1. Management of Snake Bite Victims with Respiratory Paralysis in ICU
Dr. T.R. Chandrashekar
Director Critical Care
K.R.Hospital
Bangalore
Published by
DR TRC/ KRH

2. Management of Snake Bite Victims with Respiratory Paralysis in ICU
Facts given
Snake bite which has lead to Respiratory Paralysis
Patient in ICU
Answer
Management aspects

3. How to prevent snake bites?
A world free of snakes
Nearly a quarter of us would go hungry
Are important elements in the food chain to control the rodent population- Which destroy all major crops.
The bottom line is we need snakes to survive

4. Epidemiology
India estimates in the region of 200,000 bites and 15-20,000 snake bite deaths per year
Originally made in the last century, are still quoted. No reliable national statistics are available.
Males are bitten almost twice as often as females
Majority of the bites being on the lower extremities.
50% of bites by venomous snakes are dry bites. that result in negligible envenomation.

5. FAB FOUR
In India, more than 200 species of snakes but only 52 are poisonous.
Saw-scaled viper (Echis carinatus)
Russell’s viper (Daboia russelii)
Common krait (Bungarus caeruleus)
Indian cobra (Naja naja)
Majority of bites
Nearly 70-80%
Hemotoxin
Vasculotoxin
Neurotoxic 1 2 3 4

6. Species: Medical Implications
Signs/Symptoms and Potential Treatments
Cobra
Krait
Russell’s Viper
Saw Scaled Viper
Other Vipers
Local pain/ Tissue Damage
Yes No
Ptosis/Neurotoxicity
Yes! NO
Coagulation
Renal Problems
Neostigmine & Atropine
No?

7. Syndromic approach No local signs with Neuro-toxicity- Krait
With or with out local signs and Neuo-toxicity-Cobra
With or with out Neurotoxicity and local signs and hemotoxicity-Rusell’s Viper
Local signs with hemotoxicity-Saw Scaled Viper

8. Venomous snakes Majority is by non-venomous snakes
Snake bite
Majority is by non-venomous snakes
Venomous snakes
About 50% of bites are dry
Anti snake venom
ASV -severe adverse reactions, Costly, Limited supply.
Used- benefits of ASV treatment is considered to exceed
the risks.

9. Our statistics Causes ARF, DIC, Shock, Pulmonary edema, Sepsis
45 snake bite admissions
8 Neuotoxic bites
6 required MV
33 Hemotoxic bites
20 required MV

10. Snake bite and Respiratory paralysis
More cases why ?
Neurotoxic
MV for respiratory paralysis
ASV
MV as Supportive care
Neuromuscular paralysis-
blockade of neuromuscular transmission.
Cobra- post-synaptic
Krait- pre-synaptic
Bulbar paralysis-Aspiration
Sepsis,
DIC-shock
ARF-Pulmonary edema

11. Starts early- many die before they reach hospitals
NEUROTOXICITY
Starts early- many die before they reach hospitals
Many reverse very well with ASV if started early
Less number of cases
HEMOTOXICITY
Starts late hence most of them reach hospitals
Many organ involvement hence MV is mostly supportive to buy time for organs to recover
More number of cases
70-80%
20-30%

12. Case scenario…….
34 yr old male shifted from rural health center with H/O snake bite 6 hrs back has ptosis, respiratory distress, RR 35/mt, BP 120/60, oral secretions present, absent gag and cough reflex shifted to ICU for teritary care.
On ASV 100ml stat, & 50ml in NS over 6 hrs
Oxygen 3l/mt
Patient is comfortable, vitals stable
No ptosis, distress
Patient received
in casualty
Patient is dead –what do you think went wrong ?

13. Patient is dead –what do you think went wrong ?
What could have been done better ?
Bulbar signs-probably aspirated and died
Endotracheal intubation can be placed on T-piece Ambuing or Transport Ventilator
Anticholienesterases
Neostigmine with atropine

14. Case scenario…….
34 yr old male shifted from rural health center with H/O snake bite 6 hrs back has ptosis, respiratory distress, RR 35/mt, BP 120/60, oral secretions present, absent gag and cough reflex shifted to ICU for teritary care.
On ASV 100ml stat, & 50ml in NS over 6 hrs
Oxygen 3l/mt
What are the Management issues?
Why does
Neurotoxicity occur
ASV, Anticholineesterases,
MV…

15. Snake venom components

16. Krait- Pre-synaptic action
Beta-bungarotoxin- Phospholipases A2
1) Inhibiting the release of acetylcholine from the presynaptic membrane
2) Presynaptic nerve terminals exhibited signs of irreversible physical damage and are devoid of synaptic vesicles
3) Antivenoms & anticholinesterases
have no effect
Paralysis lasts several weeks and frequently requires prolonged MV. Recovery is dependent upon regeneration of the terminal axon.

17. Cobra –post-synaptic alpha-neurotoxins “Curare-mimetic toxins’’
Bind specifically to acetylcholine receptors, preventing the interaction between acetylcholine and receptors on postsynaptic membrane.
Prevents the opening of the sodium channel associated with the acetylcholine receptor and results in neuromuscular blockade.
ASV -rapid reversal of paralysis.
Dissociation of the toxin-receptor complex, which leads to a reversal of Paralysis
Anticholinesterases reverse the neuromuscular blockade

18. Snake envenomation in a north Indian hospital
Ptosis
Ophthalmoplegia
Bulbar weakness RS
involvement
N Sharma, S Chauhan, S Faruqi, P Bhat, S Varma, Emerg Med J 2005;22:118–120

19. Neurotoxic envenoming-Examination
Ask the patient to look up and observe whether the upper lids retract fully.
Test eye movements for evidence of early external ophthalmoplegia .
Check the size and reaction of the pupils.
Krait can cause fixed, dilated non reactive pupils simulating brain stem death – however, it can recover fully
Ask the patient to open their mouth wide and protrude their tongue; early restriction often paralysis of pterygoid muscles.
The muscles flexing the neck may be paralysed, giving the “broken neck sign

20. Bulbar paralysis
Can the patient swallow or are secretions accumulating in the pharynx- an early sign of bulbar paralysis?
Ask the patient to take deep breaths in and out. “Paradoxical respiration”.
Objective measurement of ventilatory capacity is very useful. Use a peak flow metre, spirometer (FEV1 and FVC)
Ask the patient to blow into the tube of a sphygmomanometer to record the maximum expiratory pressure (mmHg).

21. Local examination
During the initial evaluation, the bite site should be examined for signs of local envenomation (edema, petechiae, bullae, oozing from the wound, etc) and for the extent of swelling.
The bite site and at least two other, more proximal, locations should be marked and the circumference of the bitten limb should be measured every 15 min thereafter, until the swelling is no longer progressing.

22. Treatment Anti Snake Venom Polyvalent /Monovalent Dose-large vs small
Timing
Repeat dose
Hypersensitivity
Anticholinesterases- Tensilon test
Mechanical ventilation

23. ASV
The decision to treat a snake bite with antivenin is largely based on clinical parameters.
Trying to capture, kill, or transport a snake for identification purposes seems of little value and possibly dangerous
ASV is polyvalent
Syndromic approach helps in examination and investigations and outcome predictions

24. Skin testing for ASV
Skin/conjunctival hypersensitivity testing does not reliably predict early or late antivenom reactions and is not recommended.

25. What is ASV?
Antivenom is immunoglobulin (usually the enzyme refined F(ab)2 fragment of IgG) purified from the serum or plasma of a horse or sheep that has been immunised with the venoms of one or more species of snake.
Monovalent or monospecific antivenom neutralises the venom
of only one species of snake
Polyvalent or polyspecific antivenom neutralises the venoms of several different species of snakes
The ASV that is available in India is a polyvalent type which is active against the commonly found snakes in India including the FAB Four.

26. Indications for ASV Neurotoxicity ARF Bleeding/coagulopathy
Myoglobinuria/haemoglobinuria
Cardiac toxicity
Local swelling involving more than half of the bitten limb
Rapid extension of swelling
Development of an enlarged tender lymph node draining the bitten limb

27. Timing of ASV
There is no consensus as to the outer limit of time of administration of antivenom. Best effects are observed within four hours of bite .
It has been noted to be effective in symptomatic patients even when administered up to 48 hours after bite.
Reports suggest that antivenom is efficacious even 6-7 days after the bite from vipers
When there are signs of local envenoming, without systemic envenoming, antivenom will be effective only if it can be given within the first few hours after the bite

28. Dose
5 vials(50ml)
5-10 vials
(50-100ml)
10-20 vials
( ml)

29. Large vs small dose High dose group 100ml stat and 100 ml every 6 hrs
Low dose group 100ml stat and 50 ml every 6 hrs
Until recovery of neurological signs
Low dose of snake antivenom is as effective as high dose in patients with severe neurotoxic snake envenoming Agarwal, Aggarwal, Gupta, et al
Emerg Med J 2005;22:397–399.

30. High vs low ASV
When a person is bitten by a snake, the major part of the
toxin gets fixed to the tissues and only a relatively small
part remains in the cirulation by the time the patient is
brought to the hospital.
Though it is useful and essential to neutralize the
circulating toxin, it is more important to treat the systems
involved effectively and aggressively.

31. Repeat dose Signs of systemic envenoming may recur within 24-48 hrs
Criteria for repeating the initial dose of antivenom
Persistence or recurrence of blood incoagulability after 1-2 hr
Deteriorating neurotoxic or cardiovascular signs after 1-2 hr
Continuing absorption- due to improved blood supply following correction of shock, hypovolaemia etc,
After elimination of antivenom
A redistribution of venom from the tissues into the vascular space.
Causes

32. Observation of the response to Antivenom
Cobra bites-Post synaptic
May begin to improve as early as 30 minutes
after anti-venom, but usually take several hours.
Krait and sea snakes- Pre synaptic
Depends on the timing of ASV administration
If delayed may not produce any action or Minimal delayed action

33. Antivenom reactions
Complement activation by IgG aggregates or residual Fc fragments or direct stimulation of mast cells or basophils by antivenom protein are more likely mechanisms for these reactions.
20%, of patients, usually more than develop a reaction
Types
Early anaphylactic reactions- within min
Pyrogenic (endotoxin) reactions- develop 1-2 hours
Late (serum sickness type) reactions- develop 1-12 (mean 7) days.
Fatal reactions have probably been under-reported as
death after snake bite is usually attributed to the venom.

34. Antivenom reactions At the earliest sign of a reaction:
Antivenom administration must be temporarily suspended
Adrenaline-0.1% solution, 1 in 1,000, 1 mg/ml is the effective treatment for early anaphylactic reactions.
IV hydrocortisone (adults 100 mg, children 2 mg/kg body weight). The corticosteroid is unlikely to act for several hours, but may prevent recurrent anaphylaxis
There is increasing evidence for anti H2 antihistamines-Ranitidine – adults 50 mg, children 1 mg/kg.
Pyrogenic reactions require- antipyretics.
In case of circulatory collapse- start fluids, inotropes along with IV adrenaline
5-day course of oral antihistamine/ Prednisolone.
Chlorpheniramine: 2 mg six hourly Prednisolone: 5 mg six hourly
Serum
sickness

35. Trial of anticholinesterase
Anticholinesterase (“Tensilon”/Edrophonium) test
Record baseline parameters
Give atropine IV
Give anticholinesterase drug edrophonium chloride (adults 10 mg, children 0.25 mg/kg body weight) given intravenously over 3 or 4 minutes
Neostigmine 25µg/kr/hr
Neostigmine 0.5 mg / 6 hr
IV atropine 0.5 mg / 12 hr
Dose of Neostigmine
Observe
Negative response
Positive response
Tearing, salivation,
muscle fasciculation, abdominal cramp,
bronchospasm, bradycardia, cardiac arrest
Improvement in ptosis, Respiratory distress, better cough effort, decrease in RR
Atropine IV
Neostigmine

36. On ASV 100ml stat, & 50ml in NS over 6 hrs Oxygen 3l/mt
34 yr old male shifted from rural health center with H/O snake bite 6 hrs back has ptosis, respiratory distress, RR 35/mt, BP 120/60, oral secretions present, absent gag and cough reflex shifted to ICU for tertiary care.
On ASV 100ml stat, & 50ml in NS over 6 hrs
Oxygen 3l/mt
Is given neostigmine 0.6mg and 0.6 mg atropine iv
You can have alive but a sicker patient
Cobra
You can have dead patient
Krait

37. Shifted to ICU placed on a Ventilator lot of secretions
Alive but a sicker patient
Shifted to ICU placed on a Ventilator lot of secretions
Do we continue anticholinesterases ?
Issues to consider
Increased secretions
Increased incidence of VAP ?
We rarely use these drugs once the patient is in the ICU under observation

38. Repeat dose Signs of systemic envenoming may recur within 24-48 hrs
Criteria for repeating the initial dose of antivenom
Persistence or recurrence of blood incoagulability after 1-2 hr
Deteriorating neurotoxic or cardiovascular signs after 1-2 hr
Continuing absorption of venom from the “depot” at the site of the bite, due to improved blood supply following correction of shock, hypovolaemia etc,
After elimination of antivenom
A redistribution of venom from the tissues into the vascular space, as the result of antivenom treatment

39. Mechanical ventilation
If patient has respiratory distress or bulbar paralysis-intubate and ventilate.
If delayed can cause aspiration or hypoxia and cardiac arrest.
Even if the facility for MV is not available
Ambuing can save the day.
This helps even during transport.
MV is not complicated is like ventilating a patient with curare over-dosage

40. ASV and children Dose of antivenom
Snakes inject the same dose of venom into children and adults.
Children must therefore be given exactly the same dose of antivenom as adults.

41. Pregnancy and snake bite
Pregnant patient is treated the same manner as the nonpregnant patient. Spontaneous abortion, bleeding, fetal death & malformations are common.
Lactating mothers can continue lactating
Fetal demise is difficult to predict because of associated symptoms, such as coagulopathy or hypotension, and complications of treatment including anaphylaxis.
Generally speaking, the severity of the mother's clinical course seems to be the best indicator of the fetal survival.

42. Treatment issues in non Neurotoxic respiratory paralysis
Aspiration can complicate MV
Respiratory paralysis due to Shock, ARF, Sepsis, etc..
MV is instituted to buy time till the organs recover
Treatment is directed towards the cause
ASV
Antibiotics
Source control-Fasciotomies ?
Dialysis
Inotropes
Blood and blood products

43. Mismatched Blood transfusion
A 25 yr old male with snake bite has signs of compartment syndrome and the pressure is 60 mmHg is undergoing surgery has a Hb of 6 gm%, is hypotensive 100/60, on noradrenalin, acidotic,coagulation profile is normal
Blood is started
After 15 mts of surgical time patient develops
Dark colored urine
Bp drops to 80/60
What are the possibilities ?
Treatment
Fluids, Mannitol,
Alkalinize the urine,
Manage electrolytes
Fasciotomy
RRT
Rhabdomyolysis
Mismatched Blood transfusion

44. Fasciotomy

45. Krait
Bites by krait, coral snake, and some cobras are associated with minimal local changes;
However, bite by the Indian cobra (Naja naja) results in tender local swelling, blistering, and necrosis. Local necrosis causes a picture of wet gangrene with a characteristic putrid smell due to the direct cytolytic action of the venom.
Skip lesions are typical findings

46. Viper
Viper bite is primarily vasculotoxic. It causes rapidly developing swelling of the bitten part.
Local necrosis is mainly ischemic as thrombosis blocks the local blood vessels and causes a dry gangrene

47. Clinical features of a compartmental syndrome
• Disproportionately severe pain
• Weakness of intracompartmental muscles
• Pain on passive stretching of intracompartmental muscles
• Hypoaesthesia of areas of skin supplied by nerves running through the compartment
• Obvious tenseness of the compartment on palpation
Early treatment with antivenom remains the best
way of preventing irreversible muscle damage
Criteria for fasciotomy in snake-bitten limbs
Haemostatic abnormalities have been corrected (antivenom, with or without clotting factors)
• Clinical evidence of an intracompartmental syndrome
• Intracompartmental pressure >40 mmHg (in adults)

48. Summary Snake bites may be by an non venomous snake or a dry bite
Not all snake bites require ASV
ASV is the main stay in the treatment of snake bites
ASV must be initiated if indicated at the earliest
Respiratory paralysis can be because of different reasons-Neurotoxicity, shock, sepsis, ARF…
MV may be main stay of treatment or just supportive depending on the cause of failure.

49. Wishing you all a wonderful 2009
Thank you
Wishing you all a wonderful 2009

50. Fasciotomy
Fasciotomy should not be carried out in snake bite patients unless or until haemostatic abnormalities have been corrected.
Clinical features of an intracompartmental syndrome are present and a high intracompartmental pressure has been confirmed by direct measurement

51. Results : In the low-dose group
High-Dose Anti-Snake Venom Versus Low-Dose Anti- Snake Venom in The Treatment of Poisonous Snake Bites — A Critical Study
Results :
In the low-dose group
Mortality rate of 10%, 18% required dialysis and 6% required ventilatory support. LOS 8.42 days
In the high-dose group
Mortality rate of 14%, 26% required dialysis 6% required ventilatory support.LOS 9.02 days
Conclusion : While there was no additional advantage in following a high-dose regime for snake bite cases, there was considerable financial gain by following the low-dose regime,
Most of the parameters showed a beneficial trend for the low-dose group though the differences were not statistically significant
JAPI • VOL. 52 • JANUARY 2004

52. High vs low ASV
Repeated high doses of ASV to restore the clotting time
to normal within the shortest time, do not seem to be
necessary to reduce the ultimate morbidity and mortality.
A smaller dose sufficient to make the clotting time graph take a downward trend is sufficient.
The body’s detoxifying system will bring down the clotting time eventually though it may take a slightly longer time.
This delay does not seem to affect the morbidity and mortality as shown by the results of this trial.