A2 Snakebite Management in Asia and Africa

A
Snakebite Management in Asia & Africa

A guide to snakebite in the key areas for mortality & morbidity
Guidelines produced by: Pakistan Medical Research Council
Endorsed by:
World Health Organization Pakistan Country Office
Pakistan Medical Association
National Program for Family Planning and Primary Health Care
Indian Journal of Emergency Pediatrics
Forward
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.
Introduction
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.
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.
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: iandsimpson@gmail.com
Contents
1.0 Snakes of Medical Significance 1.1 Introduction 1.2 Snakes of Medical Significance 1.3 South Asia 1.4 Asia Central, South East and East 1.5 West Asia 1.6 Africa South Zone 1.7 Africa West Zone 1.8 Africa North East Zone 1.9 Africa Progressive Weakness Species 2.0 Snakebite First Aid 2.1 Introduction 2.2 Inappropriate First Aid 2.3 Tight Tourniquets 2.4 Cutting and Suction 2.5 Pressure Immobilisation Method (PIM) 2.6 Other Pressure Techniques 2.7 Electricity and Ice 2.8 Washing the Wound 2.9 Traditional Remedies 2.10 Traditional Remedies: Snake Stones 2.11 Traditional Remedies: Scarification 2.12 Recommended First Aid 3.0 Patient Arrival 3.1 Introduction 3.2 Asymptomatic Arrival 3.3 Symptomatic patients 3.4 Key Interventions 3.5 Non-Critical Arrival 14 14 14 16 20 22 24 27 28 33 35 35 35 35 37 38 40 41 42 42 45 46 47 49 49 49 49 50 51
4.0 Patient Dialogue 4.1 Introduction 4.2 Time of the Bite 4.3 Snake Seen and/or Killed 4.4 Allopathic Treatment Before Hospital 4.5 Traditional Treatments Before Hospital 4.6 Activity at Time of Bite 5.0 Diagnosis: Signs and Symptoms of Envenoming 5.1 Introduction 5.2 Bleeding 5.3 Progressive Weakness 5.4 Painful Progressive Swelling 6.0 Diagnosis of Envenoming 6.1 Introduction 6.2 Visible Criteria 6.3 Simple Diagnostic Methods 6.4 Technical Diagnostic Methods 6.5 Bite marks 7.0 Anti Snake Venom 7.1 Introduction 7.2 Lyophilised ASV Vs Liquid 7.3 Monovalent Vs Polyvalent ASV 7.4 What Can ASV Do and Not Do 7.5 Swelling and ASV 7.6 ASV Safety
53 53 53 53 53 53 54 56 56 56 57 57 58 58 58 60 61 62 63 63 63 63 65 66 66
8.0 Criteria for Administering ASV 8.1 Introduction 8.2 Bleeding 8.3 Progressive Weakness 8.4 The case for Swelling and Local damage 8.5 Painful Progressive Swelling 8.6 How to Administer ASV 8.7 ASV Administration Period 9.0 ASV Dosage 9.1 Introduction 9.2 Initial Dosing Exceptions 9.3 Maximum Doses 9.4 Late Administration of ASV 9.5 ASV & Pregnancy 9.6 Paediatric ASV Dosing 9.7 Repeat Bites 9.8 South Asia ASVs 9.9 Asia Central, South East and East ASVs 9.11 West Asia ASVs 9.12 Repeat ASV Doses 9.13 Repeat ASV Doses: Bleeding 9.14 Repeat ASV Doses: Progressive Weakness 9.15 Repeat ASV Doses: Painful Progressive Swelling 9.16 Signs of Recovery 10.0 Adverse Anti Snake Venom Reactions 10.1 Introduction 10.2 Mechanism of the Reaction 10.3 Prediction of Adverse Reactions 10.4 Preventing Adverse Reactions 10.5 Treatment of Adverse Reactions 10.6 ASV Reaction Support Drugs
67 67 67 67 68 68 69 69 70 70 70 71 71 72 73 73 75 76 81 83 83 83 84 84 85 85 85 85 86 87 88 10
11.0 Neurotoxic Envenomation and Anticholinesterase Drugs 11.1 Introduction 11.2 Anticholinesterase Drugs 11.3 The Test 11.4 Anticholinesterase Drugs: Tests and Doses 12.0 Airway Support Items 12.1 Introduction 12.2 Developing World Airway Management Context 12.3 Improvised Devices 12.4 Bridging Devices 12.5 Ideal Solution 13.0 Haemotoxic Envenomation, Blood Products and Renal Failure 13.1 Introduction 13.2 Anticoagulants 13.3 Coagulants 13.4 Longer Term Issues 13.5 Renal Failure 14.0 Pain, Wound Management and the Surgical Aspects of Snakebite 14.1 Pain and Wound Management 14.2 Antibiotics 14.3 Snake Venom Ophthalmia 14.4 Surgery and Snakebite 14.5 Snakebite & Life Threatening Conditions Requiring Surgery 14.6 Debridement of Necrotic Tissue 14.7 Compartment Syndrome
90 90 90 91 91 93 93 93 94 95 97 98 98 99 99 99 100
102 102 102 103 103 103 104 104
11
15.0 Snakebite Management in Basic or Primary Care Facilities 15.1 Introduction 15.2 Patient Arrival & Assessment 15.3 Envenomation: Haemotoxic 15.4 Referral Criteria 15.5 Envenomation: Neurotoxic 15.6 Referral Criteria 15.7 Conditions and Equipment for Neurotoxic Referral 16.0 Equipping a Basic Hospital for Effective Snakebite Management 16.1 Introduction 16.2 Assumptions 16.3 Anti Snake venom 16.4 Other Support Drugs 16.5 Support Equipment 17.0 Snakebite: Risk Activities and Prevention 17.1 Introduction 17.2 Prevention Myths 17.3 The Doctors Role 18.0 Snakebite Management When ASV is Unavailable 18.1 Introduction 18.2 Guiding Principles 18.3 Actions for the Physician 19.0 Snakebite Management in Natural Disasters 19.1 Introduction 19.2 Likely Conditions and Impact 19.3 Doctors and medical Authority Response
106 106 106 106 107 107 108 108
110 110 110 111 112 113 114 114 114 115 117 117 117 118 120 120 120 121
12
20.0 Preserving and Identifying Snake Specimens 20.1 Introduction 20.2 Method of Preservation 20.3 Taking Snake Photos for Identification 20.4 Referral to an Expert 21.0 Snakebite Epidemiology 21.1 Introduction 21.2 Recent Epidemiology Studies 21.3 A Practical Approach to the Africa Asia Region 21.4 The Doctors Role
126 126 126 126 127 129 129 129 130 132
22.0 Photographic Credits 23.0 General Author Acknowledgements 24.0 References
133 134 135
13
1.0 Snakes of Medical Significance

1.1 Introduction
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.
1.2 Snakes of Medical Significance

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 snakes 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
14
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.
15
1.3 South Asia
Class
ASV Coverage
Non ASV Coverage
Naja naja PW
Naja kaouthia PW 2 Daboia russelii B Echis carinatus B Echis sochureki B
Hypnale hypnale B
II
Naja oxiana PW Bungarus caeruleus PW Bungarus fasciatus PW Ophiophagus hannah PW Macrovipera lebetina PPS Cryptelytrops albolabris PPS
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.
16
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)
17
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)
18
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)
19
1.4 Asia Central, South East and East

Class ASV Coverage Non ASV Coverage
Daboia siamensis B
Callesolasma rhodostoma B Naja kaouthia PW
Bungarus fasciatus PW
II
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 Naja sumatrana PW Naja siamensis N
Oxyuranus scutellatus canni PW/B Acanthophis antarcticus/praelongus PW Pseudechis australis B Pseudechis papaunus B/PW
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.
20
Fig 1.4.1 Central, South East and East Asia Major Species. Deinagkistrodon acutus, Callesolasma rhodostoma, Naja kaouthia, Oxyuranus scutellatus
21
Fig 1.4.2 Central, South East and East Asia Progressive Weakness: Kraits. Top Row. Bungarus candidus, B. fasciatus. Bottom. Bungarus multicinctus, B. flaviceps
22
1.5 West Asia

Cerastes cerastes PPS/B
Echis coloratus B Echis multisquamatus B Echis sochureki B Echis pyramidium PPS/B Vipera palaestinae PPS
Cerastes gasperettii PPS/B?
II
Eristicophis macmahoni PPS/PW?
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
Armenia, Azerbaijan, Bahrain, Cyprus, Georgia, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Saudi Arabia, Syria, Turkey, U.A.E., Yemen.
23
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
24
1.6 Africa: South Zone

Bitis arietans PPS
Naja nigricollis PPS N. mossambica PPS
B. gabonica PPS/B
II
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.
25
Fig 1.6.1 Southern Zone Painful Progressive Swelling: Cobras Top Row. Naja nigricollis, N. mossambica. Bottom Row. N. pallida, N. ashei
26
Fig 1.6.2 Southern Zone Painful Progressive Swelling: Vipers Top. Bitis arietans, Middle Bitis gabonica, Bottom. Bitis nasicornis
27
1.7 Africa: West Zone
Class
ASV Coverage
Non ASV Coverage
Bitis arietans PPS
Naja nigricollis PPS Echis ocellatus B
E. leucogaster B
B. gabonica PPS/B
II
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 dIvoire, 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.
28
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
29
1.8 Africa: North East Zone
Class
ASV Coverage
Non ASV Coverage
Naja nigricollis PW
E. pyramidum B E. ocellatus B Echis coloratus B
Echis leucogaster B
N. pallida PPS
II
N. ashei PPS N. nubiae PPS Naja haje PW Naja melanoleuca PW Echis multisquamatus B Cerastes cerastes PPS/B Dendroaspis polylepsis PW Dispholidus typus B
Algeria, Djibouti, Egypt, Eritrea, Ethiopia, Libya, Morocco, Sudan, Somalia, Tunisia.
30
Fig 1.8.1 North Eastern Zone Painful Progressive Swelling: Cobras Top Row. Naja nigricollis, Naja nubiae. Bottom Row. Naja pallida, Naja ashei
31
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
32
1.9 All Africa Progressive Weakness Species
Fig 1.9.1 Progressive Weakness: The mambas Top Row. Dendroaspis polylepsis, D. augusticeps .Bottom Row. D. viridis, D. jamesoni
33
Fig 1.9.2. Progressive Weakness: The cobras Top Row. Naja haje, N.annulifera. Bottom Row. Naja nivea, Hemachatus haemachatus, N. melanoleuca
34
2.0 Snakebite First Aid

2.1 Introduction
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.
2.2 Inappropriate First Aid Methods 2.3 Tight Tourniquets

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 its limited effectiveness against certain species such as elapids (Christensen 1969). Klenermans 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
35
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 Russells 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
36
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 nonexperts 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.
2.4 Cutting and Suction

Cutting the wound and the use of suction or suction devices remains controversial. However, the large number of viper bites globally, with the antihaemostatic 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,
37
1981). Consumption coagulopathy renders the victims 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.
2.5 Pressure Immobilisation Method (PIM)

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).
38
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).
39
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.
2.6 Other Pressure Techniques

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
40
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.
2.7 Electricity and Ice

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.
41
During the 1950s 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.
2.8 Washing the Wound

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).
2.9 Traditional Remedies

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
42
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.
43
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)
44
2.10 Traditional Medicine; Specific Treatment: Snake Stones

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 books 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.
45
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)
2.11 Traditional Medicine Specific Treatment: Scarification

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.
46
2.12 The Recommended First Aid Method: Do it R.I.G.H.T

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 thats 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:
R. =
Reassure the patient. 70% of all snakebites are from

non- venomous species. Only 50% of bites by venomous species actually envenomate the patient
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 dont work and can be dangerous!
G. H. =
Get to Hospital Immediately. Traditional remedies have

NO PROVEN benefit in treating snakebite.
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).
47
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
48
3.0 Patient Arrival

3.1 Introduction
Patients with snakebite arrive at the medical facility in a variety of conditions.
3.2 Asymptomatic Arrival

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)
3.3 Symptomatic Patients

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
49
results from a lack of effective treatment. Death due to fright is a convenient reason to account for inadequate treatment.
3.4 Key Interventions

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
50
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.
3.5 Non-Critical Arrival

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-
51
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.
52
4.0 Patient Dialogue

4.1 Introduction
The victim and/or bystanders present when the bite took place must be questioned to determine the following:
4.2 What was the time of the bite?

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.
4.3 Was the snake seen and/or killed?

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.
4.4 Have any allopathic treatments been taken before arrival at the present medical facility?
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.
4.5 Have any traditional treatments been taken before arrival?

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 victims vomiting may be entirely unrelated to envenomation.
53
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.
4.6 What activity was the victim carrying out at the time of the bite?
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.
54
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.
55
5.0 Diagnosis: Signs and Symptoms of Envenoming

5.1 Introduction
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.
5.2 Bleeding
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. Russells 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 Russells viper (Daboia sp)
56
5.3 Progressive Weakness

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
5.4 Painful Progressive Swelling

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
57
6.0 Diagnosis of Envenomation

6.1 Introduction
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:
6.2 Visible Criteria A. Bleeding

I. Gingival bleeding II. Haemoptysis III. Haematuria IV. Ecchymoses V. Lateral neurological signs,
58
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
59
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.
6.3 Simple Diagnostic Methods 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).
60
I. Single breath count II. Length of time upward gaze can be maintained III. Basic Grip Tests

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
6.4 Technical Diagnostic Methods A. Bleeding

I. Renal impairment Serum creatinine, urea, potassium II. Occult bleeding haemoglobin, PCV, platelets,
I. Single breath count II. FEV III. Grip Tests with Equipment

I. Saline manometer or Stryker measurement of intracompartmental pressure.
61
6.5 Bite Marks

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.
62
7.0 Anti Snake Venom (ASV)

7.1 Introduction
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.
7.2 Lyophilised or Liquid

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
7.3 Monovalent Versus Polyvalent

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 63
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.
64
7.4 What Can ASV Do and more importantly what can it NOT Do?
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 patients 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 bodys 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)
65
Some of these points should be obvious and yet they are frequently given as reasons for administering ASV.
7.5 Swelling and ASV

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.
7.6 ASV Safety

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).
WHOs reluctance to provide clear guidance on the safety issues of production and the cost impact is lamentable.
66
8.0 Criteria for Administering ASV

8.1 Introduction
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 victims 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:
8.2 Bleeding
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)
8.3 Progressive Weakness

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
67
In the above two circumstances ASV should be administered according to the dosage schedules on Pages 71-76.
8.4 The Case for Swelling and Local Damage

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.
8.5 Painful Progressive Swelling (PPS)

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
3. Compartment syndrome or major vessel entrapment
68
8.6 How to Administer ASV

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.
8.7 ASV Administration Period

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.
69
9.0 ASV Dosage

9.1 Introduction
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 manufacturers recommendations and have been marked accordingly. Care must be taken with manufacturers recommendations as such guidelines have been shown to be unreliable previously (Simpson and Norris, 2007)
9.2 Initial Dosing Exceptions

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.
70
9.3 Maximum Doses

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).
9.4 Late Administration of ASV

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.
71
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.
9.5 ASV and Pregnancy

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).
72
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).
9.6 Paediatric ASV Dosing

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.
9.7 Repeat Bites

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
73
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).
74
9.8 South Asia ASVs

Initial ASV Producer Country Species 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
8-10
20
8-10 Daboia russelii Echis carinatus
30
National Institute of Health (NIH) Islamabad Polyvalent
Pakistan
Naja naja Bungarus caeruleus
8-10
20
Daboia russelii
8-10
30
Echis sochureki
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.
75
9.9 Asia, Central, South East and East ASVs

Thai Red Cross Society Monovalent
Thailand
Daboia siamensis Callesolasma rhodostoma
5 4 10 10 5 5 10
20
Myanmar China
Cryptelytrops albolabris Naja kaouthia Bungarus fasciatus Bungarus candidus Ophiophagus hannah
20 10 10 20
Shanghai Institute of Biological Products Monovalent
China
Naja atra
Bungarus multicinctus
10
Deinagkistrodon acutus
Agkistrodon/ Gloydius halys
Bio Farma, Bandung Indonesia Polyvalent
Indonesia
Callesolasma rhodostoma Bungarus fasciatus Naja sputatrix
10
10 10
76
Taiwan CDC Vaccine Center, Taiwan
Bungarus multicinctus Naja atra 1-2 *
Trimeresurus muquosqamatus Trimeresurus stejnegeri 1-2 *
Agkistrodon acutus 1-2 * Daboia siamensis 3
Japanese Snake Institute
Rhabdophis subminiatus
Myanmar: AntiViper AV
Myanmar
Daboia siamensis
Myanmar: Bivalent AV Biological Production Division Kaketsuken Monovalent Japan Philippines
Naja kaouthia
12
Naja philippinensis
10
Agkistrodon b blomhoffii 2* Trimeresurus/Protobothrops Flavoviridis 2*
77
Commonwealth Serum Laboratories Polyvalent
Indonesia East Islands Papua West Papua
Oxyuranus scutellatus canni Acanthophis antarcticus/praelongus Pseudechis australis Pseudechis papuanus
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 *
* = Manufacturers recommended dose.
78
9.10 West Asia

National Guard Hospital Saudi Arabia Polyvalent
Saudi Arabia Oman
Bitis arietans Echis sp 1 Cerastes sp Walterinasia aegyptia
8 5 5 5
Bivalent Naja/Walterinasia
2
Razi Vaccines & Serum Research Institute Polyvalent
Iran
Echis
sochureki/ 2* 2* 2*
multisqamatus Naja oxiana Macrovipera lebetina Pseudocerastes persicus Vipera albicornuta Gloydius halys
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 *
79
Vacera/EgyVac Polyvalent
West Asia
Vipera ammodytes Vipera xanthina Vipera berus
4-6 * 4-6 * 4-6 *
* = Manufacturers 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.
80
9.11 Africa
South African Vaccine Producers (SAVP) Polyvalent
Sub Saharan Africa
Bitis arietans Bitis gabonica Naja melanoleuca Naja nivea Naja annulifera
5 10 8 8 8 20 20 20
Naja mossambica
Dendroaspis sp Hemachatus haemachatus
8 5
20
Monovalent
Echis ocellatus
Monovalent
Dispholidus typhus
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
81
Sub Vacera/EgyVac
1
Bitis arietans Echis ocellatus Naja nigricollis
8 6 10
Saharan Africa
* = Manufacturers 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.
82
9.12 Repeat ASV Doses

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.
9.13 Repeat ASV Doses: Bleeding

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.
9.14 Repeat ASV Doses: Progressive Weakness

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.
83
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.
9.15 Repeat ASV Doses: Painful Progressive Swelling

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.
9.16 Signs of Recovery

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
84
10.0 Adverse Anti Snake Venom Reactions

10.1 Introduction
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).
10.2 Mechanism of the Reaction

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
10.3 Prediction of Adverse Reactions

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.
85
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.
10.4 Preventing Adverse Reactions

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.
86
10.5 Treatment of Adverse Reactions

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
87
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 patients 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.
10.6 ASV Reaction Support Drugs

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
88
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.
89
11.0 Neurotoxic Envenomation and Anticholinesterase Drugs

11.1 Introduction
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.
11.2 Anticholinesterase Drugs

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.
90
11.3 The Test

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 longerterm administration in a patient that shows no positive response.
11.4 Anticholinesterase Drugs Test and Dosages

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.
91
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.
92
12.0 Airway Support Items

12.1 Introduction
In the case of unconscious patients suffering from neurotoxic envenoming, a number of strategies can be adopted depending on available equipment to support the patients breathing. In the vast majority of cases, if the patients 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 patients 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.
12.2 Developing World Airway Management Context

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 93
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.
12.3 Improvised Solution

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 victims 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, bagvalve-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.
94
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).
12.4 Bridging Devices

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.
95
Fig 12.1 Top Row, Resuscitation Bag, LT Tube, LMA, Nasopharyngeal Tubes Bottom Row, How to measure and fit improvised nasopharyngeal Tubes.
96
12.5 The Ideal Solution

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).
97
13.0 Haemotoxic Envenomation, Blood Products and Renal Impairment

13.1 Introduction
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- 5 /kg/minute.
98
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).
13.2 Anticoagulants
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).
13.3 Coagulants
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.
13.4 Longer Term Issues

Russells 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 Russells viper victims need to
99
ensure that no long-term pituitary sequelae are evident. In known Russells 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.
13.5 Renal Impairment

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 (TheinThan 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.
100
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).
101
14.0 Pain, Wound Management and the Surgical Aspects of Snakebite

14.1 Pain and Wound Management
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.
14.2 Antibiotics and Tetanus

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.
102
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.
14.3 Snake Venom Ophthalmia

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.
14.4 Surgery and Snakebite

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.
14.5 Snakebite & Life Threatening Conditions Requiring Surgery

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
103
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.
14.6 Debridement of Necrotic Tissue

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)
14.7 Compartment Syndrome

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
104
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.
105
15.0 Snakebite Management in Basic or Primary Care Facilities

15.1 Introduction
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.
15.2 Patient Arrival & Assessment

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.
15.3 Envenomation; Haemotoxic

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
106
appear, ASV is temporarily suspended while the reaction is dealt with and then recommenced.
15.4 Referral Criteria

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.
15.5 Envenomation; Neurotoxic

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 patients 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.
107
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.
15.6 Referral Criteria

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.
15.7 Conditions and Equipment Accompanying Neurotoxic Referral

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
108
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.
109
16.0 Equipping a Basic Hospital for Effective Snakebite Management

16.1 Introduction
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.
16.2 Assumptions
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 betterequipped 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.
110
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.
16.3 Anti Snake Venom

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.
111
16.4 Other Support Drugs

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
112
16.5 Support Equipment

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
113
17.0 Snakebite: Risk Activities and Prevention

17.1 Introduction
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 snakes habitat and carry out activities that will tend to distract them from the danger posed by a snakes presence.
17.2 Prevention Myths

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
114
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.
17.3 The Doctors Role

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.
115
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.
116
18.0 Snakebite Management When ASV is Unavailable

18.1 Introduction
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!
18.2 Guiding Principles

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 Russells 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
117
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).
18.3 Actions for the Physician

The physicians 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.
118
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 Russells viper (Daboia russelii) are capable of causing renal failure due to the action of the venom. This will need careful monitoring of the patients 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.
119
19.0 Snakebite Management in Natural Disasters

19.1 Introduction
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.
19.2 Likely Conditions and Impact

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
120
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.
19.3 Doctors and Medical Authority Response

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.
121
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 Russells viper venom included in Indian ASV is from a different species of Russells 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 122
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 Visible Neurological Signs Normal Dosage Normal Dosage
50%
Severe Shortage Criteria Incoagulable Blood 50% Normal Dose
Visible Neurological Signs
50% Normal Dose No 2nd Dose
30%
Critical Shortage Criteria Visible Bleeding
50% Normal Dose
50% Normal Dose Visible Neurological Signs No 2nd Dose
123
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 victims 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. 124
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.
125
20.0 Preserving and Identifying Snake Specimens

20.1 Introduction
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.
20.2 Method of Preservation

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.
20.3 Snake Photographs for Identification

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 126
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 authors 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
20.4 Referral for Identification to an Expert

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: ashokcaptain@rediffmail.com
Asia, North, West, South East, East John C Murphy Email ID: fordonia1@comcast.net
China Kadoorie Farm and Botanic Garden Email ID: fauna@kfbg.org
127
Africa Tom Mazuch Email ID tomas.mazuch@quick.cz somalia@seznam.cz
If new or unusual species are identified then the nature of the envenoming can be studies prospectively and published.
128
21.0 Snakebite Epidemiology

21.1 Introduction
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.
21.2 Recent Epidemiology Studies

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
25,00030,000
3,0004,000
30,000 - 40,000
Chippaux 1998
20,000
100,000
5,000
125,000
Kasturiratne et al 2008
3,529 - 32,117
15,38557,636
5402,298
19,886 - 93,945
129
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.
21. 3 A Practical Approach to the Africa Asia Region

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.
Chinas 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:
130
Area or Country Africa India Pakistan Sri Lanka Bangladesh Asia excluding South Asia and China China Assumption Total
Mortality 17,000 11,000 1.200 800 6,000 8,152
4,000 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).
131
21.4 The Doctors Role

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!
132
22.0 Photographic Credits

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.
Tom 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
133
23.0 General Acknowledgements

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 authors 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 quasimilitary 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.
134
24.0 References
Snakes of Medical Significance: South Asia
Ali Z, Begum, M. Snake bite- a medical and public health problem in Pakistan. In: Gopalakrishnakone P, Chou P eds. Snakes of medical importance: Singapore University Press Singapore; 1990:419-445 Ansari AK, Sheikh SA. Management of Vipride Snake Bite. Pak Armed Forces Med J 2000;50(1):26-28. Ariaratnam CA, Sjostrom L, Raziek Z, Abeyasinghe S, Kularatne M, Kondikara Arachchi RWK, Sheriff, et al. An open randomised comparative trial of two antivenoms for the treatment of envenoming by Sri Lankan Russells viper (Daboia russelii russelii). Trans R Soc Trop Med Hyg. 2001;95:74-80. Ariaratnam CA, Thuraisingam V, Kularatne SA, Sheriff MH, Theakston RD, de Silva A, Warrell DA. Frequent and potentially fatal envenoming by humpnosed pit vipers (Hypnale hypnale and H. nepa) in Sri Lanka: lack of effective antivenom. Trans R Soc Trop Med Hyg. 2008 Nov;102:1120-6. Bawaskar HS, Bawaskar PH, Punde DP, Inamdar MK, Dongare RB, Bhoite RR. Profile of snakebite envenoming in rural Maharashtra, India. J Assoc Physicians India. 2008;56:88-95 de Silva, A., Wijekoon, A.S.B., Jayasena, L., Abeysekara, C.K., Bao, C.X., Hutton, R.A.,Warrell, D.A. Haemostatic dysfunction and acute renal failure following envenoming by Merrems humpnosed viper (Hypnale hypnale) in Sri Lanka: first authenticated case. Trans. R. Soc. Trop. Med. Hyg. 1994;88, 209212. de Silva HJ, Fonseka MMD, Gunatilake SB, Kularatne SAM, Sellahewa KH. Anti-venom for snakebite in Sri Lanka. CMJ. 2002;2:43-5 Dharmaratne L, Gunawardena U. gemeralised bleeding tendency and acute renal failure foloowing Merrems hump-nosed viper bite. J Ceylon Coll Phy 1988;21;37-42 Gaitonde BB, Bhattacharya S. An epidemiological survey of snakebite cases in India. Snake. 1980;12:129-133 Government of India. National snakebite protocol. New Delhi: Health & Family Welfare Department:2007 Ghosh S, Maisnam I, Murmu BK, Mitra PK, Roy A, Simpson ID. A locally developed snakebite management protocol significantly reduces overall anti snake venom utilization in West Bengal, India. Wilderness Environ Med; 2008;19:267-274
135
Hati AK, Mandal M, Mukherjee H, Hati RN. Epidemiology of snake bite in the district of Burdwan, West Bengal. J. Indian. Med. Assoc. 1992;90:145-147 Imlach CJF. Mortality from snake-bite in the province of Sind. Trans Bombay Med Phys Soc. Bombay Education Society Press. 1857; III:98-106. Joseph JK, Simpson ID, Menon NC, Jose MP, Kulkarni KJ, Raghavendra GB, Warrell DA. First authenticated cases of life-threatening envenoming by the hump-nosed pit viper (Hypnale hypnale) in India. Trans R Soc Trop Med Hyg. 2007;101:85-90. Karunatilakal, D.H., Herath, G.W.D.S., Lalan, H.H.S., Perera, K.D.N.I. Envenomation by the hump nosed viper Hypnale hypnale in children: a pilot study. Sri Lanka J. Child Health 2001;30:811. Kularathna, S.A.M., Ranatunga, N., 1999. Severe systemic effect of Merrems hump-nosed viper bites. Ceylon Med. J. 44, 169170. Kasturiratne A, Pathmeswaran A, Fonseka, MMD, Lalloo, DG, Brooker, S, de Silva, HJ. Estimates of disease burden due to land-snake bite in Sri lankan hospitals. Southeast Asian J Trop Med Public Health 2005;36(3):733-740 Khan B, Naseem A. Guidelines for Management of Snake Bite Cases. Pak Armed Forces Med J 2000;50(1):51-55. Khan MS. Venomous Terrestrial Snakes of Pakistan and Snake Bite Problem. In: Gopalakrishnakone P, Chou P eds. Snakes of Medical Importance. L.IST National University of Singapore. 1990, pp 419-445 Kochar DK, Tanwar PD, Norris RL, Sabir M, Nayak KC, Agrawal TD, Purohit VP, Kochar A, Simpson ID. Rediscovery of severe saw-scaled viper (Echis sochureki) envenoming in the Thar desert region of Rajasthan, India. Wilderness Environ Med. 2007;18:75-85. Kuch U. Snake bite envenomimng in Bangladesh and the challenge of biodiversity. In (Ed) Yunus EB, Hundred years of tropical medicine. Bangladesh Association of Advancement of Tropical Medicine & The Royal Society of Tropical medicine & Hygiene 2007. Kuch U, Faiz MA, Pillai L, Ahasan HAMN, Captain A, Khaire A et al. 2006. Kraits with 17-Dorsal-Scale-Rows (Bungarus sindanus complex): Unrecognised Causes of Severe Neurotoxic Envenoming in South Asia. (Abstract) 15th World Congress on Animal, Plant and Microbial Toxins. 23rd July to 28th July Glasgow. Mal R. A Study of Snake Bite Cases. J Pak. Med. Assoc. 1994;44:289 Perumainar, M., 1977. Clinical manifestations following hump-nosed viper bites. Sri Lanka Medical Association, 90th Anniversary Sessions, Colombo, 2326 March 1977, p. 10 [abstract].
136
Premawardena, A.P., Seneviratne, S.L., Gunatilake, S.B., De Silva, H.J., 1998. Excessive fibrinolysis: the coagulopathy following Merrems humpnosed viper (Hypnale hypnale) bites. Am. J.Trop. Med. Hyg. 58, 821823. Quraishi, NA, Qureshi, HI, Simpson, ID. A contextual approach to managing snakebite in Pakistan: Snakebite treatment with particular reference to Neurotoxicity and the ideal hospital snakebite kit. J Pak Med Assoc 2008;58(6):325-333 Seir F. Snake Bite Cases in CMH Bahawalpur. Pak Armed Forces Med J 2001;51(2):173-176. Sellahewa, K.H., Kumararatne, M.P., 1994. Envenomation by the humpnosed viper (Hypnale hypnale). Am. J. Trop. Med. Hyg.51, 823825. Sellahewa, K.H., Gunawardena, G., Kumararatne, M.P., 1995. Efficacy of antivenom in the treatment of severe local envenomation by the humpnosed viper Hypnale hypnale). Am. J. Trop. Med. Hyg. 53, 260262. Sengupta, S.R., Tare, T.G., Sutar, N.K., Renapurkar, D.M.. Ecology and distribution of Echis carinatus snakes in Deogad Taluka and other areas of Maharashtra State, India. J Wild Med. 1994;5:282286. Sharma LR, Lal V, Simpson ID. Snakes of medical significance in India: the first reported case of envenoming by the Levantine viper (Macrovipera lebetina). Wilderness Environ Med. 2008;19:195-8. Sharma BD, Vad NE. Ecology of saw scaled viper Echis carinatus (Schn.). In: Sharma BD, ed. Indian Poisonous Snakes: An Ecological and Clinical Study. 1st ed. New Delhi, India: Anmol Publications PVT; 2002:148214. Sharma SK, Khanal B, Pokhrel P, Khan A, Koirala S. Snakebite re appraisal of the situation in Eastern Nepal. Toxicon. 2003;41:285-9 Simpson ID , Quraishi NA, Qureshi HI,. Snakebite management in Pakistan A guide to the latest methods of treatment. Pakistan Medical Research Council. Islamabad; 2008 Suleman M, Shahab S, Rab M. Snake Bite in the Thar Desert. J Pak Med Assoc 1998;48(10):306-308. Tamil Nadu Health Systems Project. Handbook on treatment guidelines for snake bite and scorpion sting. Government of Tamil Nadu, Chennai, India. 2008 Quraishi, NA, Qureshi, HI, Simpson, ID. A contextual approach to managing snakebite in Pakistan: Snakebite treatment with particular reference to Neurotoxicity and the ideal hospital snakebite kit. J Pak Med Assoc 2008;58:325-333
137
Sawai Y, Toriba M, Itokawa H, de Silva A, Perera GLS, Kottegoda MB. Study on deaths due to snakebite in Anuradhapura district, Sri Lanka. 1984;16:7-15 Vidal C.S. A list of the venomous snakes of north Kanara: with remarkes as to the imperfections of existing records of distribution of snakes and facts and statistics showing the influence of Echis carinata on the death rate of the Bombay presidency. J Bombay Nat Hist Soc. 1890;5:64-71. Wall F. The Poisonous Terrestrial Snakes of Our British Indian dominions (including Ceylon) and How to Recognise Them, with Symptoms of Snake Poisoning and Treatment. Delhi, India: Asiatic Publishing House Edition; 2000. Weis JR, Whatley RE, Glenn JL, Rodgers GM. Prolonged hypofibrinogenemia and protein C activation after envenoming by Echis carinatus sochureki. Am J Trop Med Hyg.1991;44:452460. Young A. Mortality from snake-bite in the province of Sind. Trans Bombay Med Phys Soc (Bombay Education Society Press). 1857;3:8687. Zafar J, Aziz S, Hamid B, Qayyum A, Alam M, Qazi R. Snake Bite Experiences at Pakistan Institute of Medical Sciences. J Pak Med Assoc 1998;48(10):308-310.
Snakes of Medical Significance: North, South East and East Asia

Afifiyan F, Armugam A, Tan CH, Gopalakrishnakone P, Kandiah Jeyaseelan. Postsynaptic -Neurotoxin Gene of the Spitting Cobra, Naja naja sputatrix: Structure, Organization, and Phylogenetic Analysis. Genome Res. 1999. 9: 259-266 doi: 10.1101/gr.9.3.259 Belt, P, Warrell, DA, Malhotra, A, Wuster, W, Thorpe, RS. (1997) Russell's viper in Indonesia: snakebite and systematics. In R.S. Thorpe, W. Wuster & A. Malhotra (Eds.), Venomous Snakes: Ecology, Evolution and Snakebite. Symposia of the Zoological Society of London. Oxford: Clarendon Press;1997: 219-234 Chan KFS, Cheung KS, Ho CY, Lam FN, Tang WS. A field guide to the venomous land snakes of Hong Kong. Hong Kong SAZ, China: Friends of the Country Parks, Cosmos Books Limited; 2006. Chan, TYK, Critchley, JAJH. An epidemiological study of the snake bites in the New territories East, Hong Kong. Ann Trop Med Para 1994;88:219-221 Sawai Y. Epidemiological study on snakebites in Asia. The Snake 1980;12:115-203 Ciszowski, K, Hartwich A. Envenoming by Malayan cobra (Naja naja sputatrix)--case report. Przegl Lek. 2004 ;61 (4):421-6
138
Cockram CS, Chan JCN, Chow, KY. Bites by the white-lipped pitviper (Trimeresurus albolabris) and other species in Hong Kong. A survey of 4 years experience at the Prince of Wales Hospital. J Trop Med Hyg 1990;93:79-86 Connolly, S, Trevett, AJ, Nwokolo, NC, Lalloo, DG, Naraqui, S, Mantle, D et al. Neuromuscular effects of Papuan taipan snake venom. Annals Neurol 1995;38:916-920. Fung, HT, Kam, CW. Efficacy and safety of snake antivenom therapy: experience of a regional hospital. Hong Kong J Emer Med 2006;13(2):70-78 Fung HT, Lam SK, Lam KK, Kam CW, Simpson ID. A survey of snakebite management knowledge amongst select physicians in Hong Kong and the implications for snakebite training. Wilderness Environ Med. 2009 Winter;20(4):364-70. Ho, M, Warrell, DA, Looareesuwan, S, Phillips, RE, Chanthavanich, P, Karbwang, J et al. Clinical significance of venom antigen levels in patients envenomed by the Malayan pit viper (Callesolasma rhodostoma). Am J Trop med Hyg 1986;35:579-87. Ho, M, Silamut, K, White, NJ, Karbwang, J, Looareesuwan, S, Phillips, RE, et al. Pharmacokinetics of three commercial antivenoms in patients envenomed by the malayan pit viper Callesolasma rhodostoma in Thailand. Am J Trop Med Hyg 1990;42:260-266 Hoffmann JJML, Vijgen M, Smeets REH, Melman PG. Haemostatic effects in vivo after snakebite by the red-necked keelback (Rhabdophis subminiatus). Blood Coag & Fibrinolysis; 3:461-464, 1992. Hutton RA, Looareesuwan, S, Ho, M, Silamut, K, Chanthavanich, P, Karbwang, J et al. Arboreal green pit vipers (genus Trimeresurus) of southeast Asia; bites by T. Albolabris and T. Macrops in Thailand and a review of the literature. Trans Roy Soc Trop Med Hyg 1990;84:866-74 Karsen, SJ, Lau, MW, Bogadek, A. Hong Kong amphibians and reptiles. Hong Kong SAZ, China: Provisional Urban Council, Hong Kong;1998. Lalloo DG, Trevett AJ, Korinhona A, Nwokolo N, Laurenson IF, Paul M, Black J, Naraqi S, Mavo B, Saweri A, et al. Snake bites by the Papuan taipan (Oxyuranus scutellatus canni): paralysis, hemostatic and electrocardiographic abnormalities, and effects of antivenom. Am J Trop Med Hyg. 1995 Jun;52:525-31. Lalloo DG, Trevett AJ, Owens D, Minei J, Naraqi S, Saweri A, Hutton RA, Theakston RD, Warrell DA. Coagulopathy following bites by the Papuan taipan (Oxyuranus scutellatus canni). Blood Coagul Fibrinolysis. 1995;6:6572.
139
Lalloo, DG, Trevett, AJ, Black, J, Mapao, J, Saweri, A, Naraqi, S. Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern papua new Guinea. Q J Med 1996;89:23-35 Leung, CB, Chan, JCN, Anandaciva, S, Cockram, CS. Russells viper envenoming in Hong Kong. J Hong Kong Med Assoc 1991;43(1):55-57 Liat LB. venomous land snakes of Malaysia. In: Gopalakrishnakone P, Chou P eds. Snakes of medical importance: Singapore University Press Singapore; 1990:387-417 McGain F, Limbo A, Williams D, Didei G, Winkel K. Snakebite mortality at Port Moresby General Hospital, Papua New Guinea, 1992-2001. MJA 2004;181:687-691 Myint-Lwin, Warrell DA, Phillips RE, Tin-Nu-Swe, Tun-Pe, Maung-MaungLay.Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment. Mitrakul, C. Effects of green pit viper (Trimeresurus erythrurus and Trimeresurus popeorum) venoms on blood coagulation, platelets and the fibrinolytic enzyme systems: studies in vivo and in vitro. Am J Clin Pathol. 1973;60:654-62 Ng, W, Cheung, WL. Snake bites in Hong Kong: a prospective study on epidemiology and pre-hospital management. HKJEM 1997;4(2):68-73 Pochanugool C, Wilde H, Jitapunkul S, Limthongkul S. Spontaneous recovery from severe neurotoxic envenoming by a Malayan krait Bungarus candidus (Linnaeus) in Thailand. Wilderness Environ Med. 1997;8(4):223-5. Rojnuckarin, P, Chanthawibun, W, Noiphrom, J, Pakmanee, N, Intragumtornchai, T. A randomised, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites. Trans Rou Soc Trop Med 2006;100:879-884. Sawai Y. Epidemiological study on snakebites in Asia. The Snake 1980;12:115-203 Than-Than, Francis N, Tin-Nu-Swe, Myint-Lwin, Tun-Pe, Soe-Soe, et al. Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma. Acta Trop. 1989;46(1):23-38. Thein-Than, Tin-Tun, Hla-Pe, Phillips RE, Myint-Lwin, Tin-Nu-Swe, Warrell DA. Development of renal function abnormalities following bites by Russell's vipers (Daboia russelii siamensis) in Myanmar. Trans R Soc Trop Med Hyg. 1991;85(3):404-9.
140
Tin M, Rai M, Maung C, et la. Bites by the king cobra (Ophiophaus hannah), in Myanmar: Successful treatment of severe neurotoxic envenoming. Q J Med New Series 1991;80:751-762 Trevett AJ, Lalloo DG, Nwokolo NC, Naraqi S, Kevau IH, Theakston RD, Warrell DA. The efficacy of antivenom in the treatment of bites by the Papuan taipan (Oxyuranus scutellatus canni). Trans R Soc Trop Med Hyg. 1995;89(3):322-5. Tun Pe, Tin Myint, Aung Htut, Aye Aye Myint, Nu Nu Aung. Envenoming by Chinese krait (Bungarus multicinctus) and banded krait (B. fasciatus) in Myanmar. Trans Roy Soc Trop Med Hyg. 1997;91:686-688 Viravan C, Looareesuwan S, Kosakarn W, Wuthiekanun V, McCarthy CJ, Stimson AF et al. A national hospital-based survey of snakes responsible for bites in Thailand. Trans R Soc Trop Med Hyg 1992;86: 100-106 Warrell DA, Clinical toxicology of snakebite in Asia In: Handbook of Clinical Toxicology of Animal Venoms and Poisons Ed White J Meier J. CRC Press 1995. Watt G, Theakston RD, Hayes CG, Yambao ML, Sangalang R, Ranao et al. Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). A placebo-controlled study. N Engl J Med. 1986;315(23):1444-8. Watt GW, Padre, L, Tuazon, L, Hayes CG. Bites by the Philippine cobra (Naja naja philippinensis): an important cause of death among rice farmers. Am J Trop Med Hyg 1987;37:636-639 Yang, JYK, Hui, H, Lee, ACW. Severe coagulopathy associated with whitelipped green pit viper bite. Hong Kong Med J 2007;13(5):392-395 Zotz RB, Mebs D, Hirche H, Paar D. Hemostatic changes due to the venom gland extract of the red-necked keelback snake (Rhabdophis subminiatus). Toxicon 1991;29 (12):1501-1508.
Snakes of Medical Significance: West Asia

Bentur Y, Raikhlin-Eisenkraft B, Galperin M. Evaluation of antivenom therapy in Vipera palaestinae bites. Toxicon 2004;44:53-57 Corkill NL. An inquiry into snakebite in Iraq. Ind Jour Med Res 1932;XX:599625 Mahaba HM. Snakebite: Epidemiology, prevention, clinical presentation and management. Annals of Saudi Medicine 2000:20:66-68
141
Hanssens Y, Deleu D, Taqi A. Etiologic and demographic characteristics of poisoning: a prospective hospital-based study in Oman. J Toxicol Clin Toxicol. 2001;39:371-80. Schneeman, M, Cathomas, R, Laidlaw, ST, El Nahas, AM, Theakston RDG, Warrell, DA. Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review. QJM 2004;97:717-727 Weis JR, Whatley RE, Glenn JL, Rodgers GM. Prolonged hypofibrinogenemia and protein C activation after envenoming by Echis carinatus sochureki. Am J Trop Med Hyg.1991;44:452460. Wuster W, Broadley, D. Get an eyeful of this: a new species of giant spitting cobra from eastern and north-eastern Africa (Squamata: Serpentes: Elapidae: Naja). Zootaxa 2007;1532: 5168.
Snakes of Medical Significance: Africa Southern Zone

Blaylock R. Epidemiology of snakebite in Eshowe, KwaZulu-Natal, South Africa. Toxicon. 2004;43:159-66. Blaylock RSM. Snake bites at Triangle Hospital January 1975 to June 1981. Centr Afr J Med 1982 ;28:1-11. Blaylock R. Snake Bites. Tropical Surgery. 2002;20:25-29 Blaylock R suggested management of snakebites in South Africa. Dermatology Review 2003;3:33-38 Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 Blaylock RS. The treatment of snakebite in Zimbabwe. Cent Afr J Med. 1982;28:237-46. Coetzer PW, Tilbury CR. The epidemiology of snakebite in northern Natal. S Afr Med J. 1982;62:206-12. Coombs MD, Dunachie SJ, Brooker S, Haynes J, Church J, Warrell DA. Snake bites in Kenya: a preliminary survey of four areas. Trans R Soc Trop Med Hyg. 1997;91:319-21. Drewes RC, Sacherer JM. A new population of carpet vipers Echis carinatus from northern Kenya. J E Afr Nat Hist Soc 1974;145:1-7. Hoffmann LAC, De Wetpotgieter S. Naja mossambica Mozambique spitting cobra or M'fezi envenomation. J Herpetol Ass Afr 1988;35:41-42.
142
McNally SL, Reitz CJ. Victims of snakebite. A 5-year study at Shongwe Hospital, Kangwane, 1978-1982. S Afr Med J. 1987;72:855-60. Muguti GI, Maramba A, Washaya CT. Snake bites in Zimbabwe: a clinical study with emphasis on the need for antivenom. Cent Afr J Med. 1994;40:838. Nhachi CF, Kasilo OM. Snake poisoning in rural Zimbabwe--a prospective study. J Appl Toxicol. 1994;14:191-3. Rippey JJ, Rippey E, Branch WR. A survey of snakebite in the Johannesburg area. S Afr Med J 1976;50:1872-1876. Snow RW, Bronzan R, Roques T, Nyamawi C, Murphy S, Marsh K, The prevalence and morbidity of snake bite and treatment-seeking behaviour among a rural Kenyan population. Ann Trop Med Parasitol 1994;88:665-671. Tilbury CR. Observations on the bite of the Mozambique spitting cobra (Naja mossambica mossambica). S Afr Med J 1982;61:308-313. Wuster W, Broadley, D. Get an eyeful of this: a new species of giant spitting cobra from eastern and north-eastern Africa (Squamata: Serpentes: Elapidae: Naja). Zootaxa 2007;1532: 5168.
Snakes of Medical Significance: Africa West Zone

Abubakar SB, Abubakar IS, Habib AG, Nasidi A, Durfa N, Yusuf PO, et al. Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria. Toxicon 2009, doi:10.1016/j.toxicon.2009.10.024 Chippaux JP, Massougbodji A, Stock RP, Alagon A and the Investigators of African Antivipymn in Benin. Clinical Trial of an F(ab)2 antivenom for African snake bites in Benin. Am J Trop med Hyg 2007;77:538-546 Chippaux JP, Lang J, Amadi-Eddine S, Fagot P, Le Mener V. Short report: treatment of snake envenomations by a new polyvalent antivenom composed of highly purified F(ab)2: results of a clinical trial in northern Cameroon. Am J Trop Med Hyg. 1999;61:1017-8. Einterz EM, Bates ME. Snakebite in northern Cameroon: 134 victims of bites by the saw-scaled or carpet viper, Echis ocellatus. Trans R Soc Trop Med Hyg. 2003;97(6):693-6.
Laing GD, Lee L, Smith DC, Landon J, Theakston RD. Experimental assessment of a new, low-cost antivenom for treatment of carpet viper (Echis ocellatus) envenoming. Toxicon. 1995;33:307-13.
143
Onuaguluchi GO. Clinical observations on snakebite in Wukari, Nigeria. Trans R Soc Trop Med Hyg. 1960;54:265-9. Pitman CRS. The saw-scaled viper or carpet viper (Echis carinatus) in Africa and its bite. J Herpetol Ass Afr 1973; 9:6-34. Pugh RNH, Bourdillon CCN, Theakston RDG, Reid HA. Bites by the carpet viper in the Niger valley. Lancet 1979; ii:625627. Trape JF, Pison G, Guyavarach E, mane Y. High mortality from snakebite in south-eastern Senegal. Trans Roy Soc Trop med Hyg 2001;95:420-423 Visser LE, Kyei-Faried S, Belcher DW. 2004. Protocols and monitoring to improve snakebite in rural Ghana. Trans. R. Soc. Trop. Med. Hyg. 2004;98:728-283 Visser LE, Kyei-Faried S, Belcher, DW, Geelhoed DW, van Leeuwen JS, van Roosmalen J. Failure of a new antivenom to treat Echis ocellatus snake bite in rural Ghana: the importance of quality surveillance. Trans R Soc Trop Med Hyg 2008;9; [Epub ahead of print] Warrell DA. Davidson N.McD, Ormerod LD, Pope H.M, Watkins BJ, Greenwood,BM, et al. Bites by the saw-scaled or carpet viper (Echis carinatus): trial of two specific antivenoms. BMJ 1974;277:437440. Warrell DA, Ormerod LD, Davidson NMcD. Bites by puff adder (Bitis arietans) in Nigeria and value of antivenom. BMJ 1975;4:697-700. Warrell DA, Ormerod LD. Snake venom ophthalmia and blindness caused by the spitting cobra (Naja nigricollis) in Nigeria. Am J Trop Med Hyg; 1976;25:525-529. Warrell D A, Arnett, C. The importance of bites by the saw-scaled or carpet viper (Echis carinatus). Epidemiological studies in Nigeria and a review of the world literature. Acta Tropica (Basel) 1976;33:307341. Warrell DA, Davidson NM, Greenwood BM, Ormerod LD, Pope, H, Watkins D et al. Poisoning by bites of the saw-scaled viper (Echis carinatus) in Nigeria. QJM 1977;181:33-62. Warrell DA, Barnes HJ, Piburn MF. Neurotoxic effects of bites by the Egyptian cobra (Naja haje) in Nigeria. Trans R Soc Trop Med Hyg 1976;1:78-79.
144
Snakebite First Aid

Alberts MB, Shalit M, Logalbo F, Suction for venomous snakebite: a study of "mock venom in a human model" Ann Emerg Med. 2004 Feb;43:181-6. Amaral CF, Campolina D, Dias MB, Bueno CM, Rezende NA. Tourniquet ineffectiveness to reduce the severity of envenoming after Crotalus durissus snake bite in Belo Horizonte, Minas Gerais, Brazil. Toxicon. 1998;36:805-8. Anker RL, Staffon WG, Loiselle DS, Anker KM, Retarding the uptake of mock venom in humans. Comparison of three first aid treatments Medical Journal of Australia 1982; I :212-214 Anker, RL. Straffon,WG. Comment on: Pantyhose compression bandage: first-aid measure for snakebite. Med. J. Aust. 1982;2:241. Anker R.L., Straffon W.G., Loiselle D.S., Anker K.M. Comparison of Three Methods Designed to Delay the Uptake of Mock Venom. Aust. Fam Phy. 1983;12:365-368 Balmain, R., McClelland, K.L. Pantyhose compression bandage: first-aid measure for snakebite. Med. J. Aust. 1982;2:240241. Bharati K, Hati AK. Snakebite Management in the Tropics. Science and Culture. 2000;66: 302-304 Blaylock, R.S.M.. Pressure immobilisation for snakebite in southern Africa remains speculative. S. Afr. Med. J. 1994;84:826827. [Erratum. S. Afr. Med. J. 1995, 85, 1310.] Blaylock, R.S.M. Reply to: Pressure immobilisation for snakebite in southern Africa remains speculative. S. Afr. Med. J. 1995;10:10401041. Bucknall N, Electrical Treatment of venomous bites and stings: a mini review. Toxicon 1991; 29: 397-400 Burgess JL, Dart RC, Egen NB, Mayersohn M. Burgess JL, Dart RC, Egen NB, Mayersohn M. Ann Emerg Med. 1992;21:1086-93. Bush SP, Snakebite suction devices dont remove venom: They just suck. Ann Emerg Med. 2004;43:181-186. Bush SP Hegewald KG, Green SM, Cardwell MD, Hayes WK, Effects of a negative-pressure venom extraction device (Extractor) on local tissue injury after artificial rattlesnake envenomation in a porcine model. Wilderness Environ Medicine 2000; 180-188 Bush SP, Green SM, Laack TA, Hayes WK, Cardwell MD, Tanen DA, Pressure Immobilisation delays mortality and increases intracompartmental
145
pressure after artificial intramuscular rattlesnake envenomation in a porcine model Annals of Emergency Medicine 2004; 44(6):599-604 Chippaux J.P., Ramos-Cerillo B., Stock R.P. Study of the Efficacy of the Black Snake on Envenomation by Snake Bite in the Murine Model. 2006 Toxicon doi:10.1016/j.toxicon.2006.11.002 Christensen P.A. The Treatment of Snakebite. S. A. Medical J. 1969; 12531258 Currie B. Pressure-immobilization first aid for snakebite - fact and fancy. 1993 XIII International Congress for Tropical Medicine and Malaria. Jomtien, Pattaya, Thailand 29 Nov-4 Dec. Toxicon 1992; 31:931-932.(abstract). Dart RC, Gustafson RA. Failure of electric shock treatment for rattlesnake envenomation. Ann Emerg Med. 1991;20:659-61. Davis D, Branch K, Egen NB, Russell FE, Gerrish K, Auerbach PS, The effect of an electrical current on snake venom toxicity. Journal of Wilderness Medicine 1992; 48-53 Duncan, AW, Tibballs, J, Sutherland, SK. Comment on: Retarding the uptake of mock venom in humans. Med. J. Aust. 1982;1, 214. Edmondson, KW. Treatment of Snakebite. MJA 1979;9:257 Fisher, M. First aid in envenomation. MJA 1982;1:198 Gellert GA, Snake venom and Insect venom extractors: An unproven therapy. The New England Journal of Medicine 1992;18:1322 German BT, Hack JB, Brewer K, Meggs WJ. Pressure-immobilization bandages delay toxicity in a porcine model of eastern coral snake (Micrurus fulvius fulvius) envenomation. Ann Emerg Med. 2005;45:603-8. Glass TG, Cooling for first aid in snakebite. N Engl J Med 1981;305: 1095. Global Snakebite Initiative. Investigating pressure bandaging for snakebite in a simulated setting; bandage type, training and the effect of transport. Melbourne, (2008) Available at: http://www.snakebiteinitiative.org/files/GICT%20Conference%202008/Session %2021/Ms.%20Elizabeth%20Canale.ppt [Accessed 11th April 2009] Gray, S, Pressure Immobilization of Snakebite. Wilderness and Environmental Medicine 2003;14: 7373. Grenard S. Veno- and arterio-occlusive tourniquets are not only harmful, they are unnecessary. Toxicon. 2000;38:1305-6.
146
Guderian RH, Mackenzie CD, Williams JF. High voltage shock treatment for snakebite. Lancet 1986; 229. Hardy DL, A review of first aid measures for pit viper bite in North America with an appraisal of ExtractorTM Suction and stun gun electroshock. 1992 In: Campbell JA, Brodie ED (eds). Biology of the Pit Vipers. Tyler, TX: Selva. 405-414. Howarth DM, Southee AS, Whyte IM, Lymphatic flow rates and first aid in simulated peripheral snake or spider envenomation. Medical Journal of Australia 1994; 161: 695-700 Ismail M.M., Aloysius D.J. Snake-bite- Prevention and First Aid. Ceylon Medical Journal 1983; 28:175-177 Khin Ohn Lim, Aye-Aye-Myint, Tun-Pe, Theingie-New, Min-Naing, Russells Viper venom levels in serum of snake bite victims in Burma Trans. R Soc Trop Med Hyg. 1984; 78: 165-168 Klenerman L, Crawley J. Limb Blood Flow in the Presence of a Tourniquet. Acta. Orthop. Scand. 1977a;48: 291-295 Klenerman L, Chakrabarti R, Mackie I, Brozovic M, Stirling Y. Changes in Haemostatic System after Application of a Tourniquet. The Lancet 1977b; May: 970-972 Knoefel P.K. Francesco Redi on vipers. Leiden EJ Brill,1988 Kroegal C, Meyer Zum Buschfelde KH Biological Basis for High-VoltageShock Treatment for Snakebite Lancet 1986; 2: 1335 McPartland JM, Foster R, Stunguns and Snakebite Lancet 1988; 2:1141 Maiden, M.J, White, J., 2006. Severe rapid-onset paralysis in a parttime soldier. Crit. Care Resusc. 8, 120122. Murrell, G. The effectiveness of the pressure/immobilization first aid technique in the case of a tiger snake bite. Med. J. Aust. 1981;2:295. Nishioka SA. Is tourniquet use ineffective in the pre-hospital management of South American rattlesnake bite? Toxicon 2000;38(2):151-2. Norris RL, Ngo J, Nolan K, Hooker G, Physicians and lay people are unable to apply Pressure Immobilisation properly in a simulated snakebite scenario. Wilderness and Environmental Medicine 2005;16:16-21 Oxer, H.F.,. Australian work in first aid of poisonous snakebite. Ann. Emerg. Med. 1982;11:228. Pantanowitza L. Tourniquets for Snakebite. E African Med. J 1997; 437
147
Pearn, J.H, Morrison, JJ, Charles, N. First aid for snakebite. Med. J. Aust. 1981;2:293294. Rogers, IR, Winkel, KD. Struan Sutherlands Rationalization of first-aid measures for elapid snakebite a commentary. Wilderness Environ. Med. 2005;16:160-163. Rosner F. Medical Writings of Moses Maimonides. Arch. Intern. Med. 1974;133:318-319 Pugh RN, Theakston RD. Fatality following use of a tourniquet after viper bite envenoming. Ann Trop Med Parasitol. 1987;81:77-8. Russell, FE. Pressure and immobilisation for snakebite remains speculative. Ann. Emerg. Med. 1982;11:701702. Russell FE, A letter on electroshock. Vet Hum Toxicol 1987; 29:320 Russell FE Another Warning about Electroshock for Snakebite Postgrad Med 1987a ;82 :32 Simes DC. Early and late removal of the pressure bandage in brown snake envenomation: a report of two cases. Crit Care Resusc. 2002;4:116-8. Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335 Simpson ID. A study of the current knowledge base in treating snakebite amongst doctors in the high risk countries of India and Pakistan does snakebite treatment training reflect the local requirement? Trans Roy Soc Trop Med Hyg 2008,102:1108-14 Simpson, ID, Tanwar, PD, Andrade, C, Kochar, DK, Norris, RL. The Ebbinghaus retention curve: training does not increase the ability to apply pressure immobilization in simulated snake biteimplications for snake bite first aid in the developing world. Trans. R Soc Trop Med Hyg 2008;102:451459 Snyder CC, Murdock RT, While GL, Kuitu JR Electric Shock Treatment for Snakebite Lancet 1989; 1:1022 Stahnke, HL. The L-C treatment of venomous bites or stings. Am. J. Trop. Med. Hyg., 1953;2:142-143 Stewart M.E., Greenland S., Hoffman J.R. First-Aid Treatment of Poisonous Snakebite: Are Currently Recommended Procedures Justified? Ann. Emer. Med. 1981;10: 331-335 Sutherland, S.K.. Mock venom in humans. Aust. Fam. Physician 1983;12: 368.
148
Sutherland, S.K. The pressure immobilisation technique. Med. J. Aust. 1994;161:700701. Sutherland, S.K. Reply to: Pressure immobilisation for snakebite in southern Africa remains speculative. S. Afr. Med. J. 1995;10:10391040. Sutherland, Coulter AR, Harris RD, Rationalisation of first aid methods for elapid snakebite Lancet 1979; i :183-186 Sutherland SK, Coulter AR. Early management of bites by the eastern diamondback rattlesnake (Crotalus adamanteus): studies in monkeys (Macaca fascicularis). Am J Trop Med Hyg. 1981;30:497-500. Sutherland SK, Harris RD, Coulter AR, Lovering KE, First aid for Cobra (Naja naja) bites. Indian Journal of Medical Research 1981;73: 266-268 Trevett A.J., Nwokolo N, Watters D.A.K., Lagani W, Vince J.D. Tourniquet Injury in a Papuan Snakebite Victim. Tropical and Geographical Medicine 1993; 45: 305-307 Tun Pe, Tin-Nu-Swe, Myint-Lwin, Warrell DA, Than-Win, The efficacy of tourniquets as a first aid measure for Russells Viper bites in Burma Trans. R Soc Trop Med Hyg 1987; 81:403-405 Tun Pe, Aye Aye Myint, Khin Ei Han et al, Local Compression pads as a first aid measure for victims of bites by Russells Viper (Daboia russelii siamensis) in Myanmar. Trans Royal Society of Trop Medicine 1995; 89:293-295 Tun Pe, Sann Mya, Aye Aye Myint, Nu Nu Aung, Khin Aye Kyu, Tin Oo, Field Trials of Efficacy of Local Compression Immobilisation First Aid Technique in Russells Viper (Daboia russelii siamensis) Bite Patients. Southeast Asian J Trop Med Public Health 2000;31:346-348 Warrell DA, Clinical Toxicology of Snakebite in Asia in Handbook of Clinical Toxicology of Animal Venoms and Poisons Ed White J Meier J. CRC Press 1995 Warrell D.A. Tropical Health: Venomous bites and stings in the tropical world. Med J. Aust. 1993;159:773-779 Warrell, D.A. 1995. Clinical toxicology of snakebite in Asia, in: White, J., Meier, J. (Eds), Handbook of Clinical Toxicology of Animal Venoms and Poisons. CRC Press, New York, pp. 493-617. Warrell, D.A. 1999. WHO/SEARO guidelines for the clinical management of snakebite in the Southeast Asian region. S.E. Asian J. Trop. Med. Pub. Hlth. 30 (Suppl 1), 1-85.
149
Warrell, D.A. 2003. Animal toxins, in:Cook GC, Zumla A (Eds), Mansons Tropical Diseases. WB Saunders, London, pp. 581618. Warrell, D.A. 2005a. Treatment of bites by adders and exotic venomous snakes. B.M.J. 321, 1244-1247. Warrell, D.A. 2005b. Guidelines for the Clinical Management of Snake Bites in the South-East Asia Region. World Health Organization, New Delhi, pp. i-67. Warrell, D.A. 2006. Australian toxinology in a global context. Toxicon. 48, 718725. Warrell DA. Snake bite. The Lancet 2010;375:77-88 Watt G, Padre L, Tuazon L, Theakston RDG, Laughlin L. Tourniquet Application after Cobra Bite: Delay in the Onset of Neurotoxicity and the Dangers of Sudden Release. Am J Trop Med Hyg 1988; 87: 618-622 White J. Snakebite an Australian perspective. Journal of Wilderness Medicine. 1991;2:219-244. Winkel, KD. Hawdon, GM, Levick, N. Pressure immobilization for neurotoxic snake bites. Ann. Emerg. Med. 1999;34:294295.
Diagnosis: Signs and Symptoms of Envenoming

Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 Ho M, Warrell MJ, Warrell DA, Bidwell D, Voller A, A critical reappraisal of the use of enzyme-linked immunosorbent assays in the study of snakebite. Toxicon 1986; 24: 211-221. Isbister GK, Williams V, Brown SGA, White J, Currie BJ. Clinically applicable laboratory end-points for treating snakebite coagulopathy. Pathology 2006;38:568-572 Modi, N.S., Modis Textbook of Medical Jurisprudence and Toxicology. N.M.Tripathi Private Limited, Bombay; 1988. Pillay, V.V., 2005. Irritants of animal origin, in: Pillay, V.V. (Ed), Modern Medical Toxicology. Jaypee Brothers Medical Publishers, New Delhi, pp. 120153. Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335
150
Anti Snake Venom (ASV)

Bebarta V, Dart RC. Effectiveness of delayed use of crotalidae polyvalent immune Fab (ovine) antivenom. J Toxicol Clin Toxicol. 2004;42:321-4. Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001;37:181-8. Gutirrez JM, Lomonte B, Len G, Rucavado A, Chaves F, Angulo Y. Trends in snakebite envenomation therapy: scientific, technological and public health considerations. Curr Pharm Des. 2007;13:2935-50. Heard K, O'Malley GF, Dart RC. Antivenom therapy in the Americas. Drugs. 1999 Jul;58:5-15. Hill RE, Bogdan GM, Dart RC. Time to reconstitution: purified Fab antivenom vs. unpurified IgG antivenom. Toxicon. 2001;39:729-31. Lavonas EJ, Gerardo CJ, O'Malley G, Arnold TC, Bush SP, Banner W Jr, Steffens M, Kerns WP 2nd. Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med. 2004;43:200-6. Lavonas EJ, Tomaszewski CA, Ford MD, Rouse AM, Kerns WP 2nd. Severe puff adder (Bitis arietans) envenomation with coagulopathy. J Toxicol Clin Toxicol. 2002;40:911-8. Offerman SR, Barry JD, Richardson WH, Tong T, Tanen D, Bush SP, Clark RF. Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.Clin Toxicol (Phila). 2009;47:61-8. Otero-Patio R, Cardoso JL, Higashi HG, Nunez V, Diaz A, Toro MF, et al. A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for bothrops snake bites in Uraba, Colombia. Am. J. Trop. Med. Hyg 1998;58(2):183-189 Otero R, Gutirrez J.M, Rojas G, Nez V, Daz A, Miranda E , et al. A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in bothrops and porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms. Toxicon 1999;37(6):895-908. Otero R, Len G, Gutirrez JM, Rojas G, Toro MF, Barona J, et al. Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of bothrops asper bites in Colombia. Trans Roy Soc Trop Med Hyg 2006;100(12):117382.
151
Sano-Martins IS, Fan HW, Castro SCB, et al. Reliability of the simple whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon. 1994;32:10451050. Simpson ID, Norris RL. The global snakebite crisis-A public health issue misunderstood, not neglected. Wilderness and Environmental Medicine, 2009;20:43-56 Simpson ID, Jacobsen IM. Anti snake venom production crisis Who told us it was uneconomic and unsustainable? Wilderness Environ Med. 2009;20:14455. Thorson A, Lavonas EJ, Rouse AM, Kerns WP 2nd. Copperhead envenomations in the Carolinas. J Toxicol Clin Toxicol. 2003;41:29-35. World Health Organisation. Progress in the characterization of venoms and standardization of antivenoms W.H.O. Offset Publ. 1981;58, 144.
Criteria for Administering ASV

Bebarta V, Dart RC. Effectiveness of delayed use of crotalidae polyvalent immune Fab (ovine) antivenom. J Toxicol Clin Toxicol. 2004;42:321-4. Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 Heard K, O'Malley GF, Dart RC. Antivenom therapy in the Americas. Drugs. 1999 Jul;58(1):5-15. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001;37:181-8. Lavonas EJ, Gerardo CJ, O'Malley G, Arnold TC, Bush SP, Banner W Jr, Steffens M, Kerns WP 2nd. Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med. 2004;43:200-6. Lavonas EJ, Tomaszewski CA, Ford MD, Rouse AM, Kerns WP 2nd. Severe puff adder (Bitis arietans) envenomation with coagulopathy. J Toxicol Clin Toxicol. 2002;40:911-8. Offerman SR, Barry JD, Richardson WH, Tong T, Tanen D, Bush SP, Clark RF. Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.Clin Toxicol (Phila). 2009;47:61-8. Sano-Martins IS, Fan HW, Castro SCB, et al. Reliability of the simple whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen
152
concentration in patients envenomed by Bothrops snakes. Toxicon. 1994;32:10451050. Thorson A, Lavonas EJ, Rouse AM, Kerns WP 2nd. Copperhead envenomations in the Carolinas. J Toxicol Clin Toxicol. 2003;41:29-35.
ASV Doses
Abubakar SB, Abubakar IS, Habib AG, Nasidi A, Durfa N, Yusuf PO, et al. Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria. Toxicon 2009, doi:10.1016/j.toxicon.2009.10.024 Agrawal PN, Aggarwal AN, Gupta D, Behara D, Prabhaker S, Jindal SK. 2001. Management of Respiratory Failure in Sever Neuroparalytic Snake Envenomation. Neurol. India 40, 25-28 Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 EgyVac. Egyptian Species. Available at: http://www.egyvac.com/egyproducts/SNAKE%20VENOM-egypt.htm [Accessed 24th January 2010] EgyVac. Turkey Species. Available at: http://www.egyvac.com/egyproducts/SNAKE%20VENOM-Turkey.htm [Accessed 24th January 2010] Ghosh S, Maisnam I, Murmu BK, Mitra PK, Roy A, Simpson ID. A locally developed snakebite management protocol significantly reduces overall anti snake venom utilization in West Bengal, India. Wilderness Environ Med; 2008;19;267-74 Government of India. National snakebite protocol. New Delhi: Health & Family Welfare Department:2007 Harish R, Digra SK. 2007. Snake bite neurotoxicity: Reversal after 84 hours. Indian Pediatics 44, 233. Kravitz J, Gerardo CJ. Copperhead snakebite treated with crotalidae polyvalent immune fab (ovine) antivenom in third trimester pregnancy.Clin Toxicol (Phila). 2006;44:353-4. Sebe A, Satar S, Acikalin A. Snakebite during pregnancy. Hum Exp Toxicol. 2005;24:341-5.
153
Seneviratne SL, de Silva CE, Fonseka MM, Pathmeswaran A, Gunatilake SB, de Silva HJ. Envenoming due to snake bite during pregnancy.Trans R Soc Trop Med Hyg. 2002;96:272-4. Sharma SK, Koirala S, Dahal G. Krait Bite Requiring High Dose Antivenom: A Case Report. Southeast Asian J Trop Med Public Health. 2002;33:170-171 Sharma SK, Chappuis F, Jha N, Bovier PA, Loutan L, Koirala S. Impact of Snakebites and Determinants of Fatal Outcomes in Southeastern Nepal. Am. J. Trop. Med. Hyg. 2004;71:234-238 Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335 Simpson, I.D., Norris, R.L, Snake antivenom product guidelines in India: the devil is in the details. Wilderness Environ Med. 2007;18:163-168 Simpson ID , Quraishi NA, Qureshi HI,. Snakebite management in Pakistan A guide to the latest methods of treatment. Pakistan Medical Research Council. Islamabad; 2008 Warrell DA. Animal toxins, in: Cook GC, Zumla A eds. Mansons Tropical Diseases. London:WB Saunders; 2003:581618. Warrell DA. Bites by venomous snakes outside the Americas. In: Auerbach PS, ed. Wilderness Medicine. St. Louis, MO: Moseby; 2007:10861123. Watt G, Meade BD, Theakston RD, Padre LP, Tuazon ML, Calubaquib C, Santiago E, Ranoa CP. Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis. Trans R Soc Trop Med Hyg. 1989;83:570-3.
Adverse Anti Snake Venom Reactions

American Association of Allergy, Asthma, and Immunology. Media resources: position statement 26. The use of epinephrine in the treatment of anaphylaxis. www.aaaai.org/media/resources/advocacy_statements/ ps26.stm (accessed Apr 2003). Ariaratnam CA, Sjostrom L, Raziek Z, Abeyasinghe S, Kularatne M, Kondikara Arachchi RWK, Sheriff, et al. An open randomised comparative trial of two antivenoms for the treatment of envenoming by Sri Lankan Russells viper (Daboia russelii russelii). Trans R Soc Trop Med Hyg. 2001;95:74-80. Gawarammana IB, Kularatne M, Abeysinga S, Dissarayake WP, Kumarasri RPV, Seranayake N, Ariyasena H, Parallel infusion of hydrocortisone chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites Med Journal of Australia. 2004;180:20-3.
154
Gutirrez JM, Lomonte B, Len G, Rucavado A, Chaves F, Angulo Y. Trends in snakebite envenomation therapy: scientific, technological and public health considerations. Curr Pharm Des. 2007;13:2935-50. Isbister GK, Tankel AS, White J, Little M, Brown SG, Spain DJ, Gavaghan CF, Currie BJ. High rate of immediate systemic hypersensitivity reactions to tiger snake antivenom. MJA 2006;184:419-20 Isbister GK, Brown SG, McDonald, E, White J, Currie BJ. Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis, MJA 2008;188:473-476 Kochar DK, Tanwar PD, Norris RL Sabir M, Nayak KC, Agrawal TD, et al. Rediscovery of severe saw scaled viper (Echis sochureki) envenoming in the Thar Desert region of Rajasthan, India. Wilderness Environ Med. 2007;18:7585 Krifi MN, El Ayeb M, Dellagi K. The improvement and standardization of antivenom production in developing countries: comparing antivenom quality, therapeutical efficiency and cost. J. Venom. Anim. Toxins 1999;5:128-141. Len G, Monge M, Rojas E, Lomonte B, Gutirrez JM. Comparison between IgG and F(ab')(2) polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions. Toxicon. 2001;39:793-801. Len G, Lomonte B, Gutirrez JM. Anticomplementary activity of equine whole IgG antivenoms: comparison of three fractionation protocols. Toxicon. 2005;45:123-8. McLean-Tooke A P C, Bethune C A, Fay A C, Spickett G P, Adrenaline in the treatment of anaphylaxis: what is the evidence? BMJ. 2003; 327: 1332-1335 Malasit P, Warrell DA, Chanthavanich P, Viravan C, Mongkolsapaya J, Singhthong B, et al. Prediction, prevention and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. BMJ. 1986;292:1720. Premawardenha A, de Silva CE, Fonseka MMD, Gunatilakee SB, de Silva HJ, Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial BMJ. 1999;318: 1041-1043 Project Team of the Resuscitation Council (UK). The emergency medical treatment of anaphylactic reactions for first medical responders and for community nurses. Revised Jan 2002. www.resus.org.uk/pages/reaction.htm (accessed Apr 2003). Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327:380-4.
155
Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol 2001;108:871-3. Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335 Sutherland, SK. Serum reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de-novo reactions to antivenoms and antitoxins. Med J Aust. 1977;1:613-5. Warrell D.A. Tropical Health: Venomous bites and stings in the tropical world. Med J. Aust. 1993;159:773-779 Warrell DA. W.H.O./SEARO Guidelines for the clinical management of snakebite in the Southeast Asian Region. SE Asian J. Trop. Med. Pub. Hlth. 1999;1:1-85. Warrell DA. Animal toxins, in: Cook GC, Zumla A eds. Mansons Tropical Diseases. London: WB Saunders; 2003:581618. Wen Fan H, Marcopito LF, Cardoso JLC, Franca FOS, Malaque CMS, Ferrari RA, Theakston RD, Warrell DA, Sequential randomised and double blind trial of Promethazine prophylaxis against early anaphylactic reactions to antivenom for Bothrops snake bites. BMJ. 1999;318:1451-1453 Williams DJ, Jensen SD, Nimorakiotakis B, Mller R, Winkel KD. Antivenom use, premedication and early adverse reactions in the management of snake bites in rural Papua New Guinea. Toxicon. 2007;49:780-92. World Health Organisation. Progress in the characterization of venoms and standardization of antivenoms W.H.O. Offset Publ. 1981;58, 144. World Health Organisation. Rabies and envenomings: a neglected public health issue. Geneva, World Health Organisation; 2007.
Neurotoxic Envenomation and Anticholinesterase Drugs

Agrawal PN, Aqqarawal AN, Gupta D, Behera D, Prabhakar S, Jindal SK, Management of Respiratory Failure in Severe Neuroparalytic Snake Envenomation Neurol India. 2001; 49(1):25-28 Akram S, Khurshid T. Successful Revival of Neurotoxic Snake Bite by Artificial Ventilation and Anticholinesterases, J Coll Physicians Surg Pak 2000; 10: 267-9. Akram S, Ishaque M, Abbas S. Mechanical ventilation in snakebite. Pak Armed Forces Medical J 2004;2;10-15
156
Auerbach P.S., Norris R.L. Disorders caused by reptile bites and marine animal exposures. In: Kaspar D.L., Fauci A.S., Longo D.L., Braunwald E., Hauser S.L., Jameson J.L., ed. Harrisons Principles of Internal Medicine 16th Ed. New York. McGraw-Hill; 2005:2593-2600 Bakar A, Ahasan N, Ahsan M. Snake bite in Bangladesh. Pak Armed Forces Med J 2006;1;10-14 Benjamin N, Rawlins M, Vale JA. Drug Therapy and Poisoning. In: Kumar P, Clark M. eds. Kumar and Clark Clinical Medicine. 5th ed. United Kingdom: WB Saunders 2002; 985-7. Bomb BS, Roy S, Kumawat DC, Bharjatya M, Do we need antisnake venom (ASV) for management of elapid ophitoxaemia? J Assoc Phys India 1996; 44: 31-33. Harris JB, Goonetilleke A. Animal Poisons and the Nervous System: What the Neurologist Needs to Know. J Neurol Neurosurg Psychiatry. 2004;75, Suppl 3:iii:40-6 Khan B, Naseem A. Guidelines for Management of Snake Bite Cases. Pak Armed Forces Med J 2000; 50: 51-5. Ramakrishnan MR, Sankaran K, Gupta GD, Chandrasekar S. 1975. External Opthalmoplegia in Elapidae Bites and its Response to Neostigmine. Neurology India. 23(2), 109-110 Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335 Simpson ID. A study of the current knowledge base in treating snakebite amongst doctors in the high risk countries of India and Pakistan does snakebite treatment training reflect the local requirement? Trans Roy Soc Trop Med Hyg 2008, doi:10.1016/j.trstmh.2008.04.013 Warrell DA, Looareesuwan S, White NJ, Theakston RD, Warrell MJ, Kosakarn W, Reid HA, Severe neurotoxin envenoming by the Malayan Krait Bungarus candidus (Linnaeus): response to anticholinesterase. BMJ. 1983; 286: 670680 Watt G, Theakston RD, Hayes CG, Yambao ML, Sangalang R, Ranao CP, Alquizalas E, Warrell DA, Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja Philippinensis) The New England Journal of Medicine 1986; 23: 1444-1448 Yee JSP, Nanling G, Afifiyan F, Donghui M, Lay PS, Armugam A et al. Snake postsynaptic neurotoxins: gene structure, phylogeny and applications in research and therapy. Biochimie 2004;86:137-149
157
Airway Support Items

Akram S, Ishaque M, Abbas S. Mechanical ventilation in snakebite. Pak Armed Forces Medical J 2004;2;10-15 Bailey AR, Hett DA. The laryngeal mask airway in resuscitation. Resuscitation 1994;28:107-110 Bajaj Y, Gadepalli C, Knight LC. Securing a nasopharyngeal airway. J Laryngol Otol. 2008;122:733-4. Gaitini L, Madrid V, Capdevila M, Arino JJ. The Laryngeal tube. Rev Esp Anestesiol Reanim. 2008;55:232-41. Murphy MF. Laryngeal mask airways. In: Walls RM (ed): Emergency Airway Management. Philadelphia, Lippincott Williams & Wilkins, pp 97-109. 2004. Murphy MF, Schneider RE. Supraglottic devices. In: Walls RM (ed): Emergency Airway Management. Philadelphia, Lippincott Williams & Wilkins, pp 110-119. 2004. Ocker H, Wenzel V, Schmucker P, Steinfath M, Drges V. A comparison of the laryngeal tube with the laryngeal mask airway during routine surgical procedures. Anesth Analg. 2002;95:1094-7 Pollack CV. The laryngeal mask airway: a comprehensive review for the Emergency Physician. J Emerg Med. 2001 Jan;20:53-66. Quraishi NA, Qureshi HI, Simpson ID. A contextual approach to managing snake bite in Pakistan: snake bite treatment with particular reference to neurotoxieity and the ideal hospital snake bite kit. J Pak Med Assoc. 2008;58:325-31. Roberts K, Whalley H, Bleetman A. The nasopharyngeal airway: dispelling myths and establishing the facts. Emerg Med J. 2005 Jun;22:394-6. Simpson ID. Snakebite Management in India, The First Few Hours: A Guide for Primary Care Physicians. J Indian Med Assoc 2007;105:324-335 Simpson ID, Jacobsen IM. Understanding and Treatment of Neurotoxic Snakebite in the Developing World: Air Today or Gone Tomorrow! Indian Journal of Emergency Pediatrics 2009;1;15-24 Springer DK, Jahr JS. The laryngeal mask airway. Safety, efficacy, and current use. Am J Anesthesiol. 1995;22:65-9. Wiese CH, Semmel T, Mller JU, Bahr J, Ocker H, Graf BM. The use of the laryngeal tube disposable (LT-D) by paramedics during out-of-hospital resuscitation-An observational study concerning ERC guidelines 2005. Resuscitation. 2008 Nov 14. [Epub ahead of print]
158
Haemotoxic Envenomation, Blood Products and Renal Failure

Burke CW. The anterior pituitary, snakebite and Sheehans syndrome. QJM 1990;276:331-33 Chugh KS, Aikat BK, Sharma BK, Dash SC, Mathew MT, Das KC. Acute renal failure following snakebite. Am J Trop med Hyg 1975;24:692-697 Eapen CK, Chandy N, Kochuvarkey KL, Zacharia PK, Thomas PJ, Ipe TI. Unusual complications of snake bite: hypopituitarism after viper bites. In: Ohsaka A, Hayashi K, Sawai Y, eds. Animal, plant and microbial toxins. New York: Plenum ,467-473, 1976. Myint Lwin, Tin Na Swe, Myint-Aye-Mu, Than Than, Thein Than, Tun Pe, Heparin Therapy in Russells Viper bite victims with disseminated intravascular coagulation: a controlled trial. Southeast Asian J Trop Med Public Health 1992;23:282-287 Paul V, Prahlad KA, Earali J, Francis S, Lewis F. Trial of heparin in viper bites. J Assoc Physicians India. 2003;51:163-6. Paul V, Pudoor A, Earali J, John B, Anil Kumar CS, Anthony T. Trial of low molecular weight heparin in the treatment of viper bites. J Assoc Physicians India. 2007;55:338-42. Shastry JCM, Date A, Carman RH, John KV. Renal failure following snake bite. Am J Trop Med Hyg 1977;26:1032-1038 Than-Than, Francis N, Tin-Nu-Swe, Myint-Lwin, Tun-Pe, Soe-Soe, et al. Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma. Acta Trop. 1989;46(1):23-38. Thein-Than, Tin-Tun, Hla-Pe, Phillips RE, Myint-Lwin, Tin-Nu-Swe, Warrell DA. Development of renal function abnormalities following bites by Russell's vipers (Daboia russelii siamensis) in Myanmar. Trans R Soc Trop Med Hyg. 1991;85(3):404-9. Tun-Pe, Phillips RE, Warrell DA, Moore RA, Tin-Nu-Swe, Myint-Lwin, Burke CW. Acute and chronic pituitary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma. Lancet 1987;2:763-7. White J. Snake venoms and coagulopathy. Toxicon 2005;45:951-967
159
Pain and Wound Management References

Anindhya C, Dev PR, Vijaya S, Vijay K, Yoga N. Surgical impliocations of snakebites. Indian J Pediatrics 2004;71:397-399 Blaylock RS. Antibiotic use and infection in snakebite victims. S Afr Med J 1999; 89:874-6, 1999 Blaylock RS. Normal oral bacterial flora from some southern African snakes. Onderstepoort J Vet Res 2001; 68: 175-82. Blaylock RSM. The identification and syndromic management of snakebite in South Africa. SA Fam Pract 2005;47:48-53 Ehui E. Kra O. Ouattara I et al. Generalized tetanus complicating a traditional medicine applied for snakebite. Bulletin de la Societe de Pathologie Exotique 2007; 100:184-5. Habib AG. Tetanus complicating snakebite in northern Nigeria: clinical presentation and public health implications. Acta Tropica. 2003; 85(1):87-91. Joseph S, Orthopedics in Trauma, in: Vasnaik M, Shashiraj E, Palatty B.U., Essentials of Emergency Medicine, New Delhi, Jaypee Brothers Medical Publishers (P) Ld: 175-183. 2003
Snakebite Management When ASV is Unavailable

Gutirrez JM, Lomonte B, Len G, Rucavado A, Chaves F, Angulo Y. Trends in snakebite envenomation therapy: scientific, technological and public health considerations. Curr Pharm Des. 2007;13:2935-50. Abubakar SB, Abubakar IS, Habib AG, Nasidi A, Durfa N, Yusuf PO, et al. Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria. Toxicon 2009, doi:10.1016/j.toxicon.2009.10.024 Offerman SR, Barry JD, Richardson WH, Tong T, Tanen D, Bush SP, Clark RF. Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model. Clin Toxicol (Phila). 2009;47:61-8.
Snakebite Epidemiology
Abubakar SB, Abubakar IS, Habib AG, Nasidi A, Durfa N, Yusuf PO, et al. Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria. Toxicon 2009, doi:10.1016/j.toxicon.2009.10.024
160
Chippaux JP. Snakebites: appraisal of the global situation. Bull. World Health Org. 1998;76:515-24 Global Snakebite Initiative. Open discussion of the global snakebite initiative concept., Melbourne, (2008) Available from: http://www.snakebiteinitiative.org/files/GICT%20Conference%202008/Audio/S ession%2016%20audio/Session%2016%20Open%20Discussion.mp3 [Accessed 11th April 2009] Harris JB, Faiz MA, Rahman MR, Jalil MM, Ahsan MF, Theakston RD et al. Snake bite in Chittagong Division, Bangladesh: a study of bitten patients who developed no signs of systemic envenoming. Trans R Soc Trop Med Hyg. 2010 Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, Premaratna, R et al. Estimating the global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 2008;5: e218. doi:10.1371/journal.pmed.0050218 Simpson ID, Blaylock RS. The Anti Snake Venom Crisis in Africa: A Suggested Manufacturers Product Guide. Wilderness and Environmental Medicine;2009;20;275-282. Simpson ID, Jacobsen IM. A Review of Anti Snake Venom Provision in Asia and Papua New Guinea: A Guide to Potential Anti Venom Products for Clinicians, Purchasers and Manufacturers. Pakistan Journal of Medical Research 2010, In Press. Swaroop S, Grabb B. Snakebite mortality in the world. Bull WHO 1954;10:35 76. World Health Organisation. Rabies and envenomings: a neglected public health issue. Geneva, World Health Organisation; 2007. World Health Organisation. Management of snake bites: Report of a regional meeting 30th November 2nd December 2009.
161

A2 Snakebite Management in Asia and Africa

Caricato da

Informazioni sul documento

Descrizione originale:

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

A2 Snakebite Management in Asia and Africa

Caricato da

Copyright:

Formati disponibili

A

Snakebite Management in Asia & Africa

Guidelines produced by: Pakistan Medical Research Council

World Health Organization Pakistan Country Office

Pakistan Medical Association

National Program for Family Planning and Primary Health Care

Indian Journal of Emergency Pediatrics

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

102 102 102 103 103 103 104 104

106 106 106 106 107 107 108 108

22.0 Photographic Credits 23.0 General Author Acknowledgements 24.0 References

133 134 135

1.0 Snakes of Medical Significance

1.2 Snakes of Medical Significance

1.3 South Asia

Non ASV Coverage

Naja kaouthia PW 2 Daboia russelii B Echis carinatus B Echis sochureki B

1.4 Asia Central, South East and East

Callesolasma rhodostoma B Naja kaouthia PW

1.5 West Asia

Cerastes cerastes PPS/B

Cerastes gasperettii PPS/B?

Eristicophis macmahoni PPS/PW?

1.6 Africa: South Zone

Bitis arietans PPS

Naja nigricollis PPS N. mossambica PPS

1.7 Africa: West Zone

Non ASV Coverage

Bitis arietans PPS

Naja nigricollis PPS Echis ocellatus B

1.8 Africa: North East Zone

Non ASV Coverage

E. pyramidum B E. ocellatus B Echis coloratus B

1.9 All Africa Progressive Weakness Species

2.0 Snakebite First Aid

2.2 Inappropriate First Aid Methods 2.3 Tight Tourniquets

Conclusions What then are our conclusions regarding tourniquet use?

2.4 Cutting and Suction

2.5 Pressure Immobilisation Method (PIM)

2.6 Other Pressure Techniques

2.7 Electricity and Ice

Electrical therapy has no role in snakebite first aid.

2.8 Washing the Wound

2.9 Traditional Remedies

2.10 Traditional Medicine; Specific Treatment: Snake Stones

2.11 Traditional Medicine Specific Treatment: Scarification

2.12 The Recommended First Aid Method: Do it R.I.G.H.T

Reassure the patient. 70% of all snakebites are from

Immobilise in the same way as a fractured limb. Use

Get to Hospital Immediately. Traditional remedies have

the doctor of any systemic symptoms such as

ptosis that manifest on the way to hospital.

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

3.0 Patient Arrival

3.2 Asymptomatic Arrival

3.3 Symptomatic Patients

3.4 Key Interventions

emergency measures, the ABCs must be implemented first.

3.5 Non-Critical Arrival

4.0 Patient Dialogue

4.2 What was the time of the bite?

4.3 Was the snake seen and/or killed?

4.5 Have any traditional treatments been taken before arrival?