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Management of Snake Bite Victims with Respiratory Paralysis in ICU

Dr. T.R. ChandrashekarDirector Critical Care K.R.HospitalBangalore

DR TRC/ KRH

Management of Snake Bite Victims with Respiratory Paralysis in ICU

Facts givenSnake bite which has lead to Respiratory

Paralysis Patient in ICUAnswerManagement aspects

How to prevent snake bites? A world free of snakes

Nearly a quarter of us would go hungryAre 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

EpidemiologyIndia 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and 15-20,000 snake bite deaths per year Originally made in the last century, are still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.

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 bitesNearly 70-80%HemotoxinVasculotoxin

Neurotoxic

1 2 43

Species: Medical Implications Signs/Symptoms and Potential Treatments

Cobra Krait Russell’s Viper Saw Scaled

Viper Other Vipers

Local pain/ Tissue Damage Yes No Yes Yes Yes

Ptosis/Neurotoxicity Yes Yes Yes! NO No

Coagulation No No Yes Yes Yes

Renal Problems No No Yes NO Yes

Neostigmine & Atropine Yes No? No? NO No

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

Snake bite

Venomous snakes

Anti snake venom

Majority is by non-venomous snakes

ASV -severe adverse reactions, Costly, Limited supply.Used- benefits of ASV treatment is considered to exceed the risks.

About 50% of bites are dry

Our statistics

Causes ARF, DIC, Shock, Pulmonary edema,

Sepsis

1998-2008 45 snake bite admissions

8 Neuotoxic bites 6 required MV

33 Hemotoxic bites 20 required MV

Snake bite and Respiratory paralysis

Neuromuscular paralysis-blockade of neuromuscular transmission.Cobra- post-synapticKrait- pre-synaptic

Bulbar paralysis-AspirationSepsis,

DIC-shockARF-Pulmonary edema

NeurotoxicMV for respiratory paralysis

ASV

MV as Supportive care

More cases why ?

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%

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 received in casualty

Patient is comfortable, vitals stable

No ptosis, distress

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

Patient is dead –what do you think went wrong ?

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

Why does Neurotoxicity occur

What are the Management issues?

ASV, Anticholineesterases,

MV…

Snake venom components

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.

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

Snake envenomation in a north Indian hospital

Ptosis

RSinvolvementBulbar

weakness

N Sharma, S Chauhan, S Faruqi, P Bhat, S Varma, Emerg Med J 2005;22:118–120

Ophthalmoplegia

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

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).

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.

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

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 polyvalentSyndromic approach helps in examination and investigations and outcome predictions

Skin testing for ASV

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

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.

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

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

Dose

5 vials(50ml)

5-10 vials(50-100ml)

10-20 vials(100-200ml)

Large vs small dose

Low dose of snake antivenom is as effective as high dose inpatients with severe neurotoxic snake envenomingAgarwal, Aggarwal, Gupta, et al

Emerg Med J 2005;22:397–399.

High dose group 100ml stat and 100 ml every 6 hrsLow dose group 100ml stat and 50 ml every 6 hrsUntil recovery of neurological signs

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.

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

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 administrationIf delayed may not produce any action or Minimal delayed action

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 1. Early anaphylactic reactions- within 10-180 min2. Pyrogenic (endotoxin) reactions- develop 1-2 hours 3. 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.

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

Serumsickness

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

Observe

Improvement in ptosis, Respiratory distress, better cough effort, decrease in RR

Tearing, salivation,muscle fasciculation, abdominal cramp,bronchospasm, bradycardia, cardiac arrest

Neostigmine

Positive response

Atropine IV

Negative response

Dose of Neostigmine

Neostigmine 25µg/kr/hr Neostigmine 0.5 mg / 6 hr IV atropine 0.5 mg / 12 hr

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 hrsOxygen 3l/mtIs given neostigmine 0.6mg and 0.6 mg atropine iv

You can have alive but a sicker patient

You can have dead patient

Cobra

Krait

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

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

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

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.

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.

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

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 ?

Rhabdomyolysis

Mismatched Blood transfusion

Treatment Fluids, Mannitol,Alkalinize the urine, Manage electrolytesFasciotomyRRT

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

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

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

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)

Early treatment with antivenom remains the best way of preventing irreversible muscle damage

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.

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

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

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.