Scorpion Envenomation Clinical Trial
Official title:
Comparative Study of Efficacy of Antiscorpion Venom Serum(AScVS)vs Prazosin in the Management of Severe Scorpion(Mesobuthus Tamulus Concanesis Pocock)Envenomation and Evaluation of Effects of the Combination of AScVS + Prazosin Therapy.
The data available for the efficacy of AScVS and prazosin is generated through different trials done in different clinical setting. Hence it was felt worthwhile to confirm the documented efficacy of AScVS and prazosin in terms of time taken for clinical recovery in a clinical trial. Along with this, effects of both the therapies on various biochemical parameters will be recorded and compared with. It was also felt necessary to study the effect of combination on the clinical outcome.
Red Scorpion (Mesobuthus Tamulus Concanesis Pocock) sting is a common medical emergency in
the coastal regions of India and is a cause for considerable morbidity and mortality.
Signs and symptoms show either cholinergic or adrenergic predominance. Cholinergic symptoms
are profuse sweating, priapism, bradycardia, increased salivary and bronchial secretions and
vomiting. Adrenergic symptoms are transient hypertension followed by hypotension,
tachycardia, tachypnoea, pulmonary edema and circulatory failure in later stages. Scorpion
venom blocks voltage dependent inactivation of sodium channels, resulting in intense
persistent voltage depolarization of autonomic nerves with massive release of catecholamines
from adrenal medulla and parasympathetic and sympathetic nerve endings.
Prazosin a selective alpha-1 blocker is used as the treatment for scorpion sting, which can
only counteract the manifestations of sympathetic over-activity. Experimentally and
clinically it is seen that scorpion venom stays in the body for 24-36 hours, as Prazosin
does not neutralize the venom, 3 hourly round the clock doses of prazosin and continuous
I.C.U. monitoring is necessary with alpha blocker therapy. However, ideal treatment modality
remains neutralization of venom in the systemic circulation.
Since 1997 enzyme refined AScVS ( Monovalent Anti-scorpion venom serum against Mesobuthus
tamulus concanesis Pocock.) has been made available by Haffkine Biopharmaceuticals, Mumbai
for field use. Throughout the konkan(western coastal Maharashtra, India) area the same
species of scorpions responsible for fatal envenomation is found.
From 1997-2002, 48 patients of serious scorpion envenomation were treated with AScVS(1).
Based on this experience a clinical scoring system for dose requirement was evolved based on
sweating, pulse rate, respiratory rate, blood pressure, CNS effects and presence of
priapism. In our experience computed doses given as intravenous bolus are more effective and
successfully ameliorated signs and symptoms in all patients. Subsequently 16 patients were
given treatment with either AScVS (n=8), Prazosin (n=5) and a combination of both (n=3) so
as to compare the effects of these available treatment modalities. It was found that the
patients receiving either AScVs or a combination showed a complete recovery approximately
within 4 hours of onset of therapy as against patients receiving Prazosin, who required 16
hours for recovery. There was no mortality in any of the group. There was not a single
incidence of anaphylaxis after administration of AScVS. Release of adrenaline in the
systemic circulation by scorpion sting itself appears to be protective against the danger of
anaphylaxis. The label on the AScVS vials states that the maximum dose is 3 vials, which can
be given either intramuscular or by intravenous route. However we used AScVS as slow bolus
intravenously and dose was decided clinically depending upon the severity of the patient
condition. (maximum 10-15vials.) Based on this experience, an open labeled, randomized
controlled parallel group clinical trial has been initiated. Eighty-three patients have been
recruited so far, 28 patients each, in AScVS and AScVS + prazosin group and 27 patients in
Prazosin group, two patients out of 27 in Prazosin group were withdrawn as both the
pediatric patients (around 12 years old) developed pulmonary edema after few hours, so AScVS
had to be given. The onset of relief (based on composite score) with AScVS or combination of
AScVS with prazosin was early and complete recovery occurred at 4.14+/- 1.6 hrs. and 3.46+/-
1.10hours. However, in patients receiving only prazosin, the clinical score was found to
worsen initially, followed by a gradual improvement and subsequent complete recovery, at
19.28 +/- 5.03 hrs. (p<0.001 vs AScVS). Recovery time with AScVS is much shorter because
after complete neutralization of venom, fresh secretion of catecholamines stop and
adrenaline and nor-adrenaline which are already in circulation have action as short as 1 to
2 minutes. These findings appear consistent with our clinical experience and indicate that
in the near future AScVS would evolve as a safe, efficacious and life saving treatment
modality for patients with severe scorpion envenomation. Use of clinical scoring system can
enable the clinician to select the optimum dose of AScVS to be administered.
Neutralization of venom is thus proved to be better than therapy for complications, akin to
the dictum 'prevention is better than cure'.
References:
1. Natu VS, Murthy RKK, Deodhar KP. Efficacy of species specific Antiscorpion venom serum
(AScVS) against severe, serious scorpion stings (mesobuthus tamulus concanesis pocock.)—An
experience from rural hospital in western Maharashtra. JAPI, 2006; 54: 283-7.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment