Outcome of scorpion sting envenomation after a protocol guided therapy
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《美国医学杂志》
Department of Pediatrics and Cardiology, JIPMER, Pondicherry, India
Abstract
Objective. Scorpion sting (SS) envenomation is a life threatening emergency in children, though not so severe in adults. Attempt to develop protocol using prazosin and dobutamine and few other drugs to treat SS. Methods. Children aged 0-13 years with a history of scorpion sting were studied. Clinical features, complications, drug therapy and outcome of the cases for the period 1992-97(N=186) was collected by the authors and also from the medical records department (RETROSPECTIVE GROUP). Cases treated during 1997-2000 (N=198) as per the protocol were recorded as PROSPECTIVE GROUP. All the cases were observed for at least for 24 hours. Cases coming within 4 hours of a sting were given a dose of Prazosin (30 mic.gm/Kg/dose) and were observed. Those who came after 4 hours & were asymptomatic received only symptomatic treatment. Cases with signs of envenomation received Prazosin every 6 hourly till recovery. Cases having acute pulmonary edema (APE) were treated with dobutamine and sodium nitroprusside drip. Complicated cases were monitored in PICU as per the protocol. Result . Complications associated with excessive parasympathetic and sympathetic stimulation were observed. Myocarditis was observed due to the toxin and excessive catecholamine, which complicated in left ventricular failure (LVF) and APE. Nearly half of the children with acute myocarditis developed APE. Death was mainly due to myocarditis and APE, with or without encephalopathy. Mortality was high in children who received steroid and antihistaminics outside and who came late (>4 hours). Conclusion. Complication rate remained almost same in both the groups . There was a significant reduction in overall mortality (P=<0.0155) and in deaths associated with APE (P=<0.0001) after the protocol guided therapy. There was also a reduction in mortality in encephalopathy group though not statistically significant. This treatment protocol and aggressive management of APE reduced the mortality due to SS significantly.
Keywords: Scorpion sting; Myocarditis; Acute pulmonary edema (APE); Prazosin; Dobutamine; Sodium nitro prusside (SNP)
Scorpion sting (SS) in children is a life threatening emergency. Most of the children with severe envenomation die due to the toxin, whereas it is a relatively less serious condition in adults. After a sting the venom enters the circulation very rapidly, with a tissue distribution half life of 5-6 minutes and peak tissue concentration is reached in 37 minutes. The excretion half-life of scorpion toxin is approximately 30 minutes.[1] It induces complications in almost all the organ systems. Most of the cases receive various drugs before coming to a referral centre and many of them in a critical condition.
Different regimens had been tried in the past like steroid. Adrenaline, cocktail of drugs containing Morphine, Pethidine, phenergan(Promethazine), Avil (Pheniramine maleate), Largactil., Lasix (frusemide) and insulin with glucose, large boluses of fluid therapy and many other drugs, Most of the deaths due to scorpion sting are attributed to cardiopulmonary complications like myocarditis and acute pulmonary edema (APE).[2],[3],[4]
Though the antivenin is available, it is species specific and works only when it is given immediately after the sting[5],[6] Its efficacy is doubtful in the present situation when cases come late and long after the toxin's peak tissue concentration time. In the absence of a consensus on management and non availability of antivenin as a routine drug in the hospitals, it is necessary to evolve an alternate strategy to treat this condition.
Prazosin, a post synaptic alpha-1 blocker has the pharmacological properties that counteracts the effects of excessive catecholamine and helps in reducing pulmonary congestion. It had been found to be an effective drug for SS in some studies involving adults.[7],[8] The present study attempts to develop a protocol using prazosin and dobutamine and few other drugs to treat SS envenomation in children.
Materials and methods
This study was conducted at a tertiary care hospital (JIPMER, PONDICHERRY) during Sep, 1997 to Dec, 2000. All the cases (0-13 years) presenting to pediatric services with a history of scorpion sting were either observed or admitted to the pediatric intensive care unit (PICU). They were classified into different groups (I-VII)depending on the complications and symptoms.
Group I PCF
GROUP II PCF + APE
GROUP III PCF + MYOCARDITIS
GROUP IV PCF + APE + MYOCARDITIS
GROUP V PCF + APE+MYOCARDITIS + ENCEPHALOPATHY
GROUP VI ENCEPHALOPATHY
GROUP VII NO COMPL ICATIONS
Myocarditis was diagnosed on the basis of clinical features i.e tachycardia, arrhythmia, gallop rhythm, systolic murmurs, ECG changes, elevated LDH (lactate dehydrogenase) and echocardiography. APE pulmonary was diagnosed on the basis of suggestive clinical features like tachypnoea, pinkish, frothy sputum impaired percussion note over lung fields, crepitations and radiological findings, complemented with decreased oxygen saturation with increased AaDo2. All of them received a dose of prazosin (30 microgram per Kg body weight) in supine position with monitoring of blood pressure (BP), heart rate (HR), respiration rate (RR) and hydration status. Cases showing signs of neurological, cardiovascular (CVS), or pulmonary complications were transferred to PICU .for monitoring and further management. Subsequent management was based on the development of complications and assignment to a particular group in protocol. Children with persistent irritability or altered sensorium, convulsions, neurologic deficit were classified as cases of encephalopathy. In the PICU children were monitored for oxygen saturation, HR, RR, BP and urine output
Cases with a history of SS who came within 4 hr, were given paracetamol for pain and a dose of Prazosin (30 microgram per Kg) tablet and were given 6 hourly till all the symptoms subsided. Asymptomatic cases that came after 4 hrs of SS, were kept under observation without prazosin.
All the symptomatic cases were given Prazosin and supportive care. Central venous pressure (CVP) was monitored in addition to routine monitoring in ICU in children who required sodium nitroprusside drip (SNP). Children with APE were put on SNP drip and dobutamine along with supportive measures and ventilated when required. They were tapered off the SNP drip after they got stabilized hemodynamically and were given prazosin in intermediate care room. Dobutamine was tapered and stopped after withdrawing prazosin. This protocol was passed by the institute research committee. Informed consent was taken from the parents before starting the treatment as per the protocol. (Prospective group) All the cases were observed for a minimum period of 24 hrs. Cases with complications were discharged after they were off the drugs for 12 hrs (Prazosin and dobutamine) and were stable for 24 hrs.
Data regarding the cases for the previous years June, 1992-Aug, 1997 was collected by the authors at the time of discharge and in few cases from the medical record division of the hospital (Retrospective group). Analysis was done in relation to complications, time interval between the sting and the admission, body weight and mortality. Fisher's exact test was used to compare the outcome between the prospective and the retrospective group. P value of < 0.05 was taken as statistically significant.
Results
384 children with scorpion sting (SS) were studied over a period of 9 years. (1992-2000) in this hospital. 186 children in retrospective group (1992-1997) were treated with a cocktail of drugs like pethidine, largactil, promethazine (Lytic cocktail), Avil. (pheniramine maleate) morphine, decadron (dexamethasone). Lasix (frusemide) and digoxin was given for myocarditis and APE. Multiple boluses of normal saline or Ringer's lactate were administered for PCF. 198 children with SS were admitted during 1997-2000. Out of them 56.4% were males and 43.6% females. Most of the cases (85%) were within 1-10 years. More number of boys had scorpion sting in 1-5 yrs of age group, though an overall both the sexes were equally affected. 17% of them had no symptoms or complications. The youngest child who survived was a 37 days old infant with APE. Children who came late were having features of excessive sympathetic activity (tachycardia, intense vasoconstriction and carditis). Few children presenting immediately after the sting (within 20 minutes) had features of parasympathetic hyperactivity (i.e. sweating, salivation, bronchospasm and vomiting)- (CHOLINERGIC ACTIVITY). But, none of these children had bradycardia. All of them responded to therapy satisfactorily within 30 minutes. 80 of the cases presented with pain at the site of the sting. 2 children who had no pain at admission developed pain after 8 hours with had myocarditis with APE.
Tachycardia in the study cases lasted for 3 to 96 hrs, whereas bradycardia improved withinin 6 hrs. Nearly 70% of cases had sinus tachycardia. Ventricular ectopics with tachycardia was noted in some of the fatal cases. Only 2 out of 6 having sinus bradycardia had APE. Priapism was noted in nearly 50% of boys, nearly three fourth had tachycardia and one fourth had hypertension. Priapism subsided within 8 hrs in all the children except in two, where it lasted for 24 hrs.
All the children (n=10) weighing 5 Kg or less had complications; but without any mortality. Its incidence reduced to 79-86% (n=178) in 6-25 Kg group and only 50% (n=10) in more than 25 Kg group. 3 cases died in 21-25 Kg group and 2 cases each in 11-15Kg and 6-10 Kg group. A 37-days-old child was the youngest victim in this study who survived APE.
Most of the children had come with cold extremities, sweating and vomiting.12.6% of the children had hypertension (>95th percentile for age) and only 3% had hypotension (<5th percentile) table1. Nearly half of the cases had neither local pain, sting marks, edema nor echymosis as evidence of SS. 2 children developed local pain at sting site, myocarditis and APE after 8 hours of admission. Their clinical features and associated complications are outlined table1.
All the cases with hypertension responded within 4 hours but hypotension took longer and variable period for recovery 6-44 hrs. Children developed myocarditis and hypotension under observation even after 12-16 hrs of the sting and took upto 18 hrs for recovery. Myocarditis was detected in 20% of cases clinically but could be diagnosed in 43% of cases after other investigations. 69% of the cases with PCF showed resolution in 8 hours with warm periphery. Only one child with myocarditis and PCF took 36 hr for recovery. 78% of cases with priapism recovered in 8 hours but it lasted upto 24 hr in 2 cases. 16 cases were seen with APE without clinical or ECG evidence of myocarditis and 8 of them had echocardiographic evidence of myocarditis. All but 3 cases with tachypnoea had APE.
Fresh crepitations appeared in the lungs even after 36 hrs of admission. S3 gallop rhythm appeared even after 41 hrs of admission and lasted for upto 72 hrs. Systolic murmur at the apex disappeared in 4 hrs in all the cases. Only in one child with APE with myocarditis the systolic murmur appeared after 12 hrs of admission and lasted for 24 hrs. Rare features observed were generalized body weakness with hypotonia, hyperthermia, shivering, extra pyramidal symptoms, giddiness, dysarthria and coma.
All the children with encephalopathy presented with signs and symptoms of encephalopathy at the time of admission 54.5% of the cases without any complications had come to the hospital within 1 hr of the sting and only 2 cases had APE within 1-4 hr of the sting. More than 80% of cases with APE, Myocarditis and Encephalopathy presented to us after 4 hrs of the sting. All the fatal cases were seen after 4 hr of the sting table2
67% of cases did not receive any treatment from outside and 76.69% of them had complications. Out of 164 complicated cases, 44 had received avil (pheniramine maleate), decadron (dexamethasone) and 53% of them developed myocarditis with APE, and 2 cases developed encephalopathy. These two drugs given along with prazosin also had higher incidence of complications.
Children admitted within 1 hr of sting had much less complications than of those who came later. Children admitted after 4 hrs of scorpion sting had significantly higher incidence of complications and mortality than of those who came earlier, (P= 0.0011, 95% C.I=0.5858-0.6998). Out of the 4 cases with multiple stings, only one had developed APE. 9 cases had late onset APE even after 1- 24 hrs of admission.
Incidence of complications remained almost same in both the groups except a slight increase in incidence of APE cases in the prospective group. The mortality rate reduced significantly in the prospective group table3. There were 20 deaths recorded in the retrospective group out of 186 admissions, whereas only 7 deaths occurred after the protocol guided therapy. (P=<0.0155, 95% CI=1.196-1.956). Two children died immediately coming to the casualty during 1997-2000 before receiving the management as per the protocol. Therefore, these were not considered as deaths in the prospective group for analysis. One of them had come with persistent seizures in coma and had a cardiac arrest and died immediately. The other child had severe APE at presentation with pink frothy sputum and circulatory collapse and had a cardiac arrest on arrival at the casualty. He could not be resuscitated.
There was a significant reduction in mortality associated with APE in the prospective group. 16 out of 20 cases with APE died during 1992-96, whereas 5 out of 59 cases with APE expired after receiving the management according to the protocol.(P=<0.0001,95% C.I=1.923-4.710) table3.
4 out of 6 cases with encephalopathy expired in the retrospective group, where as only 2 out of 8 cases with encephalopathy died in the prospective group. There was clinically a perceptible reduction in mortality in this group, though it was not statistically significant (P=0.628).
Children who received steroid and antihistaminics had a significantly higher mortality than the cases who did not receive any treatment (P= 0.0012, 95% C.I=0.1924-0.3212). Even those who received prazosin along with steroid and antihistaminics had a significantly higher mortality.(P=0.0135,95% C.I =0.0675-0.1756) than those who did not receive any drugs before admission table2.
132 cases were treated with prazosin alone and there was no death. All the 20 cases treated with prazosin survived. 5 of the 59 cases treated with SNP, prazosin and dobutamine had expired. Interestingly analysis of these cases {(1). prazosin alone, (2.) prazosin + dobutamine and (3). SNP + prazosin+dobutamine)}, revealed that the first group had significantly lower mortality than the third group. (P=0.003).
Only one child developed hypotension after the first dose of prazosin and was resuscitated with normal saline and had no other complication afterwards. He had come in less than 4 hr after the sting and was not given any further dose of prazosin. No serious side effect was documented in any of the cases who received SNP.
On follow-up of 60 cases for a period of 6 months to 2 yr, 2 children (aged 2 yr and 4 yr) had myocardial dyskinesia and dilatation of cardiac chambers and reduction of ejection fraction even after 1 year of SS. A 6 year old child continued to have mitral regurgitation without myocardial involvement or stenosis of mitral valve even after 24 months of followup and had no definite history suggestive of rheumatic fever or previous viral myocarditis. Many of the cases did not come for follow-up despite repeated postal reminders.
Discussion
Reduction in intensity of local pain at the site of the sting on development of PCF and reappearance of pain when the periphery became warm indicates restoration of circulation after a phase of intense vasoconstriction, excessive catecholamine activity. Autonomic storm after scorpion sting had been reported by others also.[8], [9],[10] Life threatening complications (APE, Myocarditis, Encephalopathy) were common in <5 Kg group similar to another study.[10] However, the mortality rate was more in > 25 Kg group contrary to another study.[8]
PCF cases with cold extremities were seen in 73% of cases, similar to 86.3% reported in literature.[8] This is probably the early stage of compensated shock due to excessive catecholamine resulting in peripheral vasoconstriction, but with out significant myocardial dysfunction. Though profuse sweating was observed only in 59% of our cases (including some fatal cases also), it was found in 97 % of cases and was conspicuously absent in fatal cases in another study.[2]
Nearly half of the cases with myocarditis had APE & many had S3 gallop and apical murmur of mitral regurgitation similar to tachyarrhythmia myocarditis in 3-75% of cases and apical murmur in 43.9% of cases in other studies.[2], [11], [12], [13]
Late onset APE could have been due to acute myocardial injury and LVF caused by the toxin and the toxin induced autonomic storm. This had been reported in 17%-34.8% cases from Saudi Arabia (SA) and India.[12],[8] 3 of the present cases had neither acidosis nor other identifiable cause for tachypnoea similar to 3% of cases reported from Saudi Arabia and could be due to toxin induced central hyperventilation.[12]
Generalized seizures and tonic posturing was seen in 3% of cases in comparison to 2-13% from India, Israel and SA. Irritability, excessive sleepiness, excessive crying to minimal stimulation (i.e. calling by name or gentle caress by the mother) was found in 28% of present cases whereas it had been reported in 42% of cases with a very high incidence of encephalopathy (21.3%) from SA.[12]
Time lapsed between the sting and the admission is probably a key factor for better outcome. Children admitted within 4 hr of the sting had much less complications than those came later (P=0.0011).Most of the cases with APE, encephalopathy and myocarditis came to us after 4 hr of the sting and had higher mortality and morbidity. However some studies from India and Saudi Arabia had observed that most of the fatal cases got admitted after 30 minutes to 3 hr of sting [2], [8], [12] we believe that early hospitalization and Prazosin therapy might have prevented complications and mortality. Usefulness of Prazosin in preventing cardiopulmonary complications had been described in adults.[8]
Most of the cases who received multiple drugs outside before coming to the emergency had complications. Children who received decadron (dexamethasone) and anti-histaminic (avil) in spite of receiving prazosin had higher mortality and complications in comparison to those who did not receive any drug (P=0.0135).There was also significant statistical difference between the groups receiving antihistamines and dexamethasone to no treatment group (p=0.00012) and 4 out of 5 deaths occurred in this group. Antihistaminics and dexamethasone alone or in combination are known to potentiate the effect of catecholamine in CVS and CNS and worsen encephalopathy.[10] Those who received multiple drugs also wasted valuable time and came late with complications in different systems.
Significant reduction in mortality (P=<0.001) was the key observation in the present study, similar to few reports from adult studies.[10], [14] Mortality was far less (p=0.003) in cases treated with prazosin alone in comparison to others who received either dobutamine, dopamine or SNP along with prazosin. This could be due to the protective effect of prazosin on cardiovascular and respiratory system. This effect was probably not so much after the onset complications. Though SS had been suggested to be a contributing factor for cardiomyopathy in later life, in the present study only 2 cases had persistent cardiac dysfunction and only one had mitral regurgitation following the SS.[15] It is difficult to draw any conclusion from this.
Reduction in mortality associated with encephalopathy 68% to 26% could be due to the usefulness of Prazosin in neutralizing the adverse effect of catecholamine released in the brain, as the catecholamine released outside the brain doesn't cross the blood brain barrier. Cerebral infarctions in different areas had been reported on C.T scan after the scorpion sting.[16]
Conclusion
In a year 30-50 children with SS are admitted in this hospital and most of them come with systemic complications. Delayed hospitalization was associated with severe life threatening complications. Treatment with steroid, antihistaminic and sympathomimetic drugs before admission was associated with poor outcome. Presence of PCF alone without cardiopulmonary compromise carried excellent prognosis with 100% recovery with treatment. Excellent result was achieved in cases with APE following the above protocol in children. Encephalopathy with or without other complications resulted in higher mortality.
Early medical attention, avoiding conventionally used harmful drugs like steroid antihistaminic and other cocktails of sedatives may reduce the complications and mortality. Many children did not come for follow-up despite repeated postal reminders and might have been asymptomatic after discharge. A long term prospective study may answer the issue of long term complications following a sting.
Acknowledgement
We are thankful to Dr. H.S. Bawasker, M.D. Physician and Dr M.S. Ranjit, M.D. Ped. Cardiologist for their suggestions and guidance during designing of the protocol.
References
1. Ismail M, Shibi A, Abdullah M. Pharmaco kinetics of I125 labeled antivenin to the venom from the scorpion Androctonus amoreuxi Toxicon 1983, 1 : 47-56.
2. Santhanakrishnan BR, Balagopal Raju V. Management of scorpion sting in children. Trop Med Hyg 1974; 77 : 133-135.
3. Murthy KRK.Vakil AE, Yeolekar RE. Insulin administration reverses the metabolic and echocardiographic changes in acute Myocarditis induced by Indian red scorpion (B tamulus) venom in experimental dogs. Ind Heart J 1990: 42 : 35-37.
4. Biswal N, Murmu Uday C, Mathai B et al. Management of scorpion envenomation. Pediatrics Today 1999; 2(4) : 420-426.
5. Belghith M, Boussarsar M, Haguiga H, Besbes L et al. Efficacy of serotherapy in scorpion sting: A matched pair study. J Clin Toxicol 1999; 37 (1): 51-57.
6. Schenone H, Fontecilla J. Scorpion sting outbreaks in recently constructed urban dwelling inhabitants. Bulletin Chi Leno De Parasitologia 1998; 53(1-2) : 35-37.
7. Miller R, Awarn A, Maxwell BB, Masson DT. Sustained reduction of cardiac impedance and preload in congestive cardiac failure with antihypertensive Prazosin. New Engl J Med 1977; 297 : 303-307.
8. Bawasker HS, Bawasker PH. Scorpion sting a review of 121 cases. J Wilderness Medicine 1991; 2 : 164-174.
9. Bawasker HS, Bawasker PH. Scorpion envenoming and the cardiovascular system. Tropical Doctor 1997; 27 : 6-9
10. Graham RM, Hettinger WA. Drug therapy-Prazosin. New Engl J Med 1979; 300 : 232 -235.
11. Elsa AM, Is mail M, Abed, Al Ahaidib MS. Androctonus Crassicauda (Olivier), a dangerous and unduly neglected scorpion - Pharmacological and clinical studies. Toxicon 1994; 32 (12) : 1599-1618.
12. El-Amino EO, Elidrissy A, Hamid HS, Sultan OM. Sofer RA. Scorpion sting, A management problem. Ann Trop Pediatr 1991; 11 : 143-48.
13. Santhanakrishnan BR, Ranganathan G, Ananthasubramanian P, Raju B. Cardiovascular manifestations of scorpion sting in children. Indian Pediatr 1977; 15 : 353-356.
14. Bawasker HS and Bawasker PH. Severe envenoming by Indian Red Scorpion (B tamulus). The use of Prazosin therapy. Q J Med 1996; 89 : 701-704.
15. Sunder Raman T, Olithiselvan M, Sethuraman KR, Narayan KA. Scorpion envenomation as a risk factor for development of cardiomyopathy. J Assoc Phys India 1999; 47(11) : 1047-1057.
16. Thaker AK, Lal R, Mishra M. Scorpion bite with multiple cerebral infarcts. Neurol India 2002; 50 : 100-102.(Biswal Niranjan, Bashir R)
Abstract
Objective. Scorpion sting (SS) envenomation is a life threatening emergency in children, though not so severe in adults. Attempt to develop protocol using prazosin and dobutamine and few other drugs to treat SS. Methods. Children aged 0-13 years with a history of scorpion sting were studied. Clinical features, complications, drug therapy and outcome of the cases for the period 1992-97(N=186) was collected by the authors and also from the medical records department (RETROSPECTIVE GROUP). Cases treated during 1997-2000 (N=198) as per the protocol were recorded as PROSPECTIVE GROUP. All the cases were observed for at least for 24 hours. Cases coming within 4 hours of a sting were given a dose of Prazosin (30 mic.gm/Kg/dose) and were observed. Those who came after 4 hours & were asymptomatic received only symptomatic treatment. Cases with signs of envenomation received Prazosin every 6 hourly till recovery. Cases having acute pulmonary edema (APE) were treated with dobutamine and sodium nitroprusside drip. Complicated cases were monitored in PICU as per the protocol. Result . Complications associated with excessive parasympathetic and sympathetic stimulation were observed. Myocarditis was observed due to the toxin and excessive catecholamine, which complicated in left ventricular failure (LVF) and APE. Nearly half of the children with acute myocarditis developed APE. Death was mainly due to myocarditis and APE, with or without encephalopathy. Mortality was high in children who received steroid and antihistaminics outside and who came late (>4 hours). Conclusion. Complication rate remained almost same in both the groups . There was a significant reduction in overall mortality (P=<0.0155) and in deaths associated with APE (P=<0.0001) after the protocol guided therapy. There was also a reduction in mortality in encephalopathy group though not statistically significant. This treatment protocol and aggressive management of APE reduced the mortality due to SS significantly.
Keywords: Scorpion sting; Myocarditis; Acute pulmonary edema (APE); Prazosin; Dobutamine; Sodium nitro prusside (SNP)
Scorpion sting (SS) in children is a life threatening emergency. Most of the children with severe envenomation die due to the toxin, whereas it is a relatively less serious condition in adults. After a sting the venom enters the circulation very rapidly, with a tissue distribution half life of 5-6 minutes and peak tissue concentration is reached in 37 minutes. The excretion half-life of scorpion toxin is approximately 30 minutes.[1] It induces complications in almost all the organ systems. Most of the cases receive various drugs before coming to a referral centre and many of them in a critical condition.
Different regimens had been tried in the past like steroid. Adrenaline, cocktail of drugs containing Morphine, Pethidine, phenergan(Promethazine), Avil (Pheniramine maleate), Largactil., Lasix (frusemide) and insulin with glucose, large boluses of fluid therapy and many other drugs, Most of the deaths due to scorpion sting are attributed to cardiopulmonary complications like myocarditis and acute pulmonary edema (APE).[2],[3],[4]
Though the antivenin is available, it is species specific and works only when it is given immediately after the sting[5],[6] Its efficacy is doubtful in the present situation when cases come late and long after the toxin's peak tissue concentration time. In the absence of a consensus on management and non availability of antivenin as a routine drug in the hospitals, it is necessary to evolve an alternate strategy to treat this condition.
Prazosin, a post synaptic alpha-1 blocker has the pharmacological properties that counteracts the effects of excessive catecholamine and helps in reducing pulmonary congestion. It had been found to be an effective drug for SS in some studies involving adults.[7],[8] The present study attempts to develop a protocol using prazosin and dobutamine and few other drugs to treat SS envenomation in children.
Materials and methods
This study was conducted at a tertiary care hospital (JIPMER, PONDICHERRY) during Sep, 1997 to Dec, 2000. All the cases (0-13 years) presenting to pediatric services with a history of scorpion sting were either observed or admitted to the pediatric intensive care unit (PICU). They were classified into different groups (I-VII)depending on the complications and symptoms.
Group I PCF
GROUP II PCF + APE
GROUP III PCF + MYOCARDITIS
GROUP IV PCF + APE + MYOCARDITIS
GROUP V PCF + APE+MYOCARDITIS + ENCEPHALOPATHY
GROUP VI ENCEPHALOPATHY
GROUP VII NO COMPL ICATIONS
Myocarditis was diagnosed on the basis of clinical features i.e tachycardia, arrhythmia, gallop rhythm, systolic murmurs, ECG changes, elevated LDH (lactate dehydrogenase) and echocardiography. APE pulmonary was diagnosed on the basis of suggestive clinical features like tachypnoea, pinkish, frothy sputum impaired percussion note over lung fields, crepitations and radiological findings, complemented with decreased oxygen saturation with increased AaDo2. All of them received a dose of prazosin (30 microgram per Kg body weight) in supine position with monitoring of blood pressure (BP), heart rate (HR), respiration rate (RR) and hydration status. Cases showing signs of neurological, cardiovascular (CVS), or pulmonary complications were transferred to PICU .for monitoring and further management. Subsequent management was based on the development of complications and assignment to a particular group in protocol. Children with persistent irritability or altered sensorium, convulsions, neurologic deficit were classified as cases of encephalopathy. In the PICU children were monitored for oxygen saturation, HR, RR, BP and urine output
Cases with a history of SS who came within 4 hr, were given paracetamol for pain and a dose of Prazosin (30 microgram per Kg) tablet and were given 6 hourly till all the symptoms subsided. Asymptomatic cases that came after 4 hrs of SS, were kept under observation without prazosin.
All the symptomatic cases were given Prazosin and supportive care. Central venous pressure (CVP) was monitored in addition to routine monitoring in ICU in children who required sodium nitroprusside drip (SNP). Children with APE were put on SNP drip and dobutamine along with supportive measures and ventilated when required. They were tapered off the SNP drip after they got stabilized hemodynamically and were given prazosin in intermediate care room. Dobutamine was tapered and stopped after withdrawing prazosin. This protocol was passed by the institute research committee. Informed consent was taken from the parents before starting the treatment as per the protocol. (Prospective group) All the cases were observed for a minimum period of 24 hrs. Cases with complications were discharged after they were off the drugs for 12 hrs (Prazosin and dobutamine) and were stable for 24 hrs.
Data regarding the cases for the previous years June, 1992-Aug, 1997 was collected by the authors at the time of discharge and in few cases from the medical record division of the hospital (Retrospective group). Analysis was done in relation to complications, time interval between the sting and the admission, body weight and mortality. Fisher's exact test was used to compare the outcome between the prospective and the retrospective group. P value of < 0.05 was taken as statistically significant.
Results
384 children with scorpion sting (SS) were studied over a period of 9 years. (1992-2000) in this hospital. 186 children in retrospective group (1992-1997) were treated with a cocktail of drugs like pethidine, largactil, promethazine (Lytic cocktail), Avil. (pheniramine maleate) morphine, decadron (dexamethasone). Lasix (frusemide) and digoxin was given for myocarditis and APE. Multiple boluses of normal saline or Ringer's lactate were administered for PCF. 198 children with SS were admitted during 1997-2000. Out of them 56.4% were males and 43.6% females. Most of the cases (85%) were within 1-10 years. More number of boys had scorpion sting in 1-5 yrs of age group, though an overall both the sexes were equally affected. 17% of them had no symptoms or complications. The youngest child who survived was a 37 days old infant with APE. Children who came late were having features of excessive sympathetic activity (tachycardia, intense vasoconstriction and carditis). Few children presenting immediately after the sting (within 20 minutes) had features of parasympathetic hyperactivity (i.e. sweating, salivation, bronchospasm and vomiting)- (CHOLINERGIC ACTIVITY). But, none of these children had bradycardia. All of them responded to therapy satisfactorily within 30 minutes. 80 of the cases presented with pain at the site of the sting. 2 children who had no pain at admission developed pain after 8 hours with had myocarditis with APE.
Tachycardia in the study cases lasted for 3 to 96 hrs, whereas bradycardia improved withinin 6 hrs. Nearly 70% of cases had sinus tachycardia. Ventricular ectopics with tachycardia was noted in some of the fatal cases. Only 2 out of 6 having sinus bradycardia had APE. Priapism was noted in nearly 50% of boys, nearly three fourth had tachycardia and one fourth had hypertension. Priapism subsided within 8 hrs in all the children except in two, where it lasted for 24 hrs.
All the children (n=10) weighing 5 Kg or less had complications; but without any mortality. Its incidence reduced to 79-86% (n=178) in 6-25 Kg group and only 50% (n=10) in more than 25 Kg group. 3 cases died in 21-25 Kg group and 2 cases each in 11-15Kg and 6-10 Kg group. A 37-days-old child was the youngest victim in this study who survived APE.
Most of the children had come with cold extremities, sweating and vomiting.12.6% of the children had hypertension (>95th percentile for age) and only 3% had hypotension (<5th percentile) table1. Nearly half of the cases had neither local pain, sting marks, edema nor echymosis as evidence of SS. 2 children developed local pain at sting site, myocarditis and APE after 8 hours of admission. Their clinical features and associated complications are outlined table1.
All the cases with hypertension responded within 4 hours but hypotension took longer and variable period for recovery 6-44 hrs. Children developed myocarditis and hypotension under observation even after 12-16 hrs of the sting and took upto 18 hrs for recovery. Myocarditis was detected in 20% of cases clinically but could be diagnosed in 43% of cases after other investigations. 69% of the cases with PCF showed resolution in 8 hours with warm periphery. Only one child with myocarditis and PCF took 36 hr for recovery. 78% of cases with priapism recovered in 8 hours but it lasted upto 24 hr in 2 cases. 16 cases were seen with APE without clinical or ECG evidence of myocarditis and 8 of them had echocardiographic evidence of myocarditis. All but 3 cases with tachypnoea had APE.
Fresh crepitations appeared in the lungs even after 36 hrs of admission. S3 gallop rhythm appeared even after 41 hrs of admission and lasted for upto 72 hrs. Systolic murmur at the apex disappeared in 4 hrs in all the cases. Only in one child with APE with myocarditis the systolic murmur appeared after 12 hrs of admission and lasted for 24 hrs. Rare features observed were generalized body weakness with hypotonia, hyperthermia, shivering, extra pyramidal symptoms, giddiness, dysarthria and coma.
All the children with encephalopathy presented with signs and symptoms of encephalopathy at the time of admission 54.5% of the cases without any complications had come to the hospital within 1 hr of the sting and only 2 cases had APE within 1-4 hr of the sting. More than 80% of cases with APE, Myocarditis and Encephalopathy presented to us after 4 hrs of the sting. All the fatal cases were seen after 4 hr of the sting table2
67% of cases did not receive any treatment from outside and 76.69% of them had complications. Out of 164 complicated cases, 44 had received avil (pheniramine maleate), decadron (dexamethasone) and 53% of them developed myocarditis with APE, and 2 cases developed encephalopathy. These two drugs given along with prazosin also had higher incidence of complications.
Children admitted within 1 hr of sting had much less complications than of those who came later. Children admitted after 4 hrs of scorpion sting had significantly higher incidence of complications and mortality than of those who came earlier, (P= 0.0011, 95% C.I=0.5858-0.6998). Out of the 4 cases with multiple stings, only one had developed APE. 9 cases had late onset APE even after 1- 24 hrs of admission.
Incidence of complications remained almost same in both the groups except a slight increase in incidence of APE cases in the prospective group. The mortality rate reduced significantly in the prospective group table3. There were 20 deaths recorded in the retrospective group out of 186 admissions, whereas only 7 deaths occurred after the protocol guided therapy. (P=<0.0155, 95% CI=1.196-1.956). Two children died immediately coming to the casualty during 1997-2000 before receiving the management as per the protocol. Therefore, these were not considered as deaths in the prospective group for analysis. One of them had come with persistent seizures in coma and had a cardiac arrest and died immediately. The other child had severe APE at presentation with pink frothy sputum and circulatory collapse and had a cardiac arrest on arrival at the casualty. He could not be resuscitated.
There was a significant reduction in mortality associated with APE in the prospective group. 16 out of 20 cases with APE died during 1992-96, whereas 5 out of 59 cases with APE expired after receiving the management according to the protocol.(P=<0.0001,95% C.I=1.923-4.710) table3.
4 out of 6 cases with encephalopathy expired in the retrospective group, where as only 2 out of 8 cases with encephalopathy died in the prospective group. There was clinically a perceptible reduction in mortality in this group, though it was not statistically significant (P=0.628).
Children who received steroid and antihistaminics had a significantly higher mortality than the cases who did not receive any treatment (P= 0.0012, 95% C.I=0.1924-0.3212). Even those who received prazosin along with steroid and antihistaminics had a significantly higher mortality.(P=0.0135,95% C.I =0.0675-0.1756) than those who did not receive any drugs before admission table2.
132 cases were treated with prazosin alone and there was no death. All the 20 cases treated with prazosin survived. 5 of the 59 cases treated with SNP, prazosin and dobutamine had expired. Interestingly analysis of these cases {(1). prazosin alone, (2.) prazosin + dobutamine and (3). SNP + prazosin+dobutamine)}, revealed that the first group had significantly lower mortality than the third group. (P=0.003).
Only one child developed hypotension after the first dose of prazosin and was resuscitated with normal saline and had no other complication afterwards. He had come in less than 4 hr after the sting and was not given any further dose of prazosin. No serious side effect was documented in any of the cases who received SNP.
On follow-up of 60 cases for a period of 6 months to 2 yr, 2 children (aged 2 yr and 4 yr) had myocardial dyskinesia and dilatation of cardiac chambers and reduction of ejection fraction even after 1 year of SS. A 6 year old child continued to have mitral regurgitation without myocardial involvement or stenosis of mitral valve even after 24 months of followup and had no definite history suggestive of rheumatic fever or previous viral myocarditis. Many of the cases did not come for follow-up despite repeated postal reminders.
Discussion
Reduction in intensity of local pain at the site of the sting on development of PCF and reappearance of pain when the periphery became warm indicates restoration of circulation after a phase of intense vasoconstriction, excessive catecholamine activity. Autonomic storm after scorpion sting had been reported by others also.[8], [9],[10] Life threatening complications (APE, Myocarditis, Encephalopathy) were common in <5 Kg group similar to another study.[10] However, the mortality rate was more in > 25 Kg group contrary to another study.[8]
PCF cases with cold extremities were seen in 73% of cases, similar to 86.3% reported in literature.[8] This is probably the early stage of compensated shock due to excessive catecholamine resulting in peripheral vasoconstriction, but with out significant myocardial dysfunction. Though profuse sweating was observed only in 59% of our cases (including some fatal cases also), it was found in 97 % of cases and was conspicuously absent in fatal cases in another study.[2]
Nearly half of the cases with myocarditis had APE & many had S3 gallop and apical murmur of mitral regurgitation similar to tachyarrhythmia myocarditis in 3-75% of cases and apical murmur in 43.9% of cases in other studies.[2], [11], [12], [13]
Late onset APE could have been due to acute myocardial injury and LVF caused by the toxin and the toxin induced autonomic storm. This had been reported in 17%-34.8% cases from Saudi Arabia (SA) and India.[12],[8] 3 of the present cases had neither acidosis nor other identifiable cause for tachypnoea similar to 3% of cases reported from Saudi Arabia and could be due to toxin induced central hyperventilation.[12]
Generalized seizures and tonic posturing was seen in 3% of cases in comparison to 2-13% from India, Israel and SA. Irritability, excessive sleepiness, excessive crying to minimal stimulation (i.e. calling by name or gentle caress by the mother) was found in 28% of present cases whereas it had been reported in 42% of cases with a very high incidence of encephalopathy (21.3%) from SA.[12]
Time lapsed between the sting and the admission is probably a key factor for better outcome. Children admitted within 4 hr of the sting had much less complications than those came later (P=0.0011).Most of the cases with APE, encephalopathy and myocarditis came to us after 4 hr of the sting and had higher mortality and morbidity. However some studies from India and Saudi Arabia had observed that most of the fatal cases got admitted after 30 minutes to 3 hr of sting [2], [8], [12] we believe that early hospitalization and Prazosin therapy might have prevented complications and mortality. Usefulness of Prazosin in preventing cardiopulmonary complications had been described in adults.[8]
Most of the cases who received multiple drugs outside before coming to the emergency had complications. Children who received decadron (dexamethasone) and anti-histaminic (avil) in spite of receiving prazosin had higher mortality and complications in comparison to those who did not receive any drug (P=0.0135).There was also significant statistical difference between the groups receiving antihistamines and dexamethasone to no treatment group (p=0.00012) and 4 out of 5 deaths occurred in this group. Antihistaminics and dexamethasone alone or in combination are known to potentiate the effect of catecholamine in CVS and CNS and worsen encephalopathy.[10] Those who received multiple drugs also wasted valuable time and came late with complications in different systems.
Significant reduction in mortality (P=<0.001) was the key observation in the present study, similar to few reports from adult studies.[10], [14] Mortality was far less (p=0.003) in cases treated with prazosin alone in comparison to others who received either dobutamine, dopamine or SNP along with prazosin. This could be due to the protective effect of prazosin on cardiovascular and respiratory system. This effect was probably not so much after the onset complications. Though SS had been suggested to be a contributing factor for cardiomyopathy in later life, in the present study only 2 cases had persistent cardiac dysfunction and only one had mitral regurgitation following the SS.[15] It is difficult to draw any conclusion from this.
Reduction in mortality associated with encephalopathy 68% to 26% could be due to the usefulness of Prazosin in neutralizing the adverse effect of catecholamine released in the brain, as the catecholamine released outside the brain doesn't cross the blood brain barrier. Cerebral infarctions in different areas had been reported on C.T scan after the scorpion sting.[16]
Conclusion
In a year 30-50 children with SS are admitted in this hospital and most of them come with systemic complications. Delayed hospitalization was associated with severe life threatening complications. Treatment with steroid, antihistaminic and sympathomimetic drugs before admission was associated with poor outcome. Presence of PCF alone without cardiopulmonary compromise carried excellent prognosis with 100% recovery with treatment. Excellent result was achieved in cases with APE following the above protocol in children. Encephalopathy with or without other complications resulted in higher mortality.
Early medical attention, avoiding conventionally used harmful drugs like steroid antihistaminic and other cocktails of sedatives may reduce the complications and mortality. Many children did not come for follow-up despite repeated postal reminders and might have been asymptomatic after discharge. A long term prospective study may answer the issue of long term complications following a sting.
Acknowledgement
We are thankful to Dr. H.S. Bawasker, M.D. Physician and Dr M.S. Ranjit, M.D. Ped. Cardiologist for their suggestions and guidance during designing of the protocol.
References
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