SNAKE BITES

Dr. WongJuly '15

Case (1)

• 17 year old boy was brought to ED with alleged snake bite over his left index finger

• Occurred at 1pm and arrived to ED at 2pm• Patient was digging for worms for fish bait and

he was suddenly bitten by a small viper like snake

• No bleeding or LOC• Left hand becomes painful and tender

• Noted 2 superficial bite marks over index finger with generalized swelling over his left hand

• Pulses were palpable, able to move his fingers, sensation intact

Case (2)

• Admission to ward, noted 6 hours after bite , Lt hand was swollen

• Swelling was decreasing on next day• Noted INR 2.08 → 1.85• Repeated next day, INR 9.75

Case (3)

• At 1pm, he was administered 2 vials of monovalen antivenom

• Subsequently started on IV Piriton 10mg stat• On the following day, noted that swelling was

subsiding and PT/INR was down-going in trend, INR 1.45

• BP remains stable• At D3 of bite, swelling has reduced and patient

was able to move his hands and discharge well

Case (4)

Introduction (1)

• Snakebite is a serious medical problem in Malaysia

• From 1978 to 2000, there were 55000 cases of snakebites recorded in the hospitals in Malaysia

• The mortality rate of snakebite in Malaysia is only 0.3 per 100000 population but the local necrotic effects of some venoms can cause prolonged morbidity or even crippling deformity

Types of snakes• In Malaysia and the coastal waters of the region, there are

at least 18 different species of venomous front fanged land snakes and more than 22 different species of sea snakes

• These venomous snakes belong to the following 5 subfamilies:1. Crotalinae: represented by the two genera Calloselasma and Trimeresurus.2. Elapinae: represented by the five genera Naja, Bungarus, Ophiophagus, Maticora and Calliophis;3. Laticaudinae, represented by the genus Laticauda4. Hydrophiini, represented by the six genera Enhydrina, Kerilia, Hydrophis, Thalassophis, Pelamis and Kolpophis5. Ephalophiini, represented by the only genus Aipysurus.

• not all snakes are venomous• In Malaysia there are approximately 40 species of

venomous snakes (18 land snakes, all 22 of sea snakes) belonging to two families:

• - Elapidae – have short, fixed front fangs. The family includes cobras, kraits, coral snakes and sea snakes.

- Viperidae – have a triangular shaped head and long, retractable fangs. The most important species in Malaysia are Calloselasma rhodostoma (Malayan pit viper) and Trimeresurus genus (green viper)

Introduction (2)

Malayan pit viper are common esp. in northern peninsular, but not found in Sabah & SarawakCobra & Malayan pit vipers cause most of snake bites in MalaysiaBites by sea snakes, coral snakes and kraits are uncommon

Introduction (3)

Snake venom is made up of > 20 components:Procoagulant enzymes (activate coagulation cascade)Phospholipase A2 (myotoxic, neurotoxic, cardiotoxic – cause haemolysis ( ↑ vascular permeability)Proteases (tissue necrosis)Polypeptide toxins (disrupt neuromuscular transmission

Biochemical composition of Snake Venoms (1)

• Dried snake venom contains mainly proteins (70-90%) and small amounts of metals, amino acids, peptides, nucleotides, carbohydrates, lipids and biogenic amines

• The protein components include enzymes and non-enzymatic proteins/polypeptides

• The main toxins in the venoms of elapid snakes (cobras, kraits and sea snakes) include: polypeptide postsynaptic neurotoxins, cardiotoxins and phospholipases A that may exhibit presynaptic neurotoxicity or myotoxicity

• The main toxins of crotalid (pit viper) snake venoms, on the other hand, are thrombin-like enzymes, hemorrhagic proteases and platelet-aggregation inducers

Biochemical composition of Snake Venoms (2)

Elapid Venom Poisoning (1)

• Elapid venoms (cobras, kraits and sea snakes) generally exhibit neurotoxicity and cardiotoxicity

• The earliest symptom of systemic elapid poisoning is a feeling of drowsiness or intoxication, which starts from 15 min to 5 hr after cobra bites

• Difficulty in opening the eyes (bilateral ptosis: eyelids may remain completely closed though the patient usually remains conscious until respiratory failure is advanced), speaking, opening the mouth, moving the lips and in swallowing follows within 1 to 4 hrs

• Breathing becomes increasingly difficult. In severe poisoning, respiratory failure sets in rapidly

Elapid Venom Poisoning (2)

Neurotoxicity (1)

Neurotoxins block transmission at the NM junctionFlaccid/Respiratory paralysisNon - physiologic drowsiness

• The neurotoxic effects are mainly at the postsynaptic level of the neuromuscular junction where the neurotoxins block acetylcholine receptors, thereby producing muscular paralysis and respiratory failure

• The major neurotoxins are usually basic polypeptides

Neurotoxicity (2)

Cardiotoxicity (1)

• Cardiotoxicity is caused by polypeptide cardiotoxin that affects both excitable and non-excitable cells, causing irreversible depolarization of the cell membrane and consequently impairing the structure and function of various cells, thus contributing to muscle paralysis and leading to circulatory and respiratory failure and systolic arrest

• Cobra venom also causes extensive local necrosis, which requires treatment

• The local necrosis is presumably caused by the combine action of cardiotoxin and phospholipase A2

• Sea snake venoms contain both polypeptide neurotoxins (homologous to elapid neurotoxins) and myotoxins, which are basic phospholipase A2.

• The venom causes respiratory failure (neurotoxic effect), myonecrosis, myoglobinemia and acute renal failure

Renal failure/rhabdomyolysis

ATN: hypotension/hypovolemia, DIC, direct toxic effect on tubules, hemoglobinuria, myoglobinuria

Generalized rhabdo: Release of myoglobin, muscle enzymes, uric acid, K (presynaptic neurotoxins)

Local necrosis

Increased vascular permeabilitySwelling and brusingMyotoxins Ischemia/thrombosisVenom ophthalmia

Pit Viper Venom Poisoning(Viperidae)

• The venom of pit vipers causes local swelling, necrosis and systemic bleeding. Hemorrhage is the outstanding symptom of systemic pit viper poisoning

• Clotting defect usually accompanies hemorrhage. The commonest and earliest hemorrhagic manifestation is hemoptysis, which may be seen as early as 20 minutes after the bite

• Bleeding from the gum is less common and follows later after the bite

• Discoid ecchymoses appear in the skin an hour or so later

• Bleeding into the brain or other vital organ may be fatal.

• In severe cases, loss of blood may lead to hypovolemic shock

• In Malayan pit viper bite, the clotting defect is primarily due to thrombocytopenia aggravated by defibrination syndrome

Pit Viper Venom Poisoning(Viperidae)

Recovery times

• In the absence of necrosis, pain after viper bites rarely exceeds 2 weeks.

• When necrosis develops (in about 10% of cases) pain may remain severe for a month.

• Swelling usually resolves completely in 2-3 weeks.

• Healing time of local necrotic lesions varies greatly according to the extent of the lesion and the treatment given, but may requires 1-6 months or longer.

Hemorrhagic effects in viper bites are also short-lived and rarely exceed a week but the coagulation defect may persist for 3-4 weeks

Neurotoxic symptoms usually resolve in 2-3 days

Management: (a) First aid (1)

Aims are to retard absorption of venom, provide basic life support & prevent further complicationsReassure victim (anxiety ↑ venom absorption)Immobilise bitten limb with splint/sling (retard venom absorption)

Management: (a) First aid (2)

Apply firm bandage for some elapid bites (delay absorption neurotoxic venom) but not for viper whose venom cause local necrosisLeave the wound alone – DO NOT incise, apply ice/other remediesTight (arterial) tourniquet are not recommended

Management: (a) First aid (3)

Do not attempt to kill the snakeHowever, if it is killed, bring snake to hospital for identificationDo not handle snake with bare hands as even a severed head can bite!Transfer victim quickly to nearest health facility

Management: (b) Treatment in hospital (1)

Do rapid clinical assessment & resuscitation, including Airway, Breathing, Circulation & level of consciousnessMonitor vital signs (BP, RR, PR)Establish IV access, give O2 & other resuscitation as indicatedHistory: inquire part of body bitten, timing, type of snake & h/o atopy

Management: (b) Treatment in hospital (2)

Examine:Bitten part for fang marks, swelling, tenderness, necrosisDistal pulses ( ↓ / or in compartment syndrome)For bleeding (tooth sockets, conjunctiva, puncture sites)For neurotoxicity (ptosis, ophthalmoplegia, bulbar & respiratory paralysis)

Management: (b) Treatment in hospital (3)

For muscle tenderness, rigidity (sea snakes)Urine for myoglobinuriaSend blood investigations (FBC, RFT, PT/PTT, GXM)Perform a 20-min whole blood clotting test(if unclotted after 20 min → suggests hypofibrinogenaemia due to pit viper bite & rule out elapid)

Management: (b) Treatment in hospital (4)

Review immunisation history: give booster ATT if indicatedVenom detection kits to identify species of snake are not available in MalaysiaAdmit to ward for at least 24 hours (unless snake is definitely non-venomous) All cases should be supervised by a physician or clinical

toxinologist who are familiar and experienced with snakebite and envenomation management in Malaysia

Management: (c) Antivenom treatment

Antivenom is only specific treatment for envenomationGive early for best resultHowever, it can be given as long as signs of systemic envenomation are still presentFor local effect, antivenom is not effective if given > few hours after envenomation

Antivenom in Hosp. Sg Bakap

Management: (d) Indications for antivenom (1)

Haemostatic abnormalities e.g. spontaneous systemic bleeding, incoagulable blood/thrombocytopenia (<100 x 109/L)NeurotoxicityCV dysfunction eg hypotension/shockGeneralised rhabdomyolysis (muscle ache & pain)

Management: (d) Indications for antivenom (2)

Significant local effect, e.g. local swelling > ½ bitten limb, extensive blistering/bruising, bites on digit/rapid progression of swellingHelpful laboratory investigations suggesting envenomation include anaemia, thrombocytopenia, leucocytosis, raised serum enzymes (CK, AST, ALT), hyperkalaemia, myolobinuria

Management: (e) Choice of antivenom (1)

If biting species is known, give monospecific/monovalent antivenom (more effective, less adverse reactions)If unknown, clinical manifestations may suggest offending species:• Local swelling + neurological signs = cobra bites• Extensive local swelling + bleeding tendency =

Malayan pit viper

Management: (e) Choice of antivenom (2)

If still uncertain, give polyvalent antivenomNo antivenom is available for Malaysian kraits, coral snakes & some species of green vipersFortunately, bites by these species are rare & usually cause only trivial envenoming

Management: (f) Dosage & route administration (1)

Amount given is usually empiricalRecommendations from manufacturers are usually conservative as they are mainly based on animal studies

Management: (f) Dosage & route administration (2)

Repeat antivenom administration until signs of envenomation resolvedGive through IV route onlyDilute antivenom in any isotonic solution (5-10ml/kg)Bigger children dilute in 500ml / IV solution) & infuse whole amount in 1h

Management: (f) Dosage & route administration (3)

Infusion may be discontinued when satisfactory improvement occurs, even if recommended dose has not been completedDo not perform sensitivity test as it poorly predicts anaphylactic reactionsDo not inject locally at bite site

Management: (f) Dosage & route administration (4)

Prepare adrenaline, hydrocortisone, antihistamine & resuscitative equipment & be ready if allergic reactions occurPretreatment with adrenaline SC remains controversialSmall controlled studies in adults showed it effective in reducing risk of reactions

Management: (f) Dosage & route administration (5)

However, its effectiveness & appropriate dosing in children have not been evaluatedThere is no strong evidence to support use of hydrocortisone/antihistamine as premedicationsConsider their use in patients with atopy

Management: (g) Antivenom reactions (1)

3 types:(a) Early anaphylactic reactionsOccur 10-180mins after starting antivenomSymptoms range from itching, urticaria, nausea, vomiting, palpitation to severe systemic anaphylaxis – hypotension, bronchospasm & laryngeal oedema

Management: (g) Antivenom reactions (2)(contd)

Stop antivenom infusion: give adrenaline IM (0.01ml/kg of 1 in 1000)Antihistamines eg. Chlorpheniramine 0.2mg/kg, hydrocortisone 4mg/kg dose & IV fluid (if hypotensive)If mild reactions restart infusion at a slower rate

Management: (g) Antivenom reactions (3)

(b) Pyrogenic reactionsDevelops 1-2h after treatment & are due to endotoxins in antivenomSymptoms include fever, rigors, vomiting, tachycardia & hypotensionGive treatment as aboveTreat fever with paracetamol & tepid sponging

Management: (g) Antivenom reactions (4)

(c) Late reactionsOccur about 1 wk laterIt is a serum sickness-like illness (fever, arthralgia, lymphadenopathy, etc)Treat with chlorpheniramine 0.2mg/kg/day in divided doses x 5dIf severe, give oral prednisolone (0.7-1mg/kg/day) x 5-7d

Management: (h) Anticholinesterases (1)

They should always be tried in severe neurotoxic envenoming, especially when no specific antivenom is available eg. bites by Malaysian krait & coral snakesThese drugs have a variable but potentially useful effect

Management: (h) Anticholinesterases (2)

Give test dose of edrophonium chloride (Tensilon) IV (0.25mg/kg, adult 10mg) with atropine sulphate IV (50-100ug/kg; adult 0.6mg)If patients respond convincingly, maintain with neostigmine methylsulphate IV (50-100ug/kg) & atropine, 4hrly by continuous infusion

Management: (i) Supportive / Ancillary treatment (1)

Clean wound with antisepticsGive analgesia to relief pain (avoid aspirin)In severe pain, use morphine (watch for respiratory depression)Give antibiotics if wound look contaminated / necrosed e.g. IV C Pen + gentamicin, amoxy-clav, erythromycin / 3rd generation cephalosporin

Management: (i) Supportive / Ancillary treatment (2)

Respiratory support – respiratory failure may require assisted ventilationWatch for intracompartment syndrome – pain, swelling, cold distal limbs & muscle paresisGet early orthopaedic / surgical opinion

Management: (i) Supportive / Ancillary treatment (3)

Patient may require urgent fasciotomyCorrect coagulation abnormalities with fresh frozen plasma & platelets before any surgeryDesloughing of necrotic tissues should be carried out as required

Management: (i) Supportive / Ancillary treatment (4)For oliguria & renal failure, e.g. due to sea snake envenomation, measure daily urine output, Sr creatinine, urea & electrolytesIf urine output fails to increase after rehydration & diuretics (e.g. frusemide), start renal dose of dopamine (2.5ug/kg/min IV infusion) & place on strict fluid balanceDialysis is rarely required

Pitfalls in management (1)

(a) Giving antivenom “prophylactically” to all snake bite victims

Not all snake bite by venomous snakes will result in envenomingOn average, 30% bites by cobra, 50% by Malayan pit vipers & 75% by sea snakes DO NOT result in envenoming

Pitfalls in management (2)(contd)

Antivenom is expensive & carries risk of causing severe anaphylactic reactions (as derived from horse / sheep serum)Hence it should be used only in patients in whom the benefits of antivenom are considered to exceed risks

Pitfalls in management (3)

(b) Delaying in giving antivenom in district hospitals until victims are transferred to referral hospitals

Antivenom should be given as soon as it is indicated to prevent morbidity & mortalityDistrict hospitals should stock important antivenoms & provide care & safe monitoring for antivenom infusion

Pitfalls in management (4)

(c) Giving polyvalent antivenom for envenoming by all types of snakes

Polyvalent antivenom does not cover ALL types of snakesE.g. Sii polyvalent (India) is effective in cobra & some kraits envenomation but is not effective against Malayan pit viperRefer to manufacturer drug insert for details

Pitfalls in management (5)

(d) Giving smaller doses of antivenom for children

Dose should be same as for adultsAmount given depends on the amount of venom injection rather than size of victim

Pitfalls in management (6)

(e) Giving pretreatment with hydrocortisone / antihistamine for snake bite victim

Snakebites do not cause allergic / anaphylactic reactionsThese drugs may be considered in those who are given ANTIVENOM

Resources:http://mstoxinology.blogspot.com/p/recs.htmlSnakebite Management Guide for Healthcare Providers in Malaysia (2014)Image Gallery of Land Snakes of Medical Importance in Malaysia (2013)Snake Antivenom Guide for UKMMC (2014)Snake Antivenom Guide for Sabah (2014)http://www.junglecraft.com.my/index.php/snake-bite/