Indian J Pediatr DOI 10.1007/s12098-015-1705-7
EDITORIAL COMMENTARY
Systemic Manifestations in Children with Scorpion Sting Envenomation: How to Manage? Subramanian Mahadevan & Ramachandran Rameshkumar
Received: 15 January 2015 / Accepted: 15 January 2015 # Dr. K C Chaudhuri Foundation 2015
Scorpion sting envenomation in children is a life-threatening, time-limiting acute medical emergency engaging resources of Pediatric emergency and intensive care units worldwide, in particular tropical and sub-tropical countries [1, 2]. Significant effects of scorpion sting envenomation are due to a massive release of sympathetic and parasympathetic neurotransmitters [1–3]. Significant factors contributing to morbidity and mortality in this envenomation are pulmonary edema, myocardial dysfunction, and multiorgan dysfunction syndrome (MODS) [3]. The probable reasons quoted are- low body weight and the larger ratio of venom to body weight in children [4]. Scorpion venom is a heterogeneous mixture with significant variation between different species. It is a mixture comprising of short neurotoxic proteins with 31–64 amino acid sequences. The neurotoxins are species-specific as well as target specific [2]. After scorpion sting, venom is usually deposited in the skin, deep into the subcutaneous tissue; complete absorption may occur in around 7–8 h while 70 % of venom concentration in blood is reached within 15 min. The varied clinical effects of envenomation depend upon scorpion species, amount of injected venom and lethal dose of the venom [1, 3]. The fatality due to scorpion sting varied from 20 to 29 %, during the latter half of the previous century despite various treatment regimens comprising of lytic cocktail, propranolol, decongestive agents, and insulin-glucose drip [1, 3]. Subsequent studies found that lytic cocktail, morphine; atropine, nifidipine, ACE inhibitors, and steroids are unhelpful in the management, rather are associated with worsening of the condition [1, 3]. Drugs that have been described as important S. Mahadevan (*) : R. Rameshkumar Pediatric Critical Care Unit, Department of Pediatrics, JIPMER Women and Children’s Hospital, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605 006, India e-mail: [email protected]
singly or in combination in the pharmacologic support of patients with scorpion envenomation, and cardiovascular manifestations are prazosin, chlorpromazime, dobutamine, nitroglycerine, sodium nitroprusside [1, 3]. Now-a-days there is negligible fatality due to severe scorpion envenomation, because of the advent of scorpion antivenom (SAV), intensive care facilities and vasodilators [1, 2]. In this issue of the Journal, Konca et al. [5] report a study from Adiyaman, Turkey, in children with systemic manifestation due to scorpion sting envenomation, managed with Doxazosin (DOX) along with polyvalent SAV and steroid. The authors addressed the question of whether to use DOX in the management of systemic manifestation due to scorpion sting envenomation in absence of pharmacological antidote prazosin. The authors’ conclusion from this retrospective study is that DOX, especially if prazosin is not available, can be recommended as an effective drug in the treatment of serious scorpion envenomation with significant sympathetic symptoms. This study has significant bearing on management of serious scorpion sting envenomation if the results are interpreted as it is. However, there are important considerations that warrant further discussion with available evidence. First, major therapeutic target is the use of DOX in systemic manifestation of scorpion sting envenomation. In the absence of standard prazosin, DOX was administrated 30 μg/kg and repeated every 3 hourly till resolution of cold extremities; similar to prazosin dose and frequency of administration [1]. Because alpha receptor stimulation plays a critical role in the systemic manifestation of scorpion sting envenomation, alpha-1 receptor antagonists include quinazoline-based prazosin [2]; in this study DOX was used. All patients received one dose of DOX, and 42.4 % patients received additional second dose. Before improvement of the cold extremities after 2nd and 3rd dose of DOX could be analyzed, majority of patients also had severe local manifestations like pain and were given analgesic and supportive care as proposed by
Indian J Pediatr
Bawaskar [1] and their associated contribution to improvement of clinical symptoms need to be considered. Second, regarding the steroid and type of antihistamine administration to all patients before DOX administration, studies including large sample size of 600 patients have found no significant difference in steroid and placebo [3, 6]. Moreover, administration of steroid might enhance the necrotizing effects of excessive catecholamines on myocardium [3]. Masking effects of steroids on DOX effects remain unknown and need to be explored. Hence, these unhelpful and rather harmful therapies should be avoided. Third, the frequency of complications reported, namely hypotension in 18.1 %, pulmonary edema 6 % and myocarditis 6 % in the study patients and improvement after DOX administration must be interpreted with caution. It is possible that the initial administration of SAV had initiated the trend towards hemodynamic stability even before DOX was administered as per the study protocol. Fourth concern is when admission to the hospital is late, the beneficial effect of antivenom and/or prazosin is questionable in severe scorpion stings similar to the index study, rationalizing DOX administration in patients who have already received polyvalent SAV [7, 8]. Recent controlled studies found that even patients present late (up to 24 h) in the hospital, particularly in a study by Pandi et al. [4], SAV and/or prazosin is effective in resolution of systemic symptoms, leads to short stay in the hospital and is effective in decreasing circulating venom, morbidity and mortality including neurotoxic symptoms [2, 4, 9–11]. It is believed that the only specific therapy for scorpion sting envenomation is SAV. Clinical recovery is significantly faster when SAV is used, and it reduces levels of circulating unbound venom and there are no serious complications or anaphylactic reactions as reported in the clinical studies [1, 2, 4, 9–11]. Current literature mentions that antivenom sera fragments bind to neutralize the free venom in the bloodstream. Apart from this action on circulating unbound venom, additionally, the antivenom creates a concentration gradient between plasma and target tissue. Venom bound to antivenom is continuously excreted, allowing for redistribution of venom toxin. The toxin in the tissues moves down the concentration gradient into the blood. In the blood, the redistributed venom is bound by the antivenom. Even if the venom is not immediately neutralized by antibodies, its removal from tissue may cause the rapid regression of
symptoms. [12] This factor may account for beneficial effects of SAV observed in children who presented late [4]. In conclusion, study by Konca et al. [5] underlines the need to streamline the process flow of administration of SAV, alpha-1 receptor antagonist and supportive therapy for safe and effective outcome in children with scorpion evenomation. Conflict of Interest None. Source of Funding None.
References 1. Bawaskar HS, Bawaskar PH. Scorpion sting: update. J Assoc Physicians India. 2012;60:46–55. 2. Isbister GK, Bawaskar HS. Scorpion envenomation. N Engl J Med. 2014;371:457–63. 3. Mahadevan S. Scorpion sting. Indian Pediatr. 2000;37:504–14. 4. Pandi K, Krishnamurthy S, Srinivasaraghavan R, Mahadevan S. Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial. Arch Dis Child. 2014;99:575–80. 5. Konca C, Tekin M, Turgut M. Doxazosin in the treatment of scorpion envenomation. Indian J Pediatr. 2014. doi:10.1007/s12098-014-1423-6. 6. Abroug F, Nouira S, Haguiga H, Elatrous S, Belghith M, Boujdaria R, et al. High-dose hydrocortisone hemisuccinate in scorpion envenomation. Ann Emerg Med. 1997;30:23–7. 7. Patil SN. A retrospective analysis of a rural set up experience with special reference to dobutamine in prazosin-resistant scorpion sting cases. J Assoc Physicians India. 2009;57:301–4. 8. Bosnak M, Levent Yilmaz H, Ece A, Yildizdas D, Yolbas I, Kocamaz H, et al. Severe scorpion envenomation in children: management in pediatric intensive care unit. Hum Exp Toxicol. 2009;28:721–8. 9. Natu VS, Kamerkar SB, Geeta K, Vidya K, Natu V, Sane S, et al. Efficacy of anti-scorpion venom serum over prazosin in the management of severe scorpion envenomation. J Postgrad Med. 2010;56: 275–80. 10. Bawaskar HS, Bawaskar PH. Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial. BMJ. 2011;342:c7136. 11. Boyer LV, Theodorou AA, Berg RA, Mallie J, Arizona Envenomation I, Chavez-Mendez A, et al. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med. 2009;360:2090–8. 12. Hammoudi-Triki D, Ferquel E, Robbe-Vincent A, Bon C, Choumet V, Laraba-Djebari F. Epidemiological data, clinical admission gradation and biological quantification by ELISA of scorpion envenomations in Algeria: effect of immunotherapy. Trans R Soc Trop Med Hyg. 2004;98:240–50.
EDITORIAL COMMENTARY
Systemic Manifestations in Children with Scorpion Sting Envenomation: How to Manage? Subramanian Mahadevan & Ramachandran Rameshkumar
Received: 15 January 2015 / Accepted: 15 January 2015 # Dr. K C Chaudhuri Foundation 2015
Scorpion sting envenomation in children is a life-threatening, time-limiting acute medical emergency engaging resources of Pediatric emergency and intensive care units worldwide, in particular tropical and sub-tropical countries [1, 2]. Significant effects of scorpion sting envenomation are due to a massive release of sympathetic and parasympathetic neurotransmitters [1–3]. Significant factors contributing to morbidity and mortality in this envenomation are pulmonary edema, myocardial dysfunction, and multiorgan dysfunction syndrome (MODS) [3]. The probable reasons quoted are- low body weight and the larger ratio of venom to body weight in children [4]. Scorpion venom is a heterogeneous mixture with significant variation between different species. It is a mixture comprising of short neurotoxic proteins with 31–64 amino acid sequences. The neurotoxins are species-specific as well as target specific [2]. After scorpion sting, venom is usually deposited in the skin, deep into the subcutaneous tissue; complete absorption may occur in around 7–8 h while 70 % of venom concentration in blood is reached within 15 min. The varied clinical effects of envenomation depend upon scorpion species, amount of injected venom and lethal dose of the venom [1, 3]. The fatality due to scorpion sting varied from 20 to 29 %, during the latter half of the previous century despite various treatment regimens comprising of lytic cocktail, propranolol, decongestive agents, and insulin-glucose drip [1, 3]. Subsequent studies found that lytic cocktail, morphine; atropine, nifidipine, ACE inhibitors, and steroids are unhelpful in the management, rather are associated with worsening of the condition [1, 3]. Drugs that have been described as important S. Mahadevan (*) : R. Rameshkumar Pediatric Critical Care Unit, Department of Pediatrics, JIPMER Women and Children’s Hospital, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605 006, India e-mail: [email protected]
singly or in combination in the pharmacologic support of patients with scorpion envenomation, and cardiovascular manifestations are prazosin, chlorpromazime, dobutamine, nitroglycerine, sodium nitroprusside [1, 3]. Now-a-days there is negligible fatality due to severe scorpion envenomation, because of the advent of scorpion antivenom (SAV), intensive care facilities and vasodilators [1, 2]. In this issue of the Journal, Konca et al. [5] report a study from Adiyaman, Turkey, in children with systemic manifestation due to scorpion sting envenomation, managed with Doxazosin (DOX) along with polyvalent SAV and steroid. The authors addressed the question of whether to use DOX in the management of systemic manifestation due to scorpion sting envenomation in absence of pharmacological antidote prazosin. The authors’ conclusion from this retrospective study is that DOX, especially if prazosin is not available, can be recommended as an effective drug in the treatment of serious scorpion envenomation with significant sympathetic symptoms. This study has significant bearing on management of serious scorpion sting envenomation if the results are interpreted as it is. However, there are important considerations that warrant further discussion with available evidence. First, major therapeutic target is the use of DOX in systemic manifestation of scorpion sting envenomation. In the absence of standard prazosin, DOX was administrated 30 μg/kg and repeated every 3 hourly till resolution of cold extremities; similar to prazosin dose and frequency of administration [1]. Because alpha receptor stimulation plays a critical role in the systemic manifestation of scorpion sting envenomation, alpha-1 receptor antagonists include quinazoline-based prazosin [2]; in this study DOX was used. All patients received one dose of DOX, and 42.4 % patients received additional second dose. Before improvement of the cold extremities after 2nd and 3rd dose of DOX could be analyzed, majority of patients also had severe local manifestations like pain and were given analgesic and supportive care as proposed by
Indian J Pediatr
Bawaskar [1] and their associated contribution to improvement of clinical symptoms need to be considered. Second, regarding the steroid and type of antihistamine administration to all patients before DOX administration, studies including large sample size of 600 patients have found no significant difference in steroid and placebo [3, 6]. Moreover, administration of steroid might enhance the necrotizing effects of excessive catecholamines on myocardium [3]. Masking effects of steroids on DOX effects remain unknown and need to be explored. Hence, these unhelpful and rather harmful therapies should be avoided. Third, the frequency of complications reported, namely hypotension in 18.1 %, pulmonary edema 6 % and myocarditis 6 % in the study patients and improvement after DOX administration must be interpreted with caution. It is possible that the initial administration of SAV had initiated the trend towards hemodynamic stability even before DOX was administered as per the study protocol. Fourth concern is when admission to the hospital is late, the beneficial effect of antivenom and/or prazosin is questionable in severe scorpion stings similar to the index study, rationalizing DOX administration in patients who have already received polyvalent SAV [7, 8]. Recent controlled studies found that even patients present late (up to 24 h) in the hospital, particularly in a study by Pandi et al. [4], SAV and/or prazosin is effective in resolution of systemic symptoms, leads to short stay in the hospital and is effective in decreasing circulating venom, morbidity and mortality including neurotoxic symptoms [2, 4, 9–11]. It is believed that the only specific therapy for scorpion sting envenomation is SAV. Clinical recovery is significantly faster when SAV is used, and it reduces levels of circulating unbound venom and there are no serious complications or anaphylactic reactions as reported in the clinical studies [1, 2, 4, 9–11]. Current literature mentions that antivenom sera fragments bind to neutralize the free venom in the bloodstream. Apart from this action on circulating unbound venom, additionally, the antivenom creates a concentration gradient between plasma and target tissue. Venom bound to antivenom is continuously excreted, allowing for redistribution of venom toxin. The toxin in the tissues moves down the concentration gradient into the blood. In the blood, the redistributed venom is bound by the antivenom. Even if the venom is not immediately neutralized by antibodies, its removal from tissue may cause the rapid regression of
symptoms. [12] This factor may account for beneficial effects of SAV observed in children who presented late [4]. In conclusion, study by Konca et al. [5] underlines the need to streamline the process flow of administration of SAV, alpha-1 receptor antagonist and supportive therapy for safe and effective outcome in children with scorpion evenomation. Conflict of Interest None. Source of Funding None.
References 1. Bawaskar HS, Bawaskar PH. Scorpion sting: update. J Assoc Physicians India. 2012;60:46–55. 2. Isbister GK, Bawaskar HS. Scorpion envenomation. N Engl J Med. 2014;371:457–63. 3. Mahadevan S. Scorpion sting. Indian Pediatr. 2000;37:504–14. 4. Pandi K, Krishnamurthy S, Srinivasaraghavan R, Mahadevan S. Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial. Arch Dis Child. 2014;99:575–80. 5. Konca C, Tekin M, Turgut M. Doxazosin in the treatment of scorpion envenomation. Indian J Pediatr. 2014. doi:10.1007/s12098-014-1423-6. 6. Abroug F, Nouira S, Haguiga H, Elatrous S, Belghith M, Boujdaria R, et al. High-dose hydrocortisone hemisuccinate in scorpion envenomation. Ann Emerg Med. 1997;30:23–7. 7. Patil SN. A retrospective analysis of a rural set up experience with special reference to dobutamine in prazosin-resistant scorpion sting cases. J Assoc Physicians India. 2009;57:301–4. 8. Bosnak M, Levent Yilmaz H, Ece A, Yildizdas D, Yolbas I, Kocamaz H, et al. Severe scorpion envenomation in children: management in pediatric intensive care unit. Hum Exp Toxicol. 2009;28:721–8. 9. Natu VS, Kamerkar SB, Geeta K, Vidya K, Natu V, Sane S, et al. Efficacy of anti-scorpion venom serum over prazosin in the management of severe scorpion envenomation. J Postgrad Med. 2010;56: 275–80. 10. Bawaskar HS, Bawaskar PH. Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial. BMJ. 2011;342:c7136. 11. Boyer LV, Theodorou AA, Berg RA, Mallie J, Arizona Envenomation I, Chavez-Mendez A, et al. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med. 2009;360:2090–8. 12. Hammoudi-Triki D, Ferquel E, Robbe-Vincent A, Bon C, Choumet V, Laraba-Djebari F. Epidemiological data, clinical admission gradation and biological quantification by ELISA of scorpion envenomations in Algeria: effect of immunotherapy. Trans R Soc Trop Med Hyg. 2004;98:240–50.
