Management of Snake Bites Dr. Cheetanand Mahadeo Registrar General Surgery GPHC

Relevance of topic The people most affected by rabid dog bites, snake bites and scorpion stings usually live in poor rural communities where medical resources are often sparse. Because they lack a strong political voice, their problems tend to be overlooked by politicians and health authorities who are based in capital cities and are poorly informed about major public health issues affecting rural areas. Consequently, the impact of these health issues, although dramatic and economically significant, does not appear as a priority in the design of national public health programmes. These are therefore the most neglected among today’s neglected global health problems… Rabies and Envenomings, a neglected public health issue, World Health Organization, http://www.who.int/bloodproducts/animal_sera/Rabies.pdf

Disclaimers Independent Study and analysis No funding provided If any medication is recommended or condemned it was based on pharmacological evidence and not commercial influence Only GPHC data was studied

International Epidemiology Only 15% of approximately 3000 species of snakes worldwide are dangerous to humans Age range 11-50 yrs Predominantly Males Most common site being Lower Limbs Summary: “5.4 million bites, about 2.5 million envenomings and over 125,000 deaths annually” , A Kasturiratne et al The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths, PLOS Medicine. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050218;jsessionid=66B81B3E56F5DABADB52D86E51BE334F

Classification of snakes Colubridae: most non-venomous snakes e.g grass snake Elapidae: Venemous: e.g. Cobras, Kriats, Mambas, Coral snakes (present in Guyana) Viperidae: Venomous: e.g. Rattlesnakes, Adders, Vipers (in Guyana, the notorious Labaria) Hydrophidae: sea snakes Modified classification from: W. Rushin, Taxonomy of snakes, 2700 species, 2004; pg 3 B S Gold et al, Bites of venomous snakes, N Engl J Med, Vol. 347, No. 5, August 1st 2002.

Bothropos atox (labaria) Photographs Of Labaria Snake from Iwokrama, Guyana

Guyana Blackback Coral Snake (Leptomicrurus collaris) Photograph taken in Region 1 Guyana

Venom Toxicology An extremely complex mixture of enzymes, peptides, glycoproteins and metal ions.Proteolytic enzymes,Arginine ester hydrolase,Thrombin-like enzyme,Collagenase,Hyaluronidase,Phospholipase A2(A), Phospholipase B, Phosphomonoesterase Phosphodiesterase, Acetylcholinesterase, RNaseDNase, 5'-Nucleotidase, NAD-ucleotidase, L- Amino acid oxidase,Lactate dehydrogenase… Component Action Serine Proteases Haemolysis Other Proteases Phospholipase A2 Myotoxic, Cardiotoxic, Neurotoxic, increases vascular permeability Hyaluronidase Tissue necrosis Neurotoxins Synaptic inhibition and paralysis

Understanding Antivenom(or antivenin or antivenene) A biologic product used in treatment of venomous bites/stings The principle of antivenom is based on that of vaccines; antibodies against proteins Monovalent (when they are effective against a given species' venom) or Polyvalent (when they are effective against a range of species, or several different species at the same time).

Production of Antivennin Made according to WHO Biological Guidelines and Good Manufacturing Practices Venom injected into Horses or Sheep Antibodies are harvested from these animals Freeze dried for reconstitution Some contain whole IgG others fragments of IgG (Fab or Fab2) Binds to circulating venom components blocking their attachment to receptors complexes are removed by Reticuloendothelial system C D Richard, (3rd Ed.) Medical Toxicology, Lippencot-Williams-Wilkins, 2009, pg 250-251

Symptomatology/Signs of Envenomation* Hematoxic (Labaria) Neurotoxic (Coral Snake) Intense pain Edema Weakness Numbness/paraesthesia Tachycardia Ecchymosis Fasciulations Metallic taste Confusion Hypotension/shock Renal failure Bleeding diathesis DIC Local necrosis Blebs Minimal pains Ptosis Diplopia Disphagia Hypersalivation Diaphoresis Hyporeflexia Respiratory depression Paralysis GREGORY JUCKETT, M.D., M.P.H., and JOHN G. HANCOX, M.D Am Fam Physician. 2002 Apr 1;65(7):1367-1375

Grading of a Snake bite (Haemotoxic) Grade Presentation Punctures or abrasions; some pain or tenderness at the bite 1- Mild Pain, tenderness, edema at the bite; perioral paresthesias may be present 2 Moderate Pain, tenderness, erythema, edema beyond the area adjacent to the bite; often, systemic manifestations and mild coagulopathy 3 Severe Intense pain and swelling of entire extremity, often with severe systemic signs and symptoms; Coagulopathy 4 Life Threatening Marked abnormal signs and symptoms; severe coagulopathy DIC GREGORY JUCKETT, M.D., M.P.H., and JOHN G. HANCOX, M.D, Am Fam Physician. 2002 Apr 1;65(7):1367-1375.

Pathophysiology of snake bites Enzymatic proteins in venom causes manifestations. Neurotoxins e.g coral snake venom, ultimately causes respiratory arrest. Specific details (1) hyaluronidase allows rapid spread of venom through subcutaneous tissues by disrupting mucopolysaccharides; (2) phospholipase A2 plays a major role in hemolysis secondary to the esterolytic effect on red cell membranes and promotes muscle necrosis; and (3) thrombogenic enzymes promote the formation of a weak fibrin clot, which, in turn, activates plasmin and results in a consumptive coagulopathy.

J White, Snake venoms and coagulopathy, J Toxicon 24(2005); 951-957

Management of the Snake bitten patient

Management begins in the field Prevention of snake bites Proper boots and leather leggings in snake infested areas Snakes generally bite only when threatened/provoked

First aid guidelines First Aid: summary of guidelines* Remove patient from area Do not attempt to capture snake for identification Calm the patient and Call for help Do not give alcohol or anti-inflammatory medications Remove constrictive clothing Splint limbs to minimize movement NO ICE PACKS NO TORNIQUETS DO NOT INCISE BITE SITE DO NOT SUCK WOUND TO REMOVE POISON *American Medical Association, American Red Cross, National Health and Research Council Australia, Indian Ministry of Health Snake bite Protocol 2007

What do we need to understand about snake bites? Envenomation is a medical emergency All principles of initial emergency care applies Rapid Triage as IMMEDIATE ABC’s to Stabilize Patient Specific treatment if available Early referral to MEDICAL staff. Early identification of the type of toxicity and management Management will be symptom guided if the type of snake is unknown

ABCDE of Trauma care Examine and manage the Airway Examine quality of Breathing and Maintain function Monitor for signs of Circulatory compromise Assess for Neurologic Dysfunction Examine the patient thoroughly for multiple sites of Exposure (>1 bite) OXYGEN, MONITORS, IV FLUIDS FOR ALL UNTIL SEVERITY OF ENVENOMATION IS QUANTIFIED Enquire about Tetanus Immunization in HPI

These patients are in pain!! Oral analgesia and IV narcotics should be considered DO NOT ADMINISTER ASPIRIN OR NSAIDS DO NOT GIVE DICLOFENAC OR OTHER INTRAMUSCULAR MEDICATIONS Splint the bite area if possible and remove all constricting bandages/tourniquets

Role of neostigmine Anticholinestrase & prolongs life of Ach - which can reverse resp.failure & neurotoxic symptoms ( post synaptic ) Neostigmine test : 1.5 -2.0 mg IM preceeded by 0.6 mg atropine IV Observe for 1 hr If victim responds , continue 0.5 mg Neostigmine IM ½ hrly with 0.6 mg Atropine IV over 8 hrs If no improvement in symptoms after 1 hr , stop Neostigmine

What baseline Laboratory tests? Haemoglobin: anaemia White cell count/differential: infective process Blood film: identify fragmented RBC’s Platelet count: thrombocytopenia Bleeding time/clotting time: bleeding diathesis Prothrombin time: bleeding diathesis Renal function: elevated creatinine, hyperkalemia Urinalysis: hematuria

Additional Investigations If severity requires or clinical examination suggests the need: ECG- severe bradycardia, ischemia etc Arterial blood Gas: severe acidosis can be present Chest X-ray: pulmonary edema, effusion or hemorrhage CT scans, esp. head: Intracranial bleeds can occur

After stabilization, what do we do? Admit for serial clinical/laboratory assessment Which ward? Usually general medical ward. The ward is determined by the severity of the envenomation and the patient’s specific requirements eg. Ventilator support, Holter monitoring, continuous oximetry etc. Seek consultation early! This includes: Toxicologist Hematologist Orthopedics Intensivist etc.

Antivenoms: to give or not to give? Antivenoms are life saving; give early CAVEAT! Give the correct antivenom for the bite. Polyvalent multiple genus/species generally do not work well and the patient can have life threatening reactions. e.g. the Rattlesnakes of USA antivenom may have no use in the South American Vipers.

No Specific Antivenom in Guyana SUERO ANTIBOTROPICO POLIVALENTE (Equine); Peruvian Antivenom Bothrops atrox Common Lancehead, Fer de lance Bothrops brazili Brazil’s Lancehead Bothrops pictus Desert Lancehead, Bothrops barnetti Barnett’s Lancehead, Bothrocophias hyoprora Amazonian Toadheaded Pit-viper B.atrox-Lachsis equine (Fab')2 antivenom, Fundacao Ezequiel Dias, Minas Gerais State, Brazil

How to use antivenom Pre-Med Step Proced. Comment Sensitivity test no Apart from the rare cases of a pre-existing sensitivity, e.g. to horse serum, sensitivity tests (intradermal, intraconjunctival) have no predictive value for an antivenom reaction (Malasit et al. 1986) Pre-Med Adren. Steroids, Antihist. Patients with atopy and previous reactions to products from Equine sources are at risk Speed of Adm. IV, 5ml/min Most effective as an IV administered medication Dose This is guided by degree of envenomation and the manufacturers usually recommend doses depending on the concentrations of Fab within antivenom. Cautions Anaphylaxis can occur http://www.vapaguide.info/page/38

drugs of controversial/unproven value Non-specific antivenoms Corticosteroids: hydrocortisone, prednisone,(steroids have a role in management of type III hypersensitivity reactions that may occur 7-21 days after a snake bite) Antihistamines and Vitamin K

Reassuring Facts Not all venomous snake bites will have venom injected (“Dry Bite”); Amount of venom depends on several factors: How hungry ? How angry? How threatened? How long since the last bite?1 No consensus, but approximately 20% of venomous snake bites will have no venom injected.2 1.http://reference.medscape.com/features/slideshow/snake-envenomation 2. Longo et al, Harrison’s Principles of internal Medicine, 18th Edition, MvGraw-Hill Co. 2012: Sect. 18, ch.396:

The Local Arena N= 240 cases from Jan 2010 to Dec 2012 Approximately 80 cases/year seen at GPHC Males =153, Females = 87 Average age of victim = 33.5 with range of 5/12 to 76 Average Hb = 12.3 with range from 2.2g/dL to 18.1g/dL WBC mean 9954; range 3600- 23000 Platelet mean 244 000; range of 8000 – 500 000 Average duration of hospitalization 4.75 days

BT, CT ordered for almost all patients PTT, PT, INR ordered for 4 patients (all values elevated) Total Packed cells transfused = 28 units Total platelets transfused 4 Units Total Plasma 460 Units; average 2 u per patient Antivenom administered to 1 patient 18 patients received corticosteroids (16 hydrocortisone and 2 prednisone) 34 patients received Vitamin K 5 patients received Desmopressin 6 patients had surgical intervention (drainage of Hematoma, Compartment syndrome, Debridement and skin grafting)

5 patients had HDU monitoring 1 patient had ICU management 100% patients received antibiotics with the most common combination being Cloxacillin/Flagyl or Augmentin/Clindamycin; few patients received 3rd generation cephalosporins 14 patients received NSAIDS orally and 1 patient received Novalgin IV; all others had IV morphine or pethidine or oral Tramadol in combination with Paracetamol.

Deaths 5 patients died (N=240) All were over 60 years old 2 = Suspected Cerebral hemorrhage 3 = Pulmonary Hemorrhage with their bleeding diathesis and DIC All were over 60 years old All came 24 hrs after the bite All had signs of multiple organ failure (elevated transaminases and creatinine average of 3.5[range 0.5-1.5])

Are there any high risk areas in Guyana?

What Ages were affected?

Simple cases

Extreme Cases

Elapidae (Coral Snake bite): full ventilatory support

Amputated Arm in Labaria bite Severe life threatening problems and untreated compartment syndrome can lead to this situation

Severe Tissue Necrosis; Labaria bite

Debridement /skin graft Photographs by Dr. Shilendra Rajkumar, Registrar, Plastic Surgery, GPHC

Summary Management begins in the field Emergency triage as immediate ABCDE takes priority Tetanus prophylaxis Early administration of Antivenom IF specific Close monitoring of coagulation profile Response guided supportive care Clotting factors to replace that consumed Plasma or Cryoprecipitate (not a substitute for antivenom but useful) Avoid dubious medications: Steroids, Antihistamines and Vitamin K Early/appropriate consultation with specialty

Thank you. Questions?