In the management of scorpion sting envenomation, the efficacy of Scorpion antivenom (SAV) has been shown in many studies [2,5,6]. The current dose of SAV used in children is primarily based on studies in the adult population [2,5]. Even after the use of 30 mL of SAV, few children may deteriorate [5,7]. Antivenom, when injected intravenously, binds to the venom and facilitates its excretion [8-10]. Subsequently, a concentration gradient of venom between the vascular compartment and the peripheral tissue compartment facilitates the redistribution of venom from peripheral tissues to the vascular compartment from where the antivenom moderates further excretion of venom [8-10]. The dose of SAV required seems to be related to the severity of envenomation, but has not been well researched. The purpose of this study was to describe the effect of the second dose of SAV in children with non-resolving envenomation.

This prospective study was undertaken in the Pediatric Critical Care Unit in a tertiary hospital in Puducherry between April 2015 and July 2016. Approval was obtained from the Institute Ethics Committee.

All children showing envenomation-Grade 2 and above were administered the first dose of three vials (30 mg) of SAV, i.e., a single 30 mL dose of monovalent M. tamulus antivenom (Haffkine Biopharma, Mumbai) in 100 mL of normal saline, which was infused intravenously over one hour. All children received oral prazosin (30 µg/kg/dose), and it was repeated every three hours until the extremities were warm as per the assessment of treating team.

A second dose of three vials (30 mL) of SAV was administered in case of persistence of an autonomic storm or worsening to higher grades of envenomation within 6 hours of the first dose. Children with myocardial dysfunction showing improvement in ejection fraction or on a tapering dose of inotropes were not treated with the second dose. The decision to administer the second dose of SAV was taken by the treating team after documenting the eligibility criteria. Clinical and biochemical data and investigations (CPK-MB, Troponin-I, 12-lead electro-cardiography (ECG) and echocardiography (ECHO) were performed at admission, and six-hourly till recovery.

The patients were divided into Group-A (received 30 mL SAV) and Group-B (received 60 mL SAV) to determine the predictors of the second dose of SAV. Continuous data, if normally distributed, was compared by Student t test and, if non-normally distributed, was compared by Mann-Whitney U test and proportions with chi-square test (Fisher exact test if cell frequencies were small). Multivariate binary regression analysis (backward: conditional method) with predefined clinical variables was done to find out the predictors of the second dose, and model fit was assessed with Hosmer and Lemeshow test. All tests were two-tailed and P value <0.05 considered as statistically significant. SPSS 20.0 software and Epi Info 7 was used for data analysis.

Seventy-six children with scorpion sting envenomation were assessed for eligibility, and 72 were enrolled (Fig.　1). Baseline characteristics, investigations, and intervention are described in Table I. Cold peripheries (94.4%) and Sweating (69%) were the most common symptoms observed. One child in Group-A required mechanical ventilation for 6 hours for pulmonary edema at admission due to excessive fluid administration at an outside hospital.

Fig. 1 Study flow chart.

TABLE I	Baseline Characteristics at The Time of Enrollment into The Study

In this study, we documented efficacy of a second dose of SAV in a subset of children with Indian red scorpion sting envenomation who did not improve after the first dose. Abnormal echocardiography at admission predicted the need for the second dose of SAV.

This was only an exploratory study, and there was no comparison arm to determine the efficacy of the second dose of SAV. Moreover, the SAV used was only against Mesobuthus tamulus; whether the results can be extrapolated to other scorpion species needs to be studied further. The delay in recovery after two doses of SAV could be due to two reasons; one is the severity of envenomation, delay in giving the antivenom or insufficient amount of antivenom. Hence, it is important to neutralize the venom in both vascular and the tissue compartment; with a higher dose of SAV, this can be considered with reasonable certainty, consistent with findings from other studies [6,9]. This would mean that children with severe envenomation might benefit from 60 mL of SAV as the first dose at admission or an early administration of the second dose of SAV (another 30 mL).

We conclude that children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of SAV, and an initial dose of 60 mL of SAV at admission may be more beneficial. The efficacy and safety of higher and repeated doses need to be confirmed by controlled trials.

Acknowledgements: Mrs S Raja Deepa (JIPMER Campus, Puducherry, India) for data entry and editing of the manuscript; Mr. Rakesh Mohindra (Punjab University, Chandigarh, India) and Ms. Thenmozhi M (CMC, Vellore, India) for helping with the statistical analysis; and Ms. Harpreet Kaur (Punjab University, Chandigarh, India), and Mrs Neelima Chadha (Tulsi Das Library, PGIMER, Chandigarh, India) for helping with medical literature search.

Contributors: RR,SM: conceptualized the study, contributed to review of literature and critically reviewed the manuscript; AA: collected the data, reviewed the literature and drafted the first version of manuscript. PS: contributed to review of literature and performed the echocardiography. All authors were involved in the management of the patients, and approved the final version of manuscript.

Funding: JIPMER intramural research grant.

Competing interest: None stated.