To the Editor: Boyer et al. (May 14 issue)1 report that amongchildren with neurotoxic effects of scorpion envenomation, scorpion-specificF(ab')2 antivenom resolved the clinical syndrome within 4 hours.In 1999, we published the results of a negative randomized,controlled trial of antivenom in patients with scorpion envenomationin southern Tunisia.2 Although neurotoxic effects are reportedin up to 78% of patients with venomous scorpion stings in NorthAfrica, we assessed the efficacy of scorpion antivenom on objectiveend points such as a change in severity grade.3 The 100% rateof resolution of neurotoxic symptoms with scorpion-specificantivenom in the study by Boyer et al. is ascribed to rapidneutralization of circulating scorpion venom; this finding hasbeen previously reported, and its clinical relevance largelydebated.4,5 The distribution range and the standard deviationaround the mean of baseline plasma venom levels in the controlgroup suggest that some patients had no detectable levels ofvenom. Was the outcome for those patients the same as that ofthe active group or that of the control group? Midazolam infusion,which affected both the primary and secondary end points, wasnot standardized according to a validated grading system. Therefore,it is difficult to identify the precise moment that resolutionof the neurotoxic syndrome occurred, and the decision to stopthe midazolam infusion might have been delayed, since it wasbased on the observation of the patient's condition by the physician-investigator.
Souheil ElAtrous, M.D. Centre Hospitalo-Universitaire Tahar Sfar Mahdia, Tunisia
References
Boyer LV, Theodorou AA, Berg RA, et al. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med 2009;360:2090-2098. [Free Full Text]
Abroug F, ElAtrous S, Nouira S, Haguiga H, Touzi N, Bouchoucha S. Serotherapy in scorpion envenomation: a randomised controlled trial. Lancet 1999;354:906-909. [CrossRef][Web of Science][Medline]
Bouaziz M, Bahloul M, Kallel H, et al. Epidemiological, clinical characteristics and outcome of severe scorpion envenomation in South Tunisia: multivariate analysis of 951 cases. Toxicon 2008;52:918-926. [Medline]
Krifi MN, Amri F, Kharrat H, El Ayeb M. Evaluation of antivenom therapy in children severely envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot) scorpions. Toxicon 1999;37:1627-1634. [Medline]
Ghalim N, El-Hafny B, Sebti F, et al. Scorpion envenomation and serotherapy in Morocco. Am J Trop Med Hyg 2000;62:277-283. [Abstract]
To the Editor: Although Boyer et al. report that F(ab')2 antivenomreversed neurotoxic signs and symptoms, one should keep in mindthat Centruroides sculpturatus does not belong to the most toxicspecies, which include several Mexican, Brazilian, and "oldworld" scorpions, whose stings may cause, in addition to neurotoxiceffects, cardiac arrhythmias, cardiogenic shock, pulmonary edema,and death. These life-threatening consequences have been shownin studies of humans and of laboratory animals.1,2
It is questionable whether the antivenom can reverse the cardiacpathophysiological effects. Several authors have shown thatantivenom, including F(ab')2, does not alleviate hemodynamicchanges or cardiogenic pulmonary edema, or prevent death,2,3and the outcome was the same for patients treated with antivenomand those treated without antivenom.3,4
De Rezende et al.5 found that although venom antigen in plasmafrom persons who had been stung by scorpions was not detected1 hour after antivenom therapy, and pain and agitation disappearedwithin a few hours, patients with pulmonary edema recoveredonly 48 hours after serotherapy.
Antivenom may be given to patients with venomous scorpion stingsto reverse neurotoxic effects, but patients should be closelyobserved and treated appropriately when secondary (cardiorespiratory)complications occur.
Shaul Sofer, M.D. Soroka University Medical Center Beer-Sheva, Israel shsofer{at}bgu.ac.il
Himmatrao S. Bawaskar, M.D. Bawaskar Hospital and ResearchCenter Maharashtra, India
Moshe Gueron, M.D. Ben-Gurion University of the Negev Beer-Sheva, Israel
References
Sofer S, Gueron M. Respiratory failure in children following envenomation by the scorpion Leiurus quinquestriatus: hemodynamic and neurological aspects. Toxicon 1988;26:931-939. [Medline]
Cupo P, Hering SE. Cardiac troponin I release after severe scorpion envenoming by Tityus serrulatus. Toxicon 2002;40:823-830. [Medline]
Abroug F, ElAtrous S, Nouira S, Haguiga H, Touzi N, Bouchoucha S. Serotherapy in scorpion envenomation: a randomised controlled trial. Lancet 1999;354:906-909. [CrossRef][Web of Science][Medline]
De Rezende NA, Dias MB, Campolina D, Chavez-Olortegni C, Diniz CR, Amaral CF. Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions. Am J Trop Med Hyg 1995;52:277-280. [Free Full Text]
The authors reply: Sofer et al. rightly point out that differencesin the venom from scorpions in various parts of the world placeinherent limitations on the generalizability of results fromstudies that involve a single geographic location. This problemis compounded by differences in medical care and in the qualityand safety of the antivenom. Envenomation by North Americanneurotoxic scorpions can, in fact, involve pulmonary edema andcardiac effects1; however, we specifically avoided includingthese effects as end points for our small clinical trial, becausethey are less consistently observed than the more florid neuromotoreffects and because slow resolution of pulmonary edema mightobscure signs of toxin reversal, a possibility that is consistentwith the observation by Sofer et al. More commonly, in our sickestpatients, neuromotor toxic effects themselves cause ventilatoryfailure, and this phenomenon is amenable to reversal with antivenom.
Differences in outcome between our study and the one by Abrouget al.2 reflect some combination of the same issues —differences in venom, in clinical study design, and in antivenompotency. Our binary primary end point was selected to show adifference between very small groups, and our decision to studychildren who were sick enough to require intensive care (correspondingapproximately to grade 3 on the severity scale used in Tunisia)ensured that reversal of the syndrome would be unambiguous.A standardized protocol, in which midazolam was used becauseof its short duration of action, allowed adjustment of the doseat 15-minute intervals. This allowed dosing to reflect the risingor diminishing severity of the syndrome, irrespective of theactual last moment of toxicity. Our findings that intravenousantivenom shortens the plasma half-life of venom are consistentwith findings of Krifi et al.3 and of Ghalim et al.,4 and ourprimary and secondary end points show the clinical correlationbetween the administration of sufficient neutralizing dosesof antivenom and the resolution of toxic effects. A direct comparisonof our study of venom neutralization with the study by Abrouget al. cannot be made because their study design did not incorporatevenom levels.
Leslie Boyer, M.D. University of Arizona Health Sciences Center Tucson, AZ boyer{at}pharmacy.arizona.edu
Alejandro Alagón, M.D., Ph.D. Universidad NacionalAutónoma de México Cuernavaca, Mexico
Andreas Theodorou, M.D. University of Arizona Health Sciences Center Tucson, AZ
References
Berg RA, Tarantino MD. Envenomation by the scorpion Centruroides exilicauda (C. sculpturatus): severe and unusual manifestations. Pediatrics 1991;87:930-933. [Free Full Text]
Abroug F, ElAtrous S, Nouira S, Haguiga H, Touzi N, Bouchoucha S. Serotherapy in scorpion envenomation: a randomised controlled trial. Lancet 1999;354:906-909. [CrossRef][Web of Science][Medline]
Krifi MN, Amri F, Kharrat H, El Ayeb M. Evaluation of antivenom therapy in children severely envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot) scorpions. Toxicon 1999;37:1627-1634. [Medline]
Ghalim N, El-Hafny B, Sebti F, et al. Scorpion envenomation and serotherapy in Morocco. Am J Trop Med Hyg 2000;62:277-283. [Abstract]
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