- Elapidae family with neurotoxins – pre and post-synaptic neurotoxins This family release acetylcholine at nerve endings at NM junctions and damage ending, preventing further release of transmitter, blocking NM transmission Neurotoxicity: ptosis, diplopia within 1-10 hrs, then progresses to dysarthria and generalized weakness - Early pre-paralytic symptoms: drowsiness, blurry vision, contraction of frontalis muscle, vomiting. Paralysis first ptosis and external ophthalmoplegia, may be as early as 15 min after bite of cobra or mamba. Or could be 10 hrs later Without antivenom, patients who are vented, can recover breathing in 1-4 days. Full recovery 3-7 days. -Endogenous opiates released by a venom component may cause drowsiness Anticholinesterase drugs by prolonging the activity of acetylcholine at NM junctions, may improve paralytic symptoms in patints bitten by snakes whose neurotoxins are predominatly post-synaptic in their action.
-Renal failure is a potential complication of envenoming even by speciies which usually cause mild envenoming. --The etiology of the renal failure is ATN (acute tubular necrosis) probably caused by hypotension or hypovolemia; DIC; direct toxic effect on tubules; rhabdo; hyperkalemia - Release of myoglobin into blood stream
- In bitten limb, increased vascular permeability leads to swelling and bruising. Venoms of some vipers can produce a generalized increase in vascular permeability resulting in edema and pulmnoary effusions local tissue necrosis results from direct actions of myotoxins and cytotoxins. Ischemia is caused by thrombosis, - venom ophthalmia: spitting cobras – intensely irritative and even destructive on conjunctiva, nasal cavity. Corneal erosions, anterior uveitis
Hypotension: from vasodilation, direct action of venom on myocardium, hypovolemia due to bleeding Profound hypotension part of syndrome within minutes of bites of certain vipers. Oligopeptides in these venoms inhibit bradykinin-activating enzymes and angiotensin converting enzymes. This is what ACE-inhibitors are based on. - Vasodilation and direct effect on myocardium may also contribute to hypotension in viper bites. Atractaspididae can causes coronary vasoconstriction and AV blocks
Coagulopathy: procoagulants and anticoagulants. Usually cause bleeding including hemorrhagic stroke - Bleeding and clotting disturbances are seen after bites by elapidaes, vipers, and colubidraes. Venom procoagulants can activate intravascular coagulation and produce consumption coagulopathy, producing bleeding - thrombocytopenia is common Combo of decreased coagulation factors, low platelets, and vessel wall damage all contribute to massive bleeding - Bleeding develops form old and recent wounds, also gingival bleeidng and epistatis, hematemesis, melena, SAH, ICH, hematuria, ecchymosis, DIC
Case• 5 year old girl was brought to ED with alleged snake bite over her left leg• Occurred at 2pm and arrived to ED at 3pm• Child was playing near her house in Paya Jaras when she was suddenly bitten by a small cobra like snake• No bleeding or LOC• Left lower leg becomes painful and tender
• Upon arrival to ED, child appears alert and concious• Not in shock, comfortableO/E• Pink, well hydrated, cooperative, not tachypnoeic• Systemic examination was normal• HR 89, BP 110/56, SpO2 100% on air
• Noted 2 bite marks over Lt lateral maleolus with erythematous skin changes surrounding it measuring 5x5cm• Her left leg was not oedematous• Pulses were palpable, able to move her toes, sensation intact• The left leg was splinted for immobilization
• Admission to ward, noted 6 hours after bite , Lt lower foot was swollen and had bluish discoloration• Swelling was increasing and has encroached mid shin, tender++, limited ROM• FBC TW 9, Hb 12.3, PLT 256,PT/ApTT normal• She was also having spiking temperature
• At 11pm, she was administered 1 vile of monovalen antivenom• Subsequenlty started on IV Augmentin• On the following day, noted that swelling was static and fever was slowly subsiding• BP remains stable• Serial FBC and coagulation profile remains normal• Child remains alert and comfortable
• At D3 of bite, swelling has reduced and child was able to move her lower limbs• She was also able to ambulate• Currently still in ward awaiting swelling to resolve• No systemic involvement subsequently
Introduction• 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 Laticauda 4. Hydrophiini, represented by the six genera Enhydrina, Kerilia, Hydrophis, Thalassophis, Pelamis and Kolpophis 5. 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)• The Malayan pit vipers are common in the northern part of Peninsular Malaysia but are not found in Sabah and Sarawak
• Epidemiological studies showed that in Malaysia, bites were mainly due to four species of land snakes : 1)Calloselasma rhodostoma (Malayan pit viper), 2)Naja naja (Asian common cobra), 3)Trimeresurus purpureomaculatus (shore pit viper) 4)Trimeresurus wagleri (Wagler’s pit viper)
Biochemical composition of Snake Venoms• 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
Elapid Venom Poisoning• 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
NeurotoxicityNeurotoxins blocktransmission at theNM junctionFlaccid/RespiratoryparalysisAnticholinesterasedrugsUnphysiologicdrowsiness
• 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
• 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/rhabdomyolysisATN: hypotension/hypovolemia,DIC, direct toxic effect on tubules,hemoglobinuria, myoglobinuriaGeneralized rhabdo: Release ofmyoglobin, muscle enzymes, uricacid, K (presynaptic neurotoxins)
Local necrosisIncreasedvascularpermeabilitySwelling andbrusingMyotoxins andcytotoxinsIschemia/thrombosisVenomophthalmia
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
Hypotension/shockVasodilationDirect action ofvenom on myocardiumBleeding/hypovolemiaVipers: profoundhypotension withinminutes (ACEinhibitors)
• Defibrination syndrome is due mainly to the action of ancrod and partly to the activation of fibrinolysis causing fibrinogenolysis.• Ancrod is a thrombin-like enzyme that acts directly on fibrinogen, releasing only fibrinopeptide A and fibrin monomers that form microclots.• The microclots formed are easily lysed by plasmin digestion.
• Thus, ancrod causes continual microcoagulation of fibronogen but the microclots are virtually simultaneously lysed.• In the presence of sufficient amount of ancrod, the rate of consumption of fibrinogen may exceeed its rate of synthesis in the liver, resulting in defibrination syndrome characterized by non-clotting blood.
• Thrombocytopenia is presumably due to the actions of platelet aggregation inducers.• Aggregoserpentin, a non-enzymatic protein with molecular weight of 28160 has been purified, it activates platelets through the activation of endogenous phospholipase A2 or C.• Anti-platelet protease may be also be involved.
• Hemorrhage is presumably due to the action of some metalloproteases that cause damage to vascular endothelium.• L-amino acid oxidases and platelet aggregation inhibitor may also play a role in the hemorrhagic action of the venom.
CoagulopathyProcoagulants andanticoagulantsIntravascular coagulation,consumption coagulopahty ThrombocytopeniaBleeding from old andrecent wounds, gingiva,epistaxis, hematemesis,melena
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.
• In patients who do not receive specific antivenin, systemic symptoms generally subside more quickly than local symptoms.• Neurotoxic symptoms usually resolve in 2-3 days.• Hemorrhagic effects in viper bites are also short-lived and rarely exceed a week but the coagulation defect may persist for 3-4 weeks
Management• The aims are to retard absorption of venom, provide basic life support and prevent further complications
Management Principles in Snake Venom Poisoning General management of snakebite poisoning includes the following measures:• adequate reassurance• immobilize the patient, particularly the bitten limb. If a tourniquet has been applied, it should be released upon admission to hospital• Treatment of local lesion: the site of the bite and blisters should be let strictly alone. Sloughs should be excised when local necrosis is obvious• Treatment of shock• Tetanus prophylaxis: Tetanus antitoxin should be given in victims in whom local necrosis developed• Specific antivenom should be given to patient with systemic poisoning• All bitten patients, even without symptom of poisoning, should be admitted to hospital for observation of at least 24 hours.
Antivenom treatment• Antivenom is the only specific treatment for envenomation.• Give as early as indicated for best result.• However, it can be given as long as the signs of systemic envenomation are still present• For local eff ect, anti venom is probably not effective if given more than a few hours after envenomation
• Monospecific (monovalent) antivenoms are more effective and less likely to cause reactions than polyspecific (polyvalent) antivenoms.• At present, however, monospecific antivenoms are available only against the three common types of Malaysian poisonous snakes (anti-Malayan pit viper, anti-Malayan cobra and anti-Enhydrina schistosa).