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WHO ROSEA Snake Bites 2e 2016 PDF
WHO ROSEA Snake Bites 2e 2016 PDF
2nd Edition
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Printed in India
Contents
i. Foreword 7
ii. Acknowledgement 8
iii. Preface 9
1 Executive summary 11
2 Prevention 17
Essentials 19
2.1 Reducing the risk of snakebites 19
2.2 Implementing preventive strategies for community education 22
2.3 Conclusion 23
CONTENTS 3
5 Clinical aspects of snakebites 89
Essentials 91
5.1 When venom has not been injected 94
5.2 When venom has been injected 94
5.2.1 Early symptoms and signs 94
5.2.2 Clinical patterns of envenoming by snakes in South East Asia 95
5.2.3 Local symptoms and signs in the bitten part 95
5.2.4 Generalized (systemic) symptoms and signs 96
5.3 Clinical syndromes of snakebite in South-East Asia 101
5.4 Long-term complications (sequelae) of snakebite 104
5.5 Symptoms and signs of seasnake envenoming 103
5.6 Symptoms and signs of cobra-spit ophthalmia 104
(eye injuries from spitting cobras)
8 Annexes 185
Annex 1 Algorithm 1: Antivenom treatment of snakebite cases 187
Annex 2 Algorithm 2: Differentiating major Asian snake species by clinical syndrome 188
Annex 3 Antivenoms for treating bites by South-East Asian snakes 191
Annex 4 Pressure-immobilization and pressure pad 195
Annex 5 Measurement of central venous pressure 197
Annex 6 Measurement of intracompartmental pressure 198
Annex 7 List of Contributors 199
CONTENTS 5
Foreword
S
nakebites are well known medical emergencies and a
cause of hospital admission in many countries. The true
scale of this problem however is unknown because of
inadequate reporting in almost every part of the world. The
South-East Asia Region is one of the world’s most affected
regions, due to its high population density, widespread
agriculture activities, presence of numerous venomous snakes
and lack of necessary community awareness to address the
problem.
The WHO Regional Office for South-East Asia had developed and published Guidelines for
the Management of Snakebites as a special issue of the South East Asian Journal of
Tropical Medicine and Public Health in 1999 followed by publication of the guidelines as
independent regional document in 2011. Considering the new technical advances in the
field, the guidelines have been revised with the help of regional and global experts. The
geographical area specifically covered by this publication includes the South-East Asia
Region of WHO. The venomous snake fauna of the South East Asia Region is rich and
diverse. It varies within and between countries. Countries such as Malaysia, Singapore,
Cambodia, Lao People’s Democratic Republic, Republic of Korea, Philippines, Pakistan
and Afghanistan may share many of the same medically-important species of snakes that
occur in the South-East Asia Region and may find these guidelines useful. This publication
aims to pass on a digest of available knowledge about all clinical aspects of snake-bite to
medically trained personnel.
I am confident that these revised guidelines will help Member States to improve the
management of snakebites in the peripheral health services and thereby reduce the
morbidity and mortality due to snakebites.
FOREWORD 7
Acknowledgements
Prof David Warrell, Emeritus Professor of Tropical Medicine, University of Oxford, UK,
wrote the draft of the guidelines. These were finalized through a meeting of experts
held at SEARO, New Delhi, in June 2016 and revised by Dr Warrell. The list of experts
who contributed can be seen at Annex 7. Contributions of all the experts and people
who helped in the production of this document are sincerely acknowledged.
Target readership
This publication aims to pass on a digest of available knowledge about all clinical aspects
of snakebites to medically trained personnel. The guidelines are intended for medical
doctors, nurses, paramedics, dispensers and community health workers who have the
responsibility of treating victims of snakebites, and also for medical and nursing students
and postgraduates as an educational resource. They aim to provide sufficient practical
information to allow medically trained personnel to assess and treat patients with
snakebites at all the different levels of the health service.
Levels of evidence
Recommendations are based largely on observational studies (“O” see below), expert
opinion (“E”) and, in some cases, comparative trials (“T”), but in only one case on formal
systematic reviews (“S”).
Symbols for the evidence used as the basis of each recommendation (in order of level
of evidence) are:
S formal systematic reviews, such as Cochrane Reviews of which there is only one in
the field of snakebites. These include more than one randomized controlled trial;
T comparative trials without formal systematic review;
O observational studies (e.g. surveillance or pharmacological data);
E expert opinion/consensus.
PREFACE 9
10 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
EXECUTIVE SUMMARY
EXECUTIVE SUMMARY 13
medical care at the hospital or dispensary.
Recommended first-aid methods
Most of the familiar methods for first-aid
emphasise reassurance, application of
treatment of snakebite, both western and a pressure-pad over the bite wound,
“traditional/herbal”, have been found immobilization of the bitten limb and
transport of the patient to a place where
to result in more harm (risk) than good they can receive medical care without
(benefit) and should be firmly discouraged. delay (O).
EXECUTIVE SUMMARY 15
16 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Prevention
PREVENTION 19
walking to and from the fields before (e.g. in the Sundarbans). Ideally, avoid
dawn and after dusk. Snakes prefer not to sleeping unprotected on the ground, but
confront large animals such as humans, if you do choose, or are forced, to sleep
and so avoid cornering them and give on the ground, or are able to sleep on a
them every opportunity to escape. raised bed, use an insecticide-impregnated
mosquito net that is well tucked-in under
Inside the house, where snakes may the mattress or sleeping mat. This will
enter in search of food or to find hiding protect against mosquitoes and other
places, do not keep livestock, especially biting insects, centipedes, scorpions, and
chickens, as they are potential prey snakes (Chappuis et al., 2007). (Fig 001)
for larger snakes and they may attract No chemical has yet been discovered that
rodents upon which many species of is effectively repellent to snakes without
snakes will prey. Store food in rodent- being so toxic as to threaten the life of
proof containers. Regularly check houses children and domestic animals.
for snakes and, if possible, avoid types
of house construction that will provide In the farm yard, compound, or
snakes with hiding places (e.g. thatched garden: Try not to provide hiding places
roofs with open eaves, mud and straw for snakes. Clear away termite mounds,
walls with large cracks and cavities, large heaps of rubbish, building materials etc.
unsealed spaces beneath floorboards). In from near the house. Do not have tree
South Asia, almost all krait (Bungarus) branches touching the house. Keep grass
bites are inflicted on people sleeping short or clear the ground around your
in their homes, usually on the floor but house and clear underneath low bushes
sometimes even in beds and under pillows so that snakes cannot hide close to the
PREVENTION 21
and on lines. The head and tail are not 2.2 Implementing preventive
easily distinguishable. Sea snakes are air- strategies for community
breathing and are therefore drowned if education
caught in drift or trawl nets, but, unlike Community education has been proved
fish, may survive if laid on the beach. to be an effective strategy for preventing
There is a risk of bites to bathers and snakebites. In the Terai region of Nepal,
those washing clothes in the muddy a group of villages was targeted for
waters of estuaries, river mouths and snakebite awareness sessions, involving
some coastlines. political leaders, female health volunteers,
community health workers, social workers,
General: Avoid snakes as far as possible, traditional healers and other villagers.
including those displayed by snake Many leaflets, banners and posters
charmers, who are frequently bitten. were distributed. As a result, snakebite
Displays by performers such as Austin incidence decreased from 502 bites to
Stevens and the late Steve Irwin on TV 315 bites/100 000 population in targeted
and social media have encouraged people villages (relative risk reduction 0.373
to risk pursuing, attacking and handling (95% CI = 0.245–0.48) but it remained
wild snakes. This should be actively constant in the control untargeted
discouraged. Never handle, threaten or villages (Sharma et al., 2013). A similar
attack a snake and never intentionally scheme in West Bengal, India involved
trap or corner a snake in an enclosed the training of 800 health workers (Vishal
space. In many parts of the Region there Santra, Simultala Conservationists). Such
are dedicated snake catchers who will programmes should be repeated every
remove snakes found in houses and year, using well-designed posters with
gardens. For example, in New Delhi, colour photographs of the medically
“if you find a snake hissing inside your significant snakes of the Region combined
house, just don’t panic or cause it any with clear recommendations for
harm. All you need to do is dial a helpline preventing snakebite. In Indonesia, since
(9871963535) and dedicated snake 2013, medical staff have collaborated
trappers will be at your doorstep to help regularly with herpetologists in learning
you” Wildlife SOS (WSOS). Keep young about snake identification and snakebite
children away from areas known to be management, while in West Papua, church
snake-infested. In occupations that carry a and other religious organizations have an
high risk of snakebite, such as rice farming important role in education campaigns
and fish farming, employers might be on snakebite. Designers of Information,
held responsible for providing protective Education and Communication (IEC)
clothing (boots). In Myanmar, farmers activities for preventing snakebites,
can take out special low-cost insurance to should bear in mind local infrastructure,
cover them specifically against snakebite, demography and topography. An example
and India’s National Health Assurance is given in Figure 01 from Duncan
Mission envisages free treatment for Hospital, Raxaul, Bihar, India (Longkumer
snakebite. et al., 2016).
Figure 01: Community Education: recommendations for health-care workers and community education from
Duncan Hospital, Raxaul, Bihar, India (see Longkumer et al., 2016)
PREVENTION 23
Religious organizations and charities
such as Rotary and Lions Clubs might
Raising community awareness about
be persuaded to promote snakebite
prevention of snakebites is the most awareness. It is especially valuable to win
effective strategy for reducing snakebite the support of high profile media figures
such as sporting heroes, film stars,
morbidity and mortality. pop stars and politicians. Education
departments should incorporate
appropriate first-aid for snakebite in
school textbooks.
The above recommendations for
preventing snakebite could be reformatted 2.3 Conclusion
for national or local use as guidelines, Raising community awareness about
training modules, leaflets, video clips and prevention of snakebites is the most
posters (Fig 001) that can be displayed effective strategy for reducing snakebite
on the walls of hospital and clinic waiting morbidity and mortality. The current
areas for the attention of patients and burden of snakebite morbidity can also
their families. At the village level, role- be mitigated by providing region-specific
playing, drama and puppets have been guidelines and training protocols for
used successfully to portray snakebite effective case management. Support
scenarios. Media such as radio and TV materials for health-care providers at
can be used for health promotion and all levels of the health service could
advantage can be taken of FM radio help to disseminate appropriate
phone-ins to publicise the problem. scientific knowledge about snakebite
Increasingly, young people and advertisers management. Ensuring an efficient
use social networking (YouTube, Twitter) supply-chain for antivenom and other
to communicate information and mobile supplies can reduce preventable deaths
phone messaging might also be employed. from snakebite.
3.2 Classification of
venomous snakes
3.2.1 Medically important species in
South-East Asia Region countries
(Gopalakrishnakone and Chou 1990;
Williams et al., 2009; WHO 2010)
Elapidae: have relatively short fixed scales (Fig 3). Some, notably cobras,
front (proteroglyph) fangs (Fig 2a). raise the front part of their body off the
This family includes cobras, king cobra, ground and spread and flatten the neck to
kraits, coral snakes, Australasian snakes form a hood (Figs 4-9). Several species of
and sea snakes. Elapidae are relatively cobra can spit their venom for one metre
long, thin, uniformly-coloured snakes or more towards the eyes of perceived
with large smooth symmetrical scales enemies. Venomous sea snakes have
(plates) on the top (dorsum) of the head flattened paddle-like tails and their ventral
(Fig 3 and Fig 9). There is no loreal (belly) scales are greatly reduced in size or
scale between the pre-ocular and nasal lost (Figs 20-24).
[c]
Figures 4: Common spectacled cobra (Naja naja): (a) Sri Lanka;
(b) Pune; (c) Kolkata; (d) Bardia, Nepal (a-c Copyright DA Warrell; [d]
d Copyright Mark O’Shea)
[b] [d]
[c]
Figures 6: Monocellate cobra (Naja kaouthia): (a) Thailand nuchal pattern; (b) Thailand; (c) West Bengal (Fig a-c: Copyright DA Warrell);
(d) Andamans cobra (Naja sagittifera) juvenile specimen (Fig d: Copyright Ashok Captain)
[c]
Figures 7: Indo-Chinese spitting cobra (Naja siamensis)
Thailand: (a) Black and white specimen with ill-defined
spectacle marking on hood; (b, c) Brown-coloured
specimen showing spectacle marking on hood
(Copyright DA Warrell)
[b]
[a]
[b]
[d]
[c] [e]
Figures 9: King cobra or hamadryad (Ophiophagus hannah) (Copyright DA Warrell)
(a) The famous king cobra dance in Yangon, Myanmar; (b) Specimen from Trang, southern Thailand more than
3.5 metres in total length; (c, d) Dorsal and lateral views of head of Thai specimens showing the two large
occipital scales which distinguish this species from cobras (Naja); (e) Pune, India (Copyright DA Warrell)
[a]
[a] [b]
[b]
[c]
Figures 12: Ceylon krait (Bungarus ceylonicus): (a) showing incomplete white bands (spots); (b) head;
(c) showing white bands and dark ventral scales. Perideniya, Sri Lanka (Copyright DA Warrell)
[a]
Figures 17: Sind krait (Bungarus sindanus): (a) specimen from Bikaner
(Copyright Rom Whitaker); (b) head of specimen from Maharashtra, India
(Copyright DA Warrell)
[b]
[a] [b]
Figures 19: Death adders (Acanthophis rugosus): (a) Specimen from West Irian, Indonesia; (b) Specimen from Seram, Indonesia
Figure 20: Papuan taipan (Oxuyuranus scutellatus) SaiBai Island, Torres Strait Islands (Copyright DA Warrell)
Figure 22: Eastern brown snake (Pseudechis textilis) Australia Figure 23: Beaked sea snake (Enhydrina schistose or
(Copyright DA Warrell) Hydrophis schistosus) Bunapas Mission, Ramu River,
Papua New Guinea (Copyright DA Warrell)
Figure 24a:
Blue spotted sea
snake (Hydrophis
cyanocinctus)
Thailand
(Copyright DA
Warrell)
[a] [b]
Figures 27: Sea krait (Laticauda colubrina) Madang, Papua New Guinea: (a) Showing blue and banded pattern
and amphibious behaviour; (b) Showing fangs (Copyright DA Warrell)
Figure 28: Head of a typical pit viper - dark green pit viper (Trimeresurus T. macrops) showing the pit organ
situated between the nostril and the eye (red arrow) (Copyright DA Warrell)
[c]
[d] [e]
Figures 29: Western Russell’s viper (Daboia russelii): (a) Specimen from Sri Lanka; (b, c) Specimens from Tamil Nadu,
southern India; (d, e) specimens from Pune, India (Copyright DA Warrell)
[a] [b]
[a] [b]
Figures 33: Malayan pit viper (Calloselasma rhodostoma) Thai specimens: (a) Showing characteristic posture and triangular
dorsal markings; (b) Showing supralabial markings (Copyright DA Warrell)
Figure 34: Mount Kinabalu pit viper (Garthia Figure 35: Mamushi or Fu-she (Gloydius
chaseni) (Copyright Prof RS Thorpe) brevicaudus) from China (Copyright DA Warrell)
[c] [d]
Figures 36 a-d: Hump-nosed viper (Hynpale hypnale) (Copyright DA Warrell)
a) Specimen from Sri Lanka; (b) Specimen from Sri Lanka showing long fangs; (c) Specimen from south western India;
(d) Specimen from south western India showing upturned snout
Figure 37:
Chinese habu
(Protobothrops
mucrosquamatus)
Specimen from
China (Copyright
DA Warrell)
[a]
Figure 40: Palm viper (Trimeresurus Craspedocephalus puniceus) Specimen from Cilacap, West Java, Indonesia
(Copyright DA Warrell)
Figure 43: Pope’s pit viper (Trimeresurus Popeia popeiorum) Thailand (Copyright DA Warrell)
[a] [b]
Figures 45 a,b: White-lipped green pit viper (Cryptelytrops albolabris) Thai specimen: (a) Showing colouring and distinctive
brown-topped tail; (b) Showing details of the head: note smooth temporal scales (Copyright DA Warrell)
[b]
Figure 46: Dark green pit viper (Trimeresurus T. macrops) Figures 47 a, b: Spot-tailed green pit viper (Cryptelytrops erythrurus) Specimen
Thai specimen (Copyright DA Warrell) from near Yangon, Myanmar: (a) Showing colouring and brown spotted tail;
(b) Showing details of head; note keeled temporal scales (Copyright DA Warrell)
Figure 48: White-lipped island viper (Trimeresurus T. insularis) specimen from Tutuala Sub-district Lautem District Timor-Leste
(Copyright Mark O'Shea)
Figure 51b:
Banded temple viper
(Tropidolaemus
semiannulatus) Borneo
Figure 52b: Yamakagashi (Rhabdophis tigrinus) (Copyright S Mishima The Snake 1974 6-1 Courtesy of Dr Y Sawai)
Figure 52j: Chequered keelback (Xenochrophis piscator) Figure 52m: Bridle snake (Dryocalamus davisoni)
brought by bite victim Chittagong Bangladesh (Copyright DA Warrell)
Figure 52o: Reticulated python (Python reticularis) containing the body of a farmer it had swallowed at Palu,
Sulawesi, Indonesia (Copyright Excel Sawuwu)
Epidemiology of snakebite
in South-East Asia Region countries
73
74 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Epidemiology of snakebite in
4
South-East Asia Region countries
Essentials: venomous snake cause no envenoming
Most published data, based on hospital (“dry bites”), a figure ranging 5-80% with
returns, are incomplete because many different species.
patients are treated by traditional healers.
However, three large, well-designed, national, Snakebite epidemics follow flooding,
community-based studies from Bangladesh, cyclones and invasion of snakes’ habitats
India and Sri Lanka have produced reliable for road building, irrigation schemes
estimates. Data are inadequately reported and logging. These activities cause long
and so snakebite should be made a notifiable term changes in climate and ecology and
disease in all South-East Asia Region encourage influx of human settlers.
countries. Death certification should use
International Classification of Diseases code Males are more often bitten than females.
T63.0 (Toxic effect of contact with venomous Peak incidence is in children and young
animals – snake venom and sea-snake adults. Pregnant women and their fetuses
venom) (ICD-10 Version:2015 http://apps. are at increased risk of dying. Snakebite
who.int/classifications/icd10/browse/2015/ is an occupational disease of farmers,
en#/T63.0) plantation workers, herders, hunters,
fishermen, fish farmers, snake restaurant
Incidence of snakebite varies diurnally and workers and snake charmers. Factors
seasonally. It is highest during agricultural contributing to fatal snakebite include
activities and seasonal rains. Most bites problems with choice and dosage of
are inflicted on the feet and ankles of antivenom, delay from visiting traditional
bare-footed agricultural workers who healers, transportation difficulties,
tread on snakes inadvertently while death in transit, airway obstruction,
walking in the dark or working in fields failure to attempt assisted ventilation or
and plantations. Snake species differ in problems in carrying it out, failure to treat
their inclination to strike when disturbed. hypovolaemia, complicating infections,
Notoriously “irritable” species include failure to observe deterioration in hospital.
Russell’s and saw-scaled vipers. Cobras and Hours usually elapse between bite and
kraits enter human dwellings. Kraits bite neurotoxic deaths from elapid envenoming
people who are asleep on the ground at and several days or longer, from viper
night. On average, about 50% of bites by envenoming.
Epidemiology of snakebite
in South-East Asia Region countries
75
Snakebite in different South-East Asia Direct estimate of deaths attributable to
Region countries snakebite in 2005 was 46 000 (99%CI 41
Bangladesh: medically important species 000-51 000), (1 snakebite death for every
include B. caeruleus, B. niger, B. walli; 2 HIV/AIDS deaths). Snakebites caused
N. kaouthia, N. naja; D. russelii and T. (T.) 0.5% of all deaths, 3% in 5-14 year-olds.
erythrurus. 97% died in rural areas, only 23% in health
facilities. The highest numbers of deaths
In 2009, 9000 people were questioned in were in Uttar Pradesh (8,700), Andhra
about 4000 randomly selected households Pradesh (5,200), and Bihar (4,500).
throughout all 6 administrative divisions.
589,919 snakebites and 6,041 deaths per Indonesia: medically important species
year were estimated in rural areas (case- throughout the >18 000 islands include
fatality 1%). B. candidus, N. sputatrix, N. sumatrana,
C. rhodostoma , T. (T.) albolabris; D.
Green pit vipers cause many bites, some siamensis and, in West Papua and Maluku,
morbidity but few deaths. D. russelii Acanthophis laevis. Hundreds of bites each
is restricted to western and southern year are treated in Sumatra, Java, East
areas. B. niger, previously unknown Kalimantan, Sulawesi, Wetar and West
in Bangladesh, has caused deaths. N. Papua.
kaouthia causes most cobra bites.
Maldives: there is one species of sea
Bhutan: medically-important species snake but no terrestrial venomous snake.
include cobras, kraits and pit-vipers. No No recent data on bites.
recent data on bites.
Myanmar: medically important
Democratic People’s Republic of species include B. magnimaculatus,
Korea: medically-important species B. multicinctus; N. kaouthia, N.
include adders (Vipera berus and V. mandalayensis; Trimeresurus (T.) albolabris,
sachalinensis), several species of mamushi T. (T.) erythrurus; D. siamensis
(genus Gloydius) and Rhabdophis tigrinus. In 2014, 15,080 bites with 305 deaths
No recent data on bites. were reported to the Ministry of Health
(case-fatality 2.02%). D. siamensis causes
India: medically important species include 90% of bites.
N. naja, N. kaouthia; B. caeruleus; D.
russelii, E. carinatus; Hypnale hypnale, Nepal: medically important species
Trimeresurus. Registrar General of India’s include B. caeruleus, B. niger, B. walli; N.
“Million Death Study” assigned causes of naja, N. kaouthia; D. russelii and Ovophis
all deaths in about 7000 randomly chosen monticola. In the Eastern Terai, there were
sample areas, each with a population 162 snakebite deaths/100 000/year. Only
of about 1000 throughout the whole 20% of deaths occurred in hospitals. Most
country. Verbal autopsy (questioning were attributed to krait. National totals of
bereaved relatives and neighbours about between 1000 bites and 200 deaths and
the circumstances of the deceased’s 20 000 bites and 1000 deaths/year have
death), proved reliable for an event as been suggested. In 2000, the Ministry of
distinctive, dramatic and memorable Health reported 480 bites with 22 deaths,
as snakebite fatality. Results were while 4,078 bites with 81 deaths were
independent of hospital underreporting recorded at 10 hospitals in eastern Nepal
and were nationally representative. (case-fatality 3-58%).
Epidemiology of snakebite
in South-East Asia Region countries
77
snakebite envenomings, and 100 000 The continuing inadequacies in the
snakebite deaths each year in Asia. reporting of snakebite incidence, morbidity
and mortality, prompts the following
In 2008 Kasturiratne et al estimated 237 recommendation.
379–1 184 550 envenomings with
15 385 - 57 636 deaths in the Asia-
Pacific region (South 14 112-33 666 Recommendation: To
– rate 0.912- 2.175/100 000/year; East remedy the deficiency in
462-4 829 – rate 0.033- 0.347/100 000/ reliable snakebite data, it is
year). Their most conservative estimate strongly recommended that
of the highest number of deaths due to snakebites should be made
snake bite was 14 000 in South Asia. a specific notifiable disease
Various studies suggest that bites with in all countries in the South-
envenoming constitute 12-50% of the East Asia Region and that
total number of bites in Asia and 18-30% death certification should
in India and Pakistan. use the specific International
Classification of Diseases code
A fundamental problem throughout T63.0 (Toxic effect of contact
much of the Region is that snakebite with venomous animals – snake
treatment has remained in the domain venom and sea-snake venom)
of traditional, herbal or ayurvedic (ICD-10 Version:2015 http://
practitioners, so that the majority of apps.who.int/classifications/
snakebite victims are not seen or recorded icd10/browse/2015/en#/T63.0 (E)
in western-style hospitals or dispensaries. (T63.0) Snake venom
For example, in Wat Promlok, Nakorn
Srithamarat, Thailand, one “moor glang
baan” (traditional therapist) treated 72-
393 snakebite victims each year between 4.2 Determinants of
1985 and 2002. snakebite incidence and
severity of envenoming
In the Terai of Nepal, a community-based The incidence of snakebites depends
study established the high fatality rate of critically on the frequency of contact
161/100 000/year, attributable mainly to between snakes and humans. Except at
krait bites (Sharma et al., 2004). Few other times of flooding, snakes are elusive and
community studies have been attempted reclusive and so contact with humans is
(Hati et al 1992). In some countries, such likely only when humans move into the
as Sri Lanka, there has, over the last two snakes’ favoured habitat (rice fields in
decades, been a dramatic shift in patients’ the case of Russell’s vipers and cobras;
preference for treatment from ayurvedic to rubber and coffee plantations in the case
western medicine. of Malayan pit vipers) or when nocturnally
active snakes are trodden upon by people
The true scale of mortality from snakebite walking along paths in the dark. Seasonal
is just beginning to be revealed, thanks to peaks of snakebite incidence are usually
three large, well-designed, community- associated with increases in agricultural
based studies that have recently been activity or seasonal rains, perhaps
published from India (Mohapatra et al., coinciding with unusual movements and
2011), Bangladesh (Rahman et al., 2010) activity by the snakes. Different species
and Sri Lanka (Ediriweera et al, 2016). of snake vary in their willingness to strike
Epidemiology of snakebite
in South-East Asia Region countries
79
(Calloselasma rhodostoma) and cobras
(Naja species) (Looareesuwan et al., 1988).
Inadequacies in ambulance transport
Factors identified as contributing to a
from rural locations to properly fatal outcome included problems with
equipped hospitals is an important antivenom use (inadequate dose or use
of a monospecific antivenom for a bite
cause of death. by a different species), delayed hospital
treatment resulting from prolonged visits
to traditional healers and problems with
catching and handling snakes for food transportation, death on the way to
(in snake restaurants), displaying and hospital, inadequate artificial ventilation or
performing with snakes (snake charmers), failure to attempt such treatment, failure
manufacturing leather (especially sea to treat hypovolaemia in shocked patients,
snakes), and in the preparation of airway obstruction, complicating infections,
traditional (Chinese) medicines. and failure to observe patients closely
after they had been admitted to hospital.
Inadequacies in ambulance transport
Snakebite: from rural locations to properly equipped
an occupational disease in hospitals is an important cause of death
South-East Asia (Gimkala et al., 2016). In India, the
majority of deaths occur outside a hospital
• Farmers (rice, etc.,)
facility (Mohapatra et al. 2011). Peripheral
• Plantation workers (rubber, hospitals often have inadequate medical
coffee, cacao, oil palm etc.) and nursing staffing. It is very important
• Herdsmen that relatives be effectively deployed to
monitor snakebite victims, particularly
• Hunters
those with neurotoxic envenoming, to
• Snake handlers (snake charmers detect progression of weakness and early
and in snake restaurants and signs of respiratory paralysis.
traditional Chinese
• pharmacies) 4.6.2 Time between snakebite
and death
• Fishermen and fish farmers
Although very rapid death after snakebite
• Sea-snake catchers (for sea-snake has, rarely, been reported (e.g. reputedly
skins, leather) “a few minutes” after a bite by the king
cobra Ophiophagus hannah), it is clear
from studies of large series of snakebite
deaths that many hours usually elapse
4.6 Death from snakebite between bite and death in the case of
4.6.1 Factors contributing to fatal elapid envenoming, and several days,
snakebite or even longer, in the case of viper
Few attempts have been made to examine envenoming (Reid 1968; Warrell 1995).
the factors responsible for death in cases
of bites by identified species of snakes. 4.7 Snakebite in different
In a study of 46 cases of identified South-East Asia Region
snakebite in Thailand, the three species countries
causing most deaths were Malayan krait For each South-East Asia Region country,
(Bungarus candidus), Malayan pit viper some information about the estimated
Epidemiology of snakebite
in South-East Asia Region countries
81
than for a non-venomous snakebite.
Cat 1: Elapidae: Bungarus
Treatment imposes a major economic
caeruleus, Bungarus niger,
burden on affected families, especially
Bungarus walli; Naja kaouthia;
in venomous snakebite cases (Hasan et
Viperidae: Daboia russelii,
al., 2012).
Trimeresurus (T.) erythrurus
Epidemiology of snakebite
in South-East Asia Region countries
83
antivenom treatment. There is variation (Trimeresurus) albolabris, Bungarus
in the pattern of syndromes across India, candidus (Kuch and Mebs 2007), spitting
with predominance of haemotoxic viper cobras (Naja sumatrana and N. sputatrix),
bites in south India and neurotoxic elapid Calloselasma rhodostoma (Java, Madura),
bites in north India. Syndrome-species Daboia siamensis (East Java, Komodo,
correlation studies in Tamil Nadu suggest Flores and Lomblen) and death adders
the validity of the main syndromes in (Acanthophis spp.)(West Irian). The
identifying the four main venomous snakes national antivenom producer BioFarma
in this geographical region: haemotoxicity manufactures a trivalent antivenom
without acute kidney injury (Echis against Naja sputatrix, Bungarus fasciatus
carinatus); haemotoxicity and neurotoxicity and Calloselasma rhodostoma. No
with or without renal failure (Daboia cases of B. fasciatus bites are known
russelii); neurotoxicity with local swelling but deaths from B. candidus (Java), D.
(Naja naja); and neurotoxicity without local siamensis (Java, Flores, Komodo) and
swelling (Bungarus caeruleus). Acanthophis (West Irian) have been
reported.
Epidemiology of snakebite
in South-East Asia Region countries
85
fasciatus; Bungarus lividus;
According to the Epidemiology Unit, Ministry
Bungarus walli; Ophiophagus
of Health, reported snakebite numbers hannah; Hemibungarus
increased from 12 175 per year in 1991 to (Sinomicrurus) macclellandii
Viperidae: Trimeresurus (T.)
peak at 37 244 in 2002 and 36 861 in 2005. septentrionalis; Cryptelytrops
Trimeresurus (T.) albolabris;
Trimeresurus (T.) erythrurus;
recorded focal incidence, for Nepal or Trimeresurus (Crapedocephalus)
for the whole world, was 162 snakebite gramineus; Gloydius himalayanus;
deaths/100 000/year, determined in the Ovophis monticola; Himalayophis
Eastern Terai (Sharma et al., 2004). In this tibetanus; Protobothrops jerdonii;
study, only 20% of the deaths occurred Trimeresurus (Viridovipera)
in hospitals. Increased risk of fatality was stejnegeri; Trimeresurus
associated with being bitten inside the (Viridovipera) yunnanensis
house while resting between 2400 and
0060 hr, suggesting bites by the common
krait (Bungarus caeruleus) (see below). Sri Lanka: According to the
Other risk factors were an initial visit to a Epidemiology Unit, Ministry of Health,
traditional healer and delayed transport reported snakebite numbers increased
to hospital. Medically important species from 12 175 per year in 1991 to peak
include Naja naja, Bungarus caeruleus, B. at 37 244 in 2002 and 36 861 in 2005.
walli and Daboia russelii. In the Kathmandu Fatalities peaked at 194 in 2000 and
valley and foothills of the Himalaya, there were 134 in 2005. There are
Ovophis monticola and Trimeresurus pit- currently 30 000 – 35 000 bites and
vipers cause some bites. Russell’s viper (D. 100-150 deaths each year. In hospitals,
russelii) causes bites in a few parts of the case fatality decreased from 3.5% in
Terai (e.g. Nawalparasi). In the country 1985 to 0.2% in 2006. However, these
as a whole, 1000 bites and 200 deaths data are based on hospital returns which
have been estimated but one survey are likely to miss at least 5% of deaths.
suggested 20 000 bites and 1000 deaths/ Comparison of hospital data with death
year (Bhetwal et al., 1998). In 2000, the certifications in Monaragala District
Ministry of Health reported 480 bites with during a 5-year period (1999-2003)
22 deaths, while 4078 bites with 81 deaths revealed a 63% underestimate by hospital
were recorded at 10 hospitals in eastern records of the true number of snakebite
Nepal. The case-fatality varied from 3 to deaths (Fox et al., 2006), partly explained
58% in different hospitals (Sharma, 2003). by the fact that 36% of snakebite
victims did not seek or achieve hospital
treatment. In Kandy district, snakebite
Cat 1: Elapidae: Bungarus fatality based on death certification
caeruleus, Bungarus niger; was 2/100 000/year during the period
Naja naja; Naja kaouthia 1967-1987, amounting to about 0.5%
Viperidae: Daboia russelii of all deaths. Bites are caused by Daboia
russelii, (30%), hump-nosed viper
Cat 2: Elapidae: Elapidae: (Hypnale hypnale) (22%), Naja naja (17%)
Bungarus bungaroides, Bungarus and kraits (mainly Bungarus caeruleus but
a few B. ceylonicus ) (15%).
Epidemiology of snakebite
in South-East Asia Region countries
87
88 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Clinical effects of snakebite
[a] [b]
[c] [d]
[e] [f]
Figures 53: Animal bite marks: (a) venomous European adder (Vipera berus); (b) venomous Western Russell’s viper (Daboia russelii) (fatal
case); (c) non-venomous back-fanged rice paddy or plumbeous water snake (Enhydris plumbea); (d) rat; (e) Brazilian wandering spider
(Phoneutria nigriventer); (f) catfish (Siluridae) (Copyright DA Warrell)
[a] [b]
[a]
Cardiovascular (Viperidae)
Visual disturbances, dizziness, faintness,
collapse, shock, hypotension, cardiac
arrhythmias, myocardial damage (reduced
ejection fraction).
[A]
[b]
Figures 60: Spontaneous systemic bleeding: (a) from gingival sulci in a patient
[a] bitten by a Malayan pit viper; (b) neck stiffness (meningism) from sub-arachnoid
haemorrhage after a saw-scaled viper bite (Copyright DA Warrell)
Figure 62: Haemoptysis from a Figure 63: Subconjunctival haemorrhages in a patient bitten by a Burmese Russell’s viper
tuberculous lung cavity in a patient (Copyright DA Warrell)
bitten by a Malayan pit viper
(Copyright DA Warrell)
[a] [b]
Figures 65a,b: Bilateral ptosis: (a) in a patient bitten by a common krait in Sri Lanka; (b) in a patient bitten by a
Russell’s viper in Sri Lankan (Copyright DA Warrell)
Figure 67: Patient bitten by a Russell’s viper in Sri Lanka. She began to pass dark brown urine containing myoglobin and haemoglobin 8
hours after the bite. (Copyright DA Warrell)
Figures 68: Haemorrhagic infarction of the anterior pituitary resulting in Sheehan’s-like syndrome (pan-hypopituitarism) after Russell’s
viper bite in Myanmar: (a) appearances at the base of the brain at autopsy in a patient who died acutely after the bite (Copyright Dr U
Hla Mon); (b) Patient presenting with symptoms and signs of panhypopituitarism three years after severe envenoming by Russell’s viper.
There is loss of secondary sexual hair and testicular atrophy (Copyright DA Warrell)
[a] [b]
Figures 70: Chronic physical handicap resulting from necrotic envenoming by Malayan pit vipers: (a) Deformity and dysfunction
after a snakebite and subsequent necrosis of the calf; (b) Squamous cell carcinoma arising at the site of a chronic skin ulcer with
osteomyelitis 8 years after the bite (Copyright DA Warrell)
[a] [b]
Figures 71: Sea-snake bite in North-west Malaysia: (a) Ptosis, facial paralysis and trismus; (b) Generalised myalgia making
passive movement of the limbs extremely painful; (c) myoglobinuria (Copyright the late H Alistair Reid)
Figure 72: Bilateral conjunctivitis in a patient who had venom spat into both eyes by an Indo-Chinese spitting cobra
(Naja siamensis) (Copyright DA Warrell)
ManageMent of snakebites
in south-east asia
105
106 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Management of snakebites
6
in South-East Asia
Essentials: asphyxiated patients. Clear airway, give
First-aid should be carried out immediately oxygen, establish intravenous access,
after the bite, by the victim or others monitor vital signs. Beware of removing
present. Most traditional methods are tight tourniquets before antivenom and
useless and harmful. To prevent deaths resuscitation facilities are available.
from respiratory paralysis or shock before
victims reach medical care, delay venom Key questions: “Where (in which part of
spread with pressure-pad or pressure- your body) were you bitten? Point to the
bandage plus immobilization, accelerate place”; “When were you bitten and what
transport to hospital (improve ambulance were you doing then?”; “Where is the
services), and train accompanying medical snake that bit you?” or “What did it look
workers in airway management, assisted like; did anyone take a picture?”; “How
ventilation and resuscitation. The snake are you feeling now?”
is valuable evidence, but should not be
pursued, killed or handled. Close-up Examination of the bitten part: extent
mobile ‘phone images ’ are useful. of tenderness/swelling, lymph nodes
draining bitten limb, early signs of
Recommended first-aid: reassurance, necrosis (blistering, demarcated altered
immobilization of the whole patient, pigmentation, putrefaction odour.
especially their bitten limb, accelerated General: blood pressure (postural drop
transport to medical care (summoned by indicates hypovolaemia), gingival sulci,
emergency telephone helpline) ideally in nose, skin and mucosae for evidence
recovery position. Unless neurotoxic elapid of bleeding, chemosis, abdominal
bite can be excluded, apply pressure-pad tenderness, loin pain and tenderness,
(simpler, more practicable than pressure- meningism, lateralising neurological
bandage immobilization). Never use, signs (asymmetrical pupils), impaired
recommend or condone tight (arterial) consciousness, bilateral ptosis, diplopia,
tourniquets. external ophthalmoplegia, mouth opening/
closing, trismus, tongue protrusion, facial
Medical treatment in dispensary or hospital muscles, gag reflex neck flexors “broken
Rapid clinical assessment accompanies neck sign”, swallowing, “paradoxical
urgent resuscitation of shocked or respiration”, fasciculations or myokymia,
ManageMent of snakebites
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107
measure ventilatory capacity. If adequately measuring INR and D-dimer unreliable in
ventilated, totally paralysed patient are snakebite victims.
fully conscious and can communicate by
flexing a digit. Conventional tests of brain Other laboratory tests: haemoglobin
death misleading. Generalised tender, concentration/haematocrit,
painful muscles and dark brown urine thrombocytopenia, neutrophil leucocytosis,
suggest rhabdomyolysis. Pregnant women: fragmented red cells (“helmet cell”,
suspect antepartum or postpartum schistocytes) signifying microangiopathic
haemorrhage, vaginal bleeding, premature haemolysis. Observe spontaneously
labour, fetal distress, intra-uterine fetal sedimented plasma for haemoglobinaemia/
death, abortion/stillbirth. myoglobinaemia.
ManageMent of snakebites
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or stimulation of mast cells/basophils by intramuscular injection of
antivenom proteins. 0.1% adrenaline, initial adult dose
0.5 ml/mg (0.01 mg/kg body weight for
Pyrogenic (endotoxin) reactions (within 1-2 children). Since severe, life-threatening
hours) involve rigors, fever (risk of febrile anaphylaxis can evolve rapidly, adrenaline
convulsions in children), vasodilatation, must be available at the bed-side
hypotension and a fall in blood pressure. and should be given at the first sign
Attributable to pyrogen contamination of anaphylaxis (e.g. when itching,
during manufacture. tachycardia, restlessness develop and a
few spots of urticaria appear). Repeat
Late (serum sickness-type) reactions (1-12, adrenaline every 5-10 minutes if reaction
mean 7, days after treatment) involve persists or worsens. Adrenaline safe in
fever, nausea, vomiting, diarrhoea, itching, pregnancy. In case of asthmatic symptoms,
recurrent urticaria, arthralgia, myalgia, given salbutamol bronchodilator. After
lymphadenopathy, periarticular swellings, adrenaline, give intravenous antihistamine
mononeuritis multiplex, proteinuria, anti-H1 blocker (e.g. chlorphenamine
immune complex nephritis, rarely maleate, adults 10 mg, children 0.2 mg/
encephalopathy. kg intravenously) and hydrocortisone
(adults 100 mg, children 2 mg/kg body
Prediction: skin and conjunctival weight). Anaphylactic shock unresponsive
“hypersensitivity” tests, often to adrenaline is treated by laying
recommended in “package inserts” patient supine, legs elevated, and giving
predict acquired IgE-mediated Type intravenous volume replacement (0.9%
I hypersensitivity to horse/sheep saline, adults 1-2 litres rapidly). Consider
proteins, but not large majority of early intravenous adrenaline infusion (adults
(anaphylactic) or late (serum sickness type) 1mg/1.0 ml of 0.1% solution in 250 ml
antivenom reactions. Their use is strongly IV fluid) infused at 15–60 drops/min
discouraged. using micro-dropper burette chamber, or
dopamine. Unresponsive bronchospasm
Prevention: or angioedema is treated with optimal
A powerful, well-designed study in Sri nebulised/inhaled and/or parenteral
Lanka showed that adrenaline (0.25 ml/ bronchodilator and oxygen.
mg of 0.1% solution subcutaneously)
given before antivenom was started Pyrogenic reactions are treated by
reduced severe reactions by 43% (95% physical cooling (undressing, tepid
CI 25–67) at 1 h and by 38% (95% CI sponging, fanning) and giving antipyretic
26–49) up to and including 48 h after paracetamol. Intravenous fluids should be
antivenom administration; hydrocortisone given to correct hypovolaemia. Patients
(200 mg intravenously) and promethazine with features of anaphylaxis should be
(25 mg intravenously) were ineffective. given adrenaline.
Hydrocortisone negated benefit of
adrenaline. Dilution and slow infusion After recovery from early reactions,
(10-120 minutes) does not alter risk of cautiously resume and complete
reactions. administration of the dose of antivenom.
At the earliest sign of early anaphylactic Late (serum sickness) reactions respond
antivenom reaction, temporarily suspend to 5-day course of oral antihistamine or,
antivenom administration and give failing that, 5-day course of prednisolone.
ManageMent of snakebites
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For acute airway obstruction (e.g.
angioedema) perform cricothyroidotomy.
if patient is unresponsive, summon
assistanceby ‘phone, open and maintain Resuscitation: if patient is unresponsive,
airway using “head tilt - chin lift” or “jaw summon assistanceby ‘phone, open and
maintain airway using “head tilt - chin lift”
thrust” manoeuvres to improve air flow or “jaw thrust” manoeuvres to improve air
by dislodging tongue and reopening flow by dislodging tongue and reopening
upper airway. Remove foreign material
upper airway. from upper airway (suction or forceps, not
finger) and insert oropharyngeal (Guedel)
airway. Administer oxygen by any available
conservatively. Respiratory paralysis: means and assess breathing. If breathing
try anticholinesterases, but without is adequate, lay victim in recovery position
delaying assisted ventilation. Haemostatic (important because of venom-induced
abnormalities: rest in bed to avoid trauma, vomiting, bleeding and hypersalivation
transfuse cryoprecipitate, fresh frozen with loss of airway-protective reflexes), but
plasma, fresh whole blood and platelets. check breathing every 2 minutes.
Shock, myocardial damage: correct
hypovolaemia and consider vasopressor If breathing is inadequate or not
drugs. In hypotension with bradycardia, try discernible, respiratory rate low,
atropine. Acute kidney injury: conservative respirations shallow, patient taking agonal
treatment or renal replacement therapy. (gasping) breaths, central cyanosis, finger
Rhabdomyolysis: correct hypovolaemia oximeter oxygen saturation <90%, end-
with intravenous fluid, acidosis with tidal PCO2 high or increasing - assisted
sodium bicarbonate. Severe local ventilation is required.
envenoming: surgical intervention,
prophylactic broad spectrum antimibiotics. Techniques:
If no health facilities are immediately
Supportive/ancillary treatment available - Expired Air Resuscitation
Neurotoxic envenoming
Indications for intubation: imminent In health care centre - Non-invasive
respiratory arrest (respiratory distress, ventilation using bag-mask/bag-mask-valve
breathing absent/inadequate); neck ventilation
muscle weakness with shallow respiration
or paradoxical breathing; secretions In hospital - Invasive Ventilation (intubation
pooling in pharynx with loss of gag/ and mechanical ventilation) for Type
cough reflexes; upper airway obstruction I respiratory failure (primary failure of
with stridor (secondary to anaphylaxis oxygenation as in pulmonary oedema
angioedema); oxygen saturation <90% in Russell’s viper envenoming) and Type
(equivalent to Pa02 <60 mmHg) despite II respiratory failure (primary ventilatory
high flow oxygen; respiratory acidosis failure due to respiratory muscle paralysis
(hypoxia PaO2 < 60 mm Hg with PaCO2 or obstruction as in elapid envenoming).
> 45 mm Hg)
Indications for invasive ventilation:
Insert cuffed endotracheal tube using patients who, despite receiving oxygen by
laryngoscope under sedation,or laryngeal mask or nasal catheters remain tachpnoeic
mask airway or i-gel supraglottic airway. (respiratory rate > 25/min), have
ManageMent of snakebites
in south-east asia
113
Renal replacement therapy/dialysis secondary infections involve aerobic and
Patient with clinical uraemia anaerobic bacteria from the snake’s oral
(encephalopathy, pericarditis etc.), fluid flora, patient’s skin and asterile incisions.
overload not responding to diuretics, Tetanus toxoid booster and prompt
hyperkalaemia or hyperkalaemic ECG antibiotic treatment of necrotic wounds is
changes, symptomatic acidosis, raised recommended.
plasma/serum creatinine and/or urea
should be transferred to a health facility Compartmental syndromes are often
where they can receive renal replacement misdiagnosed and fasciotomies performed
therapy. unnecessarily. Since classical signs of
compartment syndrome are difficult
In patients with AKI associated with to assess in snake-bitten limbs, direct
thrombotic microangiopathy, there is measurement of intracompartmental
no evidence for plasmapheresis using pressure is mandatory and fasciotomy
cryosupernatant. In patients with must not be attempted before
myoglobinuria or haemoglobinuria, haemostatic disturbances have been
correct hypovolaemia, maintain urine corrected by antivenom.
output 200-300 ml/hour, correct severe
acidosis with bicarbonate, promote Rehabilitation: conventional
alkalinise diuresis, continuing until CK physiotherapy accelerates functional
level <5000 U. recovery of the bitten limb, but is often
forgotten.
Diuretic phase of AKI: some patients
develop persistent polyuria of 5-10 Discharge assessment: discussion,
litres/24 hours and may become volume encouragement, follow-up, warning
and electrolyte depleted. about late serum sickness-type reactions
and advice about reducing risk of future
Chronic kidney disease: oliguria and snakebites are important.
dialysis-dependence for more than 4
weeks demands referral to nephrologist Management of cobra spit ophthalmia:
to consider kidney biopsy. first aid is irrigation of affected eyes and
other mucous membranes with liberal
Haemostatic disturbances: usually quantities of water; medical treatment
corrected by antivenom, but recurrent involves analgesia, exclusion of corneal
coagulopathy is possible. Exceptionally, in abrasions and application of prophylactic
patients already treated with antivenom topical antibiotics.
but who have persistent severe bleeding
or require urgent surgery, restoration Management of snakebites at different
of coagulability can be accelerated with levels of the health service: all levels
blood products. of the health service can contribute
to the management of patients with
Treatment of the bitten part: suspected snakebite. In rural areas, where
Nurse painful, swollen limb in the most snakebites are most common, transfer
comfortable position, avoiding excessively to a hospital may not be feasible, and
elevation. Leave blisters, aspirate so a lower level of health facility must
abscesses and culture pus. Necrotic tissue cope with these medical emergencies.
demands early surgical débridement Training of doctors, nurses, dispensers,
and split-skin grafting. Primary and health assistants and paramedics in
Management of snakebite
• First-aid treatment Aims of first aid
• Transport to hospital • reassure the snakebite victim
• Rapid clinical assessment and • attempt to delay systemic
resuscitation absorption of venom
• Detailed clinical assessment and • preserve life and prevent
species diagnosis complications before the patient
• Investigations/laboratory tests can receive medical care at a
• Antivenom treatment dispensary or hospital
• Observing the response to • control distressing or dangerous
antivenom early symptoms of envenoming
• Deciding whether further dose(s) • arrange the transport of the
of antivenom are needed patient to a place where they
• Supportive/ancillary treatment can receive medical care
• Treatment of the bitten part ABOVE ALL, AIM TO DO NO
HARM!
• Rehabilitation
• Treatment of chronic
complications
6.2.2 The danger of respiratory
• Advising how to avoid future bites paralysis and shock
The greatest fear is that a snakebite victim
might develop fatal respiratory paralysis
6.2 First-aid treatment or shock before reaching a place where
6.2.1 Principles of first-aid they may be resuscitated (Looareesuwan
First-aid treatment is carried out et al., 1988). This risk may be reduced
immediately or very soon after the bite, by speeding up transport to hospital,
before the patient reaches a dispensary by improving free ambulance services
or hospital. It can be performed by the (Gimkala et al., 2016) or by recruiting
snakebite victim himself/herself or by village-based motor cyclist volunteers
anyone else who is present and able. who transport the victim propped
ManageMent of snakebites
in south-east asia
115
hands as even a severed head can
bite! Several close-up mobile ‘phone
images of the snake should be taken if
possible to allow expert identification.
upright between the driver in front and • Immobilize the whole of the patient’s
a supporting pillion passenger behind. body by laying him/her down in a
This has proved effective in villages in the comfortable and safe position, ideally
Nepal Terai (Sharma et al., 2013) (Figure in the recovery position (lying prone
73). Medical workers can be trained on the left side in case vomiting
in airway management and assisted threatens to result in aspiration), and
ventilation (see below). The special danger immobilize the bitten limb with a splint
of rapidly developing paralytic envenoming or sling. Any movement or muscular
after bites by some elapid snakes has contraction, even undressing or
prompted the use of pressure-bandage walking, will increase absorption and
immobilization (Sutherland et al., 1979) spread of venom by squeezing veins
and pressure-pad immobilization (Anker and lymphatics.
1982; Tun-Pe et al.,1995b )(ANNEX 4).
Pressure bandage immobilization requires • Unless the possibility of an elapid
equipment (long elasticated bandages and bite can confidently be excluded,
splints) (Canale et al., 2009; Currie et al., apply pressure-pad immobilization
2008 ) and skill. (See ANNEX 4), or, if the necessary
equipment and skills are available,
As far as the snake is concerned - do pressure-bandage immobilization. In
not attempt to kill it as this may be Myanmar, the pressure-pad method
dangerous.However, if the snake has has proved effective in reducing spread
already been killed, it should be taken to of venom in victims of Russell’s viper
the dispensary or hospital with the patient bite (Tun Pe et al., 1995b). Pressure-
in case it can be identified. However, do bandage immobilization has not
not handle the snake with your bare become widely used in this Region,
ManageMent of snakebites
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117
6.4 Treatment in the
dispensary or hospital Rapid primary clinical assessment
(Warrell 1990; 1995) and resuscitation: ABCDE
approach
Airway
Medical management of
envenomed patients in dispensary Breathing (respiratory movements)
or hospital Circulation (arterial pulse)
• Rapid primary clinical assessment Disability of the nervous system (level
and resuscitation of consciousness)
• Detailed clinical history, physical Exposure and environmental control
examination and species diagnosis (protect from cold, risk of drowning
• Simple test of blood coagulability etc)
[20-minute-whole-blood-clotting-
test (20WBCT)]
Airway patency, respiratory movements,
• Antivenom: indications, initial arterial pulse and level of consciousness
and repeated dosage, response, must be checked immediately. Record the
reactions vital signs.
• Treatment of organ and system
failures The Glasgow Coma Scale cannot be used
to assess the level of consciousness of
• Treatment of the bitten limb
patients paralysed by neurotoxic venoms
• Rehabilitation, restoration of (see below).
function
• Advice at discharge from hospital Clinical situations in which
and follow-up snakebite victims might require
urgent resuscitation:
• Preventive health education a) Profound hypotension and shock:
towards reducing risk of future resulting from direct cardiovascular
bites effects of the venom or secondary
effects, such as hypovolaemia, release
of inflammatory vasoactive mediators,
6.4.1 Rapid primary clinical haemorrhagic shock or rarely primary
assessment and resuscitation anaphylaxis induced by the venom itself.
Snakebite is a medical emergency:
history, symptoms and signs must be b) Terminal respiratory failure: from
obtained rapidly so that appropriate, progressive neurotoxic envenoming
urgent and life-saving treatment can that has led to paralysis of the
be given respiratory muscles; or simple airway
obstruction.
Cardiopulmonary resuscitation may be
needed, including administration of c) Respiratory distress: from
oxygen and establishment of intravenous generalized increase in capillary
access. permeability (Russell’s viper bite victims)
f) Late results of severe envenoming: take a picture?” If the snake has been
in someone arriving days/weeks after the killed and brought, or an adequate
bite: with severe bleeding/blood clotting photo image is available (e.g. taken
disturbances, acute kidney injury or by mobile ‘phone at the scene of the
septicaemia complicating local necrosis. bite), its correct identification can be
very helpful. If it is obviously a harmless
6.4.2 Detailed clinical assessment and species (or not a snake at all!), the
species diagnosis patient can be quickly reassured and
discharged from hospital. If it was
6.4.2.1 History killed and left at home, send someone
A precise history of the circumstances to fetch it, in whatever condition!
of the bite and the progression of local 4. “How are you feeling now?”
and systemic symptoms and signs is very
important. Have any symptoms of envenoming
developed?
Four useful initial questions:
1. “Where (in what part of your body) were A common early symptom of systemic
you bitten? Point to the place” Observe envenoming is vomiting and, after
any local signs – fang marks, swelling, bites by some species, fainting and
bruising, persistent bleeding, pre- collapsing (sometimes causing injury)
hospital traditional treatment. with transient unconsciousness and
features of anaphylaxis (angioedema etc.).
2. “When were you bitten and what were Patients who become defibrinogenated
you doing when were you bitten?” If or thrombocytopenic may begin to bleed
the bite was very recent, there may not from old, partially-healed wounds as well
have been time for signs of envenoming as bleeding persistently from the fang
to develop. If the patient was bitten at marks. The patient should be asked how
night while asleep, a krait was probably much urine they have passed since the bite
implicated; if in a paddy field, a cobra or and whether it was a normal colour or very
Russell’s viper; if while tending fruit trees, dark (implying haemoglobin/myoglobin –
a green pit viper; if while swimming or uria). Patients who complain of sleepiness,
wading in water a cobra (fresh water) or drooping eyelids or blurred or double
sea snake (sea or estuary). vision may have neurotoxic envenoming.
An important early symptom of sea snake
3. “Where is the snake that bit you?” envenoming that may develop as soon as
or “What did it look like; did anyone 30 minutes after the bite is generalized
ManageMent of snakebites
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119
pain, tenderness and stiffness of muscles lines noted. A bitten limb may be
and trismus. tensely oedematous, cold, immobile,
painful on passive movement and
with impalpable arterial pulses. These
Early clues that a patient has appearances may suggest intravascular
severe envenoming: thrombosis, which is exceptionally rare
after snakebite, or a compartmental
• Snake identified as a very
syndrome, which is uncommon. If
dangerous one or a large
possible, intracompartmental pressure
specimen
should be measured (see Annex 5) and
• Widely spaced fang puncture the blood flow and patency of arteries
marks or evidence of multiple and veins assessed (e.g. by doppler
strikes ultrasound). Early signs of necrosis may
• Rapid early extension of local include blistering, demarcated darkening
swelling from the site of the bite (easily confused with bruising) (Fig 54
d, e, Fig 69) or paleness of the skin, loss
• Early tender enlargement of local of sensation and a smell of putrefaction
lymph nodes, indicating spread of (rotting flesh).
venom in the
• lymphatic system General examination: Measure the
blood pressure (sitting up and lying
• Early systemic symptoms:
to detect a postural drop indicative of
collapse (hypotension, shock),
hypovolaemia – see 14 Management
nausea, vomiting, diarrhoea,
of hypotension and shock) and heart
severe headache, “heaviness”
rate. Examine the skin and mucous
of the eyelids, inappropriate
membranes for evidence of petechiae,
(pathological) drowsiness or early
purpura, discoid haemorrhages (Fig
ptosis/ophthalmoplegia
64b) and, ecchymoses, the conjunctivae,
• Early spontaneous systemic for haemorrhages (Fig 63) and
bleeding chemosis (Fig 58), and the optic fundi
• No urine passed since the bite for retinal haemorrhages. Examine
the gingival sulci thoroughly, using a
• Passage of dark brown/black urine torch and spatula/tongue depressor, as
these may show the earliest evidence
of spontaneous systemic bleeding (Fig
6.4.2.2 Physical examination 60a), a very valuable sign. Examine
This should start with careful assessment the nose for epistaxis. Abdominal
of the site of the bite and signs of local tenderness may suggest gastrointestinal
envenoming. or retroperitoneal bleeding. Loin (low
back) pain and tenderness suggest
Examination of the bitten part: The acute renal ischaemia (Russell’s viper
extent of swelling, which is usually also bites). Subarachnoid haemorrhage is
the extent of tenderness to palpation suggested by neck stiffness (meningism)
(start proximally and squeeze gently (Fig 60b). Intracranial haemorrhage is
while watching the patient’s expression), suggested by lateralising neurological
should be recorded. Lymph nodes signs, asymmetrical pupils, convulsions or
draining the limb should be palpated and impaired consciousness (in the absence
overlying ecchymoses and lymphangitic of respiratory or circulatory failure).
Figure 77: Broken neck sign in a child envenomed by a krait in Sri Lanka Figure 76: Examination for ability to open the mouth
(Copyright DA Warrell) and protrude the tongue in a patient with neurotoxic
envenoming from the Malayan krait (Copyright DA Warrell)
Can the patient swallow or are (abdomen expands rather than the chest
secretions accumulating in the pharynx, on attempted inspiration) indicates
an early sign of bulbar paralysis? Ask that the diaphragm is still contracting
the patient to take deep breaths in but that the intercostal muscles and
and out. “Paradoxical respiration” accessory muscles of inspiration are
ManageMent of snakebites
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121
profound generalized flaccid paralysis from
neurotoxic envenoming are fully conscious
(Fig 78).
ManageMent of snakebites
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123
apparatus - a new, clean, dry, ordinary glass these cases, surface activation of blood
vessel (tube, bottle or syringe). coagulation by the glass surface, mediated
by Hageman Factor XII is lacking or has
been destroyed by cleaning with the result
20 minute whole blood clotting
that blood coagulation is not activated and
test (20WBCT)
the blood will not clot.
• Place 2 mls of freshly sampled
venous blood in a small, new, dry,
A major difficulty is that many hospitals/
glass vessel
dispensaries in countries where snakebites-
• Leave undisturbed for 20 minutes
are common, cannot afford to provide a
at ambient temperature
new, unwashed, un-recycled bottle, tube,
• Tip the vessel once
syringe or other vessel for each test and
• If the blood is still liquid
ordinary glass tubes/vessels may be difficult
(unclotted) and runs out, the
to purchase in this age of plastic. However,
patient has hypofibrinogenaemia
the commonly used recycled glass
(“incoagulable blood”) as a result
antibiotic bottles can be made suitable and
of venom-induced consumption
reliable, provided that they are cleaned
coagulopathy
by washing with “normal 0.9% saline”
• In the South-East Asia Region,
for intravenous infusion, without any
incoagulable blood is diagnostic
added detergent of other cleansing agent,
of a viper bite and rules out an
followed by hot air drying.
elapid bite
• Warning! If the vessel used
Variants of the 20WBCT, such as the 30
for the test is not made of
minute WBCT, “2,3,5 syringe test” used in
ordinary glass, or if it has
Myanmar, or the capillary tube test have
been cleaned with detergent,
not been standardised or validated and
its wall may not stimulate
are susceptible to the same risks of false
clotting of the blood sample
positivity outlined above.
(surface activation of factor
XII – Hageman factor) and test
False negative results: a “false
will be invalid
negative” (i.e. clotting) 20WBCT may
• If there is any doubt, repeat the
occur in patients with milder degrees
test in duplicate, including a
of coagulopathy. The 20WBCT is less
healthy “control” (blood from a
sensitive to mild depletion of fibrinogen
healthy person such as a relative)
and other clotting factors, in the early
stages of evolving snake venom induced
Problems with the 20WBCT DIC and consumption coagulopathy, than
False positive results: a “false positive” laboratory tests such as prothrombin time
(i.e. non-clotting) 20WBCT in a patient (PT), activated partial thromboplastin time
who is not envenomed and has normal (aPPT), and fibrinogen assay. The 20WBCT
blood coagulation, results from the use of becomes positive (i.e. non-clotting) at
a tube, bottle, syringe or other vessel that is plasma fibrinogen concentrations below
made of plastic, polystyrene, polypropylene 0.5g/L (Sano-Martins et al., 1994). A
rather than ordinary glass, or a glass vessel study of 20WBCT in victims of taipan bites
that has been cleaned with detergent, soap (Oxyuranus scutellatus) in Papua New
or washing fluid or is wet or contaminated, Guinea found that a positive 20WBCT
or in the case of some glass syringes, (i.e. non-clotting) was associated with
has a lubricant that is anticoagulant. In a median PT of 120.0s (IQR 24.4-200s),
ManageMent of snakebites
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6.6.2 Other tests of blood haematocrit: a transient increase
coagulation indicates haemoconcentration resulting
More sensitive laboratory tests that are from a generalized increase in capillary
rapid and relatively simple to perform permeability (e.g. in Russell’s viper bite).
are plasma prothrombin time (PT) or
activated partial thromboplastin time More often, there is a decrease reflecting
(aPPT) and measurement of fibrin(ogen) blood loss or, in the case of Indian,
related antigens, also known as fibrin Thai and Sri Lankan Russell’s viper bite,
degradation products (FDP) or fibrin intravascular haemolysis.
split products (FSP), by agglutination of
sensitized latex particles or of D-dimer Platelet count: this may be decreased
(cross-linked fibrin fragments) by assays in victims of envenoming by vipers and
using monoclonal antibodies that detect Australasian elapids.
an epitope that is present in the factor
XIIIa–crosslinked fragment D domain of White blood cell count: an early
fibrin. The International Normalized Ratio neutrophil leucocytosis is evidence of
(INR) is the patient’s PT divided by the systemic envenoming by any species.
laboratory control PT (normal range 0.8 Lymphopenia has been described in
- 1.2). An abnormal INR result, indicating patients envenomed by Australasian
coagulopathy, is 1.2 or above. Point of Elapidae.
care (bed-side) devices for measuring
INR and D-dimer are expensive and are Blood film: fragmented red cells
unreliable in snakebite victims (Cubitt (“helmet cell”, schistocytes) are seen
et al., 2013). Measurement of plasma when there is microangiopathic
concentrations of fibrinogen and other haemolysis or thrombotic
individual clotting factors are more microangiopathy (TMA). Haemolytic
demanding in time and laboratory skills. uraemic syndrome (HUS) consists of
persistent, profound thrombocytopenia,
Thrombo-elastography (TEG) and microangiopathic haemolytic anaemia
thromboelastometry (TEM, ROTEG, (fragmented red cells, “helmet cells”,
ROTEM) have been suggested as a or schistocytes) and acute kidney
simple bed-side method for assessing injury. It is associated with envenoming
coagulopathy in snakebite victims but the by Russell’s vipers, hump-nosed pit
equipment is expensive. Analysis of the vipers and Australian Elapidae. The
TEG tracing provides measures of time pathophysiology of TMA is unknown,
to initiation of clotting, speed of clot but in other diseases, such as thrombotic
formation and clot strength that reflect thrombocytopenic purpura (TPP), it is
coagulation factor activity, fibrinolysis thought to be due to deficiency of the
and platelet function. In a study of metalloproteinase ADAMTS 13 which
envenomed children in South Africa, cleaves von Willebrand multimers. These
TEG predicted severe bleeding diathesis multimers initiate platelet activation
in 50% of patients with 94% sensitivity and formation of microthrombi which
(Hadley et al., 1999). It has also been is the key factor in the development of
used in envenomed dogs (Armentano et acute kidney injury. In an Australian tiger
al., 2014). snake (Notechis scutatus) bite victim
with TMA, ADAMTS 13 levels were
6.6.3 Other laboratory tests normal before and after plasmapheresis
Haemoglobin concentration/ with cryosupernatant (Ho et al., 2010).
ManageMent of snakebites
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127
infarcts in the brain (subarachnoid, that has been immunised with the venoms
subdural, cerebral, cerebellar, brainstem) of one or more species of snake. “Specific”
(Figs 61b, 61c, 52d), spinal cord, antivenom, implies that the antivenom
peritoneum and elsewhere in Russell’s has been raised against the venom of the
viper victims in India, Sri Lanka and snake that has bitten the patient and that
Myanmar. Cerebral imaging has shown it can therefore be expected to contain
pituitary shrinkage in cases of chronic specific antibody that will neutralize that
panhypopituitarism and unexplained particular venom and perhaps the venoms
haemorrhagic and demyelinating of closely related species (paraspecific
leucoencephalopathies after Russell’s viper neutralization). Monovalent (monospecific)
bites in India. Imaging can show oedema antivenom neutralizes the venom of
and haemorrhage in fascial compartment only one species of snake. Polyvalent
muscles and the degree of osteomyletis (polyspecific) antivenom neutralizes
and soft tissue changes in chronic the venoms of several different species
snakebite ulcers that have undergone of snakes, usually the most important
malignant change to squamous cell species, from a medical point of view, in a
carcinomas (Marjolin’s ulcers). particular geographical area.
ManageMent of snakebites
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• Local swelling involving more than half give antivenom for as long as evidence
of the bitten limb (in the absence of of the coagulopathy persists. Whether
a tourniquet) within 48 hr of the bite antivenom can prevent local necrosis
Swelling after bites on the digits (toes remains controversial, but there is some
and especially fingers) clinical evidence that, to be effective in
this situation, it must be given within the
• Rapid extension of swelling (for first few hours after the bite (Warrell et
example beyond the wrist or ankle al., 1976; Tilbury 1982).
within a few hours of bites on the
hands or feet) 6.7.5 Antivenom reactions
A substantial proportion of patients
• Development of an enlarged tender develop reactions, either early (within
lymph node draining the bitten limb a few hours) or late (5 days or more)
after being given antivenom. In Sri
6.7.3 Inappropriate use of antivenom Lanka, Indian polyvalent antivenoms
In some parts of the world, a small incur reactions in as many as 81% of
standard dose of antivenom is given recipients and severe reactions in as
routinely to any patient claiming to many as 43% (Ariaratnam et al. 2001,
have been bitten by a snake, irrespective de Silva et al, 2016). In India, these
of symptoms or signs of envenoming. antivenoms cause reactions in 5.6 to
Sometimes the local community are 56% of recipients, 10-15% of which are
so frightened of snakebite that they moderate to severe (Srimannarayana
compel the doctor to give antivenom et al., 2004; Deshpande et al., 2013;
against medical judgement. Even doctors Cherian et al., 2013; Menon et al.,
themselves may administer antivenom to 2016a). Other antivenoms have much
patients envenomed by snakes against lower reported reaction rates. In
which the antivenom is known to be Thailand, among 254 patients receiving
ineffective (Seneviratne et al, 2000). Thai Red Cross (TRC) antivenoms during
1997–2006, early reactions occurred
in 9 (3.5%) including 3 (1.2%) with
Inappropriate use of antivenom hypotension. Most patients were being
should be strongly discouraged treated for Trimeresurus (84%) and Naja
as they expose patients who may (13%) bites, in whom the incidence
not need treatment to the risks of reactions was 2.3% and 12.5%
of antivenom reactions; they also respectively, reflecting the difference
waste valuable and scarce stocks in dose (3 and 10 vials respectively)
of antivenom. (Thiansookon and Rojnukarin, 2008).
In Australia, use of CSL antivenoms
incurred early anaphylactic reactions
6.7.4 How long after the bite in 25% and severe raections in 5% of
can antivenom be expected to be recipients (Isbister et al., 2008). The risk
effective? of antivenom reactions is dose-related,
Antivenom treatment should be given except in rare cases in which there has
as soon as it is indicated. It may reverse been sensitisation (IgE-mediated Type
systemic envenoming even when this has I hypersensitivity) by previous exposure
persisted for several days or, in the case to animal serum, for example to equine
of haemostatic abnormalities, for two or antivenom, tetanus-immune globulin or
more weeks. It is, therefore, appropriate to rabies-immune globulin.
[a]
Figures 80: Early anaphylactic reaction to antivenom: (a, b) urticaria and pruritus of the
trunk and face; (c) life-threatening angioedema of face tongue, gums, throat, neck and
upper airway (Copyright DA Warrell)
ManageMent of snakebites
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(adrenaline) *adult dose 0.25mg of 0.1%
solution is given just before antivenom
Adrenaline (epinephrine) is the most
treatment is started (see below), followed
effective treatment for anaphylactic by an intravenous anti-H1antihistamines
reactions, by reducing bronchospasm and such as chlorphenamine. In asthmatic
patients, prophylactic use of an inhaled
capillary permeability. adrenergic β2 agonist such as salbutamol
may prevent bronchospasm.
ManageMent of snakebites
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133
Additional treatment: After epinephrine
Recommendation: based on (adrenaline), patients with bronchospasm
the results of a powerful and should be given an inhaled short-acting β2
well-designed trial in Sri Lanka, agonist bronchodilator such as salbutamol
routine use of prophylactic or terbutaline ideally by oxygen-
adrenaline is recommended driven nebuliser) and an antihistamine
before antivenom treatment, anti-H1 blocker can be given, such as
except in those older patients chlorphenamine maleate (adults 10
in whom there is evidence mg, children 0.2 mg/kg by intravenous
or suspicion of underlying injection over a few minutes). Intravenous
cerebrovascular disease and hydrocortisone (adults 100 mg, children
when the particular antivenom in 2 mg/kg body weight) can be given,
use has a proven low incidence but it is unlikely to act for several hours.
of reactions (<5%). The adult Corticosteroids do not reduce the risk of
dose of epinephrine (adrenaline) recurrence (biphasic) anaphylaxis (Grunau
is 0.25ml of 0.1% solution (0.25 et al., 2015).
mg) by sub-cutaneous injection
(children 0.005 ml/kg body Anaphylaxis unresponsive to
weight of 0.1% solution) (T). intramuscular epinephrine
(adrenaline): a few patients may not
Use of histamine anti-H1 and respond to single or repeated doses of
anti-H2 blockers, corticosteroid, intramuscular epinephrine (adrenaline).
and the rate of intravenous
infusion of antivenom (between Patients who remain shocked and
10 and 120 minutes), do not hypotensive should be laid supine with
affect the incidence or severity of their legs elevated and given intravenous
early antivenom reactions (T,O). volume replacement with 0.9% saline
(1-2 litres rapidly in an adult). Intravenous
epinephrine (adrenaline) infusion should
6.7.5.4 Treatment of antivenom be considered [adult dose 1mg (1.0 ml)
reactions of 0.1% solution in 250 ml 5% dextrose
Early anaphylactic antivenom or 0.9% saline - i.e. 4 μ (micro) g/ml
reactions: Epinephrine (adrenaline) is concentration) - infused at 1–4 μ (micro)
given intramuscularly (ideally into the g/minute (15–60 drops/min usin a
upper lateral thigh) in an initial dose microdropper burette chamber), increasing
of 0.5 mg for adults, 0.01 mg/kg body to maximum 10 μ (micro) g/min] and,
weight for children. Because severe, in patients who remain hypotensive, a
life-threatening anaphylaxis can evolve vasopressor agent such as dopamine [dose
so rapidly, epinephrine (adrenaline) 400mg in 500ml 5% dextrose or 0.9%
should be given at the very first sign of saline infused at 2–5 μ (micro) g/kg/min].
a reaction, even when only a few spots
of urticaria have appeared or at the start Patients who remain dyspnoeic, with
of itching, tachycardia or restlessness. bronchospasm or angioedema, should
The dose can be repeated every 5-10 be propped up at 45 degrees and given
minutes if the reaction persists or the supplemental oxygen by any available
symptoms become worse. Adrenaline has route together with optimal nebulised/
proved safe in pregnant women, whereas inhaled and/or parenteral bronchodilator
anaphylaxis can induce abortion. (β2 agonist) (Kemp and Kemp 2014).
ManageMent of snakebites
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135
Storage and shelf-life: to retain their Freeze-dried (lyophilised) antivenoms
full potency within the limits of stated are reconstituted, usually with 10 ml of
expiry dates, lyophilised antivenoms sterile water for injection per ampoule.
(shelf life about 5 years) should be stored If the freeze-dried protein is difficult to
at below 25ºC and liquid antivenoms dissolve, it may have been denatured by
(shelf life 2-3 years) should be stored a faulty freeze-drying technique during
at 2-8 ºC and not frozen. Ideally, manufacture (WHO, 2010).
antivenoms should be used before the
stated expiry dates but, provided that Two methods of administration are
they have been properly stored, they can recommended:
be expected to retain useful activity for
months or even years after these dates 1. Intravenous “push” injection:
(WHO, 1981; O’Leary et al., 2009). TRC reconstituted freeze-dried antivenom
antivenoms retain their potency after 5 or neat liquid antivenom is given by
years even when stored temperatures slow intravenous injection (not more
of 25-50 °C (Prof Sumana Komvilai, than 2 ml/minute). This method has
personal communication). the advantage that the doctor, nurse,
or dispenser giving the antivenom must
In patients with severe envenoming, remain with the patient during the
recently expired antivenoms may time when some early reactions may
be used if there is no alternative. develop. It is also economical, saving
However, liquid antivenoms that have the use of intravenous fluids, giving
become opaque or which contain sets, cannulae etc.
visible particles should not be used
as precipitation of protein indicates 2. Intravenous infusion: reconstituted
loss of activity and an increased risk of freeze-dried or neat liquid antivenom is
reactions. diluted in about 5 ml of isotonic fluid
per kg body weight (i.e. about 250 ml
6.7.7 Administration of antivenom of isotonic saline or 5% dextrose in the
case of an adult patient) and is infused
at a constant rate over a period of
• Epinephrine (adrenaline) about 30-60 minutes.
should always be available
at the bed-side, ideally
drawn up in readiness, Patients must be closely observed
before antivenom is for at least one hour after
administered. starting intravenous antivenom
administration, so that early
• Antivenom should be given anaphylactic antivenom reactions
by the intravenous (iv) route can be detected and treated early
whenever possible, either with epinephrine (adrenaline).
by slow iv “push” injection
(maximum 2 ml/minute) Local administration of antivenom
or by iv infusion diluted in at the site of the bite is not
about 5 ml of isotonic fluid recommended! Although this
per kg body weight over route may seem rational, it
about 30-60 minutes. should not be used as it is
0.4
ManageMent of snakebites
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137
6.7.8 Dosage of antivenom “push” injection, is followed by infusion
(Table 1 and Annex 3) of 4 vials over 4 hours, and, as long as
Initial dose of antivenom signs of envenoming persist, 4 vials over
A fundamental piece of information for 4 hours every 4 hours for a further 12
those treating envenomed patients is hours, followed by 2 vials over 4 hours,
the average initial dose of a particular repeated until recovery. Following this
antivenom appropriate for different regimen, cumulative doses may reach 140
levels of clinical severity in patients bitten vials (1000 ml) in patients with neurotoxic
by different species. Unfortunately, envenoming by kraits (Magar et al., 2013).
these data, based on clinical trials, are A recent study in Nepal compared the
rarely available. In any case, since the effectiveness and safety of this regimen
neutralizing power of antivenoms varies with a single higher initial dose of 10
from batch to batch, and between vials given over 1 hour in patients with
different antivenoms, the results of a neurotoxic envenoming. There was no
clinical trial may soon become obsolete if statistically significant difference between
the manufacturers change the strength the two regimens in the proportion of
of their antivenom. This happened patients reaching the primary endpoint
in Myanmar in the 1990s, when the (48.7% in the low initial dose arm
national producer arbitrarily halved the versus 38.5% in the high initial dose
strength of their antivenom. As a result, arm, p=0.264). Likewise, there was no
medical personnel must usually rely difference in the incidence of antivenom
on manufacturers’ recommendations reactions (53.8% of patients given the
stated in the package insert. These high dose compared to 52.6% given the
are usually based on laboratory assays low initial dose). Among the 51 patients
in which venom and antivenom are in whom the snake species could be
incubated in vitro before being injected identified, 29 had been bitten by cobras
into the test animals, usually mice. The (Naja spp) and 22 by kraits (Bungarus
recommended dose is usually the amount spp.). Patients bitten by kraits were more
of antivenom required to neutralize the severely envenomed and recovered less
average venom yield when captive snakes often (40.9% versus 96.5%, p<0.001)
are milked of their venom, but, quite and more slowly (mean recovery time 18
apart from many theoretical objections hours versus 5 hours, p<0.001) than did
to this protocol, the maximum venom patients bitten by cobras. These findings
yield may be seriously underestimated suggested that there was no difference in
(Tun Pe and Khin Aung Cho, 1986). effectiveness and safety between initially
In practice, the choice of an initial low and high doses of antivenom for
dose of antivenom is usually empirical. neurotoxic snakebite in southern Nepal,
Some antivenom dosage regimens and that systemic envenoming due to krait
recommended in national management bites was less responsive to antivenom
guidelines seem illogical, based on what than that following cobra bites (Alirol E,
is known of the pharmacokinetics and Sharma SK et al., in press). Since the high
pharmacodynamics of venom-antivenom single initial dose was non-inferior to the
interactions. low initial dose (but much higher total
dose), the former is preferred on grounds
Nepal: the Nepalese national guidelines of cost and convenience.
recommend prolonged and repeated
dosage of antivenom. An initial dose India: there have been many publications
of 2 vials of antivenom given by IV on treatment of snakebite with national
ManageMent of snakebites
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139
2008). A randomized, double-blind, geographical intra-species venom
placebo-controlled trial of TRC Green Pit variation, lack of adequate neutralizing
Viper antivenin in patients bitten by these antibodies against key toxic venom
Trimeresurus species who had marked proteins, inability of the antibodies to
limb swelling, but no severe coagulopathy neutralize toxins that are tissue bound or
suggested that antivenom accelerated to reverse the pathological consequences
resolution of local swelling, although not of tissue injury. Envenoming by the larger
to a clinically useful degree (Rojnukarin et northern sub-species of saw-scaled viper
al., 2006). (Echis carinatus sochureki) requires larger
antivenom doses (Kochar et al., 2007)
and envenoming by Russell’s vipers in
Reasons for antivenom Kerala and Maharashtra require higher
ineffectiveness antivenom doses (Warrell et al., 2013).
Biochemical studies have shown variations
There is an urgent need for in venom composition in different parts
well-designed and adequately- of India for Naja naja (Mukherjee and
powered national clinical dose- Maity., 1998; Shashidharamurthy and
finding studies to establish Kemparaju, 2007) and Daboia russelii
initial doses of antivenom for (Jayanthi and Gowda, 1988; Prasad et al.,
patients with different severities 1999). Antivenom raised against venom
of envenoming by the major from one geographical location may not
medically important species in be as effective against envenoming in
the Region. These should focus other geographical locations. In India,
on bites by reliably-identified most of the venom used for antivenom
species, should be randomised, manufacture is obtained from the Irula
comparing two doses of the cooperative in Mammallapuram (Warrell
same antivenom or two different et al., 2013). A recent comparison of two
antivenoms, should have commercially available antivenoms showed
objective end-points to assess that one had a higher protein content, and
effectiveness and safety, and antibody binding and neutralizing capacity
should, ideally, be blinded to for Echis carinatus and Daboia russellii
exclude bias. venom. Indian polyvalent antivenoms
are raised against venoms of the classic
“big four” species and may not neutralize
There have been anecdotal and venoms of other medically important
unpublished reports of clinical snakes, such as monocellate cobra (N.
ineffectiveness of individual batches of kaouthia) in the North-East and any of the
antivenom. The variable efficacy may Indian pit-vipers, notably the hump-nosed
be due to lower antibody titre, reduced pit-viper (Hypnale hypnale) and Malabar
antibody binding specificities and lack pit-viper (Trimeresurus (Craspedocephalus)
of antibodies to low molecular weight malabaricus) of the south-west coast.
proteins. Studies have shown batch
to batch variability in effectiveness Suggested initial doses of some of
of Indian antivenoms, manifested by the available antivenoms are given in
increased complications and mortality Table 1 (by species of snake), based
with particular batches (Zachariah A, on clinical experience; and in Annex 3
personal communication; Zacharaiah, (by country),based on manufacturers’
2015). Possible explanations include recommendations.
Acanthophis species death adder CSL1 Death Adder or Polyvalent Antivenom 1-3 vials
Bungarus multicinctus Chinese krait Shanghai Vaccine & Serum Institute 5 vials
NIPM Taipei Naja-Bungarus antivenin 5 vials
Calloselasma (Agkistrodon) Malayan pit viper TRC3 Malayan Pit Viper Antivenin
Monovalent 30-50 ml
rhodostoma OR TRC3 Hemato Polyvalent 30-30 ml
Naja kaouthia monocellate Thai cobra TRC3 Cobra Antivenin Mono 100 ml
OR TRC3 Neuro Polyvalent 100 ml
Naja naja, N oxiana Indian cobras Indian manufacturers2 polyvalent 50 ml
Ophiophagus hannah king cobra TRC3 King Cobra Antivenin Mono 100 ml
OR TRC3 Neuro Polyvalent 100 ml
Pseudonaja species Australian brown CSL1 Brown Snake or Polyvalent 1-2 vials
snakes Antivenom\
Pseudechis species Australian black snakes CSL1 Black Snake Antivenom 1-3 vials
Trimeresurus (T.) albolabris Green pit-vipers TRC3 Green Pit Viper Antivenin 30-50 ml
T. (T.) macrops etc. OR TRC3 Hemato Polyvalent 30-50 ml
1
CSL, Parkville, Australia http://www.toxinology.com/fusebox.cfm?staticaction=generic_static_files/avp-csl-01.html
2
Indian Manufacturers: Bharat Serums & Vaccines, Mumbai https://www.bharatserums.com/; Central Research Institute, Kasauli http://www.
nti.org/learn/facilities/145/ ; Haffkine Biopharma, Mumbai; Serum Institute of India, Pune http://www.seruminstitute.com/content/products/
product_list.htm ; Vins Bioproducts, Hyderabad: Premium Serums and Vaccines, Narayangaon http://www.premiumserums.com/
3
Thai Red Cross, Queen Saovabha Memorial Institute, Bangkok, Thailand http://www.snake-antivenin.com/
ManageMent of snakebites
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141
f) Active haemolysis and
Snakes inject the same dose rhabdomyolysis may cease within a
of venom into children and few hours and urine colour returns to
adults. Children must therefore normal.
be given exactly the same
dose of antivenom as adults 6.7.9 Recurrence of systemic
Antivenom manufacturers, health envenoming
institutions and medical research In patients envenomed by vipers,
organizations should encourage after an initial response to antivenom
and promote the proper clinical (cessation of bleeding, restoration of
testing of antivenoms as with blood coagulability), signs of systemic
other therapeutic agents. This envenoming may recur within 24-48 hours.
is the only reliable guide to the
initial dose (and safety) of an This is attributable to:
antivenom. 1. continuing absorption of venom from
the “depot” at the site of the bite,
perhaps promoted by improved blood
Observation of the response to supply following correction of shock,
antivenom: If an adequate dose of hypovolaemia etc., after elimination
an appropriate antivenom has been of antivenom (range of elimination
administered, the following responses may half-lives: IgG 45 hours; F(ab’)2 80-100
be seen. hours; Fab 12-18 hours) (Ho et al.,
1986; Ho et al., 1990)
a) General: the patient feels better.
Nausea, headache and generalized 2. redistribution of venom from the
aches and pains may disappear very tissues into the vascular space, as the
quickly. This may be partly attributable result of antivenom treatment (Rivière
to a placebo effect. et al.,1997).
b) Spontaneous systemic bleeding
(e.g. from the gums) usually stops Recurrent neurotoxic envenoming after
within 15-30 minutes. treatment of cobra bite has also been
c) Blood coagulability (as measured described.
by 20WBCT) is usually restored in 3-9
hours. Bleeding from new and partly 5.7.10 Criteria for repeating the initial
healed wounds usually stops much dose of antivenom
sooner than this.
d) In shocked patients, blood pressure
Criteria for giving more
may increase within the first 30-60
antivenom
minutes and arrhythmias such as sinus
bradycardia may resolve. • Persistence or
e) Neurotoxic envenoming of the post- recurrence of blood
synaptic type (cobra bites) may begin incoagulability after 6 hr or
to improve as early as 30 minutes after of bleeding after 1-2 hr
antivenom (Faiz et al., cobra bites in
• Deteriorating neurotoxic
press), but may take several hours.
or cardiovascular signs
Envenoming by presynaptic toxins
after 1 hr
(kraits and sea snakes) will not respond
in this way.
ManageMent of snakebites
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143
be treated with antivenom. Surgical antivenom and fresh-frozen
intervention may be needed but the risks plasma or clotting factors will be
of surgery in a patient with consumption needed to control bleeding after this
coagulopathy, thrombocytopenia and procedure.)
enhanced fibrinolysis must be balanced
against the life threatening complications In urgent situations where acute airway
of local envenoming. Prophylactic broad obstruction has developed and where
spectrum antimicrobial treatment is the patient cannot be intubated,
justified (see below). cricothyroidotomy will establish an airway
faster than tracheostomy.
6.9 Supportive/ancillary
treatment
Antivenom treatment can be expected to Although artificial ventilation was
neutralize free circulating venom, prevent first suggested for neurotoxic
progression of envenoming and allow envenoming 140 years ago,
recovery. However, these processes take patients continue to die of
time and the severely envenomed patient asphyxiation because some
may require life support systems such as doctors believe that antivenom
treatment of shock, assisted ventilation alone is sufficient treatment.
and renal dialysis until the severely
damaged organs and tissues have had
time to recover. 6.9.2 Practical guide to airway
management and respiratory support
6.9.1 Treatment of neurotoxic The following guidelines have been
envenoming produced specifically to aid health care
workers in the acute management
of snakebite patients. However, it is
Antivenom treatment alone important to recognize that the techniques
cannot be relied upon to save the described below are applicable to the care
life of a patient with bulbar and of all critically ill patients.
respiratory paralysis.
The techniques discussed below are not
complicated. However, expert instruction
Death may result from aspiration, airway is desirable, ideally from a fully trained
obstruction or respiratory failure. A doctor, nurse, first-aid worker or other
clear airway must be maintained. Once health professional, with experience in
there is loss of gag reflex and pooling resuscitation, airway management, use
of secretions in the pharynx, failure of of the necessary equipment, intubation
the cough reflex or respiratory distress, and assisted ventilation. These techniques
a cuffed endotracheal, laryngeal mask must be practised frequently, under
airway or i-gel supraglottic airway should supervision, using a manikin (dummy/
be inserted. If this is impossible for model – see Fig 82a) or, but only where
any reason, or the need for prolonged appropriate and culturally acceptable, a
ventilation is anticipated, a tracheostomy dead body in the mortuary, to acquire
should be performed and a snugly- essential understanding of the anatomy
fitting or cuffed tracheostomy tube of the upper airway and the techniques
inserted (Caution – in patients with themselves, and to maintain an adequate
uncorrected coagulopathy, more baseline level of skill (Fig 82b).
Resuscitation
This follows the general principles of life
support given below:
DRABCDE
D - DANGER
R - RESPONSE
A - AIRWAY
B – BREATHING
C - CIRCULATION
D - DISABILITY
Figure 82: Treatment of neurotoxic envenoming: (a) Training health workers in
E – EXPOSE THE PATIENT techniques of endrotracheal intubation and airway management in Papua New
(Only DRAB are discussed here) Guinea (Copyright DJ Williams)
ManageMent of snakebites
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145
2. In a health centre: emergency cart catheter (attempts should not be longer
and defibrillator are summoned. Once than 10 seconds) or by using forceps.
the EMS/emergency cart has been Use of a gloved finger is discouraged
summoned, the rescuer starts airway as this may push the material or object
management further down the airway and may put
the rescuer at risk of being bitten.
A – AIRWAY PROTECTION AND
MANAGEMENT Finally, insert an oropharyngeal (Guedel)
Basic Airway Management (BAM) airway (OPA), measured to suit the
Opening and maintaining the airway: patient (from the corner of the mouth
The airway can be opened using the to the angle of the jaw), being sure to
“head tilt - chin lift” manoeuvre (Fig avoid causing trauma to the lips and
82c), bringing the patient’s head into the mouth, especially if there is evidence of
“sniffing” position. If there is any suspicion bleeding or the if the patient has been
of cervical spine trauma, jaw thrust should bitten by a snake which causes bleeding
be used rather than this procedure. abnormalities. While nasopharyngeal
airway (NPA) devices are better tolerated
by semi-conscious patients, who may
still have a gag reflex, or in those who
have trismus, they are more likely to
cause nasal bleeding, and so are not
preferred.
ManageMent of snakebites
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147
(Fig 82e) i-gel supraglottic airway and hence the risk of hypoxia) experience
is required.
ManageMent of snakebites
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149
patient’s mouth and deliver a breath over
a second, enough to see the chest rise,
If chest movement is inadequate, a
and allowing 4 seconds for exhalation
correctly-sized OPA should be inserted. before giving a second breath. In the case
This will usually assist with air flow in and of a small child the mouth and nose may
be covered by the rescuer’s mouth.
out of the lungs. If there is no bleeding
disorder, a NPA (or 2) may be used instead Assisted ventilation by this means will
provide a maximum of approximately only
of, or in addition to, an OPA. 16% inspired oxygen concentration (FIO2
0.16).
Deliver 2 initial “rescue breaths” as follows • The clinical circumstances, e.g. the
(Fig 82h): close the patient’s nose with likely diagnosis, the age of the patient
one hand and pull the jaw down with (the rescuer might reasonably persist
the other, and place your mouth over the for longer if the patient is a small
child), or the distance from medical
assistance or from more advanced
health care facilities;
ManageMent of snakebites
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151
endotracheal intubation (insertion of • Physiotherapy (including chest
an ETT) should be performed and the physiotherapy, regular turning to
patient placed on a ventilator, attended prevent pressure areas and lung
constantly by a suitably qualified nurse, collapse, and maintenance of the range
with a suitably qualified doctor always of motion of paralysed, immobile
on call to provide additional assistance, if joints and muscles, as well as limbs
required. Tube blockages are a frequent where significant cytotoxicity and tissue
cause of morbidity and mortality. They damage has occurred).
are prevented by regular suctioning,
humidification and training of staff to • Eye care (synthetic tears and closure
recognize the symptoms of a blocked tube. of the eyelids to prevent drying and
damage to corneas in patients on
Sedation for patients being ventilators).
mechanically ventilated: fentanyl 2-40
microg/hour and midazolam 2-4 mg/hour • Safe and effective weaning from
OR (to avoid acute kidney injury) morphine ventilation.
1-5 mg/hour with lorazepam 1-2 mg/hour.
Always be careful to minimize trauma
Adequacy of respiratory assistance can to the airway of a snakebite patient; this
be assessed by reversal of clinical signs of includes the insertion of basic airway
inadequate respiration and stabilization devices, advanced airway devices and
of SpO2 and end-tidal CO2 (where gastric tubes. Orogastric tubes are much
available) and improvement in the victim’s preferred over nasogastric ones – the
level of consciousness if respiratory latter often lead to bleeding which is
failure was the sole cause of his/her difficult to deal with in the patient who
unresponsiveness. However, assessing the has a coagulopathy, and may even
level of consciousness of a patient with lead inexperienced staff to give more
neurotoxic envenoming can be difficult antivenom or blood products when these
because of their often generalized flaccid are not necessary.
paralysis, such that the normal method of
ascertaining the level of consciousness (the Such care also applies to the insertion of
Glasgow Coma Scale – GCS) is irrelevant intravenous catheters and urinary (urethral)
since the patient is unable to open their catheters. Central venous lines may be
eyes, unable to speak and often unable inserted, if required and possible, but the
to obey commands. They are, contrary insertion site will depend on the presence
to common belief, awake, able to hear or absence of a bleeding disorder. Intra-
everything which is said around them. They arterial lines may be useful in many
should be sedated during the period of respects, but, again, are discouraged in
their ventilation. the presence of a bleeding disorder.
[a] [b]
A trial of anticholinesterase Figures 83: Anti-cholinesterase: (a) Before and (b) after intravenous atropine
followed by intravenous edrophonium chloride in a patient envenomed by a
(e.g. “Tensilon test”) should Malayan krait (Bungarus candidus) (Copyright DA Warrell)
be performed in every patient
with neurotoxic envenoming,
as it would be in any patient 10-20 minutes (edrophonium) for
with suspected myasthenia signs of improved neuromuscular
gravis. However, this should not transmission. Ptosis may disappear
delay antivenom treatment or (Fig 83) and ventilatory capacity
endotracheal intubation. Patients (peak flow, FEV-1 or maximum
must be observed closely as they expiratory pressure) may improve.
may deteriorate while the trial
of anticholinesterase is being 4. Patients who respond convincingly
carried out can be maintained on neostigmine
methylsulphate, 0.5-2.5 mg every
1-3 hours up to 10 mg/24 hours
Procedure maximum for adults or 0.01-0.04
1. Baseline observations or mg/kg every 2-4 hours for children
measurements are made against by intramuscular, intravenous or
which to assess the effectiveness of subcutaneous injection together
the anticholinesterase. with atropine to block muscarinic
side effects. Patients able to swallow
2. Atropine sulphate (0.6 mg for tablets may be maintained on
adults; 50 µg/kg for children) or atropine 0.6 mg twice each day,
glycopyrronium is given by intravenous neostigmine 15 mg four times each
injection followed by neostigmine day or pyridostigmine 60 mg four
bromide or methylsulphate times each day.
(Prostigmin) (or distigmine,
pyridostigmine, ambenomium etc. in
appropriate doses) by intramuscular Anticholinesterase (e.g.
injection 0.02 mg/kg for adults, 0.04 “Tensilon”) test
mg/kg for children. Short acting • Baseline observations
edrophonium chloride (Tensilon) is • Give atropine intravenously
ideal for this test but is rarely available • Give anticholinesterase
in the Region. It is given by slow drug (e.g. neostigmine
intravenous injection in an adult dose intramuscularly)
of 10 mg, or 0.25 mg/kg for children. • Observe effect
• If positive, institute regular
3. The patient is observed over the atropine and neostigmine
next 30-60 minutes (neostigmine) or
ManageMent of snakebites
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153
Suggested method: in a patient with
bilateral ptosis from neurotoxic snake-bite,
the distance between the upper and lower
lid margins of both eyes (palpebral fissures)
is measured using a mm ruler. Digital
pressure is applied to the frontalis muscle to
avoid its influencing upper eyelid retraction.
An ice-filled plastic glove or frozen ice pack
is then gently applied to one eyelid for 2
minutes, after which the palpebral fissures
of both eyes are immediately re-measured.
A more-than-2mm difference in palpebral
fissure between the cooled and control
eyelids might be considered a positive result
(Fig 84).
ManageMent of snakebites
in south-east asia
155
from haemorrhagic infarction of the In patients with any of the above
anterior pituitary may contribute to features, the following should be
shock, while neurological manifestations monitored
of hypoclycaemia, such as impaired
consciousness, extensor posturing and • other signs of “uraemia syndrome”
other involuntary movements, may be • pulse rate
presenting signs that respond to a test • blood pressure, lying and sitting, to
dose of intravenous 50% dextrose injection detect postural hypotension (see 14
(Warrell, 2009) (Tun-Pe et al., 1987) (Fig Treatment of hypotension and shock)
52a). Hydrocortisone, fluid and electrolyte • respiratory rate
replacement may needed acutely in these • temperature
patients. In chronic cases, addition of • height of jugular venous pulse
thyroxin, oestrogen or testosterone may be • auscultation of lung bases for
needed (Antonypillai et al., 2011; Jeevagan crepitations
et al., 2013). • fluid balance chart and/or daily weight
6.9.5 Treatment of oliguria and acute 6.9.5.1 Oliguric phase of renal failure
kidney injury Most, but not all, patients with acute
(Sitprija and Boonpucknavig 1979; renal failure are oliguric, defined as a
Chugh 1989) urine output of less than 400 ml/day or
less than 30 ml/hour (children less than
0.5ml/kg bodyweight /hour). Conservative
Detection of acute kidney injury management may tide the patient over,
avoiding the need for renal replacement
• Abrupt (within 48h) reduction therapy (dialysis).
in kidney function (Acute
Kidney Injury Network criteria) If the patient has intravascular volume
Decreasing or no urine output depletion, indicated by supine or postural
(<0.5 mL/kg/h for more than hypotension, or empty neck veins,
6 h) proceed as follows:
Increase in serum creatinine
concentration [serum 1. Establish intravenous access
creatinine ≥26.5 μmol/L (≥0.3
mg/dL)] or increasing by ≥150 2. Give a cautious fluid challenge: an
- 200% (x 1.5 - 2) compared to adult patient can be given 250-500
baseline [?urea] ml of isotonic saline over one hour
or, until the jugular venous pressure/
• Clinical “uraemia syndrome”: central venous pressure has risen to
nausea, vomiting, 8-10 cm above the sternal angle (with
acidotic (“Kussmaul”) the patient propped up at 45º). The
breathing patient must be closely observed while
hiccups, fetor, this is being done. The fluid challenge
drowsiness, confusion, coma, must be stopped
flapping tremor, muscle immediately if pulmonary oedema
twitching, convulsions develops. If the urine output does not
pericardial friction rub, improve it is reasonable to perform a
signs of fluid overload furosemide stress/challenge test (see
below for details).
ManageMent of snakebites
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157
only, should be given if serum potassium profoundly acidotic (deep sighing
>6.5 mmol/l or ECG changes “Kussmaul” respirations, very low
plasma bicarbonate concentration
• Calcium Gluconate 10%: 0.5 ml/kg or very low pH - <7.10),Sodium
10 ml slow intravenous injection over bicarbonate should be given.
2-5 minutes if haemodynamically Based on volume of distribution of
unstable, or over 15-20min if stable bicarbonate which is 40% of body
(onset of action 3 minutes). Check weight, bicarbonate deficit can be
for normalisation of ECG. Repeat if calculated. Usually 2-3 ampoules
necessary. (40 ml. of 8.4% sodium bicarbonate
equivalent to 1 mmol/ml) in 5%
• β2 agonist aerosol by inhaler (e.g. dextrose water, or half of the
salbutamol nebulisation 5mg q 1-2h calculated deficit can be replaced in
- onset of action 30 minutes - up to 3-4 hours. Severe acidosis in snakebite
10-20 mg. is usually associated with acute renal
failure. Volume expansion by sodium
• Give 50 ml of 50% dextrose with 10 bicarbonate can cause fluid overload.
units of soluble insulin intravenously Therefore, if there is no clinical
(onset of action 15 minutes) improvement dialysis is required.
Caution: Intravenous bicarbonate may
• Sodium Bicarbonate 8.4% 1 ml/kg IV precipitate profound hypocalcaemia
slow over 5 minutes and fitting, especially in patients with
rhabdomyolysis.
Followed by a low potassium diet.
8. Management of severe acidosis 9. Renal replacement therapy Dialysis
If the patient is hypotensive and (Fig 86)
ManageMent of snakebites
in south-east asia
159
6.9.5.4 Diuretic phase of renal failure urgent surgery, once specific antivenom
Some patients will develop polyuria that is has been given to neutralize venom
as important and as life-threatening as the procoagulants and other antihaemostatic
oliguric phase. Urine output increases to toxins, restoration of coagulability and
5-10 litres/24 hours following the period platelet function can be accelerated by
of anuria. The patient may become volume giving fresh frozen plasma, cryoprecipitate
depleted so that salt and water must be (fibrinogen, factor VIII), fresh whole blood
carefully replaced. or platelet concentrates.
Hypokalaemia may develop, in which case
a diet rich in potassium (fruit and fruit
juices) is recommended. Heparin is ineffective against
venom-induced thrombin and
6.9.5.5 Renal recovery phase may cause bleeding on its own
The diuretic phase may last for months account. It should never be used
after Russell’s viper bite. in cases of snakebite.
ManageMent of snakebites
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161
[a] [b]
Figure 87: Results of unnecessary fasciotomies in snakebite victims in Thailand: (a)
profuse bleeding in a patient with mild local envenoming but severe coagulopathy
following bites by green pit vipers (Trimeresurus T. albolabris); (b) Residual skin loss
and exposure of tendons following fasciotomy for mild local envenoming in a patient
bitten by a green pit viper (Trimeresurus T. albolabris) (Copyright the late Sornchai
Looareesuwan); (c) Persistent bleeding for 10 days, resulting in haemorrhagic shock
despite transfusion of 20 unites of blood, in a victim of Malayan pit viper bite in whom
fasciotomy was performed before adequate antivenom treatment had been given to
correct the coagulopathy (Copyright DA Warrell)
of envenomed muscle
Clinical features of a
within such tight fascial
compartmental syndrome
compartments could
• Disproportionately severe pain
result in an increase
• Weakness of intracompartmental
in tissue pressure
muscles
above the venous
• Pain on passive stretching of
pressure, resulting in
intracompartmental muscles
ischaemia. However,
• Hypoaesthesia of areas of skin
the classical signs of
supplied by nerves running
an intracompartmental
through the compartment
pressure syndrome
• Obvious tenseness of the
may be difficult to
compartment on palpation
assess in snakebite
victims and many
unnecessary, dangerous
and debilitating Detection of arterial pulses by palpation
fasciotomies are or doppler ultrasound probes, does not
performed, especially exclude intracompartmental ischaemia.
where surgeons The most reliable test is to measure
rather than physicians intracompartmental pressure directly
have the primary through a cannula introduced into the
[c]
responsibility for compartment and connected to a pressure
managing snakebite transducer or manometer (Annex 5). In
cases (Fig 87). Fasciotomy is generally orthopaedic practice, intracompartmental
falling out of favour for the treatment of pressures exceeding 40 mmHg (less in
snake-bitten limbs (Cumpston, 2011). children) may carry a risk of ischaemic
ManageMent of snakebites
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163
effective but, by rendering the eye
temporarily insensitive, may allow
Consists of urgent irrigating the affected eyes
trauma to the cornea. They should be
and other mucous membranes with liberal applied only once and the eye must
quantities of water, saline, Ringer’s lactate, be protected until sensation returns.
By overcoming blepharospasm,
milk or any other available bland liquid. these drugs may allow more efficient
irrigation.
ManageMent of snakebites
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165
kg maximum 100mg/kg/day) or 9. Assess the need and feasibility of
codeine phosphate (adult dose 30-60 transporting the patient to a higher
mg maximum 240 mg in 24 hours; level of the health service (see A above)
children more than 2 years old, 0.5 especially in case of:
mg/kg, maximum 2 mg/kg/day) can
be given every 4-6 hours by mouth as a. Substantial bleeding, 20WBCT still
required (not aspirin or non-steroidal positive (non-clotting) 6 hours after
anti-inflammatory drugs which can initial antivenom dose
cause bleeding). b. Progressive paralysis (muscle weakness)
or respiratory difficulty
4. Antivenom: if the patient fulfils c. Reduced urine output
criteria for antivenom treatment and d. Anaphylaxis –unresponsive to
if the necessary skills, equipment, adrenaline
antivenom, adrenaline and other e. Shock/hypotension- unresponsive to
necessary drugs are available, give fluids
antivenom. These skills include f. Severe local necrosis or signs suggestive
ability to diagnose local and systemic of compartment syndrome
envenoming, set up intravenous
infusion or intravenous injection, 10. Discourage the use of ineffective
identify the early signs of anaphylaxis and potentially harmful drugs (e.g.
and treat it with intramuscular corticosteroids, antihistamines, and
adrenaline. Reasess for repeated heparin).
dose(s) of antivenom. If no antivenom
is available, transfer to a hospital. C. At the District Hospital
Proceed as in B above plus:
5. If the patient is shocked/
hypotensive: give cautious 1. Assessment: carry out a more
intravenous fluid challenge (adult detailed clinical and laboratory
250-500 ml of 0.9% saline) to correct assessment including biochemical and
hypovolaemic shock. haematological measurements, ECG or
radiography, as indicated.
6. If the patient has evidence of
respiratory paralysis: give oxygen 2. Antivenom: if no antivenom is
by mask, consider atropine and available, transfer to a hospital that has
neostigmine, and transfer to hospital. antivenom or treat conservatively; this
It is assumed that assisted ventilation may require transfusion of blood or
other than by a tight-fitting face mask fresh frozen plasma (see above).
connected to an anaesthetic (Ambu)
bag will not be possible at this level. 3. Analgesia: (see B above) and, if
required, consider stronger parenteral
7. If the patient is oliguric: initiate opioid drugs as required all with
conservative management. great caution (e.g. subcutaneous,
intramuscular or even intravenous
8. The bite wound: if necrotic, tampered pethidine, initial adult dose 50-
with (incisions etc.) or obviously 100 mg; children 1-1.5 mg/kg; or
septic, give antibiotics and tetanus morphine, initial adult dose 5-10 mg;
prophylaxis. children 0.03-0.05 mg/kg,).
ManageMent of snakebites
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167
requires an appropriate infrastructure of 4. Antihistamines (H1 blockers) and
facilities and drugs at each level, training corticosteroids
of personnel, epidemiological monitoring Benefits: late serum sickness-type
and community education. reactions
ManageMent of snakebites
in south-east asia
169
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Annexes 185
186 GUIDELINES FOR THE
MANAGEMENT OF SNAKEBITES
Algorithm: Diagnosis of snakebite
1 annex
YES NO YES
YES NO
Figure 89a. Algorithm for diagnosis of the snake responsible for a bite in Sri Lanka (Ariaratnam et al., 2009)
Annexes 187
2 annex
Algorithm: Differentiating major Asian
snake species by clinical syndrome
These should be created based on local data so that they can be relevant for local use. The
example below is intended for use in Sri Lanka (Ariaratnam et al., 2009).
VIPERIDAE
Daboia russelii Echis carinatus
elapidae
Hydrophis cyanocinctus
Figure 89b: Syndromic approach to snakebite management in Sri Lanka: venomous snakes of Sri Lanka (Ariaratnam et al., 2009)
Annexes 189
Clinical spectrum of syndromes of snakebites, Sri Lanka
Species No. Local effects Coagulopathy Neurotoxicity Renal toxicity Myotoxicity
(%) (%) (%) (%) (%)
Common krait 88 9 - 95 - -
Cobra 45 91 - 80 - -
Cobra 78 96
Hump-nosed viper 10 97
Annexes 191
C. India 3. Bengal Chemicals and
Polyvalent antivenoms raised in equines Pharmaceuticals Ltd,
against venoms of Bungarus caeruleus, 6 Ganesh Chunder Avenue 700013
Naja naja, Daboia russelii, Echis carinatus Kolkota
collected in Mamallapuram, Tamil Nadu Tel: +91-33-2237-1525
but more recently also from other areas Fax:+91-33-2225-7697
(to be confirmed). Antivenoms are (currently stopped production)
lyophilised (reconstituted to 10ml per vial)
or liquid. 4. King Institute, Chennai (in 2016,
announced resumption of production
Recommended initial dosage for all these after a 15 year break)
antivenoms is:
Bungarus caeruleus: 10-20 vials Private sector
Naja naja: 10-20 vials
Daboia/Vipera russelli: 10 vials 1. Serum Institute of India
Echis carinatus: 5 vials (10 vials for E. c. 212/2, Hadapsar
sochureki in N and NW India) Off Soli Poonawalla Road 411028 Pune
Tel:+91-20-26993900
Note: venoms of other species (including Fax:+91-20-26993921
hump-nosed pit-viper Hypnale hypnale (reduced/stopped production)
– SW India and Sri Lanka, and all other
pit-vipers) are not covered by Indian 2. VINS Bioproducts Ltd
polyvalent antivenoms, nor are venoms by 806,Essjay House,
Naja, Daboia or Echis species, sea snakes Road Nr 3, Banjara Hills 500034
or other species occurring outside India. Hyderabad Tel:+91-40-23354550,
Fax:+91-40-23350410 Cobra
Annual production estimates of Antivenin, Russell’s Antivenin, Anti
number of 10 ml vials of polyvalent snake Venom Polyvalent
antivenom (“ASV”) (2015-16) are given in (production 2015-16: 1 000 000 vials)
parentheses.
3. Biological E. (Evans) Limited 18/1 and
Public sector 3, Azamabad 500020 Hyderabad
1. Central Research Institute, Kasauli Tel:+91-40-30213999,
173204 Kasauli (H.P.) Fax:+91-40-27615309
Tel:+91-1-792-72114 E-mail info@biologicale.co.in
Fax:+91-1-792-72049 (production 2015-16: 500 000 vials of
(reduced/stopped production)] liquid antivenom only)
Annexes 193
(no recent information available) D. russelii, E. carinatus, H. hypnale, and
Dr. Birjees Mazher Kazi, Executive Director N. naja. It showed satisfactory preclinical
National Institute of Health, Islamabad potency and will be subjected to clinical
Tel: (051) 9255117 trials in Sri Lanka. Antivenom against
Fax: (051) 9255099, 9255125 B. caeruleus is also being developed, to
Email: edoffice@isb.apollo. provide cover against all five medically
net.pk webmaster@nih.org.pk important snakes.
Contact: Shahid Akhtar
(liquid and lyophilized antivenoms, L. Thailand
10 ml/ampoule) The Thai Red Cross Society (production
Polyvalent anti-snake venom serum capacity 75 000 – 82 000 vials/year)
(B. caeruleus, E. carinatus, N. naja, Queen Saovabha Memorial Institute,
V. lebetina (=Macrovipera lebetina), 1871 Rama VI Road, Bangkok 10330
V. russelli (= Daboia russelii) Tel +662-2520161-4;
Recommended initial dose: 5 vials for Echis Fax +662-2540212;
carinatus, 10 vials for other species. Telex 82535 THRESCO TH)
(freeze-dried monovalent antivenoms, 10
J. Taiwan ml/ampoule)
National Institute of Preventive Medicine,
161 Kun-Yang Street, Nan-Kang, 1. Cobra antivenom (Naja kaouthia):
Taipei, ROC 11513 recommended dose 100 ml*
Tel +8862-7859215; 2. King cobra antivenin (Ophiophagus
Fax +8862-7853944. hannah): 50 ml*
Contact: Dr Gong-Ren Wang, Director 4. Russell’s viper antivenin (Daboia
(lyophilised antivenoms, 10 ml/ampoule) siamensis): 30 ml*
Bungarus multicinctus and N atra bivalent 5. Malayan pit viper antivenin
antivenom (Calloselasma rhodostoma): 30 ml*
Trimeresurus mucrosquamatus 6. Green pit viper antivenin (Cryptelytrops
(= Protobothrops mucrosquamatus) and – Trimeresurus albolabris): 30 ml*
Trimeresurus grammineus (= Viridovipera 7. Malayan Krait Antivenin (Bungarus
stejnegeri) bivalent antivenom candidus): 50 ml*
Recommended initial dose: 5 vials (freeze-dried polyvalent antivenoms, 10
Agkistrodon acutus (= Deinagkistrodon ml/ampoule)
acutus) antivenom Neuro polyvalent (raised against 1-3
Recommended initial dose: ? and 7): 20 ml* for all species
Annexes 195
4.5 metres long should be used (Canale et a rigid splint. The bandage is bound firmly
al., 2009). If that it not available, any long (at a pressure of 50-70 mmHg), but not
strips of material can be used. The bandage so tightly that the peripheral pulse (radial,
is bound firmly around the entire bitten posterior tibial, dorsalis pedis) is occluded
limb, starting distally around the fingers or that the patient develops severe
or toes and moving proximally, to include (ischaemic) pain in the limb.
Sutherland’s Pressure bandage -immobilisation: Elastic (not crepe) bandages 10 cm wide x 3.5 - 4.5 m long
Figure 91: Pressure-bandage immobilization: left – lower limb; right - upper limb (Copyright Dr David J Williams)
Annexes 197
6 annex
Measurement of intracompartmental pressure
Measurement of intracompartmental way tap, the system is connected, through
pressure in tensely swollen snake- a side arm to a blood pressure transducer
bitten limbs or saline or mercury manometer (Fig 93a).
To confirm a clinical suspicion of The system is filled with sterile isotonic
intracompartmental syndrome the saline. If a syringe-type infusion pump
pressure inside the particular compartment and arterial blood pressure transducer
should be measured directly (Matsen with monitor is used, the pressure can
1980; Mars and Hadley 1998; Mars et al., be measured continuously at a very slow
1991). rate of infusion (eg 0.7 ml/day). If a saline
or mercury manometer is used, a much
The threshold pressure required to higher rate of infusion is required to
initiate the flow of liquid into the fascial initiate flow into the compartment. These
compartment is a measure of the tissue systems are not suitable for continuous
pressure inside that compartment. With intracompartmental pressure monitoring.
full sterile precautions and after infiltrating Alternatively, the simple but expensive
local anaesthetic, a 21 or 22 gauge Stryker pressure monitor can be used
cannula, approximately 3-4 cm long, is (Fig 93b).
inserted into the compartment through
or around an introducing 20 or 21 gauge Whatever system is employed, the zero
needle. The cannula is connected through point in the pressure measuring device
narrow pressure tubing to a syringe or low must be aligned to the level at which the
speed infusion pump. Through a three- cannula enters the fascial compartment.
[a] [b]
Figures 93: Measurement of intracompartmental pressure to exclude compartment syndrome in a snakebite victim: (a) infusion pump, saline
manometer system in use for measuring the tissue pressure inside the anterior tibial compartment; (b) Stryker pressure monitor in use for
measurement of intracompartmental pressure (Copyright DA Warrell)
Annexes 199
Myanmar pharmaceutical Industry Professor Christeine Ariaranee
Ministry of Industry Gnanathasan
Yangon, Myanmar Professor in Medicine,
Faculty of Medicine,
Professor Khin Thida Thwin University of Colombo
Programme Manager, Colombo, Sri Lanka
WHO Snakebite Control Project, Myanmar
Professor and Head of Department Dr H.M.K. Wickramanayake
Department of Renal Medicine, Director
University of Medicine (I) Primary Care Services, Ministry of
500 Beded Yangon Speciality Hospital Healthcare & Nutrition
Yangon, Myanmar Colombo, Sri Lanka
Annexes 201
VENOMOUS SNAKES OF THE searo REGION,
THEIR VENOMS, AND THE PATHOPHYSIOLOGY...
203
Snakebites are well-known medical emergencies in many parts of the world, especially
in rural areas. Agricultural workers and children are the most affected. The incidence
of snakebite mortality is particularly high in South-East Asia. Rational use of snake
anti-venom can substantially reduce mortality and morbidity due to snakebites.
These guidelines are a revised and updated version of Regional Guidelines for the
Management of snakebites published by the WHO Regional Office in South-East Asia
in 2011. These guidelines aim to promote the rational management of snakebite cases
in various health facilities where trained health functionaries and quality snake anti-
venom are available.
ISBN: 978-92-9022-530-0