SCORPIONISM

1. SCORPIONISM

2. Case presentation • A 18 year old male patient suffered a scorpion bite on the lateral aspect of his foot. • The killed scorpion was not available for identification. • He was taken to a local hospital and treated with analgesics and iv fluids. • Once the patient’s general condition worsened he was referred to our Poison control unit for further management.

3. Case presentation continued • He was admitted with symptoms of palpitations, breathlessness and excruciating pain at the site of sting . • On examination patient was anxious, diaphoretic, tachypneic. • His pulse rate was 124/min;RR-35/min and BP-90/60mmHg. • Auscultation of lung fields revealed bibasal rales upto his nipple level. Cardiovascular examination was unremarkable but for tachycardia.

4. Case presentation continued • His oxygen saturation on room air was 90%. • After blood was drawn immediately for appropriate investigations and securing a wide bore iv line an ECG and Chest X ray were procured. • ABG showed the patient to have type I respiratory failure. • Chest X Ray was suggestive of Pulmonary edema. • ECG showed sinus tachycardia, LAD,ST depression in V4,5,6;suggestive of myocarditis.

5. Case presentation continued • He was immediately treated with anti failure measures- Back rest ,ionotropic support with dopamine and mechanical ventilation with a PEEP of 5cmH2O for respiratory support.L-Carnitine was added for its cardioprotective action. • Over the next two days patient showed significant improvement in general condition and the pulmonary edema resolved. • Pt. was weaned off the ventilator and extubated on day 3.

6. Once his hemodynamic status was stable he was shifted for echocardiogram which revealed normal cardiac status.Repeat ECGs showed partial reversion of changes over the next 5 days. • During the course of five days patient did not develop any neurological deficits other than paresthesias around the site of sting.

7. Patient was discharged on the fifth day with a diagnosis of :Scorpion sting envenomation causing acute myocarditis leading to acute left ventricular failure and pulmonary edema.

8. Scorpion sting with myocarditis • From May 2004 to March 2006 - 80 cases of scorpion sting have been managed in our IMCU. • Mortality rate is zero. • In the past six months we have had twenty four cases of which 15 cases showed signs of severe envenomation. • Majority of the cases showed signs of cardiovascular toxicity.

9. Name Age sex No. of days Symptoms on admission HR on admission BP ECG changes Other investigations 1 Murali 14 M 4 Chest pain,anxiety 150/min 140/80 Tall T waves in lateral leads. Troponin I-97ng/ml 2 David 36 M 2 Sweating,pain 120/min 130/90 NSR 3 Gunasekaran 44 M 1 Pain, anxiety 130/min 110/70 NSR 4 Thimmaiah 69 M 1 Pain, Chest pain 80/min 140/90 ST elevation in V5,V6 CPK 650 IU/l (50-200 IU/L) 5 Sillamma 35 F 1 Pain at bite site 120/min 130/90 NSR

10. Name Age sex No. of days Symptoms on admission HR on admission BP ECG changes Other investigations 6 Venda 30 F 6 Pain, chest pain, palpitations 142/min 110/70 Sinus tachycardia.ST depression in II, III, aVF, V3-6. ECHO-Mild LV dysfunction. Global hypokinesia of LV. Trivial MR,TR.EF-40%. 7 Paneer Selvan 28 M 2 Pain, anxiety 90/min 140/90 ST depression in lateral leads. 8 Rajendran 25 M 4 Profuse sweating , pilorection, palpitaions 140/min 130/90 Tall peaked T waves in anterolateral leads.

11. Name Age sex No. of days Symptoms on admission HR on admission BP ECG changes Other investigations 9 Muruganandam 29 M 5 Breathlessness, dizziness, pain 150/min 80/50 ST depression in lateral leads Echo-Normal study 10 Arasalai 25 F 1 Pain at bite site 86/min 110/70 NSR 11 Suseela 45 F 3 Drowsy, disoriented 130/min 110/80 ST depression in V 3-6

12. Scorpions • Scorpions capable of inflicting fatal stings in humans are all members of families Buthus and Scorpionidae • Out of 1500 scorpion species, 50 are dangerous to humans • Among the 86 species of scorpions in India, Mesobuthus tamulus and Palamneus swammer-dami are of medical importance. • The epidemiological features of a patient who has been envenomed show a disposition for rural areas (73%), with most of the stings occurring in the summer months between 6:00 pm and 12:00 am (49%) and a second peak from 6:00 am to 12:00 pm (30%). Both of these peaks coincide maximum human activity with maximum scorpion activity.

13. Distribution • Buthus - Mediterranean area • Parabuthus - Western and Southern Africa • Mesobuthus - Asia • Tityus - Central and South America, Caribbean • Leiurus - Northern Africa and Middle East • Androctonus - Northern Africa to Southeast Asia • Centruroides - Southwest USA, Mexico, Central America

14. Symptomology of specific scorpion species • Mesobuthus, Tityus, and Leiurus - Tend to cause severe cardiovascular symptoms • Centruroides - Tend to cause neurological symptoms • Hemiscorpius - Tend to cause tissue necrosis

15. Worldwide, there are about 100,000 cases of scorpion envenomation resulting in approximately 5000 deaths per year. • Reliable statistics are not readily available for this common rural accident . • Case fatality rates of 3-22% were reported among children hospitalized for scorpion stings in India, Saudi Arabia and South Africa.

16. Pathophysiology • Venom deposited via the intravenous route can cause symptoms only 4-7 minutes after the injection, with a peak tissue concentration in 30 minutes and an overall toxin elimination half-life of 4.2-13.4 hours through the urine. • The venom is composed of varying concentrations of neurotoxin, cardiotoxin, nephrotoxin, hemolytic toxin, phosphodiesterases, phospholipases, hyaluronidases, glycosaminoglycans, histamine, serotonin, tryptophan, and cytokine releasers. • The long-chain polypeptide neurotoxin causes stabilization of voltage-dependent sodium channels in the open position, leading to continuous, prolonged, repetitive firing of the somatic, sympathetic, and parasympathetic neurons.

17. Effect of Venom on Ion Channels, Alpha Receptors and Myocardium • The toxin acts by opening sodium channel at presynaptic nerve terminals and inhibiting calcium dependant potassium channels. Autonomic storm is thus initiated • Alpha receptors stimulation by the toxin plays a major role, resulting in hypertension, tachycardia, myocardial dysfunction, pulmonary edema and cool extremities(17). • The unopposed effects of alpha receptors stimulation lead to suppression of insulin secretion, hyperglycemia, hyperkalemia, free fatty acids and free radical accumulation injurious to myocardium.

18. Morbidity/Mortality • Most deaths occur during the first 24 hours after the sting and are secondary to respiratory or cardiovascular failure. • Children and elderly persons are at the greatest risk for morbidity and mortality • Patients in rural areas tend to fare worse than patients in urban areas because of the delay in getting medical help due to a longer travel time to medical centers.

19. Prognostic factors • Scorpion species,Scorpion age, size, and nutritional status • Number of stings and quantity of venom injected • Depth of the sting penetration • Composition of the venom • Site of envenomation: Closer proximity of the sting to the head and torso results in quicker venom absorption into the central circulation and a quicker onset of symptoms. • Age of the victim,Health of the victim • Weight of the victim relative to amount of venom • Presence of comorbidities • Treatment effectiveness

20. History • Time of envenomation • Nature of the incident • Description of the scorpion • Local and systemic symptoms

21. Physical examination • The signs occur within a few minutes after the sting and usually progress to a maximum severity within 5 hours. • Usually has 4 signs, with the most common being mydriasis, nystagmus, hypersalivation, dysphagia, and restlessness.

22. Local signs • A sharp burning pain sensation at the sting site, followed by pruritus, erythema, local tissue swelling, and ascending hyperesthesia, • The tap test is administered by tapping at the sting site. • A macule or papule appears initially at the sting site, occurring within the first hour of the sting. • Pain, erythema, induration, and wheal may be present.

23. Cardiovascular signs Hypertension is described as follows: • Secondary to catecholamine and renin stimulation • Observed as early as within 4 minutes after the sting • Lasts a few hours • High enough to produce hypertensive encephalopathy • Hypotension - Less common and occurs secondary to excess acetylcholine or catecholamine depletion

24. Tachycardia is greater than 130 beats per minute, although bradycardia can be observed. • Transient apical pansystolic murmur is consistent with papillary muscle damage. • Cardiovascular collapse occurs secondary to biventricular dysfunction and profuse loss of fluids from sweating, vomiting, diarrhea, and hypersalivation.

25. Cardiovascular collapse • Observed in 7-38% of cardiovascular cases • Mild envenomation - Vascular effect with vasoconstriction hypertension • Moderate envenomation - Left ventricular failure hypotension with and without an elevated pulmonary artery wedge pressure, depending on fluid status of the patient • Severe envenomation - Biventricular cardiogenic shock • Cardiac dysfunctions attributed to catecholamine-induced increases in myocardial metabolism oxygen demand (leading to myocardial ischemia–induced myocardial hypoperfusion) and to the direct effects of the toxin (leading to myocarditis)

26. Central nervous system signs • Thalamus-induced systemic paresthesia occurs in all 4 limbs. • Patients experience venom-induced cerebral thrombosis and strokes. • The level of consciousness is altered, especially with restlessness, confusion, or delirium. • Patients have abnormal behavior. • Ataxia is also a sign.

27. Autonomic nervous system signs Sympathetic signs • Hyperthermia • Tachypnea • Tachycardia • Hypertension • Arrhythmia • Hyperkinetic pulmonary edema • Hyperglycemia • Diaphoresis • Piloerection • Restlessness and apprehension • Hyperexcitability and convulsions

28. Parasympathetic signs • Bronchoconstriction • Bradycardia • Hypotension • Salivation, lacrimation, urination, diarrhea, and gastric emesis (SLUDGE) • Rhinorrhea and bronchorrhea • Goose pimple skin • Loss of bowel and bladder control • Priapism • Dysphagia • Miosis • Generalized weakness

29. Cranial nerve signs • Classic rotary eye movement may result in ptosis, nystagmus, and blurred vision. • Mydriasis is a sign. • Patients may have tongue fasciculations. • Dysphagia, dysarthria, and stridor occur secondary to pharyngeal reflex loss or muscle spasm. • Patients may present with excessive salivation and drooling.

30. Respiratory signs • Tachypnea may be present. • Pulmonary edema with hemoptysis and a normal-sized heart is observed in 7-32% of respiratory cases. • Respiratory failure may occur secondary to diaphragm paralysis, alveolar hypoventilation, and bronchorrhea.

31. Allergic signs • Patients may have urticaria. • Angioedema is reported. • Patients may present with bronchospasm. • Anaphylaxis is possible.

32. Grading of envenomation • Grade I: Signs of peripheral failure with cold and clammy extremities, sweating, restlessness and hypotension. • Grade II: Grade I signs with sudden onset of tachycardia, gallop rhythm, nausea and vomiting ( suggestive of myocarditis). • Grade III:Grade I signs with neurotoxic manifestations. The Scorpion Antivenin IP. should be administered at the earliest.

33. Lab studies • Obtain a CBC count for leukocytosis and hemolysis in patients with stings from the Hemiscorpius species. • Electrolyte evaluation is warranted in patients with venom-induced salivation, vomiting, and diarrhea. • Coagulation parameters should be measured for venom-induced defibrination because, at high concentrations, the venom is an anticoagulant. • Glucose levels should be measured to evaluate for hyperglycemia from liver and pancreas dysfunction. • Creatine kinase and urinalysis help evaluate for venom-induced excessive motor rhabdomyolysis.

34. Patients may have increased aspartate aminotransferase and alanine aminotransferase levels from venom-induced liver cell destruction. • Increased catecholamine, aldosterone, renin angiotensin, and antidiuretic hormone levels are detected a few hours after the sting. The increased levels persist for 6 hours, after which a gradual decline occurs. • Interleukin (IL)–1 levels are elevated in all envenomations. • High levels of IL-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor are present in severe envenomations. • Radiolabeled antibodies or immunoenzymatic assays help quantify the serum venom level because an association exists between the clinical signs of envenomation and this level.

35. Imaging studies • Unilateral pulmonary edema may be seen on chest x-ray films because of the venom effect on pulmonary vascular permeability. • Echocardiography findings are discussed as follows: • Echocardiography is more sensitive than electrocardiography and creatine kinase assays for assessing myocardial compromise after a scorpion sting. • Findings show a diffuse global biventricular hypokinesis with a decreased left and right ventricular ejection fraction of approximately 0.14-0.38. This dysfunction can appear just a few hours after the sting and usually normalizes within 4-8 days. • Serial echocardiography findings show that the return of left ventricular function to a normal state correlates to clinical cardiorespiratory improvement. • Color-flow Doppler study findings show mitral incompetence, probably secondary to venom-induced dilated cardiomyopathy.

36. Electrocardiogram ECG changes persist for 10-12 days before normalizing. Rhythm disturbances are not dose-dependent but are related to the venom composition. • Sinus tachycardia - Most common rhythm • QTc prolongation - 53% • ST changes - 39% • T-wave inversion - 39% • Ventricular repolarization abnormalities - 15% • Bundle-branch block - 12.8% • First-degree block - 10.2%

37. Local treatment • Use ice bags to reduce pain and to slow the absorption of venom via vasoconstriction. This is most effective during the first 2 hours following the sting. • Immobilize the affected part in a functional position below the level of the heart to delay venom absorption. • Apply a topical or local anesthetic agent to the wound to decrease paresthesia; this tends to be more effective than opiates.

38. Administer local wound care and topical antibiotic to the wound. • Administer tetanus prophylaxis. • Administer systemic antibiotics if signs of secondary infection occur. • Administer muscle relaxants for severe muscle spasms (ie, benzodiazepines.)

39. Specific treatment • Monitor vital signs (eg, pulse oximetry; heart rate, blood pressure, and respiratory rate monitor). • Use invasive monitoring for patients who are unstable hemodynamically. • Administer oxygen. • Administer intravenous fluids to help prevent hypovolemia from vomiting, diarrhea, sweating, hypersalivation, and insensible water loss from a tropical environment. • Perform intubation and institute mechanical ventilation with end-tidal carbon dioxide monitoring for patients in respiratory distress.

40. Specific treatment continued • Antivenin is the treatment of choice after supportive care is established. The quantity to be used is determined by the clinical severity of patients and by their evolution over time. • Scorpion Antivenin IP is of equine origin derived from the plasma of the horses, ponies, mules, etc., that have been hyperimmunized against the venom of Red Scorpion(Mesobuthus tamulus concanesis, Pocock)earlier called as Buthus tamulus.

41. Specific treatment continued • The Scorpion Antivenin IP. is indicated for all stings caused by Red Scorpion (Mesobuthus tamulus concanesis, Pocock) venom where patient presents with clinical signs and symptoms of envenomation. Carry out the sensitivity test on the patient. Inject subcutaneously 0.1 ml. of the serum diluted 1:10. Observe the patient for 30 minutes for local or general reactions, if any. In the absence of adverse reactions, administer the requisite dose by the chosen route of injection. • ADVERSE DRUG REACTIONS: This serum being heterologous is liable to cause sensitivity reactions in occasional patient.

42. Role of Prazosin • Prazosin–a competitive post-synaptic alpha1, adreno-receptor antagonist–should be the first line of management, since alpha receptors stimulation plays a major role in the evaluation of clinical spectrum. • It decreases the preload, afterload and blood pressure without increasing the heart rate. • Prazosin can be given irrespective of blood pressure provided there is no hypovolemia. • Prazosin suppresses sympathetic outflow and activates venom-inhibited potassium channels.

43. Role of Prazosin continued • Prazosin by inhibiting phospho-diesterase enzyme and by inhibiting the formation of inositol triphosphate makes this possible. cGMP, a second messenger of nitric oxide in vascular endothelium (eNOS) and myocardium prevents further myocardial injury. • The metabolic and hormonal effects of alpha receptors stimulation are reversed by prazosin. • Thus prazosin is a cellular and pharmacologic antidote to the actions of scorpion venom and it is also cardioprotective.

44. Prazosin is available as scored 1 mg tablet. The dose recommended is 30 microgram/kg/dose • This is given as an immediate measure in all with evidence of autonomic storm. It should not be given as prophylaxis when pain is the only symptom. • If needed, intravenous maintenance fluids should be given to correct dehydration due to excessive sweating and vomiting. • Prazosin should be repeated in the same dose at the end of 3 hours according to clinical response and later every 6 hours till extremities are warm, dry and peripheral veins are visible easily. • The time lapse between the sting and administration of prazosin for symptoms of autonomic storm determines the outcome

45. Don’ts Do not use traditional remedies such as incisions, suction, tornique or the application of ointments. Do not use alcohol swabs to clean the area as it will facilitate the absorbtion of the toxin. Do not administer antivenom if no signs or symptoms of severe envenomation presents itself. Do not administer spider or snake antivenom. Do not administer atropine to reduce salivation as it may lead to unopposed adrenergic reaction. Do not administer barbiturates, opiates, morphine or morphine derivatives as this could greatly increase convulsions and cause respiratory distress.

46. Messages • Scorpion venom is a potent sympathetic stimulator • Cardiac manifestations are common in Indian red scorpion envenomation. • Alpha receptors stimulation plays a major role in evolution of myocardial dysfunction and acute pulmonary edema. • Prazosin–an alpha adrenoreceptor antagonist–is antidote to venom action. • Time lapse between the sting and administration of Prazosin for autonomic storm determines the outcome.

47. S.no Year No. of cases Male Female 11-20 21-30 31-40 41-50 51-60 61-70 1. 2004 26 14 12 5+1 4 6 7 3 - 2. 2005 41 23 18 7 12 12 7 2 1 3. 2006 12 07 05 2 3 3 4 - - Scorpion Sting