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COMPARISON OF DIFFERENT
DOSING PROTOCOLS OF ANTI
SNAKE VENOM (ASV) IN
SNAKE BITE CASES
GUIDE: DR SACHIN HOSKATTI
STUDENT:DR SUSHMA S
BIRADAR
Journal of clinical and diagnostic
research,2017
• Snakebite is an acute life threatening time
limiting medical emergency
• Total number of bites may be more than 5.4
million,2.5 million envenomation and 1.25 lakh
deaths worldwide
• Though snakebite is a life threatening centuries
old condition, it was included in the list of
neglected tropical diseases by World Health
Organization in the year 2009 (Warrell and WHO
2009; Bawaskar HS 2014).
• The estimated death in India is 50,000/ yr, an
underestimate because of lack of proper
registration of snakebite
• 66-163/1 lakh population suffer from snake
bite annually with mortality of 1.1 to 2.4/1
lakh population and case fatality rate of 1.7%
to 20%
• The “Big four”
• Naja naja(Common cobra)
• Bungarus caeruleus(common krait)
• Vipera russelii(russels viper)
• Echis carinatus(Saw scaled viper)
• Medically important species and anti-snake
venom (ASV) is the only specific antidote
• Kraits are active during night hours, often
biting a persons sleeping on floor bed
• Maximum Viper and Cobra bites occur during
the day or early darkness, while watering the
plantation or walking bare foot in grown grass
or soybean crops
FIRST AID PROTOCOL
• CARRY = Do not allow victim to walk even for a short distance; just
carry him in any form, specially when bite is at leg.
• No - Tourniquate
• No - Electrotherapy
• No - Cutting
• No - Pressure immobilization
• Nitric oxide donor (Nitrogesic ointment/ Nitrate Spray)
• R = Reassure the patient. 70% of all snakebites are from non-venomous
species. Only 50% of bites by venomous species actually envenomate the
patient.
• I = Immobilize in the same way as a fractured limb. Use bandages or cloth
to hold the splints, not to block the blood supply or apply pressure. Do not
apply any compression in the form of tight ligatures, they don’t work and
can be dangerous!
• G H = Get to Hospital Immediately. Traditional remedies have NO
PROVEN benefit in treating snakebite.
• T = Tell the Doctor of any systemic symptoms that manifest on the way of
hospital.
Suspected snake bite
• Overt bite occult bite
History of bite no history of bite(?krait)
Nonvenoumous(70) neuroparalytic with no
/venomous(30) local signs,severe
abdominal pain,vomiting
asymptomatic symptomatic
ASV,AN,ventilation)
anxiety,palpitations,tachycardia
symptomatic
• Progressive painful Neuroparalytic Vasculotoxic
Swelling Cobra Russels s viper
saw scale viper
Viper Krait
Local necrosis Ptosis bleeding
Diplopia DIC,shock,AKI
Ecchymosis Dysarthia
Blistering Dysphonia
Painful swelling Dyspnea
Compartment syndrome Dysphagia
Asv,supportive,blood
transfusion,dialysis
Paralysis
ASV ASV,AN,ASSISTED VENTILATION
20 minute whole blood clotting test (20 WBCT):
It is a bedside test.
• Place 2 ml of freshly sampled venous blood in a small glass
test tube and leave undisturbed for 20 minutes at ambient
temperature.
• Gently tilt the test tube to see if the blood is still liquid; the
patient has hypofibrinogenaemia (“incoagulable” blood or
“not clotted”) as a result of venom-induced consumption
coagulopathy
• If blood clot is formed and signs and symptoms of neurotoxic
envenomation present, classify as neurotoxic envenomation
• If there is any doubt, repeat the test in duplicate, including
a “control” (blood from a healthy person).
• Counsel patient and relatives in the beginning that,
20WBCT may be repeated several times before giving any
medication.
• If clotted, the test should be carried out every 1 h from
admission for three hours and then 6 hourly for 24 hours.
• In case test is non-clotting, repeat 6 hour after
administration of loading dose of ASV.
• In case of neurotoxic envenomation repeat clotting test
after 6 hours.
FEATURE COBRA KRAITS RUSSELS
VIPER
SAW SCALED
VIPER
HUMPED
NOSE VIPER
Local
pain/tissue
damage
Yes NO Yes Yes Yes
Ptosis,
neurological
sign
Yes Yes No No No
Hemostatic
abnormality
No May occur Yes Yes Yes
Renal
complication
No No Yes No Yes
Response to
neostigmine
Yes ± No No No
Response to
ASV
Yes Yes yes yes No
FATAL DOSE VENOM
NEUTRALISED
BY 1 ML OF
ASV
TOTAL ASV
COBRA 120 0.6MG 200ml
RUSSELLS
VIPER
150 0.6mg 250ml
KRAIT 60 0.45mg 134ml
ECHIS
CARINATUS
80 0.45mg 10.22ml
ASV ADMINISTRATION CRITERIA
• SYSTEMIC ENVENOMING
• Evidence of coagulopathy: Primarily detected by
20WBCT or visible spontaneous systemic bleeding.
• Evidence of neurotoxicity: ptosis, external
ophthalmoplegia, muscle paralysis, inability to lift the
head etc.
• Cardiovascular abnormalities: hypotension, shock,
cardiac arrhythmia, abnormal ECG.
• Persistent and severe vomiting or abdominal pain.
• Severe Current Local envenoming
• Severe current, local swelling involving more than half of
the bitten limb (in the absence of a tourniquet). In the case
of severe swelling after bites on the digits (toes and
especially fingers) after a bite from a known necrotic
species.
• Rapid extension of swelling (for example beyond thewaist
or ankle within a few hours of bites on the hands or feet).
Swelling a number of hours old is not grounds for giving
ASV.
• Purely local swelling, even if accompanied by bite mark
from an apparently venomous snake, is not grounds for
administering ASV.
• Dose of ASV for neuroparalytic snakebite –
ASV 10 vials stat as infusion over 30 minutes
followed by 2nd dose of 10 vials after 1 hour if
no improvement within 1st hour.
Dose of ASV for vasculotoxic snakebite –
Two regimens low dose infusion therapy and high dose
intermittent bolus therapy can be used. Low dose infusion
therapy is as effective as high dose intermittent bolus therapy
and also saves scarce ASV doses (Expert Consensus).
• – Low Dose infusion therapy – 10 vials for Russel’s viper or 6
vials for Saw scaled viper as stat as infusion over 30 minutes
followed by 2 vials every 6 hours as infusion in 100 ml of
normal saline till clotting time normalizes or for 3 days
whichever is earlier.
• – High dose intermittent bolus therapy - 10 vials of
polyvalent ASV stat over 30 minutes as infusion, followed by
6 vials 6 hourly as bolus therapy till clotting time normalizes
and/or local swelling subsides.
• – No ASV for Sea snakebite or pit viper bite as available
ASV does not contain antibodies against them.
ASV dose in pregnancy
• Pregnant women are treated in exactly the same way
as other victims. The same dosage of ASV is given.
• Refer the victim to a gynecologist for assessment of
any impact on the foetus.
• ASV dose in children
• Children also are given exactly the same dose of ASV
as adults as snakes inject the same amount of venom
into children and adult.
• Infusion: liquid or reconstituted ASV is diluted in 5-10
ml/kg body weight of normal saline. However, reduce
amount of fluid in running bottle to 200 ml to avoid
fluid over load.
Repeat dose of ASV
Vasculotoxic or haemotoxic envenomation
• Repeat clotting test every 6 hours until coagulation is
restored.
• Administer ASV every 6 h until coagulation is
restored
• Maximum 30 vials
Repeat dose: neuroparalytic or neurotoxic
envenomation
• Repeat ASV when there is worsening neurotoxic or
cardiovascular signs even after 1–2 h.
• Maximum dose 20 vials of ASV for neurotoxically
envenomed patients
Victims who arrive late
• Sometimes victims arrive late after the bite, often after
several days, usually with acute kidney injury.
• Determine current venom activity such as bleeding in
case of viperine envenomation.
• Perform 20WBCT and determine if any coagulopathy is
present then administer ASV.
• If no coagulopathy is evident, treat kidney injury, if any.
ASV GOLDEN HOURS-within 4 hours
• Monitoring of Patients on ASV therapy
• All patients should be watched carefully every 5
min for first 30 min, then at 15 min for 2 hours for
manifestation of a reaction.
• At the earliest sign of an adverse reaction
suspend temporarily.
• Maintain a strict intake output chart and note
colour of urine to detect acute kidney injury
early.
ASV REACTION
• NO ASV TEST DOSE MUST BE ADMINISTERED.
• Rarely patients may develop severe life-
threatening anaphylaxis characterized by
hypotension, bronchospasm, and angioedema.
• However, 20%-60% patients treated with ASV
develop either early or late mild reactions.
• Early anaphylactic reactions occurs within 10–
180 min of start of therapy and is characterized
by itching, urticaria, dry cough, nausea and
vomiting, abdominal colic, diarrhoea,
tachycardia, and fever.
• Pyrogenic reactions usually develop 1–2 h after treatment.
Chills and rigors, fever, and hypotension.
• These reactions are caused by contamination of the ASV with
pyrogens during the manufacturing process.
• Any new sign or symptom after starting the ASV in drip
should be suspected as a reaction to ASV.
• Late (serum sickness–type) reactions develop 1–12 (mean 7)
days after treatment
• fever, nausea, vomiting, diarrhoea, itching, recurrent urticaria,
arthralgia, myalgia, lymphadenopathy, immune complex
nephritis and, rarely, encephalopathy.
•
• Treatment of Early ASV reaction
• Stop ASV temporarily.
• Start fresh IV normal saline infusion with a new IV set
• Administer Epinephrine (adrenaline) (1 in 1,000 solution, 0.5
mg (i e 0.5 ml) in adults intramuscular over deltoid or over
thigh; In children 0.01 mg/kg body weight) for early
anaphylactic and pyrogenic ASV reactions.
• Administer Chlorpheniramine maleate (adult dose 10 mg, in
children 0.2 mg/kg) intravenously.
• Role of Hydrocortisone in managing ASV reaction is not
proved.
• Once the patient has recovered, re-start ASV slowly for 10-15
minutes keeping the patient under close observation. Then
resume normal drip rate.
• For high risk patients
• In patients with history of hypersensitivity or
exposure to animal serum such as equine ASV,
tetanus-immune globulin or rabies-immune globulin
in past, severe atopic conditions:
• Give ASV only if they have signs of systemic
envenoming.
• Give Inj. Hydrocortisone 200 mg and
Chlorpheniramine maleate 22.75 mg prior to the
administration of ASV.
• Inj. Adrenaline 0.25 ml of 1:1000 (as available in one
ampoule of 1 ml) Subcutaneously just before adding
ASV to the running IV fluid.
Treatment of Late (serum sickness–type)
reactions
• Inj. Chlorpheniramine 2 mg in adults (In
children 0.25 mg/kg/day) 6 hourly for 5 days.
• In patients who fail to respond within
24–48 h give a 5-day course of
Prednisolone (5 mg 6 hourly in adults and 0.7
mg/kg/day in divided doses in children.
MANAGEMENT NEUROTOXIC
(NEUROPARALYTIC) ENVENOMATION
• Oxygen and assisted ventilation
• Administer ‘Atropine Neostigmine (AN)’ schedule
described as below
• Atropine 0.6 mg followed by neostigmine (1.5mg) to be
given IV stat and repeat dose of neostigmine 0.5 mg
with atropine every 30 minutes for 5 doses (In children,
Inj. Atropine 0.05 mg/kg followed by Inj. Neostigmine
0.04 mg/kg Intravenous and repeat dose 0.01 mg/kg
every 30 minutes for 5 doses).
• A fixed dose combination of Neostigmine and
glycopyrolate IV can also be used
• Tapering dose at 1 hour, 2 hour, 6 hours and
12 hour.
• After 30 minutes, any improvement should be
visible by an improvement in ptosis.
• Positive response to “AN” trial is measured as
50% or more recovery of the ptosis in one
hour.
• Stop Atropine neostigmine (AN) dosage schedule
if:
• Patient has complete recovery from neuroparalysis.
Rarely patient can have recurrence, carefully watch
patients for recurrence.
• Patient shows side effects in the form of
fasciculations or bradycardia.
• If there is no improvement after 3 doses.
• If there is no improvement after 3 doses of
atropine neostigmine (within 1 h), this indicates
probable Krait bite.
• Krait affects pre-synaptic fibres where calcium ion
acts as neurotransmitter.
• Give Inj. Calcium gluconate 10ml IV (in children 1-
2 ml/kg (1:1 dilution) slowly over 5-10 min every
6 hourly and continue till neuroparalysis recovers
which may last for 5-7 days.
MANAGEMENT OF VASCULOTOXIC
SNAKEBITE:
• Volume Replacement in snake bite
• TO Give fluid challenge of 2l of isotonic saline
for 1 hour and maintain cvp of 8-10cm
• To watch for hematuria,bleeding
manifestations
• Closely monitor urine output and maintain 1
ml/kg/h urine output
• Forced Alkaline Diuresis –oliguria,
• within first 24 hours of the bite to avoid
pigment nephropathy leading to acute tubular
necrosis (ATN).
• If patient responds to first cycle continue for
3 cycles
• – If there is no response to furosemide
discontinue FAD and refer patient
immediately to a higher center for dialysis.
Indications for dialysis are:
• Absolute value of Blood urea >130 mg/dl
• Sr. Creatinine > 4 mg/dl
• Evidence of hypercatabolism in the form of daily rise in
blood urea 30 mg/dL (BUN > 15), Sr. Creatinine > 1 mg/dL,
Sr. Potassium > 1 mEq/L and fall in bicarbonate >2 mmol/L
• Fluid overload leading to pulmonary oedema
• Hyperkalaemia (>7 mmol/l (or hyperkalaemic ECG
changes)
• unresponsive to conservative management.
• Uremic complications – encephalopathy, pericarditis.
Shock
• Correct hypovolaemia with colloid/crystalloids,
controlled by observation of the central venous
pressure.
• Infusion of isotonic crystalloids or albumin, with
boluses of up to 20 ml/kg for crystalloids (or
albumin equivalent) over 5 to 10 mins titrated to
reversing hypotension, increasing urine output,
and attaining normal capillary refill, peripheral
pulses and level of consciousness without
inducing lung crepitations or hepatomegaly.
• Ionotropic support given if improved on fluid
resuscitation
• In sepsis, noadrenaline is the inotropic agent of
choice. Treat patients with hypotension
associated with bradycardia with atropine.
• coagulopathy – in case of prolonged CT, PT, aPTT
administer fresh frozen plasma (FFP) infusion
Administer 10-15 ml/kg of FFP within over 30–60
min within 4 hours of ASV administration
AIM OF STUDY
• To obtain data on proportion of poisonous
snake among all snake bite cases
• To compare modified low dose ASV protocol
versus conventional ASV protocol
Methodology
• Retrospective study conducted at a tertiary
care teaching hospital, Pune, Maharashtra,
India.
• A total of 247 snake bite cases were admitted
to the hospital during June 2012 to September
2012, were summarised as case records
• These records reviewed and analysed
Modified protocol for vasculotoxic
snakes
• 5 vials ASV stat followed by 2 vials repeated six hourly
till normalization of Whole Blood Clotting Time (WBCT)
to less than 20 minutes.
• In case of frank bleeding, the dose was 10 vials of ASV
stat and five vials at two hourly intervals if bleeding
continued.
• If frank bleeding occurred after the first dose, repeat
dose was five vials at six hourly intervals in place of
two vials, till bleeding stopped.
• If patient presented with severe cellulitis the dose was
five vials stat, Two vials ASV was repeated six hourly
only if cellulitis was spreading.
Modified protocol for neurotoxic snake
bites
• 5 ASV vials stat followed by 5 vials ASV
repeated once after two hours, if symptoms
were unimproved or progressing.
• Patients showing no response to neostigmine
or requiring ventilator support were
administered 10 vials stat and 10 vials after
two hours.
• No neurotoxic snake bite patient received
more than 20 vials in total
results
PARAMETER CONVENTIONAL
PROTOCOL(N=77)
MODIFIED
PROTOCOL(N=78)
AGE(YEARS) 39.26±1.73 36.19±1.78
SEX(M:F) 46:31 47:31
ASV VIALS 28.17±2.75 10.74±0.95
NUMBER OF PATIENTS
REQUIRING FFP
18 12
FFP UNITS(BAGS) 7.33±1.51 4.08±0.43
NUMBER OF PATIENTS
REQUIRING DIALYSIS
2 5
DURATION OF STAY IN
HOSPITAL
4.81 4.88
NUMBER OF PPATIENTS IN
MICU
15 31
• Of the 78 cases with known outcome in
modified protocol group, five had mixed, six
had neurotoxic and 67 had vasculotoxic
manifestations.
• The average requirements of ASV were
11.19±3.99 vials for vasculotoxic
manifestations and 7.5±1.11 vials for
neurotoxic manifestations (p=0.029)
• The ASV requirement for mixed
manifestations was intermediate (8.6±1.50
vials).
• Mortality was 8 of 67 (11.94%) with
vasculotoxic manifestations and 1 of 5 (20%)
with mixed manifestations
• No deaths (0%) among those with neurotoxic
manifestations
• A single vial of polyvalent ASV costs around
687.00 INR and the average reduction of
around 17.43 vials achieved with the modified
protocol results is significant reduction in
average cost of ASV by 11974.41 INR per
treated patient.
Other studies
• Kothari D et al., compared a low dose continuous
intravenous regimen (20 ml over two hours
followed by 20 ml every 24 hours) with high dose
intermittent bolus regimen (30-100 ml over one
hour followed by of 30-100 ml every 24 hours) of
ASV till correction of coagulation parameters or
neurological signs in total 100 patients and
reported that low dose ASV had lower mortality
and shorter duration for recovery of coagulation
parameters and hospital stay as well as the
reaction to ASV was not different
• Thomas PP and Jacob J et al., compared a protocol of
four ampoules of antivenom in the first hour, four in
the next two hours, four in the next three hours, and
then three every subsequent three hours to one group
with two ampoules of antivenom in the first hour, two
in the next two hours, and two every subsequent three
hours to another group till clotting time became
normal (under 10 minutes) followed by two or three
ampoules of antivenom over 24 hours to neutralise any
further venom that might be absorbed. They observed
that the low dose protocol was as effective as the
higher doses
• Paul V et al., treated snake bite cases with six
vials or 12 vials of ASV, irrespective of type of
snake or severity of bite and concluded that
high dose of ASV did not offer any additional
advantage. On the contrary, most of the
parameters like mortality, duration of hospital
stay and need for dialysis showed a beneficial
trend for the low-dose group along with
considerable financial gain
• A systematic review of five randomized clinical
trials comparing low versus high dose ASV in
poisonous snake bite reported that low-dose
ASV is equivalent or may be superior to high-
dose ASV in management of poisonous snake
bite.
• They also found that low dose is highly cost-
effective as compared to the high dose
• In the present study, we found that our
modified protocol resulted in significant
reduction in requirement for ASV without any
adverse impact on outcome.
• The duration for hospitalization and mortality
was similar in both groups.
• The patients from modified protocol group
required fewer average number of dialysis and
relatively fewer units of fresh frozen plasma
REFERENCES
• STANDARD TREATMENT GUIDELINES ,Management of Snake Bite,Quick
Reference Guide,January 2016,Ministry of Health & Family
Welfare,Government of India
•
Comparison of Different Dosing Protocols of Anti-Snake Venom (ASV)
indiaSnake Bite Cases, BR DaSwani1, aS ChanDanwale2, DB KaDam3,
BB GhonGane4, VS GhoRPaDe5, hC manu6, Journal of Clinical and
Diagnostic Research. 2017 Sep, Vol-11(9): FC17-FC21
Management of Snake Bite in India
• Shibendu Ghosh, Prabuddha Mukhopadhyay.JAPI
•
•
•
•
Snake bite - ASV Protocols and Management - Antisnake Venom

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Snake bite - ASV Protocols and Management - Antisnake Venom

  • 1. COMPARISON OF DIFFERENT DOSING PROTOCOLS OF ANTI SNAKE VENOM (ASV) IN SNAKE BITE CASES GUIDE: DR SACHIN HOSKATTI STUDENT:DR SUSHMA S BIRADAR Journal of clinical and diagnostic research,2017
  • 2. • Snakebite is an acute life threatening time limiting medical emergency • Total number of bites may be more than 5.4 million,2.5 million envenomation and 1.25 lakh deaths worldwide • Though snakebite is a life threatening centuries old condition, it was included in the list of neglected tropical diseases by World Health Organization in the year 2009 (Warrell and WHO 2009; Bawaskar HS 2014).
  • 3. • The estimated death in India is 50,000/ yr, an underestimate because of lack of proper registration of snakebite • 66-163/1 lakh population suffer from snake bite annually with mortality of 1.1 to 2.4/1 lakh population and case fatality rate of 1.7% to 20%
  • 4. • The “Big four” • Naja naja(Common cobra) • Bungarus caeruleus(common krait) • Vipera russelii(russels viper) • Echis carinatus(Saw scaled viper) • Medically important species and anti-snake venom (ASV) is the only specific antidote
  • 5.
  • 6. • Kraits are active during night hours, often biting a persons sleeping on floor bed • Maximum Viper and Cobra bites occur during the day or early darkness, while watering the plantation or walking bare foot in grown grass or soybean crops
  • 7. FIRST AID PROTOCOL • CARRY = Do not allow victim to walk even for a short distance; just carry him in any form, specially when bite is at leg. • No - Tourniquate • No - Electrotherapy • No - Cutting • No - Pressure immobilization • Nitric oxide donor (Nitrogesic ointment/ Nitrate Spray) • R = Reassure the patient. 70% of all snakebites are from non-venomous species. Only 50% of bites by venomous species actually envenomate the patient. • I = Immobilize in the same way as a fractured limb. Use bandages or cloth to hold the splints, not to block the blood supply or apply pressure. Do not apply any compression in the form of tight ligatures, they don’t work and can be dangerous! • G H = Get to Hospital Immediately. Traditional remedies have NO PROVEN benefit in treating snakebite. • T = Tell the Doctor of any systemic symptoms that manifest on the way of hospital.
  • 8.
  • 9.
  • 10. Suspected snake bite • Overt bite occult bite History of bite no history of bite(?krait) Nonvenoumous(70) neuroparalytic with no /venomous(30) local signs,severe abdominal pain,vomiting asymptomatic symptomatic ASV,AN,ventilation) anxiety,palpitations,tachycardia
  • 11. symptomatic • Progressive painful Neuroparalytic Vasculotoxic Swelling Cobra Russels s viper saw scale viper Viper Krait Local necrosis Ptosis bleeding Diplopia DIC,shock,AKI Ecchymosis Dysarthia Blistering Dysphonia Painful swelling Dyspnea Compartment syndrome Dysphagia Asv,supportive,blood transfusion,dialysis Paralysis ASV ASV,AN,ASSISTED VENTILATION
  • 12. 20 minute whole blood clotting test (20 WBCT): It is a bedside test. • Place 2 ml of freshly sampled venous blood in a small glass test tube and leave undisturbed for 20 minutes at ambient temperature. • Gently tilt the test tube to see if the blood is still liquid; the patient has hypofibrinogenaemia (“incoagulable” blood or “not clotted”) as a result of venom-induced consumption coagulopathy • If blood clot is formed and signs and symptoms of neurotoxic envenomation present, classify as neurotoxic envenomation
  • 13. • If there is any doubt, repeat the test in duplicate, including a “control” (blood from a healthy person). • Counsel patient and relatives in the beginning that, 20WBCT may be repeated several times before giving any medication. • If clotted, the test should be carried out every 1 h from admission for three hours and then 6 hourly for 24 hours. • In case test is non-clotting, repeat 6 hour after administration of loading dose of ASV. • In case of neurotoxic envenomation repeat clotting test after 6 hours.
  • 14. FEATURE COBRA KRAITS RUSSELS VIPER SAW SCALED VIPER HUMPED NOSE VIPER Local pain/tissue damage Yes NO Yes Yes Yes Ptosis, neurological sign Yes Yes No No No Hemostatic abnormality No May occur Yes Yes Yes Renal complication No No Yes No Yes Response to neostigmine Yes ± No No No Response to ASV Yes Yes yes yes No
  • 15. FATAL DOSE VENOM NEUTRALISED BY 1 ML OF ASV TOTAL ASV COBRA 120 0.6MG 200ml RUSSELLS VIPER 150 0.6mg 250ml KRAIT 60 0.45mg 134ml ECHIS CARINATUS 80 0.45mg 10.22ml
  • 16. ASV ADMINISTRATION CRITERIA • SYSTEMIC ENVENOMING • Evidence of coagulopathy: Primarily detected by 20WBCT or visible spontaneous systemic bleeding. • Evidence of neurotoxicity: ptosis, external ophthalmoplegia, muscle paralysis, inability to lift the head etc. • Cardiovascular abnormalities: hypotension, shock, cardiac arrhythmia, abnormal ECG. • Persistent and severe vomiting or abdominal pain.
  • 17.
  • 18.
  • 19. • Severe Current Local envenoming • Severe current, local swelling involving more than half of the bitten limb (in the absence of a tourniquet). In the case of severe swelling after bites on the digits (toes and especially fingers) after a bite from a known necrotic species. • Rapid extension of swelling (for example beyond thewaist or ankle within a few hours of bites on the hands or feet). Swelling a number of hours old is not grounds for giving ASV. • Purely local swelling, even if accompanied by bite mark from an apparently venomous snake, is not grounds for administering ASV.
  • 20.
  • 21. • Dose of ASV for neuroparalytic snakebite – ASV 10 vials stat as infusion over 30 minutes followed by 2nd dose of 10 vials after 1 hour if no improvement within 1st hour.
  • 22. Dose of ASV for vasculotoxic snakebite – Two regimens low dose infusion therapy and high dose intermittent bolus therapy can be used. Low dose infusion therapy is as effective as high dose intermittent bolus therapy and also saves scarce ASV doses (Expert Consensus). • – Low Dose infusion therapy – 10 vials for Russel’s viper or 6 vials for Saw scaled viper as stat as infusion over 30 minutes followed by 2 vials every 6 hours as infusion in 100 ml of normal saline till clotting time normalizes or for 3 days whichever is earlier. • – High dose intermittent bolus therapy - 10 vials of polyvalent ASV stat over 30 minutes as infusion, followed by 6 vials 6 hourly as bolus therapy till clotting time normalizes and/or local swelling subsides. • – No ASV for Sea snakebite or pit viper bite as available ASV does not contain antibodies against them.
  • 23. ASV dose in pregnancy • Pregnant women are treated in exactly the same way as other victims. The same dosage of ASV is given. • Refer the victim to a gynecologist for assessment of any impact on the foetus.
  • 24. • ASV dose in children • Children also are given exactly the same dose of ASV as adults as snakes inject the same amount of venom into children and adult. • Infusion: liquid or reconstituted ASV is diluted in 5-10 ml/kg body weight of normal saline. However, reduce amount of fluid in running bottle to 200 ml to avoid fluid over load.
  • 25. Repeat dose of ASV Vasculotoxic or haemotoxic envenomation • Repeat clotting test every 6 hours until coagulation is restored. • Administer ASV every 6 h until coagulation is restored • Maximum 30 vials
  • 26. Repeat dose: neuroparalytic or neurotoxic envenomation • Repeat ASV when there is worsening neurotoxic or cardiovascular signs even after 1–2 h. • Maximum dose 20 vials of ASV for neurotoxically envenomed patients
  • 27. Victims who arrive late • Sometimes victims arrive late after the bite, often after several days, usually with acute kidney injury. • Determine current venom activity such as bleeding in case of viperine envenomation. • Perform 20WBCT and determine if any coagulopathy is present then administer ASV. • If no coagulopathy is evident, treat kidney injury, if any. ASV GOLDEN HOURS-within 4 hours
  • 28. • Monitoring of Patients on ASV therapy • All patients should be watched carefully every 5 min for first 30 min, then at 15 min for 2 hours for manifestation of a reaction. • At the earliest sign of an adverse reaction suspend temporarily. • Maintain a strict intake output chart and note colour of urine to detect acute kidney injury early.
  • 29. ASV REACTION • NO ASV TEST DOSE MUST BE ADMINISTERED. • Rarely patients may develop severe life- threatening anaphylaxis characterized by hypotension, bronchospasm, and angioedema. • However, 20%-60% patients treated with ASV develop either early or late mild reactions. • Early anaphylactic reactions occurs within 10– 180 min of start of therapy and is characterized by itching, urticaria, dry cough, nausea and vomiting, abdominal colic, diarrhoea, tachycardia, and fever.
  • 30. • Pyrogenic reactions usually develop 1–2 h after treatment. Chills and rigors, fever, and hypotension. • These reactions are caused by contamination of the ASV with pyrogens during the manufacturing process. • Any new sign or symptom after starting the ASV in drip should be suspected as a reaction to ASV. • Late (serum sickness–type) reactions develop 1–12 (mean 7) days after treatment • fever, nausea, vomiting, diarrhoea, itching, recurrent urticaria, arthralgia, myalgia, lymphadenopathy, immune complex nephritis and, rarely, encephalopathy. •
  • 31. • Treatment of Early ASV reaction • Stop ASV temporarily. • Start fresh IV normal saline infusion with a new IV set • Administer Epinephrine (adrenaline) (1 in 1,000 solution, 0.5 mg (i e 0.5 ml) in adults intramuscular over deltoid or over thigh; In children 0.01 mg/kg body weight) for early anaphylactic and pyrogenic ASV reactions. • Administer Chlorpheniramine maleate (adult dose 10 mg, in children 0.2 mg/kg) intravenously. • Role of Hydrocortisone in managing ASV reaction is not proved. • Once the patient has recovered, re-start ASV slowly for 10-15 minutes keeping the patient under close observation. Then resume normal drip rate.
  • 32. • For high risk patients • In patients with history of hypersensitivity or exposure to animal serum such as equine ASV, tetanus-immune globulin or rabies-immune globulin in past, severe atopic conditions: • Give ASV only if they have signs of systemic envenoming. • Give Inj. Hydrocortisone 200 mg and Chlorpheniramine maleate 22.75 mg prior to the administration of ASV. • Inj. Adrenaline 0.25 ml of 1:1000 (as available in one ampoule of 1 ml) Subcutaneously just before adding ASV to the running IV fluid.
  • 33. Treatment of Late (serum sickness–type) reactions • Inj. Chlorpheniramine 2 mg in adults (In children 0.25 mg/kg/day) 6 hourly for 5 days. • In patients who fail to respond within 24–48 h give a 5-day course of Prednisolone (5 mg 6 hourly in adults and 0.7 mg/kg/day in divided doses in children.
  • 34. MANAGEMENT NEUROTOXIC (NEUROPARALYTIC) ENVENOMATION • Oxygen and assisted ventilation • Administer ‘Atropine Neostigmine (AN)’ schedule described as below • Atropine 0.6 mg followed by neostigmine (1.5mg) to be given IV stat and repeat dose of neostigmine 0.5 mg with atropine every 30 minutes for 5 doses (In children, Inj. Atropine 0.05 mg/kg followed by Inj. Neostigmine 0.04 mg/kg Intravenous and repeat dose 0.01 mg/kg every 30 minutes for 5 doses). • A fixed dose combination of Neostigmine and glycopyrolate IV can also be used
  • 35. • Tapering dose at 1 hour, 2 hour, 6 hours and 12 hour. • After 30 minutes, any improvement should be visible by an improvement in ptosis. • Positive response to “AN” trial is measured as 50% or more recovery of the ptosis in one hour.
  • 36. • Stop Atropine neostigmine (AN) dosage schedule if: • Patient has complete recovery from neuroparalysis. Rarely patient can have recurrence, carefully watch patients for recurrence. • Patient shows side effects in the form of fasciculations or bradycardia. • If there is no improvement after 3 doses.
  • 37. • If there is no improvement after 3 doses of atropine neostigmine (within 1 h), this indicates probable Krait bite. • Krait affects pre-synaptic fibres where calcium ion acts as neurotransmitter. • Give Inj. Calcium gluconate 10ml IV (in children 1- 2 ml/kg (1:1 dilution) slowly over 5-10 min every 6 hourly and continue till neuroparalysis recovers which may last for 5-7 days.
  • 38. MANAGEMENT OF VASCULOTOXIC SNAKEBITE: • Volume Replacement in snake bite • TO Give fluid challenge of 2l of isotonic saline for 1 hour and maintain cvp of 8-10cm • To watch for hematuria,bleeding manifestations • Closely monitor urine output and maintain 1 ml/kg/h urine output
  • 39. • Forced Alkaline Diuresis –oliguria, • within first 24 hours of the bite to avoid pigment nephropathy leading to acute tubular necrosis (ATN). • If patient responds to first cycle continue for 3 cycles • – If there is no response to furosemide discontinue FAD and refer patient immediately to a higher center for dialysis.
  • 40. Indications for dialysis are: • Absolute value of Blood urea >130 mg/dl • Sr. Creatinine > 4 mg/dl • Evidence of hypercatabolism in the form of daily rise in blood urea 30 mg/dL (BUN > 15), Sr. Creatinine > 1 mg/dL, Sr. Potassium > 1 mEq/L and fall in bicarbonate >2 mmol/L • Fluid overload leading to pulmonary oedema • Hyperkalaemia (>7 mmol/l (or hyperkalaemic ECG changes) • unresponsive to conservative management. • Uremic complications – encephalopathy, pericarditis.
  • 41. Shock • Correct hypovolaemia with colloid/crystalloids, controlled by observation of the central venous pressure. • Infusion of isotonic crystalloids or albumin, with boluses of up to 20 ml/kg for crystalloids (or albumin equivalent) over 5 to 10 mins titrated to reversing hypotension, increasing urine output, and attaining normal capillary refill, peripheral pulses and level of consciousness without inducing lung crepitations or hepatomegaly.
  • 42. • Ionotropic support given if improved on fluid resuscitation • In sepsis, noadrenaline is the inotropic agent of choice. Treat patients with hypotension associated with bradycardia with atropine. • coagulopathy – in case of prolonged CT, PT, aPTT administer fresh frozen plasma (FFP) infusion Administer 10-15 ml/kg of FFP within over 30–60 min within 4 hours of ASV administration
  • 43. AIM OF STUDY • To obtain data on proportion of poisonous snake among all snake bite cases • To compare modified low dose ASV protocol versus conventional ASV protocol
  • 44. Methodology • Retrospective study conducted at a tertiary care teaching hospital, Pune, Maharashtra, India. • A total of 247 snake bite cases were admitted to the hospital during June 2012 to September 2012, were summarised as case records • These records reviewed and analysed
  • 45. Modified protocol for vasculotoxic snakes • 5 vials ASV stat followed by 2 vials repeated six hourly till normalization of Whole Blood Clotting Time (WBCT) to less than 20 minutes. • In case of frank bleeding, the dose was 10 vials of ASV stat and five vials at two hourly intervals if bleeding continued. • If frank bleeding occurred after the first dose, repeat dose was five vials at six hourly intervals in place of two vials, till bleeding stopped. • If patient presented with severe cellulitis the dose was five vials stat, Two vials ASV was repeated six hourly only if cellulitis was spreading.
  • 46. Modified protocol for neurotoxic snake bites • 5 ASV vials stat followed by 5 vials ASV repeated once after two hours, if symptoms were unimproved or progressing. • Patients showing no response to neostigmine or requiring ventilator support were administered 10 vials stat and 10 vials after two hours. • No neurotoxic snake bite patient received more than 20 vials in total
  • 47. results PARAMETER CONVENTIONAL PROTOCOL(N=77) MODIFIED PROTOCOL(N=78) AGE(YEARS) 39.26±1.73 36.19±1.78 SEX(M:F) 46:31 47:31 ASV VIALS 28.17±2.75 10.74±0.95 NUMBER OF PATIENTS REQUIRING FFP 18 12 FFP UNITS(BAGS) 7.33±1.51 4.08±0.43 NUMBER OF PATIENTS REQUIRING DIALYSIS 2 5 DURATION OF STAY IN HOSPITAL 4.81 4.88 NUMBER OF PPATIENTS IN MICU 15 31
  • 48. • Of the 78 cases with known outcome in modified protocol group, five had mixed, six had neurotoxic and 67 had vasculotoxic manifestations. • The average requirements of ASV were 11.19±3.99 vials for vasculotoxic manifestations and 7.5±1.11 vials for neurotoxic manifestations (p=0.029)
  • 49. • The ASV requirement for mixed manifestations was intermediate (8.6±1.50 vials). • Mortality was 8 of 67 (11.94%) with vasculotoxic manifestations and 1 of 5 (20%) with mixed manifestations • No deaths (0%) among those with neurotoxic manifestations
  • 50. • A single vial of polyvalent ASV costs around 687.00 INR and the average reduction of around 17.43 vials achieved with the modified protocol results is significant reduction in average cost of ASV by 11974.41 INR per treated patient.
  • 51. Other studies • Kothari D et al., compared a low dose continuous intravenous regimen (20 ml over two hours followed by 20 ml every 24 hours) with high dose intermittent bolus regimen (30-100 ml over one hour followed by of 30-100 ml every 24 hours) of ASV till correction of coagulation parameters or neurological signs in total 100 patients and reported that low dose ASV had lower mortality and shorter duration for recovery of coagulation parameters and hospital stay as well as the reaction to ASV was not different
  • 52. • Thomas PP and Jacob J et al., compared a protocol of four ampoules of antivenom in the first hour, four in the next two hours, four in the next three hours, and then three every subsequent three hours to one group with two ampoules of antivenom in the first hour, two in the next two hours, and two every subsequent three hours to another group till clotting time became normal (under 10 minutes) followed by two or three ampoules of antivenom over 24 hours to neutralise any further venom that might be absorbed. They observed that the low dose protocol was as effective as the higher doses
  • 53. • Paul V et al., treated snake bite cases with six vials or 12 vials of ASV, irrespective of type of snake or severity of bite and concluded that high dose of ASV did not offer any additional advantage. On the contrary, most of the parameters like mortality, duration of hospital stay and need for dialysis showed a beneficial trend for the low-dose group along with considerable financial gain
  • 54. • A systematic review of five randomized clinical trials comparing low versus high dose ASV in poisonous snake bite reported that low-dose ASV is equivalent or may be superior to high- dose ASV in management of poisonous snake bite. • They also found that low dose is highly cost- effective as compared to the high dose
  • 55. • In the present study, we found that our modified protocol resulted in significant reduction in requirement for ASV without any adverse impact on outcome. • The duration for hospitalization and mortality was similar in both groups. • The patients from modified protocol group required fewer average number of dialysis and relatively fewer units of fresh frozen plasma
  • 56. REFERENCES • STANDARD TREATMENT GUIDELINES ,Management of Snake Bite,Quick Reference Guide,January 2016,Ministry of Health & Family Welfare,Government of India • Comparison of Different Dosing Protocols of Anti-Snake Venom (ASV) indiaSnake Bite Cases, BR DaSwani1, aS ChanDanwale2, DB KaDam3, BB GhonGane4, VS GhoRPaDe5, hC manu6, Journal of Clinical and Diagnostic Research. 2017 Sep, Vol-11(9): FC17-FC21 Management of Snake Bite in India • Shibendu Ghosh, Prabuddha Mukhopadhyay.JAPI • • • •