Scorpion sting: a review of 121 cases

Transcription

1 Journal of Wilderness Medicine 2, (1991) ORIGINAL ARTICLE Scorpion sting: a review of 121 cases H.S. BAWASKAR and P.H. BAWASKAR Prabhat Colony, Savitri Marg, Mahad Dist-Raigad , Maharashtra, India Scorpion sting is a hazardous and potentially lethal condition. One hundred twenty-one scorpion sting patients were admitted to hospitals in Mahad Maharashtra state, India, during Sixtysix (54.5%) victims had hypertension (mean blood pressure 96 to 160 [average 118.6) mmhg). Twenty-four (19.5%) victims demonstrated tachycardia, with heart rates ranging from 110 to 215 (average 156) beats per minute. Twenty-two (18.8%) had pulmonary edema, while nine (8.5%) died. Analysis of our data suggests that cardiovascular morbidity and mortality depends upon the time between the stings and hospitalization or administration of vasodilators. Current management of scorpion envenomation consists of rapid reduction of hypertension with sublingual nifedipine, postsynaptic alpha adrenergic blockade with prazosin hydrochloride, and digoxin therapy for myocardial failure. Massive pulmonary edema can be treated with sodium nitroprusside. In our setting, mortality is reduced by early hospitalization, even though specific antivenin is not available in India. Key words: sting, envenomation, pulmonary edema, vasodilators Introduction Scorpion envenomations are common in tropical and subtropical regions [1-7]. They are frequent occurrences in rural India. Buthotus tamulus (red scorpion, Fig. 1) stings are frequent in coastal areas of India [3-8]. The venom of this species is a potent autonomic stimulator [5-9]. Severity of symptoms depends upon the size of the victim, season, and time lapse between sting and hospitalization [7,9,10,11]. Vomiting, profuse sweating, priapism, mild pain at the sting site, local urticaria, and cool extremities are early signs of autonomic stimulation due to scorpion sting [8]. Palamneus gravimanus (black scorpion, Fig. 2) is a larger species present in our region, but does not cause systemic manifestations with its painful sting. High mortality from scorpion stings has been reported from Israel and Brazil [5,12]. P.M. Mundie from India reported 23 deaths out of 78 cases from our region [3]. However, no deaths occurred in Israel during 1989, irrespective of whether or not antiserum was administered [13]. Scorpion antivenin is not available in India [7]. It has been argued that its availability would not reduce morbidity and mortality, because scorpion venom is very rapidly distributed to the tissue, with an estimated half life of 5-6 min; peak tissue concentrations of venom are reached within 37 min. Intravenously-administered antivenom would require about 40 times longer to reach peak tissue concentrations. This might also explain the ineffectiveness of scorpion antivenom given 15 min following the injection of scorpion venom [14]. We report here our experience with 121 cases of scorpion envenomation studied during the period of /91 $ Chapman and Hall Ltd

2 Scorpion sting: a review of121 cases 165 Fig. 1. Buthotus tamu[us, the red scorpion [Mesobuthus tamu[us) Patients One hundred and twenty-one victims of scorpion sting were admitted to our hospital in Mahad Maharashtra state, India. They were divided into the following groups, according to major clinical features or fatal outcome: 1) hypertension; 2) tachycardia; 3) pulmonary edema; and 4) fatality (Tables 1, 2, and 3). Hypertension group Sixty-six victims (41 male, 25 female) ages 3 months to 65 years (average 16.2) suffered a scorpion sting (average 2.9) h prior to hospitalization. Soon after the sting, all victims perspired profusely and suffered local pain of mild intensity at the site of sting, while 57 (86.4%) persons vomited once or twice soon after. Priapism was occasionally present in males who vomited. A parasternal lift and apical grade 2/6 systolic murmur of

3 166 Bawaskar and Bawaskar Fig. 2. Palamneus gravimanus, the black scorpion. mitral regurgitation were present in 29 (43.9%) victims for 8-72 (mean 18) h. Fiftyseven (86.3%) patients had cold extremities which took 6-72 (average 17.9) h to warm after oral prazosin hydrochloride, and six (9%) persons developed pulmonary edema, which responded to sodium nitroprusside drip. Admission mean blood pressures ranged from 90 to 160 (mean 118.6) mmhg. Sublingual nifedipine (5 mg for children and 10 mg for adults) was followed by oral prazosin (250 micrograms for children and 500 micrograms for adults repeated as necessary) (Table 4). Tachycardia Twenty-four victims (14 male, 10 female) ages 6 months to 29 years (average 10.9) evaluated (average 6.9) h after a scorpion sting, had heart rates between 110 and 215 (average 155.5) beats per min. An apical systolic grade 2/6 murmur, prominent S3

4 Scorpion sting: a review of121 cases 167 Table 1. Age and sex distribution of scorpion sting victims. Age in years Hypertension Tachycardia Pulmonary edema Total Male Female Male Female Male Female Male Female < and above Total Table 2. Clinical demographics of scorpion sting victims. Clinical manifestations Numberof Male:Female Age in years patients Time between sting and admission (h) Time before clinical improvement (h) Hypertension 46 (20:26) 3 x Tachycardia 24 (15:9) 6 x Pulmonary edema 22 (14:8) Fatal 9 (6:3) 6 x x = Months Table 3. Seasonal distribution of scorpion stings and clinical presentation. Clinical Hypertension Tachycardia Pulmonary edema Fatal Years Month January 1 1 February March April May June July August September October November December Totals

5 Table 4. Response to sublingual nifedipine. No. Age Sex Time between sting Admission blood Bloodpressure (mmhg) after sublingual nifedipine (years) and admission pressure (mmhg) (hours:minutes) 15 Min 30 Min 45 Min 60 Min 90 Min 120 Min 1. 8 Male 6 120/ / /70 100/80 100/70 100/80 100/ Male 4:55 180/ /98 130/90 130/80 130/80 140/80 120/ Male 1 200/ / / /84 120/84 120/70 120/ mon. Female 0: Male 1: Female 1:30 160/ / /90 120/80 120/80 110/80 110/80

6 Scorpion sting: a review of 121 cases 169 gallop, and cold extremities persisted for (average 12.5) h. Three persons characterized by these physical findings subsequently developed acute pulmonary edema. All cases from the tachycardia group had profuse sweating. Vomiting and priapism were reduced or absent in cases reported six or more hours after the sting. All persons recovered with oral prazosin, intravenous digoxin and aminophylline, and supplemental oxygen. Acute, severe pulmonary oedema was treated in some cases with sodium nitroprusside. These cases were characterized by persons with hemoptysis and severe cyanosis. Pulmonary edema Twenty-two victims (14 male, 8 female) ages 7-48 (average 19) years developed acute pulmonary edema (average 10.4) h after being stung. All of them vomited and sweated profusely after the sting. Ten male patients had priapism without pulmonary edema. The remaining four male patients, who reported 19, 14, 48, and 15.5 h, respectively, after the sting in acute pulmonary oedema, no longer suffered priapism. Thirteen victims had massive pulmonary oedema with intractable coughing, hemoptysis, and frothy sputum. They all recovered with administration of sodium nitroprusside, digoxin, aminophylline, furosemide, prazosin hydrochloride, and oxygen. The remainder did not require a sodium nitroprusside drip. Fatal cases Nine victims (6 male, 3 female) ages 6 months to 29 years (average 6) presented (average 14) hours after scorpion sting in circulatory failure with massive pulmonary edema (Table 5). Unfortunately, we do not have autopsy data. Electrocardiographic changes Electrocardiographic changes included peaked T waves, ST segment depression, left anterior hemiblock, Q waves, ST segment elevation, prolonged OT interval, T wave inversion, acute infarction pattern, and ventricular bigeminy. In the hypertensive group, depressed ST segments in infero-iateral leads were common, with tented T waves in leads V2-V6. Prolonged QTC intervals occasionally persisted for up to 3-4 days. Subsequent T wave inversions persisted for 3-4 weeks, Table 5. Fatal cases. No. Age Sex Month Time between Heart rate Bloodpressure sting and (bpm) admission (h) Male Female Female Male Male Male Female Male Female October September June June April April April August August / bpm = beats per minute

7 170 Bawaskar and Bawaskar while five cases showed a ventricular bigeminy pattern. Twelve persons had left anterior hemiblock (LAHB); one had a junctional rhythm. In the tachycardia group, there was often a pattern of injury, typified by Q waves or ST segment elevation in leads I and AVL. Eight cases had LAHB, which persisted for up to h. The pulmonary edema group showed Q waves or ST segment elevation in leads I and AVL consistent with acute infarction pattern. Fifteen persons developed LAHB with a widened QRS complex and QTC interval prolonged to s. Fatal cases showed injury patterns with low voltage in lead I suggestive of hypoxia and left ventricular injury. Discussion Vomiting, profuse sweating and priapism are premonitory diagnostic signs of autonomic stimulation as a result of Buthotus tamulus envenomation [8]. In our patients, we observed a similar pattern, although with less vomiting in the hypertensive group. Priapism, which we attributed to parasympathetic stimulation rather than venous congestion, was reduced or absnet 6 h post sting, even when there were signs of severe congestive heart failure. The degree of priapism did not correlate with prognosis or improvement in cardiovascular manifestations. In our series and in others, early clinical signs and symptoms of severe scorpion sting reflected autonomic stimulation and included mild to severe pain at the sting site, local oedema, cool extremities, urticaria, vomiting, profuse and diffuse sweating, priapism, parasternal lift, excessive salivation, hypertension, brady- and tachyarrhythmias, and ventricular premature contractions. Early electrocardiographic changes include peaked T waves in leads V2-V6, Q waves, ST segment elevation in leads I and AVL, and left anterior hemiblock [6,8,10]. Pain seemed to disappear with peripheral vasoconstriction and to reappear following vasodilation with prazosin. Thus, in our experience, return of local pain was suggestive of clinical improvement. Severity of presenting cardiovascular manifestations depends upon the time lapse between the sting and administration of a vasodilator. Severity of a scorpion sting depends upon the age of the victim, season, and size of the scorpion. Stings were predominantly reported in the months of April, May, and June (49%), with lesser numbers of occurrences in September, October and November (29%). Because of high environmental temperatures, young farmers usually work with minimal clothing in the field during planting and harvest seasons. Thus, it is not surprising that 75% of stings afflicted victims below the age of 20. The severity of cardiovascular manifestations and fatal cases in young victims attests to the potential potency of the venom. Indeed, pulmonary edema was seen to develop within 2.5 h after a sting; 2 victims died within 3.5 h of a sting. Parenthetically, most of the scorpions were approximately half the size of a human adult palm. The maximum increase in serum epinephrine occurs within a few hours after a sting and may persist for hours, after which it declines gradually [15]. Scorpion venom releases catecholamines from the sympathetic nervous system which stimulate the adrenergic receptors and account for hypertension [5,11,16]. Venom also increases left ventricular contractility, stimulates the adrenal glands and autonomic nervous system, and stimulates nerve fibers of myocytes and cardiac cells in culture. The toxin affects myocardial cells directly by augmentation of calcium activity linked to cardiac contractility [17, 18, 19, 20,21,22].

8 Scorpion sting: a review of 121 cases 171 Tachycardia Tachycardia is a catecholamine effect caused by toxin stimulation of beta adrenergic receptors [16,23,24]. The rhythm disturbances observed in most experimental studies are not dose-dependent, but related to the adrenergic and cholinergic effects of different scorpion species [25]. Premature ventricular depolarization observed in hypertensive patients for short duration may be of similar origin. Most of the ECG abnormalities resemble closely those seen in patients with congenital QT interval syndrome. It may be assumed that the catecholamines released in patients following a scorpion sting provoke non-homogeneity of atrial and ventricular repolarization, which plays a major role in the pathogenesis of arrhythmias and ST-T wave changes [26,27]. Pulmonary edema Catecholamines released following a sting induce increased left ventricular contractility, systemic blood pressure, and peripheral impedance. A sudden decrease in left ventricular compliance impairs diastolic filling, which is also adversely affected by tachycardia. The sudden increase in systemic impedance impairs left ventricular emptying [14, 17]. Myocardial hypoxia induced by the large amounts of circulating catecholamines and acute arterial hypertension of adrenergic origin causes left ventricular failure and pulmonary edema. Propranolol does not appear to prevent pulmonary edema induced by scorpion toxin, while phenoxybenzamine prevents it totally [23, 28]. The severity of pulmonary edema is directly related to the dose of toxin, duration of intoxication, and perhaps to the velocity of rise (generation of afterload) of systemic arterial pressure following injection of scorpion toxin. In addition, the edema may be explained, at least in part, by a direct hemodynamic effect and the release of substances which increase vascular permeability. Myocardial damage, attributed to sympathomimetic over-stimulation, also plays a role in the pathogenesis of heart failure and pulmonary edema. The venom may have a direct myocardial effect in addition to its stimulatory properties. Because atropine would intensify the tachycardia and theoretically raise systemic arterial pressure, it should be avoided [29]. Clinical therapy On the basis of clinical manifestations and known pathophysiology of scorpion envenomation, we rationalized management without the use of antiserum. We treated patients in our facility with what was available to us. Oral nifedipine was administered for rapid reduction of hypertension, while the peripheral effects of the venom were blocked with an alpha blocker (prazosin hydrochloride). Other adjuncts included digoxin, aminophylline, oxygen, diuretics, and sodium nitroprusside. We have yet to use antivenin. Nifedipine Single dose sublingual nifedipine induced significant reductions in blood pressure within 10 min, with maximum effects seen after approximately 1 h (Table 4). We felt that nifedipine helped reduce myocardial contractility. The ability of this calcium channel antagonist to block the direct effects of the venom in isolated strips of atrium and ventricle in guinea pigs and rabbits after autonomic blockade strongly suggests direct myocardial involvement ofthe venom in calcium-mediated biological processes [18, 22]. The slow calcium channelblocker helps relax smooth muscle in arteries, veins and bronchi Oles, while it reduces release of kinins and histamine [30, 31]

9 172 Bawaskar and Bawaskar Prazosin hydrochloride Blockade of alpha adrenergic receptors with phenoxybenzamine prevented the hypertensive effect and pulmonary edema induced by scorpion toxin in the rat. Ganglionic blockade did not prevent the blood pressure rise, supporting a peripheral action of the venom. Atropine in combination with propranolol could not prevent or attenuate the venom-induced changes. However, phentolamine returned the abnormal hemodynamics towards normal [11, 15,23). The duration of effect of phentolamine as an alpha blocking agent is short. Prazosin is ten times more potent on molar basis than is phentolamine. The plasma half title is 1-2 h two hours, but the hypotensive action is more prolonged. Reduction in arteriolar resistance is dose dependent. The hypotensive action of prazosin is mediated predominantly by interference with alpha adrenergic stimulation of resistance vessels, in a reversal of epinephrine effect. Prazosin resembles the vasodilator sodium nitroprusside, and is unique among oral vasodilator agents studied to date in possessing combined effects on both aortic impedance and cardiac preload. In the myocardium, phosphodiesterase inhibition by prazosin leads to increased levels of cyclic GMP. As a consequence, cardiac responsiveness to sympathetic stimulation is blunted [7, 10,32,33). For our patients, the sustained dual action of prazosin on ventricular impedance and preload was useful in the setting of severe congestive cardiac failure, particularly because it does not produce tachycardia [34, 35). Sodium nitroprusside and digitalis Sodium nitroprusside was used because of its fast action, ability to be titrated, and absence of tachyphylaxis. It is a pure vasodilator without any action on the sympathetic nervous system. The fall in pulmonary capillary pressure (enhanced ventilation) appeared to precede the fall in arterial blood pressure. With careful dosage adjustment, it was often possible to produce pulmonary improvement with little or not change in mean arterial pressure. Symptoms and signs of pulmonary congestion promptly cleared in patients with pulmonary edema [36, 37). Autopsies of unanesthetized rats killed one hour after Lv. injection of scorpion toxin showed pulmonary edema and cardiac dilatation. Based upon these reports, we have given digitalis to patients with severe sinus tachycardia and clinical evidence of congestive heart failure and pulmonary edema [23). Antivenom Antivenom therapy has been advocated as the only specific treatment for scorpion stings. We believe this is incorrect. Unfortunately, none of the reports have specifically mentioned that antivenom is effective in prevention or abolition of the cardiovascular manifestations in human scorpionism. Although antivenom given before injection of scorpion toxin almost totally prevents the cardiac effects in rats, administration after toxin injection does not abolish them [12, 14). In human scorpionism, entirely differentfrom experimental, the clinical manifestations are related to many factors. By the time persons are hospitalized, they all exhibit cardiac manifestations. We do not agree that antivenom will necessarily reduce further morbidity and mortality. One might even argue that there is negligible role for antivenom in human scorpionism. This is substantiated by a study using radiolabeled antivenom showing that peak tissue concentrations of venom are reached within 37 min. The immunoglobulins

10 Scorpion sting: a review of 121 cases 173 (antivenom) would require significantly longer to reach peak tissue concentrations, particularly since antivenom is injected several hours after a scorpion sting [38]. Irrespective of antivenom administration, cardiovascular morbidity and mortality have been reported similarly [6,29]. The effectiveness of serotherapy emphasizes that heart venom concentration is maximal and antivenom concentration is minimal. Therefore, the possibility of neutralizing the venom is probably very small. Infarction patterns and arrhythmias occurred min after venom injection. We feel that cardiac abnormalities result from accumulation of the venom in cardiac tissues and, indirectly, through the release of autopharmacologic substances. Treatment with specific effector blockers is more rapid and effective than serotherapy, especially when patients are seen late after a sting [39, 41]. In summary, we propose that aggressive medical management directed at the organ systems specifically affected by scorpion venom can be effective. A reasonable prospective study will be necessary to confirm or refute whether antivenin lowers morbidity and mortality. References 1. Bawaskar, H.S. Scorpion sting and cardiovascular complications. Indian Heart J 1977; 29, Gaitonde, B.B., Jadhav, S.S. and Bawaskar, H.S. Pulmonary oedema after scorpion sting. Lancet 1978; MundIe, P.M. Scorpion sting. Br Med J 1961; 1, Goyffon, M., Vachon, M. and Broglio, N. Epidemiology and clinical characteristics of the scorpion envenomation in Tunesia. Toxicon 1982; 20, Gueron, M. and Yarom, R. Cardiovascular manifestations of severe scorpion sting. Chest 1970; 57, Yona, A, Yarom, M., Memet, A and Kalman, G. Scorpion sting in children. Clin Pediatr 1985; 24, Bawaskar, H.S. and Bawaskar, P.H. Stings by red scorpion (Buthotus tamulus) in Maharashtra state, India, a clinical study. Trans R Soc Trop Med Hyg 1989; 83, Bawaskar, H.S. Diagnostic cardiac premonitory signs and symptoms of red scorpion sting. Lancet 1982; Gueron, M. and Waizmann, S. Catecholamines and myocardial damage in scorpion sting. Am Heart Jl969; 75, Bawaskar, H.S. and Bawaskar, P.H. Prazosin for vasodilator treatment of acute pulmonary oedema due to scorpion sting. Ann Trop Med Parasitol1987; 81, Gueron, M., Adolph, R., Grupp, I., Grupp, 0., Gabel, M. and Fowler, N.O. Hemodynamic and myocardial consequences of scorpion venom. Am J Cardiol1980; 45, Campos, J.A, Silva, O.S., Lapez, M. and Freire-maia, L. Signs, symptoms and treatment of severe scorpion poisoning in children. In: Eaker, D. and Wadstrom, T., eds. Natural Toxins. Oxford: Pergamon, 1980, Gueron, M. (Personal communication) 14. Gueron, M., Ovsyshcher, I. What is the treatment for the cardiovascular manifestations of scorpion envenomation? Toxicon 1987; 25, Rohayem, H. Scorpion toxin and antagonistic drugs. J Trop Med Hyg 1953; 56, Moss, J., Kasic, T., Henry, D.P. and Kopin, 1.1. Scorpion venom induced discharge of catecholamines, accompanied by hypertension. Brain Res 1973; 54, Poon-King, T. Myocarditis from scorpion sting. Br MedJ 1964; 3, Fayet, G., Couraud, F., Miranda, F. and Lissitsky, S. Electro-optical system for monitoring

11 174 Bawaskar and Bawaskar activity of heart cells in culture application to the study of several drugs and scorpion toxins. Eur J Pharmacol, 1974; 29, Couraud, F., Rochat, H. and Lissitsky, S. Binding of scorpion neurotoxins to chick embryonic heart cells in culture and relationship of calcium uptake and membrane potential. Biochemistry 1980; 19, Zlotkin, E., Miranda, F. and Rochet, H. Chemistry and pharmacology of buthidae scorpion venoms. In: Bettini, S. ed. Handbook of Experimental Pharmacology. Vol. 48. Anthropod venoms. Berlin: Springer Verlag, 1978, Grupp, I.L., Grupp, G., Gueron, M., Adolph, R and Fowler, N.O. Effects of the venom of the yellow scorpion isolated male performing guinea pig heart. Toxicon 1980; Yarom, R and Braun, K. CA2+ changes in the myocardium scorpion venom injections. J Mol Cell Cardiol(1971); 2, Freire-maia, L., Pinto, G.I. and Fransco, I. Mechanism cardiovascular effects produced by purified scorpion toxin in the rat. J Pharmacol Exp Ther 1974; 188, Corrado, AP., Antonio, A and Diniz, C.R Brazilian pathetic postganglionic stimulant. J Pharmacol Exp Ther 1968; 161, Ismail, M., Osman, O.H. and Petkovic, D. Electrocardiographic studies with scorpion venom. Toxicon 1976; 14, Ovsyshcher, I. and Gueron, M. Congenital QT interval prolongation. Isr J Med Sci 1978;8, Schwartz, P., Periti, M. and Malliani, A The long QT interval. Am Heart J 1975; 89, Gueron, H., Stern, J. and Cohen, W. Severe myocardial damage and heart failure in scorpion sting. Am J Cardio 1967; 19, Freire-maia, L. and Campos, J.A Response to the letter to the editor by Gueron and Ovsyschcher on the treatment of cardiovascular manifestations of scorpion envenomation. Toxicon 1987; 25, Harbans, S., Wasir, H.S., Seshogiri, P.R Acute blood pressure lowering effect of sublingual nifedipine, a clinical study. Clin Sci 1982; 63, Wasir, H.S. and Rao, P.S. Acute blood pressure lowering effect of sublingual nifedipine - a variable dose clinical study. Indian Heart J 1983; 35, Lowenstein,J. and Steele, M.J. Appraisal and reappraisal ofcardiac therapy, prazosin AmerHeart J 1978; 95, Graham, M.R and Pettinger, W.A Drug therapy, prazosin, N Engl J Med, 1979; 300, Miller, R., Awan, N.A, Maxwell, K.S. and Mason, D.T. Sustained reduction of cardiac impedance and preload in congestive heart failure with the antihypertensive vasodilators prazosin. N Engl J Med 1977; 297, Bawaskar, H.S. and Bawaskar, P.H. Prazosin in management of cardiovascular manifestations of scorpion sting. Lancet 1986; Schlant, RC., Tsagaris, T.S. and Robertson, RJ. Studies on the acute cardiovascular effects of intravenous sodium nitroprusside. Am J Cardiol1962; 9, Franciosa, J.A, Guina, N.H., Limas, c.j., Rodrigubra, E.R, Cohn, J.N. Improved left ventricular function during nitroprusside infusion in acute myocardial infarction. Lancet 1972; Ismail, M., Rerteiz, G., Osman, O.H. and Sidra, M.S. Distribution of 125 labelled scorpion venom in rat tissue. Toxicon 1974; 14, Ismail, M. and Elsalam, A.B.D. Are the toxicological effects of scorpion envenomation related to tissue venom concentration? Toxicon 1988; 3, Gueron, M. and Sofer, S. Vasodilators and calcium blocking agents as treatment of cardiovascular manifestations of human scorpion envenomation. Toxicon 1990; 28,