Animal Poisoning Snake and scorpion poisoning presnted by

Animal Poisoning Snake and scorpion poisoning presnted by Elzahraa Ahmed Elrefaie Ali Assistant lecturer of Clinical Toxicology section 1&2 1

Snake poisoning 2

-Snakes are elongated, cylindrical, and carnivorous reptiles that are coldblooded, thus, they tend to disappear in winter (Hibernate). - All snakes shed their skin periodically, and during this period they become inactive and seek seclusion Classification of Snakes: The most serious toxic snakes belong to 3 main families: [I] Family Elapidae: - In Egypt, they are distributed in the Middle and Upper Egypt near the water canals and the adjacent areas of agricultural lands and deserts. - They include the most dangerous snakes as: Naja haje = Egyptian Cobra Naja nigricollis = Spitting Cobra [II] Family Viperidae: - They lives in the deserts away from humans. - They include: Cerastes cerastes. III] Family Crotalidae: They are not found in Egypt but are distributed mainly in America. 3 - They include: Rattle snake.

Effects of snake envenomation (Pathophysiology): 1 - Frightens effect: victim's fear reaction → neurogenic shock, cardiac arrest or cerebral stroke. 2 - Biologic effects: They are either: a- Local effects: 1 - Cytotoxic effects: in the form of tissue destruction, necrosis and sloughing. 2 - Proteolytic effects: in the form of precipitation of the protein in the contact cells and tissues. b- Systemic effect: it may take one or more of the following: 1 - Neurotoxic effect (motor & sensory). 2 - Cardiotoxic effect: - Myocarditis, pericarditis and arrhythmias 3 - Haemotoxic effect: - in the form of coagulopathy, Cytotoxic effect on the RBCs and the blood vessels and altered phagocytic activity of the WBCs. 4 - Allergic reaction : - as a result of histamine release. 4

Management of snake bitten case: In general, management means how to deal with a case (diagnosis & treatment). Diagnosis is by clinical picture, investigations & differential diagnosis. A)- Clinical picture: 1)- Local manifestations: - All these manifestations are more marked with the hemorrhagic vipers bites (Viperidae), and less marked with paralytic snakes (Cobra). They are in the form of: a- Local pain: - It varies from mild to intolerable pain. b- Fang marks: -Variable in shape, depth, number & distance between marks according to snake species. - Usually 1 -2 in number. - Associated with hemorrhagic odema. c- Swelling & odema: - which may extend to involve the entire limb as in case of vipers. d- Hemorrhagic bullae & regional lymphadenopathy. 5 e- Tissue necrosis (at site of bite).

2)- Systemic manifestations: a- General manifestation: -Sweating & chills. -Numbness, tingling. -Nausea, vomiting. -Muscle fasciculation, weakness. b- Hematological manifestations: These manifestations are more common in case of viper bites and less common in case of paralytic snakes. They include: 1 - Bleeding tendencies in the form of: -Bleeding from site of bite. -Bleeding from body orifices (haematuria, haematemesis, melena). -Bleeding into body cavities e. g. intracranial hemorrhage. -Ecchymotic patches of skin. 2 - Consumption coagulopathy: Consumption of coagulation factors especially fibrinogen → ↓ fibrinogen &↑ fibrinogen degradation product (FDPs) → DIC 3 - Hemolysis of RBCs → hemolytic 6 jaundice

c- Neurological manifestation: These manifestations are more evident in case of cobra bites and sea snake bites due to affection of the myoneural junction by the neurotoxic venom. They include: 1 - Bilateral ptosis. 2 - Progressive generalized muscle weakness & paralysis. 3 - Ophthalmoplegia & bulbar palsy. 4 - Respiratory muscle paralysis→ respiratory difficulty with shallow ineffective respiration→ respiratory failure, cardiac arrest & death. 5 - Psychotic changes, convulsions. d- Cardiovascular manifestations: 1 - Hypotension, shock, circulatory collapse 2 - Carditis, cardiomyopathy 3 - ECG changes & dysrrhythmias e- Genitourinary manifestations: 1 - Vaginal bleeding 2 - Hematuria & proteinuria 3 - Acute tubular necrosis & acute renal failure (ARF) f- Ocular manifestations: Direct contact of the venom with eyes→ pain, photophobia, 7 Conjunctivitis and corneal opacities

B) Investigations 1 - Baseline studies, including: - Complete blood count (C. B. C. ). - Serum electrolytes - Urine and stool analysis. 2 - Coagulation studies, including: - Coagulation time. - Bleeding time. - Platelet count. - Prothrombin time (P. T. ) - Partial thromboplastine time (PTT). -Fibrinogen level and fibrin split products. 3 - BUN & serum creatinine. 4 - Arterial blood gases (A. B. G. ): To monitor acid-base balance. 5 - Serum muscular enzymes: - (A. S. T. , C. P. K. ) to detect the occurrence of rhabdomyolysis. 6 - E. C. G. and continuous cardiac monitoring. 8

C) Treatment : It includes the following: 1 - First aid measures. 2 - Hospitalization: - if there are: a) No manifestations -----close observation for 6 -8 hrs. b) Manifestations-----supportive, symptomatic& specific measures. *First aid measures: 1 - Reassurance to avoid the frightness effect 2 - Immobilization: - as if it is a fractured limb by using whatever available method 3 - Sedation (to relieve severe agitation). 4 - Tourniquet (or constricting ligature) should be: -Applied proximal to sting. -Tight enough to occlude both the lymphatic & venous flow only. -Removed every 15 minutes for 2 -3 minutes to avoid ischemia. 5 - Incision and suction of the wound at the site of bite: - It becomes a point of controversy as: It may increase the damaged tissues at the site of bite and may increase bleeding from the wound 9 in case of hemorrhagic viper bites.

*Supportive measures: A: maintain patent airway B: suction of secretions , oxygen & ETT± MV C: insert 2 I. V lines *Symptomatic treatment: -Prophylactic antibiotics and antitetanic serum (toxoid) -Pulmonary oedema &/or hypoxia: MV+ PEEP (positive end expiratory pressure) -Antihypertensive drugs in severe hypertension. -Vasopressors for shock. - Antidysrrhythmics for dysrhythmia. 10

*Specific measures: ► Polyvalent SAV (snake anti-venom) ► Fresh blood transfusion in case of coagulopathy Polyvalent ASV (anti-snake antivenom) ● It is suspension of venom neutralizing antibodies from the sera of hyper -immunized animal (horse). Indications : - When the patient has signs and symptoms suggestive of severe or progressive local or systemic manifestations of envenomation. a) Local manifestations: *Local swelling> 1/2 involved limb *Rapid extension of swelling *Enlarged tender lymph nodes draining the bitten limb 11

b)- Systemic manifestations *Coagulopathy (visible spontaneous bleeding). *Hemoglobinuria , myoglobinuria. *ARF. *CVS abnormalities (hypotension, shock, dysrrhyhmia). *Neurotoxicity: ptosis, ophthalmoplgia. *Persistent severe vomiting 12

Time & Route of administration: ASV must be administered as early as possible and through venous route. Dose No local manifestations -No systemic manifestations ~~~~ None Mild Local manifestations -No systemic manifestations -No laboratory changes~~~ 3 -5 vials Moderate Local away from site of bite -Systemic manifestations Laboratory changes ~~~~ 5 -10 vials Severe local manifestations -Severe systemic manifestations -Serious laboratory changes ~~~~ 10 -15 vials 13

Reactions to ASV ► One signs of the following signs &/or symptoms can develop: - Nausea, vomiting and diarrhea - Angioedema - Bronchospasm - Fever & chills - Itching, urticaria - Hypotension and tachycardia. ► How to manage? 1 - Discontinue SAV & give 0. 5 mg of 1: 1000 adrenaline IM +100 mg hydrocortisone IV + 10 mg antihistaminic IV. 2 - Once the patient recovered, restart SAV slowly for 10 -15 minutes with close observation. 14

scorpion poisoning

Composition of scorpion venom: * Low molecular weight proteins: Mainly neurotoxic *No or minimal enzymes: Phospholipase A 2. *Free amnioacids: Tryptophan, histamine. Serotonin, . . . etc.

Toxicity of Scorpion Venom a- Site of action The most potent toxin is the neurotoxin, and is responsible for causing cell impairment in nerves, muscles, and the heart (act mainly on excitable cells of nerves and muscles). b- Action 1 - Central -----malignant hyperthermia & convulsion. 2 - Peripheral------direct & indirect a) Direct - stimulation of the heart - stimulation of alpha adrenergic receptors-----vasoconstriction, cold extremities, tachycardia, hypertension & pulmonary odema. b ) Indirect ---- stimulation of postganglionic fibers of both elements of autonomic nervous system and adrenal glands with release of catecholamines

Mechanism of action Scorpion stimulates neuro-endocrinal immunological axis. (1) Nervous system *Blocks the Ca activated (dependant) potassium channels. *Stabilization of voltage-dependent Na channels in the open position, leading to continuous, prolonged, repetitive firing of the somatic, sympathetic, and parasympathetic neurons (2) Endocrinal system Release of excessive neurotransmitters such as epinephrine, norepinephrine and acetylcholine, evokes an “autonomic storm”.

(3) Immune system - Venom release catecholamines, corticosteroids, kinins & PGs which induce release of immunological mediators as cytokines - Pro-inflammatory cytokines induce tissue injury, inflammatory response. N. B - Neurotoxins of scorpion venom content is highly lethal than neurotoxin of snake venom.

Clinical presentation: - The clinical course of envenomation can be divided into 4 -grades as in the following scale: Grade I: Local pain or paraesthesia at the site of sting. Grade II: Pain or paraesthesia away from the site of sting. Grade III: One or more of the following systemic effects: (1) General manifestations: 1 - Sweating and cold extremities, despite trunkal hyperthermia. 2 - Thirst, dehydration and fever up to 42°C (2) Neuropsychatric manifestation: 1 - Cranial nerve dysfunction: - Blurred vision , disturbed eye movement and constricted pupils. - Dysphagia and excessive salivation. - Tinnitus and slurred speech

2 - Neurologic dysfunction: - Involuntary movements and jerky motility. - Agitation, restlessness, and confusion. - Convulsions, altered conscious level, or coma. - Malignant hyperthermia. (3) Cardiovascular manifestations: 1 - Tachy arrhythmias & hypertension. 2 - Heart failure, hypotension and circulatory collapse. 3 - Cardiomyopathy & toxic Myocarditis, 4 - E. C. G. changes: Depressed S-T segment & inverted T-wave (injury pattern). 5 - Autonomic storm(initial transient parasympathetic stimulation followed by prolonged sympathetic stimulation.

• 4) Respiratory manifestations: 1 - Tachypnea & respiratory distress. 2 - Rhonchi & crepitations. 3 - Pulmonary edema: It may be cardiogenic or non-cardiogenic in origin. (5) G. I. T. manifestations: - Severe vomiting, diarrhea, and may be hematemsis.

Grade IV: The patient has all of the above manifestations (local & systemic). Generally, the scorpion stings are dangerous in children (below 10 years) and in elderly (above 60 years) poor outcome: • Altered conscious level. * Seizures. • Shock or hypotension. * ECG changes. • Pulmonary edema. * Malignant hyperthermia.

Investigations: Routine investigations include the following * Complete blood count (C. B. C. ) * Serum electrolytes (Na+, K+, Cl-, HCO 3) * Arterial blood gases (A B. G ). * BUN & serum creatinine. * Serum enzymes (C. P. K. , A. S. T. , A. L. T. )

Treatment: [I] First-aid measures: [II] Definitive Therapy: (At hospital) in the form of: (1) No manifestations - Close observation for 3 -4 hr is usually what is needed. (2) Life-threatening manifestations: * Ensure patent airway. * Endotracheal intubation & suction of the secretions. * Establish an I. V. line. * Cardio version (medical or electrical) in case of cardiac arrest or serious ventricular arrhythmias

3) Specific measures: (Antivenom) - It should be considered for: (i) Overt cases ( with clinical manifestations). (ii) After stabilization of life-threatening manifestations. - Dose: - Skin test (hypersensitivity) must be performed before the administration to avoid anaphylaxis. - Start with one ampoule I. M. - If there is no response within 0. 5 - 1 hr. , the dose can be repeated up to 3 ampoules I. M. - In severe cases � 1 -5 ampoules can be given by slow i. v. drip method.

Prazocin a) It is a physiological and pharmacologic antidote to the actions of scorpion venom. It is a competitive post-synaptic alpha 1, adrenoreceptor antagonist & should be the first line of management, since alpha receptors stimulation plays a major role in the evolution of clinical spectrum. b) It is also cardioprotective as follow: 1 - Suppresses sympathetic outflow 2 - It decreases the preload, afterload and blood pressure without increasing the heart rate. 3 - Activates venom-inhibited potassium channels. ► Dose The recommended dose is 30 microgram/kg/dose. (250 -500 micg/3 hr)

Dobutamine 1 - Victims who presented in due to both ventricular dysfunction, clinically characterized by (hypotension, shock, tachycardia, delirium with or without pulmonary edema and warm extremities), these cases improves with dobutamine infusion 5 -20 microgram /kg/min. 2 - In children with pulmonary edema with or without hypertension, management should be directed towards relieving afterload without compromising preload

(4) Symptomatic and supportive measures: 1 - I. V. fluid replacement. 2 - Antihypertensive drugs in case of severe hypertension Na nitroprusside 3 - Vasopressors in case of shock (Dobutamine). 4 - Treatment of arrhythmias according to its type. 5 - Fresh blood transfusion in case of coagulopathy. 6 - Pulmonary edema and/or hypoxia: Mechanical ventilation with positiveend expiratory pressure (PEEP). 7 - Prophylactic antibiotics & antitetanic serum (toxoid).