaakkee VVeennoomm ((AASSVV))


ASV is the result of inoculating, typically horses, with small amounts of

combinations of snake venoms in order to generate a hyperimmune response.

The antibodies against the venom are collected in serum extracted from the

horse and either precipitated out of solution or remain in solution when non

IgG elements are precipitated. The product is either subjected to a digestive

enzyme such as pepsin or papain to either remove or minimise the Fc portion

of the antibody, as this was believed to reduce the level of adverse reactions.

Following purification it is ready to administer.

77..22 LLyyoopphhiilliisseedd oorr LLiiqquuiidd

ASV comes in two forms lyophilised or powdered and liquid. Lyophilised ASV

is simply liquid ASV freeze-dried. There is NO evidence that clinically one

form is better at neutralising venom than the other.

They each have advantages or disadvantages that must be considered:

Lyophilised

Liquid

Advantages

Long Shelf Life (5 Years)

Requires no cold chain

Advantages

Speed of reconstitution immediate

Disadvantages

Speed of reconstitution of 30-60

minutes (Hill et al, 2001)

Disadvantages

Short Shelf Life (2 years)

Requires a cold chain

77..33 MMoonnoovvaalleenntt VVeerrssuuss PPoollyyvvaalleenntt

The call for monovalent ASVs because “they are cheaper” is another example

of intuition being emphasised over evidence. ASV production economics are

complex and in many of the developing countries, which have a low cost of

64

ASV, the use of monovalent ASVs may actually INCREASE the cost of the

final product as batch, testing, distribution & storage costs for specific ASVs

may be higher.

It must be remembered that:

1. The majority of victims do not bring the dead snake for identification

2. Doctors are unreliable in making a correct identification even if the

snake is brought

3. ELISA testing kits would need to be provided

4. A number of monovalent ASVs would need to be provided to many

physicians which has planning, logistical & cost implications

5. Producing a separate batch for each monovalent ASV may well

increase the costs of production and testing versus polyvalent ASVs.

Very few countries have ELISA testing despite it being referred to for nearly

30 years; the main example is Australia where it is used to identify biting

species NOT level of envenomation (World Health Organisation, 1981).

There are key problems with monovalent ASVs that are often overlooked:

1. The clinical symptoms to administer the ASV must be clear and

mutually exclusive. If two species cause the same symptom,

monovalent ASVs are not useful. A good example of this is the case of

China where both the Chinese cobra (Naja atra and the White-lipped

pit viper (Cryptelytrops albolabris) produce significant local swelling.

Local doctors have difficulty in determining whether to use SIBP Naja

atra ASV or TRC Green pit viper ASV.

2. If ELISA is to be developed:

i. It is costly to develop the base product

ii. It must be rigorously tested to eliminate false positives and

negatives

iii. It must be based on local snakes; the kits cannot be imported

If your country does not have it now, then it will be many years before it is

reliably available.

65

77..44 WWhhaatt CCaann AASSVV DDoo aanndd mmoorree iimmppoorrttaannttllyy wwhhaatt ccaann iitt NNOOTT

DDoo??

It is vital to remember the capabilities and limitations of ASV if it is to be used

effectively.

ASV Can:

1) Bind to a venom molecule that it is effective against and neutralise that

venom molecule rendering it unable to bind to the target cell but only

whilst the venom molecule is circulating in the blood or lymph and is

unbound.

ASV prevents the patient’s condition from worsening by neutralising venom

that otherwise could have bound and completed its damaging effect on the

victim. It does not reverse anything nor does it make the patient better. The

latter is the result of the body’s normal functions, such as the liver replacing

clotting factors, being able to return to normal by the elimination of the

circulating venom.

ASV Cannot:

1) Reverse necrotic action of the venom on tissue

2) Reverse local swelling

3) Reverse renal failure

4) Reverse coagulopathy; the liver does this.

5) Reverse pre synaptic envenoming; the nerve damage is structural and

large quantities of ASV are ineffective, the body must regenerate

synaptic vesicles

6) Prevent local necrosis; the damage is done too quickly and the venom

is in the tissue and therefore not reachable by the ASV (Gutierrez et

al, 2007)

7) Prevent local swelling; the damage is done too quickly and the venom

is in the tissue and therefore not reachable by the ASV (Gutierrez et al,

2007)

66

Some of these points should be obvious and yet they are frequently given as

reasons for administering ASV.

77..55 SSwweelllliinngg aanndd AASSVV

The most controversial aspect of ASV use is in the case of swelling. The role

of ASV in the case of swelling centres on whether:

1. Swelling can be controlled or reduced by ASV

2. Swelling is a useful criteria for administering ASV

Swelling: Control or Reduction?

The proposed evidential support for ASV to be able to control swelling comes

principally from the U.S.A. A number of studies purport to show that ASV has

brought swelling under control (Heard et al, 1999; Thorson et al, 2003;

Lavonas et al, 2004). These studies are not robust however, as they link the

causal of administering ASV with the outcome of halted swelling: envenoming

is a dynamic process and the halting of the swelling may be due to the fact

that the oedema-causing portion of the venom is exhausted.

77..66 AASSVV SSaaffeettyy

Much has been written about ASV safety, particularly the need for F(ab)2

products because of safety. Safety in terms of the level of ASV reactions is

clearly an issue but so is cost. The more costly an ASV, the less likely it is to

be purchased in sufficient quantities by developing country health authorities.

Recent evidence now shows that whole IgG products have similar safety

profiles to F(ab)2 products (Otero et al, 1999; Otero-Patino et al, 1998; Otero

et al, 2006). Whole IgG products are cheaper to produce, particularly if

caprylic acid fractionation of the antibody is used (Simpson and Norris, 2009;

Simpson and Jacobsen, 2009).

WHO’s reluctance to provide clear guidance on the safety issues of

production and the cost impact is lamentable.

67

88..00 CCrriitteerriiaa ffoorr AAddmmiinniisstteerriinngg AASSVV


Criteria for administering ASV and the relevant signs and symptoms to use

have also lacked clarity. This results in the strong possibility that ASV is being

administered to patients who are NOT in fact envenomed and thus

contributing to the perceived shortage of ASV.

The key question for the physician to answer is:

“Is there evidence of unbound circulating venom currently present in

the victim’s blood stream or lymph NOW which is capable of being

neutralised by the ASV at hand?”

There is little dispute that the answer “YES” is indicated in the first two of the

below cases:

88..22 BBlleeeeddiinngg

Criteria for administering ASV are:

1. Incoagulable blood determined by a 20 Minute Whole Blood Clotting

Test in a new, clean glass and dry test tube (Sano-Martins et al, 1994).

2. Systemic bleeding, not local bruising

3. Laboratory evidence of coagulopathy

4. Muscle pain or myoglobinuria clinically detected as dark brown urine

(Indonesia East Islands, Papua and West Papua)

88..33 PPrrooggrreessssiivvee WWeeaakknneessss

Grounds for administering ASV are:

1. Neurological signs i.e. ptosis, opthalmoplegia, excessive salivation,

bulbar paralysis, inability to swallow, metallic taste in the mouth

respiratory distress

68

In the above two circumstances ASV should be administered according to the

dosage schedules on Pages 71-76.

88..44 TThhee CCaassee ffoorr SSwweelllliinngg aanndd LLooccaall DDaammaaggee

The above two categories are universally used for the administration of ASV,

however there is a third category that is widely used in a number of different

ways which is far more controversial and surrounded with myth and

inconclusive “evidence” (Heard et al, 1999; Dart and McNally, 2001; Lavonas

et al, 2002; Thorson et al, 2003; Bebarta and Dart, 2004; Lavonas et al, 2004;

Offerman et al, 2009).

Swelling requires the doctor to make a decision as to whether they accept

either or both the following principles for which there is no evidence and which

many authorities reject:

II. ASV can pass the blood tissue barrier

III. Swelling is indicative that systemic symptoms will occur and

therefore ASV will be required

IF swelling is to be used as a criteria for administering ASV then evidence

must be present that the swelling is both CURRENT and SEVERE, simple

bite site swelling is NOT grounds for giving ASV.

88..55 PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg ((PPPPSS))

ASV is suggested in the following cases (Blaylock, 2005):

1. Swelling reaching 15cms or more for 1 hour; swelling after bites to the

extremities reaching the knee or elbow by 4 hours; swelling involving

the whole limb within 8 hours or swelling extending onto the trunk

2. Swelling threatening airway compromise or shortness of breath

33.. Compartment syndrome or major vessel entrapment

69

88..66 HHooww ttoo AAddmmiinniisstteerr AASSVV

ASV is administered in one of two main ways:

• Intravenously via direct injection or

• Continuous infusion.

ASV is not administered intra muscularly or around the bite site, although

intuitively this may seem sensible. ASV has a large molecular size and

therefore intra muscular injection results in slow ASV absorption into the blood

stream; use of this route may also cause haematoma. The use of ASV around

the bite site to reduce local effects such as swelling or necrosis has no

evidential support (Offerman et al, 2009).

Lyophilised ASV is reconstituted with saline and gently rolled between the

fingers until the powder has dissolved; it should not be shaken. When

reconstituted it should be mixed with approximately 250ml of saline in the

same way as liquid ASV.

88..77 AASSVV AAddmmiinniissttrraattiioonn PPeerriioodd

ASV should be administered over 1 hour or less. There is no reason to

administer ASV over a longer period such as 4 hours, 12 hours or 24 hours;

which is sometimes carried out in developing countries.

It is often recommended that ASV should be administered for a period after

coagulation has been restored or recovery is evidenced in neurotoxic

envenomation to prevent recurrence. This practice has largely derived from

the U.S. where a smaller antibody is used in the local ASV, which results in a

much shorter half-life and thus more rapid clearance from the system. This is

not required in ASVs in Africa or Asia and simply wastes resources.

70

99..00 AASSVV DDoossaaggee


Determining the dosage of ASV to administer to a patient is rarely justified by

empirical trial data. However, there are a small number of ASV providers in

developing countries and it is thus possible to determine likely dosage levels

based on each individual ASV.

In an attempt to guide physicians, where possible, maximum dose levels have

been provided. The amount of snake venom, injected by the snake is not

infinite; it will have an upper range. There is a tendency amongst physicians

to believe that more ASV is better, and to continue using ASV past the point

where the amount of ASV given is in excess of the maximum amount of

venom possible. This is both wasteful of resources and expensive.

Some dosage guidelines are based on manufacturer’s recommendations and

have been marked accordingly. Care must be taken with manufacturer’s

recommendations as such guidelines have been shown to be unreliable

previously (Simpson and Norris, 2007)

99..22 IInniittiiaall DDoossiinngg EExxcceeppttiioonnss

A major exception to the initial dosing guidelines is in the case of need for vital

life saving surgery to resolve a serious complication of snakebite. For

example, in the case of intracranial bleed, with a requirement for surgery to

remove the clot, it is vital to restore coagulation in the shortest possible time.

In such situations, a very large dose of ASV will be required to ensure

coagulation is restored in a single dose over 1 hour. The initial dose should

therefore be 2-3 times the normal starting dose and significant care needs to

be taken to observe any adverse reactions due to the volume of protein being

administered.

71

99..33 MMaaxxiimmuumm DDoosseess

Where possible, maximum recommendations for ASV have been provided.

These are based on the principle that the amount of ASV required is that

necessary to neutralise all the venom injected by the snake LESS that venom

which has already bound to the target cell and is thus unavailable for

neutralisation. Each vial of ASV neutralises a given amount of venom from the

species against which it is effective. The snake has a finite amount of venom

it is able to inject. If we knew the maximum amount a snake could inject then

the maximum number of vials of ASV could be established on a simple

mathematical basis. This, and the average amount of venom injected would

be very valuable knowledge and indeed where it is available has enabled

rational dose strategies to be developed.

The important point to note is that there is always a maximum dose of ASV

required as defined above. There is no rationale for administering very large

doses of ASV where there is no evidence of currently circulating venom

(Agrawal et al, 2001; Sharma et al 2002; Sharma et al, 2006; Harish and

Digra, 2007).

99..44 LLaattee AAddmmiinniissttrraattiioonn ooff AASSVV

A frequent question is, what is the latest period that ASV can be administered

after the bite? Often patients can spend many hours or days travelling to

medical care or spend time on traditional treatments before seeking allopathic

care. This is a very simple problem and the answer is determined by

symptoms and logic.

PW envenomed patients who wait many hours or days before seeking

medical aid will be dead if they are envenomed! It is therefore unlikely that a

late arriving patient, bitten by a PW species will require ASV.

Patients bitten by Bleeding species should be assessed by use of the 20

WBCT and if the blood is incoagulable, ASV should be administered. If the

blood is coagulable ASV is not required.

72

In patients bitten by PPS species,

1. The venom would be already bound and thus unneutralisable

2. The venom is probably unable to be reached by the ASV as we

have seen in Section 7.5

In PPS cases that arrive late, no ASV should be given.

99..55 AASSVV aanndd PPrreeggnnaannccyy

There is little study data on snakebite during pregnancy, mainly due to the fact

that much of the literature comes from developed countries where women

working in rural areas whilst pregnant are rare. Snakebite during pregnancy is

not common (Seneviratne et al, 2002; Sebe et al, (2005).

It is unclear if snake venom or components or ASV cross the placenta

(Seneviratne et al, 2002).

The common expectation that snakebite invariably leads to spontaneous

abortion of the foetus is not supported by available data. In one study in Sri

Lanka, only 30% of victims aborted (Seneviratne et al, 2002).

In the case of an envenomed victim, ASV is required to neutralise the

unbound venom in the normal way.

ASV should be given:

1. In the same dose and

2. Under the same criteria as standard victims.

Where ASV is given there is good maternal outcome (Seneviratne et al,

2002).

73

The period of greatest risk appears to be during the first trimester and with

cases of systemic envenoming, particularly with systemic bleeding and

coagulopathy (Seneviratne et al, 2002).

This would indicate that wherever possible, patients in the first trimester, with

systemic signs of envenomation particularly bleeding, should be referred to a

gynaecologist for specialised review. In cases of spontaneous abortion this

usually occurred within 7 days of the bite (Seneviratne et al, 2002).

99..66 PPaaeeddiiaattrriicc AASSVV DDoossiinngg

There is often confusion as to the starting dose for children, which

concentrates on their body size. It has been argued that children should

receive less ASV due to their smaller body size or larger doses as their blood

volume is less and therefore venom can spread faster.

The answer to this question lies in clearly understanding the role of ASV. Its

function is to neutralise unbound venom, injected by the venomous snake.

Snakes do not vary the amount of venom injected into children or adults and

therefore the dose of ASV for children is THE SAME as that for adults.

99..77 RReeppeeaatt BBiitteess

It is rare for a patient to be bitten again, following a bite from a venomous

species. Repeat bites however do carry a slight increased risk of adverse

reaction to the ASV, as it has been administered previously.

The dosage schedule for ASV in the event of a second bite is however

unchanged. The same starting dose and repeat dose schedule as for a

normal bite applies. If there is concern of an adverse reaction due to a second

administration of ASV, then a prophylactic regimen of adrenaline can be

considered. Any reaction should be handled in the normal way.

It is worth noting that it is fashionable amongst ‘herpetologists’ with

questionable competence to claim that they have been told by a doctor that

74

they ‘can not have ASV again’ as it threatens their life due to previous bites.

This seems to be regarded as a ‘macho’ badge of achievement by some.

This statement should be treated with high suspicion and the doctor should

treat the victim and any reactions in the normal way in the normal way

(Section 10).

75

99..88 SSoouutthh AAssiiaa AASSVVss

ASV Producer

Country

Species

Initial

Dose

Vials

Maximum

Dose

Suggestion

Vins Bioproducts

Bharat Serums

Serum Institute of

India

Haffkine

Bengal Chemicals

Biological E

Polyvalent

India

Sri Lanka

Nepal

Bangladesh

Pakistan

Naja naja

Bungarus

caeruleus

Daboia russelii

Echis carinatus

8-10

8-10

20

30

National Institute of

Health (NIH)

Islamabad

Polyvalent

Pakistan

Naja naja

Bungarus

caeruleus

Daboia russelii

Echis sochureki

8-10

8-10

4

20

30

12

Notes

1. Indian ASV is manufactured containing venom almost exclusively from snakes

captured in Tamil Nadu in South India. The Echis species venom is Echis carinatus

2. NIH ASV is made using venom from Sindh Province. The Echis species is Echis

sochureki and the cobra species is largely the paternless Naja naja.

3. Macrovipera lebetina, Bungarus fasciatus and Naja oxiana ASVs are available id

required, see Pages 72 & 74

4. Indian ASV is NOT a substitute for other Asian regions.

76

99..99 AAssiiaa,, CCeennttrraall,, SSoouutthh EEaasstt aanndd EEaasstt AASSVVss

ASV Producer

Country

Species

Initial

Dose

Vials

Maximum

Dose

Suggestion

Thai Red Cross

Society

Monovalent

Thailand

Myanmar

China

Daboia siamensis

Callesolasma rhodostoma

Cryptelytrops albolabris

Naja kaouthia

Bungarus fasciatus

Bungarus candidus

Ophiophagus hannah

5

4

10

10

5

5

10

20

20

10

10

20

Shanghai

Institute of

Biological

Products

Monovalent

China

Naja atra

Bungarus multicinctus

Deinagkistrodon acutus

Agkistrodon/ Gloydius halys

5

5

4

1

5

10

Bio Farma,

Bandung

Indonesia

Polyvalent

Indonesia

Callesolasma rhodostoma

Bungarus fasciatus

Naja sputatrix

10

10

10

77

Taiwan CDC

Vaccine

Center, Taiwan

Bungarus multicinctus

Naja atra

Trimeresurus

muquosqamatus

Trimeresurus stejnegeri

Agkistrodon acutus

Daboia siamensis

1-2 *

1-2 *

1-2 *

3

Japanese

Snake Institute

Rhabdophis subminiatus

2

Myanmar: Anti-

Viper AV

Myanmar:

Bivalent AV

Myanmar

Daboia siamensis

Naja kaouthia

4

6

12

Biological

Production

Division

Philippines Naja philippinensis 10

Kaketsuken

Monovalent

Japan Agkistrodon b blomhoffii

Trimeresurus/Protobothrops

Flavoviridis

2 *

2 *

78

Commonwealth

Serum

Laboratories

Polyvalent

Indonesia

East

Islands

Papua

West

Papua

Oxyuranus scutellatus canni

Acanthophis

antarcticus/praelongus

Pseudechis australis

Pseudechis papuanus

1

1

1

1

Institute of

Immunology

Zagreb

European Viper

Antiserum

Polyvalent

Central

Asia

V. ammodytes

V. aspis

V. berus

V. lebetina

V. xanthina

V. ursinii

2-4 *

2-4 *

2-4 *

2-4 *

2-4 *

2-4 *

* = Manufacturer’s recommended dose.

79

99..1100 WWeesstt AAssiiaa

ASV Producer

Country

Species

Initial

Dose

Vials

Maximum

Dose

Suggestion

National Guard

Hospital

Saudi Arabia

Polyvalent

Bivalent

Naja/Walterinasia

Saudi Arabia

Oman

Bitis arietans

Echis sp 1

Cerastes sp

Walterinasia

aegyptia

8

5

5

5

5

Razi Vaccines &

Serum Research

Institute

Polyvalent

Iran

Echis 2 sochureki/

multisqamatus

Naja oxiana

Macrovipera

lebetina

Pseudocerastes

persicus

Vipera albicornuta

Gloydius halys

2 *

2 *

2 *

2 *

2 *

2 *

Institute of

Immunology

Zagreb

European Viper

Antiserum

Polyvalent

West Asia

V. ammodytes

V. aspis

V. berus

V. lebetina

V. xanthina

V. ursinii

2-4 *

2-4 *

2-4 *

2-4 *

2-4 *

2-4 *

80

Vacera/EgyVac

Polyvalent

West Asia

Vipera ammodytes

Vipera xanthina

Vipera berus

4-6 *

4-6 *

4-6 *

* = Manufacturer’s recommended dose. Notes

1. Echis species in Saudi Arabia are E. coloratus, E. pyramidum, E.

sochureki and E. khosatskii.

2. Echis species described as Echis carinatus are collected from South

West Iran and are likely to be Echis sochureki in the main but also E.

multisquamatus.

81

99..1111 AAffrriiccaa

ASV Producer

Country

Species

Initial

Dose

Vials

Maximum

Dose

Suggestion

South African

Vaccine

Producers

(SAVP)

Polyvalent

Monovalent

Monovalent

Sub

Saharan

Africa

Bitis arietans

Bitis gabonica

Naja melanoleuca

Naja nivea

Naja annulifera

Naja mossambica

Dendroaspis sp

Hemachatus

haemachatus

Echis ocellatus

Dispholidus typhus

5

10

8

8

8

5

8

5

2

2

20

20

20

20

Sanofi Pasteur

Fav Afrique

Polyvalent

Africa

Bitis arietans

Bitis gabonica

Echis ocellatus

Echis leucogaster

Naja haje

Naja melanoleuca

Naja nigricollis

Dendroaspis polylepsis

Dendroaspis jamesoni

Dendroaspis viridis

8

10

10

10

10

10

10

10

10

10

20

20

20

20

82

Vacera/EgyVac 1

Sub

Saharan

Africa

Bitis arietans

Echis ocellatus

Naja nigricollis

8

6

10

* = Manufacturer’s recommended dose.

Note 1. Vacera/EgyVac also produce a 16 species polyvalent ASV for ‘Egyptian

Species’ including Sub-Saharan species of unknown capability or effectiveness.

Dosage recommendations from the manufacturer are 4-6 vials for all species. The

number of species included and the fixed initial dose independent of species raises

concerns as to its effectiveness.

83

99..1122 RReeppeeaatt AASSVV DDoosseess

In a significant number of snakebites, the initial dose of ASV will not be

sufficient to neutralise all circulating venom and additional ASV will be

required.

99..1133 RReeppeeaatt AASSVV DDoosseess:: BBlleeeeddiinngg

In cases where ASV has been given in response to incoagulable blood,

measured by the 20 WBCT, 6 hours should elapse following the completion of

the initial dose of ASV. This period is required to enable the liver to restore

clotting factors to levels sufficient to provide coagulation.

After 6 hours, a further 20 WBCT is carried out. If the blood is still

incoagulable, then a second dose of ASV is given. It is usual to repeat the

same dose of ASV as was given initially. This approach is continued on a 6

hourly basis until coagulation is restored or until the maximum level of ASV is

reached if known.

If following a repeat 20 WBCT, blood is coagulable no further ASV is required.

99..1144 RReeppeeaatt AASSVV DDoosseess:: PPrrooggrreessssiivvee WWeeaakknneessss

In Progressive Weakness cases the speed of venom action and the risk of

respiratory compromise mandates a faster reassessment and repeat dose

regimen.

Following the completion of the initial dose a period of 1 hour is allowed to

elapse. The patient is reassessed and if the symptoms have worsened, i.e.

paralysis has descended further a second dose is given at the same dosage

as the initial dose.

If after 1 hour, following completion of the initial dose, symptoms have not

worsened, a further hour is allowed to pass. If the patient has not improved or

has worsened a second dose is given at this stage, at the same level as the

initial dose.

84

Following the second dose of ASV, no further ASV is administered. At this

stage it is very likely that circulating venom will be neutralised and the patient

will either recover or proceed to respiratory failure. Supportive measures

should be taken in line with the guidelines in Section 12.0.

99..1155 RReeppeeaatt AASSVV DDoosseess:: PPaaiinnffuull PPrrooggrreessssiivvee SSwweelllliinngg

In the case of bites where the key symptom is Painful Progressive Swelling,

repeat ASV doses have to be considered carefully. Often this will be a

decision of the individual doctor. The case for ASV having any role is such

bites is controversial and ASV is often a limited resource. In such cases if the

approach adopted is to give an initial dose, a second dose will likely be

unnecessary. All the evidence points to the damage being done by PPS

toxins very quickly after the bite and by moving through the tissues

commencing with the bite site.

It therefore makes little sense to give a second dose in such cases, as there

will be no unbound venom that can be neutralised.

99..1166 SSiiggnnss ooff RReeccoovveerryy

If the initial or subsequent dose/doses of ASV is adequate than signs of

recovery will be evident:

1. Blood coagulation will be restored

2. Systemic bleeding may stop as early as 30 minutes after the first dose

is given

3. Hypotension may be controlled in 30 minutes to 1 hour.

4. Neurological signs may stop descending and gradual recovery in

function may be evident

85

1100..00 AAddvveerrssee AAnnttii SSnnaakkee VVeennoomm RReeaaccttiioonnss


The concept of adverse reactions to ASV has had a significant negative

impact on snakebite treatment far in excess of the actual risk. Reported levels

of ASV reactions have been very high, the risk of fatal anaphylactoid reactions

stressed; with the result that doctors have been reluctant to treat victims

(World Health Organisation, 1981; Warrell, 1993; Warrell, 1999; Ariaratnam et

al, 2001; Warrell, 2003; Isbister et al, 2006; World Health Organisation, 2007;

Simpson, 2008). These reactions however, if managed correctly can be easily

treated in even the most basic medical facilities and moves for improvements

in ASV quality need to be balanced with costs of so doing (Krifi et al, 1999).

1100..22 MMeecchhaanniissmm ooff tthhee RReeaaccttiioonn

The specific mechanism responsible for generating adverse reactions is not

clear.

1. Complement activation directly by the ASV proteins

There is some evidence that ASV is able to activate complement in

vitro (Sutherland, 1977; Leon et al, 2001; Leon et al, 2005)

2. Complement activation mediated by immune complexes

1100..33 PPrreeddiiccttiioonn ooff AAddvveerrssee RReeaaccttiioonnss

A frequently used mechanism in response to ASV reactions is to try and

predict them with the use of a ‘test dose’. An intra dermal test dose is

administered to the victim, approximately 30 minutes is allowed to elapse and

inspection is used to determine if any wheals are present indicating sensitivity.

Skin tests are widely used in testing for Type I hypersensitivity allergic

reactions. They indicate high levels of IgE in the presence of a specific

allergen.

86

They are of no use in predicting ASV reactions for the following reasons:

1. They are non predictive – ASV reactions are complement activated and

not mediated by IgG, they are also de novo reactions (Malasit et al,

1986; Gutierrez et al, 2007)

2. They waste time when the patient needs ASV

3. They may pre-sensitise the patient and make a severe reaction more

likely when the major amount of ASV is administered.

1100..44 PPrreevveennttiinngg AAddvveerrssee RReeaaccttiioonnss

The use of prophylactic drugs to prevent adverse reactions to ASV is

common. Despite the fact that developed country ASVs are often regarded as

superior products, reaction rates of 25% or higher are reported when using

these ASVs (Isbister et al, 2006; Isbister et al, 2008).

The prophylactic approach is based largely on two studies in Sri Lanka, which

appeared to show that prophylactic doses of adrenaline or hydrocortisone and

antihistamine prevented reactions (Premawardenha et al, 1999;

Gawarammana et al, 2004). Both these studies were statistically

underpowered, with one stopping half way through the study as the results at

that stage were regarded as good! Other poorly constructed retrospective

studies also appear to support the use of premedication to prevent reactions

(Williams et al, 2007). Other studies have shown no benefit to prophylactic

regimens (Isbister et al, 2008)

A study in Brazil indicated that antihistamine alone was not effective in

preventing reaction (Wen-Fan et al, 1999).

The conclusion with respect to prophylactic regimens to prevent adverse

reactions is that they probably do no harm but there is no compelling evidence

that they are effective.

87

1100..55 TTrreeaattmmeenntt ooff AAddvveerrssee RReeaaccttiioonnss

ASV reactions are straightforward to manage if:

1. They are identified early

2. They are treated immediately

3. They are treated with the drug of choice

4. The correct mode of administration of the drug is used

5. Correct reassessment period is used

Step 1: Identified Early

Many ASV reactions pass unnoticed as the doctor is not actively looking for

them. Local experience with the ASV will almost certainly establish an

average time to onset of the reaction. For example, with Indian ASVs the

average onset time for reactions is 20 minutes (Kochar et al, 2007). This is a

key period to examine the patient carefully, particularly across the trunk, as

this is where reactions are first evident. A useful technique is to shine a torch

across the trunk as this casts the urticaria in shadow.

Step 2: Treated Immediately

At the first sign of a reaction, stop the ASV. The first signs include a single

patch of urticaria or any itching. Often the patient will become restless just

before these signs and symptoms manifest.

Step 3: Drug of Choice

The correct drug of choice and the immediate response is adrenaline

(Sampson et al, 1992; Project Team of the Resuscitation Council (UK), 2002;

McClean-Tooke et al, 2003). Ideally 2 syringes should be drawn up ready if

the ASV is known to cause frequent reactions.

0.5 mg adrenaline is made ready, 0.01 mg/kg for paediatric cases

88

Step 4: Correct Mode of Administration

The critical factor in managing ASV reactions is speed! The longer the

reaction persists, the longer will be the period the victim is without ASV and

the more venom will be permitted to bind to the target cells. Therefore speed

of effect of adrenaline is critical.

The mode of administration therefore is intramuscular (IM). The deltoid

muscle is the best site (American Association of Allergy, Asthma, and

Immunology, 2003; McClean-Tooke et al, 2003; Simons et al, 2001).

The time for adrenaline to reach peak effect is 8 minutes via the IM route and

34 minutes via the subcutaneous route (Simpson, 2007). Despite a

preponderance of doctors who would use the subcutaneous route, IM is the

first option (Simons et al, 2001; Simpson, 2008).

Step 5: Correct Reassessment Period

Once the initial dose of adrenaline is given IM, the patient is closely

monitored. Around 3 minutes, the patients pulse rate should begin to increase

confirming the drug was correctly administered IM. At 8 minutes, the

adrenaline will reach peak levels and at this stage 5-7 minutes are spent

examining the patient for signs of improvement. If none are evident or the

patient’s condition has worsened, a second dose is administered IM. In very

rare cases, a third dose may be necessary.

The majority of patients will respond to a single dose, the remainder will

respond to the second dose. Using the IM route it is possible to administer 2

doses of adrenaline in the same time, as it would take a single dose of

subcutaneous adrenaline to reach peak effect.

1100..66 AASSVV RReeaaccttiioonn SSuuppppoorrtt DDrruuggss

In addition and as a secondary support to adrenaline to provide long term

protection against anaphylactoid reaction, 100mg of hydrocortisone and an

H1 antihistamine, such as Pheniramine maleate can be used at 22.5mg IV or

89

Promethazine HCl can be used at 25mg IM, or 10mg chlorpheniramine

maleate if available, can be administered IV.

The paediatric dose is of Phenimarine maleate at 0.5mg/kg/ day IV or

Promethazine HCl can be used at 0.3-0.5mg/kg IM or 0.2mg/kg of

chlorphenimarine maleate IV and 2mg/kg of hydrocortisone IV.

90

1111..00 NNeeuurroottooxxiicc EEnnvveennoommaattiioonn aanndd AAnnttiicchhoolliinneesstteerraassee DDrruuggss


Many of the frequently used western textbooks provide little guidance on how

to manage neurotoxic snakebite due to the low level of incidence in the

countries concerned (Benjamin et al, 2004; Auerbach and Norris, 2005;

Simpson, 2008). Key interventions, such as the use of anticholinesterases are

omitted (Bakar et al, 2006; Simpson, 2007; Simpson, 2008).

Neurotoxic snake venom acts in two main ways that leads to mortality, with

other specialised effects in some snake species. The key action of the venom

is paralysis of muscles concerned in respiration leading to asphyxia and

respiratory failure.

Postsynaptic toxins such as those in the cobra species demonstrate a high

level of affinity to bind with the acetylcholine receptor of the motor synapses

thus preventing neuromuscular transmission (Watt et al, 1986; Yee et al,

2004). A key objective therefore is to increase the time that acetylcholine is

available to bind to free receptors, by eliminating cholinesterase.

1111..22 AAnnttiicchhoolliinneesstteerraassee DDrruuggss

Anticholinesterase drugs work by eliminating cholinesterase and prolonging

the life of acetylcholine increasing the possibility of binding to a free receptor.

It is important that this fact is communicated to medical administration officials

as often anticholinesterase drugs are available but are not distributed to front

line hospitals, as the drug is mainly associated with use by anaesthetists in

hospitals with surgical capability. In hospitals that deal with post synaptic

envenoming the drug should be readily available.

91

1111..33 TThhee TTeesstt

An anticholinesterase is administered following the baseline measurement of

a simple test of neurological function (Simpson, 2007). These simple tests are

usually:

• Single breath count

• Length of time upward gaze can be maintained

They can also include:

• Intra incisor distance

• Length of time grip can be maintained

• Others

The baseline measure is noted and used to assess the efficacy of the

anticholinesterase. Once the test drug is administered, repeating the baseline

test to identify improvement assesses the results. If no improvement is noted

the use of the anticholinesterase is discontinued. There is no role for longer-

term administration in a patient that shows no positive response.

1111..44 AAnnttiicchhoolliinneesstteerraassee DDrruuggss TTeesstt aanndd DDoossaaggeess

The most commonly available drug is neostigmine methylsulphate. Other

drugs include edrophonium or ‘Tensilon’, which despite being recommended

to developing world doctors, is uncommon in developing countries (Khan and

Naseem, 2000).

Neostigmine

1. 1.5 mg is administered IM

2. 0.6 mg atropine is administered IV to counter muscarinic effects

Paediatric dosage is 0.04 mg/kg IM & 0.05mg/kg atropine IV

The peak plasma effect is at 20 minutes so repeating the baseline test should

be carried out at 10-minute intervals.

92

Assessment Period = 1 hour

In the event of improvement neostigmine is continued every 30 minutes with

0.5 mg administered IM with atropine as required.

Edrophonium

1. 10 mg is administered IV

2. 0.6 mg atropine administered IV to counter muscarinic effects

Paediatric dosage is 0.25 mg/kg IM & 0.05mg/kg atropine IV

Assessment Period = 20 minutes

In the event of improvement neostigmine is continued thereafter every 30

minutes with 0.5 mg administered IM with atropine as required.

There is little doubt that anticholinesterase drugs are effective in postsynaptic

envenoming (Ramakrishnan et al, 1975). The evidence is much less clear in

cases of presynaptic envenoming (Warrell et al, 1983; Akram and Khurshid,

2000; Akram et al, 2002).

Mention of anticholinesterase drugs being used, as a substitute for ASV

should only be considered if no ASV is available (Bomb et al, 1996). The

more venom that can be neutralised before it binds to target receptors

reduces the severity of the envenomation.

93

1122..00 AAiirrwwaayy SSuuppppoorrtt IItteemmss


In the case of unconscious patients suffering from neurotoxic envenoming, a

number of strategies can be adopted depending on available equipment to

support the patient’s breathing. In the vast majority of cases, if the patient’s

breathing is maintained, they will survive. The critical period is usually the

journey from the initial contact with medical care to the more advanced

hospital with mechanical ventilation. If treating the patient in a peripheral

hospital with no access to mechanical ventilation, the patient’s inability to

perform a neck lift will trigger referral to a better-equipped hospital. The

patient, either conscious or unconscious will require airway support on the

journey, as that is where respiratory failure is likely to occur. A number of

options are available.

1122..22 DDeevveellooppiinngg WWoorrlldd AAiirrwwaayy MMaannaaggeemmeenntt CCoonntteexxtt

It is necessary to maintain a sense of reality with regard to airway support in

developing countries. The following are key considerations in drawing up the

below guidelines:

1. In most areas, neurotoxic snakebite will be less significant in terms of

numbers when compared to viperine snakebite which is mainly

coagulopathic

2. The ideal solution with respiratory compromise or failure is

endotracheal intubation and support on a mechanical ventilator

3. Many doctors are not sufficiently well trained, experienced or confident

to carry out endotracheal intubation and therefore do not attempt it

4. The vast majority of medical facilities are NOT equipped with

mechanical ventilators

5. Those facilities that are equipped with ventilators have very few and

they are invariably already in use and under pressure

6. In disaster situations, such as floods or cyclones e.g. Cyclone Nargis,

power will be interrupted and road travel will be virtually impossible due

to flooding and fallen trees! The focus of W.H.O. nominated experts in

94

the aftermath of Cyclone Nargis who concentrated on mechanical

ventilation and intubation in the snakebite guidelines, demonstrates the

lack of understanding of airway support conditions in developing

countries.

Solutions therefore range from the improvised, which are most likely to be

used, to the bridging solution and then ultimately the ideal.

1122..33 IImmpprroovviisseedd SSoolluuttiioonn

In many primary care hospitals facilities are basic and airway support

equipment is limited. Usually the equipment consists of a resuscitation bag

alone, which can be used to maintain a victim’s air supply in the short term.

Family members or friends can be instructed in the use of this equipment

should it become necessary on the journey. The important points to

communicate are that the mask should be placed over both the nose and

mouth in a rolling manner starting at the bridge of the nose. Preferably, bag-

valve-mask ventilations are given using the “C-E” grips [thumb and index

finger of each hand forming a “C” over top of the mask and long, ring and little

fingers forming an “E” under the jaw – pressing the mask onto the face]. The

bag should be squeezed at a specific cadence of “squeeze – release –

release.” This method ensures the victim receives a good quantity of air but

also allows time for exhalation.

However, in cases of neurotoxic envenomation, if respiratory failure occurs it

will be due to flaccid paralysis and there is a strong likelihood that the tongue

will fall back and obstruct the airway. The effective functioning of a

resuscitation bag in these circumstances will be highly limited.

Nasopharyngeal airway (NPA) support is an excellent emergency measure in

these situations (Bajaj et al, 2008). If available, NPAs should be inserted

before transportation to the referral hospital, which will dramatically increase

the probability of effective respiratory support during the journey.

95

It is possible however to improvise nasopharyngeal tubes (NT) from

endotracheal tubes (ET), which are usually readily available or can be

obtained easily. Two rubber or plastic size 6.5 ET tubes for females, size 7 for

males or size 5 for either can be adapted to provide NT (Roberts et al, 2005).

The tubes are cut to the distance between the nostril and the tragus,

lubricated and inserted into the nostrils of a conscious or unconscious patient

(Quraishi et al, 2008; Simpson and Jacobsen, 2009).

Cut to the correct length they will not trigger the gagging reflex and thus can

be used when a patient is conscious (Simpson and Jacobsen, 2009). In the

event that a patient cannot perform a neck lift and is to be transferred to a

better-equipped hospital, the tubes can be inserted and the individuals

accompanying the victim instructed to use the resuscitation bag if the victim

stops breathing (Simpson and Jacobsen, 2009).

1122..44 BBrriiddggiinngg DDeevviicceess

An improved solution is the use of an airway-bridging device such as a

laryngeal tube (LT) or laryngeal mask airway (LMA) (Simpson, 2007). These

devices are not “definitive” airways (defined as a cuffed endotracheal tube

positioned below the vocal cords), but provide excellent airway support. They

are inserted blindly and give a very high percentage possibility of being

inserted correctly (Bailey and Hett, 1994; Springer and Jahr, 1995; Pollack,

2001; Murphy, 2004; Murphy and Schneider, 2004; Weiss et al, 2008).

Use of such airways by accompanying laypersons has not been studied, but it

is very possible that the lay provider can adequately ventilate the unconscious

victim during transfer using a properly placed laryngeal tube. The creation of a

better seal makes the use of an LT tube more preferable over rough journeys

experienced when transporting snakebite victims in many developing

countries (Ocker et al, 2002; Gaitini et al, 2008)

Use of the LMA requires greater skill in maintaining proper positioning,

making it a less optimal choice for use by untrained individuals.

96

Fig 12.1 Top Row, Resuscitation Bag, LT Tube, LMA, Nasopharyngeal Tubes Bottom Row, How to measure and fit improvised nasopharyngeal Tubes.

97

1122..55 TThhee IIddeeaall SSoolluuttiioonn

The ideal solution is the ability to endotracheally intubate the victim and

provide a definitive airway defined as placing a cuffed tube below the vocal

chords (Akram et al, 2004). However, in primary care centres in many

developing countries, the equipment is unavailable and doctor confidence in

performing intubation is not high (Simpson, 2007; Simpson and Jacobsen,

2009).

The endpoint therapy will be a mechanical ventilator to provide long-term

respiratory support. In presynaptic envenoming, the period of ventilation may

be extensive whilst the body restores synaptic vesicles (Harris and

Goonetilleke, 2005).

However, in developing countries, where such facilities are limited, an

improvised or bridging solution is necessary to ensure the victim survives the

inevitable journey. Developed world derived protocols advising endotracheal

intubation or tracheostomy, once loss of the gag reflex or pooling of

secretions occurs is simply impractical in most developing world facilities

(Warrell, 1999; Simpson and Jacobsen, 2009).

98

1133..00 HHaaeemmoottooxxiicc EEnnvveennoommaattiioonn,, BBlloooodd PPrroodduuccttss aanndd RReennaall IImmppaaiirrmmeenntt


The presence of systemic bleeding with or without hypotension is a common

feature of snakebite, particularly in the case of viperine bites.

Hypotension, severe reductions in haemoglobin concentration, platelet

reductions i.e. thrombocytopenia, or frank bleeding can increase the pressure

to administer blood related products.

Hypotension due to action of the venom can have a number of causes in

snakebite, ranging from loss of circulating volume due to haemorrhaging,

vasodilation due to the action of the venom or direct venom effects on the

heart.

In the majority of cases the timely use of ASV will stop systemic bleeding.

However in some cases the bleeding may continue to a point where further

treatment should be considered.

Test for hypovolaemia by examining the blood pressure lying down and sitting

up, to establish a postural drop.

Treatment is by means of plasma expanders and raising the foot of the bed.

There is no conclusive trial evidence to support a preference for colloids or

crystalloids. In addition fresh frozen plasma or factors present a possibility in

order to boost volume and restore factors. In many areas, particularly in

developing countries, the only available alternative will be fresh blood.

In cases where generalised capillary permeability has been established a

vasoconstrictor such as dopamine can be used. Dosing is 2.5- 5µ /kg/minute.

99

The major point to note is that clotting must have been re-established before

additional measures are taken. Adding clotting factors, FFP, cryoprecipitate or

whole blood in the presence of un-neutralised venom will increase the amount

of degradation products with the accompanying risk to the renal function

(White, 2005).

1133..22 AAnnttiiccooaagguullaannttss

Other drugs such as heparin have been intuitively thought to be beneficial in

snakebite induced coagulation and DIC and apparently supported but by very

weak research (Paul et al, 2003; Paul et al, 2008). However, like much of

what is intuitively recommended in snakebite, heparin is contraindicated.

Venom induced thrombin is resistant to Heparin, the effects of heparin on

antithrombin III are negated due to the elimination of ATIII by the time heparin

is administered and in itself heparin can cause bleeding. In the case of trial

evidence, heparin has been shown to have no beneficial effect (Myint-Lwin et

al, 1992; White, 2005).

1133..33 CCooaagguullaannttss

When there are signs of current bleeding such as bleeding from the gums,

there is the intuitive thought that coagulants can play a role in inhibiting

bleeding. For example, drugs such as Botropase, a coagulant, are sometimes

used in response to visible bleeding. It is however, a compound derived from

the venom of one of two South American pit vipers both of which cause

coagulation by activating the clotting cascade. It uses the same means to

achieve coagulation as the snake concerned in the envenomation and should

not be used in viper bites as it simply prolongs the coagulation abnormality by

causing consumption coagulopathy in the same way.

1133..44 LLoonnggeerr TTeerrmm IIssssuueess

Russell’s viper bites are known to cause acute pituitary adrenal insufficiency

(Eapen et al 1976; Tun Pe et al, 1987). This condition may contribute to shock

and in the limited case study evidence appears to occur in cases where shock

has been present. Follow-up checks on known Russell’s viper victims need to

100

ensure that no long-term pituitary sequelae are evident. In known Russell’s

viper areas, patients who present with symptoms such as reduced secondary

hair growth or lethargy or reduced libido should be asked if they have suffered

snakebite in the past.

1133..55 RReennaall IImmppaaiirrmmeenntt

Renal failure is a common complication of species such as Russell's Viper.

The contributory factors are intravascular haemolysis, DIC, direct

nephrotoxicity and hypotension and rhabdomyolysis (Chugh et al, 1975,

Shastry et al, 1977; Than-Than et al, 1989).

Renal damage can develop very early and even when the patient arrives at

hospital soon after the bite, the damage may already have been done (Thein-

Than et al, 1991). Studies have shown that even when ASV is administered

within 1-2 hours after the bite, it was incapable of preventing Acute Renal

Failure. A victim in renal failure is evidence of the previous action of venom

either directly on the kidney or by fibrin deposition. It is not evidence that the

victim has currently has un-neutralised venom in the system and therefore

requires ASV (Warrell, 1999).

The following are indications of renal failure:

Declining or no urine output although not all cases of renal failure exhibits

oliguria

Blood Bio-Chemistry

Serum Creatinine > 5mg/dl or rise of > 1mg / day.

Urea > 200mg/dl

Potassium > 5.6 mmol/l Confirm hyperkalaemia with ECG.

Evidence of Uraemia or metabolic acidosis.

101

Declining renal parameters require referral to a specialist nephrologist with

access to dialysis equipment. Peritoneal dialysis could be performed in

secondary care centres. Haemodialysis is preferable in cases of hypotension

or hyperkalaemia (Shastry et al, 1977).

102

1144..00 PPaaiinn,, WWoouunndd MMaannaaggeemmeenntt aanndd tthhee SSuurrggiiccaall AAssppeeccttss ooff SSnnaakkeebbiittee

1144..11 PPaaiinn aanndd WWoouunndd MMaannaaggeemmeenntt

Snakebite is painful! The action of the spreading factor and tissue damaging

toxins in the venom can cause significant pain at the bite site and in the bitten

limb. Pain relief is a vital but often overlooked aspect of snakebite

management.

The drug of choice is Paracetamol, Adult dose of 500-1000mg 4-6 hourly.

Paediatric dose 10mg/kg every 4-6 hourly orally.

If available, mild opiates such as Tramadol, 50 mg can be used orally for relief

of severe pain. In cases of severe pain at a tertiary centre, Tramadol can be

given IV. Aspirin should not be used due to its adverse impact on

haemostasis due to inhibition of platelet aggregation. Do not use non-steroidal

anti-inflammatory drugs (NSAIDs) as they can cause bleeding. This can be

particularly dangerous in a patient already having coagulopathy.

1144..22 AAnnttiibbiioottiiccss aanndd TTeettaannuuss

There are many factors that contribute to potential infection in snakebite,

including poor or dangerous first aid, oral snake flora and environmental

factors (Ehui et al, 2007; Habib, 2003). There has been considerable

confusion concerning the role of antibiotics in snakebite management. Some

texts have argued for routine prophylaxis with antibiotics, due to the bacterial

content of the snakes mouth and saliva, others have argued against routine

prophylaxis, reserving antibiotics for use only where local necrosis is present

(Blaylock, 2001).

Routine use of antibiotics in snakebite is unnecessary. However In specific

snake species, e,g, Malayan pit viper (Callesolasma rhodostoma) and

Chinese cobra (Naja atra) routine use is advised.

103

In cases where the victim has cut the wound or in cases of necrosis, antibiotic

use is advised (Blaylock, 1999). Where wound infection is suspected a

regimen of oral levofloxacin and amoxicillin/clavulanate should be

administered.

Tetanus booster doses should be given although these can be delayed until

coagulation is restored in cases with incoagulable blood. In many areas

tetanus inoculation will not be thorough and tetanus toxoid should thus be

given.

1144..33 SSnnaakkee VVeennoomm OOpphhtthhaallmmiiaa

In both Africa and Asia, a number of the cobras are not neurotoxic in nature

but rather spit venom at the victim in order to escape. This venom is directed

at the eyes and causes extreme pain and conjunctivitis. The eyes should be

immediately irrigated with large quantities of water or other non-irritant liquid.

Pain relief has been reported with the administration of 0.5% adrenaline eye

drops. Topical antimicrobials should be administered unless corneal damage

can be excluded.

1144..44 SSuurrggeerryy aanndd SSnnaakkeebbiittee

Surgical interventions are a contributory factor in resolving snakebite but must

be used with caution. In developing countries surgical procedures can be

carried out unnecessarily based on reliance on developed world approaches.

Some interventions are necessary and should be deployed when required

such as life saving procedures and removal of necrotic tissue. Others such as

fasciotomy should be used sparingly and under very defined conditions.

1144..55 SSnnaakkeebbiittee && LLiiffee TThhrreeaatteenniinngg CCoonnddiittiioonnss RReeqquuiirriinngg

SSuurrggeerryy

A particularly serious consequence of snakebite is intra cranial bleeds. These

frequently result in mortality and perhaps represent the worst of all

complications. Key to survival is surgical intervention to remove the clot and

thereby relieve pressure within the cranial cavity. Before surgery can take

104

place coagulation must be restored rapidly and thus a very larger initial dose

of ASV is given in excess of the normal dosage levels in order to ensure

restoration of coagulation within a 6-hour period.

It is recognised that this large initial dose may be in excess of the required

amount to achieve neutralisation of the venom. The critical point here is that

coagulation must be definitively restored in the shortest period i.e. 6 hours,

and thus the risk of exceeding the required amount is acceptable to ensure

life saving surgery can take place.

1144..66 DDeebbrriiddeemmeenntt ooff NNeeccrroottiicc TTiissssuuee

Local and extensive necrosis resulting from venom action may necessitate

debridement of necrotic tissue. The necrotic area should be kept clean and

topical agents can be applied (Anindhya et al, 2004).

In most rural settings the victim will need referral to a facility that can perform

surgery and is equipped with a surgeon.

It is worth waiting 5-7 days before commencing a debridement of necrotic

tissue in order that the line of demarcation between viable and non-viable

tissue can be specified (Blaylock, 2005)

1144..77 CCoommppaarrttmmeenntt SSyynnddrroommee

Compartment syndrome is a widely used concept in snakebite and is

undoubtedly overused in many areas. The sight of the ‘6 Ps’:

1. Pain on passive stretching

2. Pain out of proportion

3. Pulselessness

4. Pallor

5. Parasthesia

6. Paralysis

105

will often lead to a fasciotomy to ‘release the pressure’ and enable arterial

perfusion to the limb (Joseph, 2003). However, this approach must be used

with caution in developing countries. Visual impression is a highly unreliable

guide to estimating intra-compartmental pressure.

In a small case study in India, using a Stryker monitor, despite grossly swollen

limbs, which matched the 6Ps, only one case from 12 achieved an

intracompartmental pressure where fasciotomy would be considered. By the

time coagulation was restored in the victim, the intracompartmental pressure

had reduced to normal levels.

What is important is that the intra-compartmental pressure should be

measured objectively using saline manometers or newer specialised

equipment such as the Stryker Intra-compartmental Pressure Monitoring

Equipment (Anindhya et al, 2004).

The patient should be referred to a surgical specialist but it is worth the

treating clinician ensuring that objective criteria are used to assess the actual

intracompartmental pressure in the limb.

The limb can be raised in the initial stages to see if swelling is reduced.

However, this is controversial as there is no trial evidence to support its

effectiveness.

106

1155..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt iinn BBaassiicc oorr PPrriimmaarryy CCaarree FFaacciilliittiieess


A key objective of this protocol is to enable doctors in Primary Care Facilities

(PCF) or Basic Care Facilities (BCF) to treat snakebite with confidence. These

facilities are the backbone of medical care in developing countries but are

poorly equipped and with only one or a small number of doctors that staff

them.

Evidence suggests that even when equipped with anti snake venom,

PCF/BCF doctors lack the confidence to treat snakebite due to the absence of

a protocol tailored to their needs and outlining how they should proceed within

their context and setting. The following summarizes a sequence of activities to

be carried out in these settings for optimal response.

1155..22 PPaattiieenntt AArrrriivvaall && AAsssseessssmmeenntt

Patient should be placed under observation for 24 hours

The snake, if brought, should be carefully examined and identified if possible.

Pain management should be considered.

20WBCT in clean, new, dry, glass test tubes should be carried out every 30

minutes for the 1st 3 hours and then hourly after that.

Attention should be paid for any visible neurological symptoms.

Severe, current, local swelling should be identified

If no symptoms develop after 24 hours the patient can be discharged with a

Tetanus Toxoid.

1155..33 EEnnvveennoommaattiioonn;; HHaaeemmoottooxxiicc

If the patient has evidence of haemotoxic envenomation, determined by

20WBCT, then the initial dose of ASV is administered over 1 hour. Adrenaline

is made ready in two syringes of 0.5mg 1:1000 for IM administration if

symptoms of any adverse reaction appear (see Section 10). If symptoms do

107

appear, ASV is temporarily suspended while the reaction is dealt with and

then recommenced.

1155..44 RReeffeerrrraall CCrriitteerriiaa

Once ASV administration is finished and any adverse reaction dealt with the

patient should be automatically referred to a higher centre with facilities for

blood analysis to determine any systemic bleeding or renal impairment.

The 6-hour rule ensures that a six-hour window is now available in which to

transport the patient.

1155..55 EEnnvveennoommaattiioonn;; NNeeuurroottooxxiicc

If the patient shows signs of neurotoxic envenomation the initial dose of ASV

is administered over 1 hour.

Adrenaline is made ready in two syringes of 0.5mg 1:1000 for IM

administration if symptoms of any adverse reaction appear. If symptoms do

appear, ASV is temporarily suspended while the reaction is dealt with and

then recommenced (see Section 10).

A neostigmine test is administered using 1.5-2.0mg of neostigmine IM plus

0.6mg of atropine IV. An objective measure such as single breath count is

used to assess the improvement or lack of improvement given by the

neostigmine over 1 hour. If there is no improvement in the objective measure

the neostigmine is stopped. If there is improvement 0.5mg neostigmine is

given IM every 30 minutes with atropine until recovery. Usually this recovery

is very rapid.

If after 1 hour from the end of the first dose of ASV, the patient’s symptoms

have not worsened i.e. paralysis has not descended further, a second full

dose of ASV is given over 1 hour. ASV is then completed for this patient.

108

If after 2 hours the patient has not shown worsening symptoms, but has not

improved, a second dose of ASV is given over 1 hour. ASV administration is

now complete for this patient.

1155..66 RReeffeerrrraall CCrriitteerriiaa

The primary consideration, in the case of neurotoxic bites, is respiratory

failure requiring long-term mechanical ventilation (see Section 12.). Whilst it is

entirely possible to maintain a neurotoxic victim by simply using a

resuscitation bag, this should always be used in a last resort; the ideal means

of support remains a mechanical ventilator operated by qualified staff.

BCF/PCF and even many referral hospitals are not equipped with mechanical

ventilators. The most important factor therefore is when to refer a patient to a

hospital with a ventilator and under what conditions.

The key criteria to determine whether respiratory failure, requiring mechanical

ventilation is likely, is the ‘neck lift’. Neurotoxic patients should be frequently

checked on their ability to perform a neck lift. If they are able to carry out the

action then treatment should continue until recovery in the BCF/PCF.

If the patient reaches the stage when a neck lift cannot be carried out then the

patient should be immediately referred to a hospital with a mechanical

ventilator.

1155..77 CCoonnddiittiioonnss aanndd EEqquuiippmmeenntt AAccccoommppaannyyiinngg NNeeuurroottooxxiicc

RReeffeerrrraall

The primary consideration is to be equipped to provide respiration support to

the victim if respiratory failure develops before or during the journey to the

institution with mechanical ventilation.

The key priority is to transfer the patient with a facemask, resuscitation bag

and a person, other than the driver of the vehicle, who is trained of how to use

109

these devices. If respiration fails then the victim must be given artificial

respiration until arrival at the institution.

Greater success can be achieved with two additional approaches, prior to

despatch

In the conscious patient, two Nasopharyngeal Tubes (NP) should be inserted

before referral (see Section 12). These will enable effective resuscitation with

the resuscitation bag by not allowing the tongue to fall back and block the

airway, without triggering the gagging reflex. Improvised Nasopharyngeal

tubes can be made by cutting down size 5 endotracheal tubes to the required

length i.e. from the tragus to the nostril (see Section 12). NP tubes should be

prepared and kept with the snakebite kit in the Basic Medical Facility. This is

preferable as the patient may well be unable to perform a neck lift but still

remain conscious and breathing. The danger will be that respiratory failure will

occur after the patient has left the BCF/PCF and before arriving at the

eventual institution. In that case the patient will be pre-prepared for the use of

a resuscitation bag by the use of NP tubes.

In the unconscious patient, a Laryngeal Mask Airway or preferably a

Laryngeal Tube Airway should be inserted before referral, which will enable

more effective ventilatory support to be provided with a resuscitation bag until

the patient reaches an institution with the facility of mechanical ventilation.

110

1166..00 EEqquuiippppiinngg aa BBaassiicc HHoossppiittaall ffoorr EEffffeeccttiivvee SSnnaakkeebbiittee MMaannaaggeemmeenntt


There is a view that snakebite should only be handled in well-equipped

hospitals. Patients often report to their local primary care facility and are

transferred to better-equipped facilities, often many miles away. This is a less

than ideal solution, as the venom action will proceed unopposed by ASV,

during the journey. Thus large amounts of venom that could be easily

neutralised by ASV will proceed to carry out the damage to their intended

target. Delay at this stage exposes the victim to a potentially critical risk as if

the patient is envenomed,

However, with a few basic drugs and equipment, it is possible to manage

most snakebite in the most primitive settings.

1166..22 AAssssuummppttiioonnss

The assumption in this section is that this is a basic setting i.e. without

laboratory analysis capability, mechanical ventilator or renal dialysis

capability. In such a situation the following basic principles apply:

1. Victims with coagulopathy will require eventual transfer to a better-

equipped hospital, due to the requirement to test for occult bleeding or

renal failure.

2. Once the initial dose of ASV is given to a victim with coagulopathy, a

six-hour window is available before ASV will require re-administration.

3. Neurotoxically envenomed patients can be treated entirely locally, if

there is no evidence of respiratory failure and a need for long-term

mechanical ventilation.

4. The trigger to indicate respiratory failure as being imminent is the

failure of a patient to be able to perform a neck lift.

111

5. If the patient is unable to perform a neck lift, this will require transfer to

a better-equipped hospital with a ventilator BUT will crucially require

airway support for the journey as described in Section 12.

6. ASV requirement will be limited to a single dose per patient with

coagulopathy and two doses for a patient with neurotoxic envenoming.

1166..33 AAnnttii SSnnaakkee VVeennoomm

Choice of ASV

The type of ASV used will be determined by availability, cost and

effectiveness of the cold chain. Lyophilised ASV, in powdered form has a

shelf life of 5 years and requires merely to be kept out of direct sunlight. Liquid

AV/ASV, which is easier to administer, has a shelf life of two years and

requires refrigeration.

Holding Quantities of ASV

Holding quantity can be established using the following equation:

(xd X 1.2) t where:

x =number of envenomings on average per month

d = the maximum number of vials likely to be applied at the medical facility to

a single patient i.e. 2 doses to a Neurotoxically envenomed patient

t = length of time normally experienced for replenishment in months.

Suppose we are dealing with a basic facility with two envenomings per month

then x=2: the maximum dose required per patient determines a key part of

usage, so for example, if the maximum dose for a patient at a basic facility is

2 doses of 10 vials for a neurotoxic patient, d = 20. 1.2 represents the safety

factor to ensure greater than minimal stock is available. The restocking time in

months is represented by t. If the restocking period is 2 months for ASV to be

replaced the equation would require 2 X 20 X 1.2 X 2 = 96 vials would be the

ASV base stock amount.

112

1166..44 OOtthheerr SSuuppppoorrtt DDrruuggss

The following drugs should be held, stocking assumptions for each anticipated

bite in a given period are as follows: -

Adrenaline

Adult dosage of 0.5mg of 1:1000 with a potential of three doses maximum per

patient (i.e. stock of a minimum 10 vials)

Hydrocortisone and Antihistamine

Adult dosage of antihistamine and hydrocortisone: only one application per

patient is normally required before referral (i.e. stock of 10 vials)

Neostigmine and Atropine

Adult dosage of 1.5mg for neostigmine and 0.6mg atropine for the test phase

of treatment: ongoing support if test shows positive response is 0.5mg

neostigmine every 30 minutes. Victims who are responsive usually recover

quite rapidly so assume a dosage requirement of 12 hours i.e. 24 x 0.5mg

ampoules. Further atropine may also be required @ 1 ampoule of 0.6mg

atropine for every 5-6 ampoules of 0.5mg neostigmine.

Dose required per neurotoxic bite would be about 30 ampoules (0.5 mg) of

neostigmine and five ampoules of atropine.

Paracetamol:

500mg tablets

IV fluids

Normal Saline, Ringer Lactate and 5 % Dextrose

113

1166..55 SSuuppppoorrtt EEqquuiippmmeenntt

Routine

Syringes and/or IV sets for ASV usage and drug administration

Clean, New GLASS Test Tubes (plastic test tubes or syringes are useless in

this setting)

Blood Pressure Monitor

Resuscitation bag with mask(s)

Nasopharyngeal Airways (These can be improvised using size 5-7

Endotracheal Tubes cut to the required length

Preferred Additional Equipment

Oxygen Cylinder

Some basic medical facilities already possess oxygen cylinders. For example,

many basic medical facilities are equipped with a 40cft cylinder. This can be

used not only for application of oxygen to a victim but newer equipment is

becoming available that enables the cylinder to power a gas ventilator.

Airway Support Equipment

Laryngeal tube / LMA

Endo Tracheal tubes

114

1177..00 SSnnaakkeebbiittee:: RRiisskk AAccttiivviittiieess aanndd PPrreevveennttiioonn


Snakebite prevention is an important activity and can make a contribution to

reducing snakebite. It must be looked at with a degree of realism if it is to be

successful. Snakebite is primarily a problem of developing world rural

communities. Rural activities will always place participants at risk as they

must, by definition, enter the snake’s habitat and carry out activities that will

tend to distract them from the danger posed by a snake’s presence.

1177..22 PPrreevveennttiioonn MMyytthhss

Most herpetologists and snakebite experts naively assume that education will

cause rural workers to significantly reduce their risk of bites.

Recommendations are many as to how to prevent bites, but in reality the

scope for such reductions are minimal. The advice not to keep rubbish near

the home is fine in western environments but completely misplaced in

countries that have no organised refuse collection, where rubbish is simply

thrown into a convenient spot.

The recommendation to wear protective footwear, such as boots when rice

harvesting, is fine from a western perspective and yet in 45C temperatures

impractical. The author witnessed a western multinational company, which

insisted that its employees wore snake protective boots when working in the

fields. The response from the employees was to cut large holes in the boots to

ensure they were cool enough to be able to wear.

Much snake prevention advice is dubious in its effectiveness. For example, it

is frequently reported that sleeping on a cot prevents snakebite; it has also

been reported that religious groups such as Hindus are more at risk as they

sleep on the floor. Muslims that sleep on cots are reported to be at less risk

and yet the Islamic Republic of Pakistan has the third highest death toll from

snakebite. This risk can also be increased as vegetable products such as

115

onions are placed on the cot to ‘repel’ snakes, yet paradoxically have the

effect of attracting rats up onto the cot, swiftly followed by snakes!

Certain periods are also reported to present greater risk but probably for the

wrong reasons. Monsoon rains are described as driving snakes from their

holes, causing greater numbers of bites and yet this is probably incorrect.

Analysis of the snakes that are brought with victims to the hospital during the

start of the monsoon rains show they are mainly recently hatched juveniles.

Snakes give birth at the commencement of the rainy season, as food sources

such as frogs are abundant. Large numbers of juvenile snakes moving about,

looking for food and territories are the much more likely cause of the increase

in snakebite. Victims need to be looking not for a large snake seeking refuge,

but many small snakes that are more difficult to see!

Physical protection methods such as ditches, chemical and floral repellents

are also often recommended. The military still employs ditches around army

camps to prevent snake ingress, however snakes cross such ditches easily.

There are no chemical or plant repellents that deter snakes; the author has

captured snakes resting in plants that allegedly ‘repel’ them.

1177..33 TThhee DDooccttoorrss RRoollee

The key role that the physician plays in snakebite prevention is determining

which specific activities are largely responsible for causing the bites in a given

area.

When activities involved in snakebite are specifically examined, the outcome

usually indicates that 3 or 4 key activities result in 80% plus of the snakebites.

For example, in India, China and Africa, grass cutting is a particularly risky

activity.

116

The rural practice of cutting grass manually, with a cutting device in the right

hand and grasping the grass with the left hand, places the left hand in close

proximity with the stationary snake in the long grass. It is a frequent cause of

bites on the left hand. Cutting of high-level crops such as millet, particularly by

women, often results in walking up and down rows of the crop, with the focus

of attention upwards on the crop. The victim will be walking and cutting, but

not looking downwards where the snake is resting.

117

1188..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt WWhheenn AASSVV iiss UUnnaavvaaiillaabbllee


Despite ASV shortages being a known phenomenon for a number of decades,

precious little has been done to rectify the situation. Papers have frequently

been produced outlining a potential ASV solution but implementation has

been completely absent.

Dealing with an envenomation without ASV is a difficult activity that requires

tough decisions to be taken; it is not for the squeamish!

1188..22 GGuuiiddiinngg PPrriinncciipplleess

Nothing is available in the form of trial data but some assumptions are

enduring and should form the basis for guiding the physician in how to

manage in such circumstances.

1. In the vast majority of envenomations from venomous species mortality

is not 100% in untreated cases. In some major contributors to

snakebite envenomations such as the African carpet viper (Echis

ocellatus) and the Indian Russell’s viper (Daboia russelii) the untreated

mortality rate is around 10-20% (Abubakar et al, 2009).

2. In species such as the black mamba (Dendroaspis polylepsis), which

does have a high mortality rate, the mode of death is neurotoxic and

good preparation to manage respiratory compromise will increase the

success rate of managing a bite.

3. The mode of death further reduces the risk of death in an

envenomation without ASV. The key modes of death are, spontaneous

bleeding, shock, renal failure and respiratory arrest. Not all cases of

haemotoxic envenoming result in spontaneous bleeding. A great many

simply involve coagulation abnormalities without spontaneous

bleeding. In the case of renal failure it is doubtful that ASV has any role

118

in preventing it, in any event. Respiratory failure can be managed as a

separate event in the absence of ASV.

4. The case for the use of ASV in dealing with swelling is inconclusive

and there is thus a strong possibility that a lack of ASV in cases that

only cause Painful Progressive Swelling is not a significant problem in

any event (Gutierrez et al, 2007; Offerman et al, 2009).

1188..33 AAccttiioonnss ffoorr tthhee PPhhyyssiicciiaann

The physician’s role will be confined to reducing the risk of death outlined in

the above principles. The following may be useful actions that can be taken:

1. Preparations for Managing Respiratory Failure.

The first step is to secure a resuscitation bag and ideally an emergency

airway support device such as an LMA or LT Tube. In addition, a

number of size 5-7 ET tubes should be obtained to create improvised

nasopharyngeal tubes if required. Ensure that any support staff are

trained in the correct use of the resuscitation bag (See Section 12.3). In

many rural areas, basic medical workers are present in villages and

small towns, often to cope with maternity and basic inoculation matters.

It is essential to ensure that these staff can effectively support

respiration with a resuscitation bag. The physician should provide

training to ensure that this is the case.

2. Preparing to Manage Life Threatening Spontaneous Bleeding

Spontaneous bleeding is a common outcome from snakebite. It is

manifest in a variety of symptoms from gingival bleeding,

haematemesis, haemoptysis, bleeding from the bite site, ecchymoses

and the more serious symptoms such as intra cranial bleed etc. These

outcomes become serious if they progress to life threatening

conditions, which is by no means inevitable.

119

The victim will need life saving surgery in the case of an intracranial

bleed and the potential outcome is very poor. Coagulation will need to

be restored before any surgery can be contemplated.

In the case of other bleeding, the major risk is hypotension and shock.

Maintaining adequate stocks of fluids to increase volume is vital as this

will be the first line of response. If whole blood is required, it will be

useful if the physician has a list of healthy persons’ blood groups that

can be utilised to provide a transfusion in an emergency.

Patients should be kept as immobile as possible in order to avoid any

further cause of bleeding.

3. Preparing to Manage Renal Complications

Many species, such as Russell’s viper (Daboia russelii) are capable of

causing renal failure due to the action of the venom. This will need

careful monitoring of the patient’s fluid output and lab tests if available

to determine if renal failure is occurring. If renal impairment is

suspected the patient should be referred to a facility with dialysis

capability.

120

1199..00 SSnnaakkeebbiittee MMaannaaggeemmeenntt iinn NNaattuurraall DDiissaasstteerrss


Although the vast majority of snakebites take place in developing countries

with less than optimum facilities, there is a worse scenario. Some areas, such

as the Indian Ocean bordering countries are particularly prone to natural

disasters such as cyclones, tsunami and flooding, although these conditions

are often yearly events in some areas. These disasters present unique

problems and a process for dealing with snakebite in such calamities is

useful.

1199..22 LLiikkeellyy CCoonnddiittiioonnss aanndd IImmppaacctt

The following are the most likely consequences of such a disaster and their

impact on snakebite management.

1. Snakebites may increase in number particularly in flooding.

Snakebite is a seasonal medical issue with peaks coinciding with the

rainy season in many areas. Natural disasters such as flooding can

cause an additional peak in the number of bites, which can overwhelm

local medical capabilities. This can be particularly acute, as other

medical conditions will also increase in number due to the natural

calamity.

2. ASV supplies will be unavailable or scarce.

Many countries with serious snakebite problems either have a strategic

shortage of ASV or a tactical shortage in that ASV is located at larger

hospitals that may well be inaccessible following the disaster.

3. Power supplies and Road transportation will be disrupted.

The main effect in this case will be that victim referral to better

equipped hospitals will be seriously reduced or blocked altogether until

roads are restored. Victims bitten by species that cause occult bleeding

or renal failure will thus be unlikely to be readily transported to a

121

hospital that has laboratory facilities to diagnose the problem or

equipped with dialysis equipment. Similarly neurotoxic victims will not

be able to be referred to a hospital with a mechanical ventilator and

any referral, if indeed possible, will be much delayed and take longer

and thus require better airway management on the journey.

1199..33 DDooccttoorrss aanndd MMeeddiiccaall AAuutthhoorriittyy RReessppoonnssee

Despite many natural disasters such as earthquakes being unpredictable,

many other events such as floods are entirely predictable. The flooding each

year in Sindh Province in Pakistan is a regular occurrence and contingency

plans can be effectively implemented. The following guidelines, based on the

above principles can greatly reduce the risk from snakebite.

1. Snakebites may increase in number particularly in flooding.

1.1. Pre Planning

In many cases, natural disasters such as flooding are entirely

predictable. For example, in Sindh Province in Pakistan, the yearly

flooding of the Indus in certain Districts is well known. ASV supplies

can be stockpiled and sent to strategic centers before the flood

season. The National Institute of Health in Islamabad carries out such

a policy. Additional supplies of ASV can be pre-ordered and placed in

key locations. Prior notification enables the producer to schedule

delivery in good time.

1.2. Protocol Distribution

Snakebite management in disaster settings requires that physicians

are very well trained in how to manage snakebite in a local setting.

Distribution of local protocols for managing snakebites such as those

in this guideline, increase doctor confidence and optimal patient

outcomes. Refresher guidelines from health officials, circulated to

treating physicians can be of enormous assistance and local medical

organisations can hold workshops prior to the risk season.

122

1.3. Drug Distribution

ASV should of course be distributed as widely as possible due to the

likely interruption of road transport. It is also essential that support

drugs such as anticholinesterases are made widely available in areas

where postsynaptic envenoming can be expected. Such drugs are

normally reserved for hospitals with operating facilities, as it is

believed by health officials that such drugs are only used in an

operating theatre environment. In the absence of ASV or in support

they can make a critical contribution in the treatment of a postsynaptic

envenoming.

2. ASV supplies will be unavailable or scarce.

2.1. Pre Order for known Risks

ASV supplies should be pre-ordered and located in key medical

facilities. Attention should be given by health officials to ensuring that

the correct ASV is ordered. ASV is species specific and sourcing ASV

from countries with different species, albeit with an ASV surplus is

counterproductive.

Following Cyclone Nargis W.H.O. considered purchasing Indian ASV

for use in Myanmar despite the fact that the Russell’s viper venom

included in Indian ASV is from a different species of Russell’s viper

than that in Myanmar. Health officials should establish potential

substitutes for domestically produced ASV, in case of shortage.

2.2. Provide Adverse Conditions ASV Administration Criteria and

Dosage Guidelines

Shortages of ASV will require tough decisions in order to maximise the

number of victims that can be treated and to ensure ASV is used in the

most critical cases. There are no empirically determined guidelines for

using ASV when shortages exist. The following recommendations

however may help in prioritising criteria for administering ASV and

dosage impacts under conditions of increased shortage. None of these

123

guidelines are ideal but may give some guidance to the treating

physician.

ASV Quantities

Versus

Requirement

ASV Administration Criteria

Initial and Further

Dosage

100 %

Normal Operating Criteria

Incoagulable Blood

Visible Neurological Signs

Severe Current Swelling (If in

normal use)

Normal Dosage

70%

Adjusted Criteria

Incoagulable Blood


Normal Dosage

Normal Dosage

50%

Severe Shortage Criteria

Incoagulable Blood


50% Normal Dose

50% Normal Dose

No 2nd Dose

30%

Critical Shortage Criteria

Visible Bleeding


50% Normal Dose

50% Normal Dose

No 2nd Dose

124

2.3. Emphasise Support Drugs and Equipment

In cases where snakebite may rapidly increase, careful consideration

and action should be given by health officials to ensuring vital support

drugs are provided to all health facilities.

The key drug in this case is the anticholinesterases e.g. neostigmine

or edrophonium. The benefit of these drugs in managing postsynaptic

envenomings cannot be overstated. However, these drugs are often

thought of as the domain of anaesthetists in surgical facilities and are

thus not supplied to more basic facilities even when readily available.

This is the result of health officials not being briefed on their

importance to neurotoxic envenoming.

3. Power Supply and Road transportation will be disrupted.

3.1 Position Airway Management Equipment

Neurotoxic snakebite victims represent a significant threat as with

serious envenomations long term ventilation will be required to

maintain breathing until the victim either clears the post synaptic

venom by normal means or generates new synaptic vesicles in the

case of pre synaptic envenoming. In the former case, this requires

hours, possibly days of ventilation, in the latter often many days of

ventilation.

As stated above, access to mechanical ventilation is the best option

but this will be unlikely in a disaster situation. Not only will ventilators

be inaccessible, but also their usage is likely to be high due to other

medical conditions.

The normal method of dealing with patients who require ventilation, in

the absence of a ventilator or where a ventilator is unavailable

through usage, is for the victim’s family or friends to provide support

with a resuscitation bag until an alternative can be found. This is often

the case, even in tertiary hospitals equipped with ventilators.

125

In neurotoxic envenomings. The key consideration is flaccid paralysis

during which the tongue falls back and obstructs the airway.

Laypersons will be using the bag but the obstruction will prevent the

patient from receiving the air being pumped. A simple method of

dramatically improving the effectiveness of resuscitation bag support

is to provide nasopharyngeal airways which can be readily fitted, do

not trigger the gagging reflex if sized correctly and can be simply

inserted even by paramedical personnel. In most cases actual NPAs

are not available but can be readily improvised using the guidelines in

Section 12.

The ET tubes required to improvise the NPAs are very cheap and

readily available. They should be supplied to all health facilities with a

potential exposure to neurotoxic envenomation. In addition, they will

be available to support other instances where airway support will be

required and are thus multi functional.

3.2 Provide Improvised Transfusion Facilities Locally

In areas with high levels of viperine envenomation where

spontaneous bleeding may be a critical issue, access to improvised

blood transfusion can be useful. Prior blood testing to establish blood

grouping in local people to ensure knowledge of the whereabouts of

applicable donors will be very useful.

126

2200..00 PPrreesseerrvviinngg aanndd IIddeennttiiffyyiinngg SSnnaakkee SSppeecciimmeennss


Despite the influence of National Geographic Channel and the like, the

impression that the medically important species have been definitively

identified is erroneous. A key problem is that herpetology is often misleading

and carried out by non-experts who help to spread myths about which species

are present in which location and which species are causing the most bites.

The discredited notion of the ‘Big Four’ snakes of India is still adhered to by

‘authorities’ that have not done the required work or are not prepared to admit

that their knowledge is not extensive. The doctor can make a major

contribution to understanding which are the key biting species in an area by

preserving all dead snakes that are brought with the victim. An expert should

then reliably identify these species and a clearer understanding obtained.

Before preparation the snake should be photographed, a digital camera is

best, and the images sent to an expert by email. The snake should be kept

and cross referenced to the patient in case any further detailed analysis is

required.

2200..22 MMeetthhoodd ooff PPrreesseerrvvaattiioonn

Snakes should be preserved in formalin, which is readily available, in a glass

airtight jar. Formalin should be diluted 1 part formalin to 9 parts water. The

new solution should be poured over the specimen in the jar and sealed. The

specimen should be labelled with:

1. Patient name

2. Patient record number to enable clinical history to be examined

3. Believed species.

2200..33 SSnnaakkee PPhhoottooggrraapphhss ffoorr IIddeennttiiffiiccaattiioonn

A useful means of snake identification is to use photographs of a dead

specimen, which can be sent to an expert for tentative identification. This

method is not definitive as snake identification is a complicated exercise. In

127

complex cases it may require an expert carrying out a detailed analysis of the

specimen itself.

For photographic identification, the following are the best shots to take of the

dead specimen. Grateful thanks for this advice to Ashok Captain, the best

herpetologist in the author’s experience!

1. A full top shot of the specimen showing body colour and any patterning

2. A close up of the head taken from the side to enable the scales on the

face to be seen

3. If the snake DOES NOT have a plain belly then a shot of the belly

showing the markings

If the snake has a pit between the nostril and the eye then:

1. A shot of the top of the head from above

2. A shot of the tail area in close up

2200..44 RReeffeerrrraall ffoorr IIddeennttiiffiiccaattiioonn ttoo aann EExxppeerrtt

If the above photographs can be taken and made available, the following

experts have kindly agreed to try and provide a tentative identification:

South Asia

Ashok Captain

Email ID: [email protected]

Asia, North, West, South East, East

John C Murphy


China

Kadoorie Farm and Botanic Garden





128

Africa

Tomáš Mazuch

Email ID [email protected] [email protected]

If new or unusual species are identified then the nature of the envenoming

can be studies prospectively and published.



129

2211..00 SSnnaakkeebbiittee EEppiiddeemmiioollooggyy


Despite the fact that attempts have been made for nearly 60 years to

establish the true burden of snakebite mortality and morbidity, chaos reigns

and “our figures are so vulnerable” (Global Snakebite Initiative, 2008). In part

this is due to the fact that snakebite numbers are sought for many purposes

and this inhibits the process. Unfortunately snakebite epidemiology has now

become relegated primarily to a means to justify funding from agencies and

organisations (Global Snakebite Initiative, 2008) and not to address product

(ASV) requirements.

2211..22 RReecceenntt EEppiiddeemmiioollooggyy SSttuuddiieess��

An examination of the three major exercises to establish the data leads to the

conclusion that the numbers are becoming wider ranged and less useful

(Swaroop and Grabb, 1954; Chippaux, 1998, Kasturiratne et al, 2008).

Source Data

Africa

Asia

Latin

America

Total

Swaroop and Grab 1954

400 - 1,000

25,000-

30,000

3,000-

4,000

30,000 - 40,000

Chippaux 1998

20,000

100,000

5,000

125,000

Kasturiratne et al 2008

3,529 - 32,117

15,385-

57,636

540-

2,298

19,886 - 93,945

130

The most recent study contains fundamental flaws that also cast doubt on the

veracity of the work. For example, the high-end mortality and envenoming

numbers for Pakistan, imply a 50% mortality rate from envenomed victims

which beggars belief. The untreated mortality rate from Echis species has

been reported at 20% and therefore a mortality rate more than double this

level is not credible (Kasturiratne et al, 2008; Abubakar et al, 2009). A 2009

WHO SEARO meeting claimed that India had mortality numbers that were

‘widely agreed’ and yet proceeded to show 3 separate mortality numbers in a

26 page report! (WHO, 2009)

There is still utter confusion between “cases” i.e. those victims that go to

hospital complaining of snakebite and “envenomings” i.e. those patients with

snakebite who ARE envenomed AND require ASV. “Cases” are often taken

as “envenomings” which increases snakebite morbidity numbers (Global

Snakebite Initiative, 2008; Kasturiratne et al, 2008)

It is interesting how when funding justification becomes the rationale, all

numbers are higher than would be expected.

2211.. 33 AA PPrraaccttiiccaall AApppprrooaacchh ttoo tthhee AAffrriiccaa AAssiiaa RReeggiioonn

Two studies have approached the problem of epidemiology from the

perspective of envenomings, as these figures are the most significant if

adequate levels of ASV are to be forecasted and produced (Simpson and

Blaylock 2009; Simpson and Jacobsen, 2010). The African study suggests

174,000 envenomings per annum, based on sound ASV administration

criteria and hospital records. The Asian paper suggests that excluding South

Asia and China the figure for envenomings is 81,000 per annum. There is little

doubt that South Asia represents the most significant region for snakebite and

snakebite mortality.

China’s figures are unknown but even if we exclude these figures the mortality

number can be estimated with a reasonable degree of accuracy. Assuming a

mortality percentage of 10% mortality would be:

131

Area or Country

Mortality

Africa 17,000

India 11,000

Pakistan 1.200

Sri Lanka 800

Bangladesh 6,000

Asia excluding

South Asia and China

8,152

China Assumption 4,000

Total 48,152

The mortality percentage is an assumption but not unreasonable. The

untreated percentage for Echis species, one of the largest contributors to the

bite numbers is approximately 20% (Abubakar et al, 2009).

The numbers for Bangladesh has been taken from the as yet unpublished but

reported study by the Bangladesh Ministry of Health, which indicated a

snakebite mortality level of 6,000 per annum. However, a recent study of

hospital cases reports that the percentage of victims who go to hospital

following snakebite but who are NOT in fact envenomed is 60% (Harris et al,

2010). This is one of the key weaknesses of community-based surveys, which

rely on lay people diagnosing snakebite and any related mortality. Despite this

fact, when funding is the objective, community surveys are the method of

choice as they invariably deliver higher numbers (Global Snakebite Initiative,

2008).

132

2211..44 TThhee DDooccttoorr’’ss RRoollee

Doctors can play a key role in firming up epidemiology numbers. The

recommended method is;

1. Implement an effective Protocol for diagnosis of envenoming such as

this approach

2. Record number of victims attending hospitals, which are defined as

“Cases”.

3. Record the number of “true” envenomings indicated by this protocol.

4. Calculate the discrete population covered by your facility. Ideally any

leakage to other clinics should be accounted for and an attempt to

involve that clinic in the study should be made.

5. When a discrete population can be identified, convert the number of

envenomings and deaths to a rate per 100,000 population and publish

the results!

133

2222..00 PPhhoottooggrraapphhiicc CCrreeddiittss

The following colleagues contributed photographs to this Guideline and I

would like to acknowledge my gratitude for their contribution. All other

photographs are the authors.

Tomáš Mazuch

Front Cover Dendroaspis viridis

Photo 1.5.1 Echis pyrimidium and Cerastes cerastes

Photo 1.6.1 Naja nigricollis, Naja ashei and Naja pallida

Photo 1.6.2 Bitis arietans

Photo 1.7.1 Bitis rhinoceros, Bitis nasicornis and Echis ocellatus

Photo 1.8.1 Naja nigricollis, Naja nubiae, Naja pallida and Naja ashei

Photo 1.8.2 Echis pyrimidium, Echis ocellatus and Cerastes cerastes

Photo 1.9.1 Dendroaspis augusticeps, Dendroaspis polylepsis and

Dendroaspis viridis

Photo 1.9.2 Naja haje, Naja annulifera and Naja melanoleuca

John C Murphy

Photo 1.3.1 Naja naja Sri Lanka

Photo 1.3.3 Daboia russelii Sri Lanka and Hypnale hypnale Sri Lanka

Photo 1.4.1 Deinagkistrodon acutus, Callesolasma rhodostoma, Naja

kaouthia, Oxyuranus scutellatus

Photo 1.4.2 Bungarus candidus, Bungarus fasciatus and Bungarus flaviceps

Photo 1.5.1 Vipera palaestinae, Echis coloratus and Macrovipera lebetina

Photo 1.6.2 Bitis nasicornis

Photo 1.8.2 Cerastes vipera and Cerastes cerastes

Photo 1.9.1 Dendroaspis jamesoni

Earl Hewitt

Photo 2.1 Scarification first aid

Photo 5.2 Necrosis from Echis ocellatus

134

2233..00 GGeenneerraall AAcckknnoowwlleeddggeemmeennttss

First the author would like to acknowledge the patience and dignity of the

many thousands of rural snakebite victims who have been treated during the

author’s work. If more snakebite experts met them, they might actually get it!

They are often forgotten in snakebite literature and deserve a great deal more

than snakebite experts currently provide.

In addition, enormous thanks to many developing world colleagues in India,

Pakistan, China and Africa that have enabled this work to be produced.

Particularly, the doctors, S. Mahadevan, CK Eapen, Vivek Lal, Mabel Vasnaik,

Arvind Mathur, Joseph K Joseph, C. Rajendiran, Soumitra Ghosh, Sharda

Peshin, Surjit Singh, Jeffrey Fung, KK Lam and Earl Hewitt.

Political figures worthy of specific mention for their support and

encouragement include Dr Surya Kanta Mishra and Mr Narpat Singh Rajvi.

Specific thanks to Dr Huma Qureshi (Executive Director, Pakistan Medical

Research Council) whose support in Pakistan was honest, effective and victim

orientated. The first review in the Thar Desert was harrowing and no other

official of her seniority would have braved the trip. Also to Nasreen Nomani

(National Institute of Health, Pakistan) a dedicated champion of anti snake

venom production from whom I learned a lot.

To Ashok Captain for reassuring me that not all herpetologists need blond

hair, sunglasses, near death experiences or sensational posing in quasi-

military garb to be successful and useful. Also Paul Crow, Michael Lau and

Garry Ades of KFBG.

To the many developed world ‘snakebite authorities’ whose lack of

understanding of developing world environments prompts so little success in

improving snakebite, thanks for keeping me out of your meetings, it has

improved my knowledge enormously.

135

2244..00 RReeffeerreenncceess

SSnnaakkeess ooff MMeeddiiccaall SSiiggnniiffiiccaannccee:: SSoouutthh AAssiiaa

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