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 doi: https://doi.org/10.1136/bmj.c7136 (Published 05 January 2011) Cite this as: BMJ 2011;342:c7136
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Reply from authors
We are grateful for comments by Abroug F et all regarding recent
trial of scorpion antivenom (1). Mesobuthus tamulus venom evokes severe
autonomic storm due to sodium channel activation. Clinical manifestations
depends upon the time lapsed between sting and hospitalization (2,3 ) and
administration of prazosin(4 ) and scorpion antivenom plus prazosin (1
).Recovery time depends upon the time interval of dose of prazosin
administered. It is reduced to < 11.5 hours if prazosin
administered at 3 hourly interval( 4). The chosen end point was addressed
in detail (1 ). A short coming was that the primary outcome, time to
recovery , was a subjective. This was the only best available option
at rural setting with nil staff with restricted resources at village (
5,6 ). Hypertension , tachycardia , hypotension , cardiac arrhythmias ,
shock and pulmonary edema is spectrum of on going process evoked due to
hypercatecholanimia.. Pulmonary edema accompanied with tachycardia
included in grade 2 .
We did not agree with DR. Natu regarding prazosin should be
reserved for case having raised blood pressure. Prazosin reduces pre load
and left ventricular impendence without raising heart rate. It is the
pharmacological and physiological antidote to venom action (7,8 ).
Prazosin raises the blood pressure in a victim having hypotension due to
scorpion sting provided hypovolumia are well corrected (3). Prazosin
improves the peripheral circulation and hasten the absorption of venom
from site bite, which can be neutralized by circulating antivenom
resulting in rapid recovery(1). This action of prazosin helps to reduce the
total requirement of scorpion antivenom. Unnecessary high doses of
expensive and not freely available scorpion antivenom as mentioned by Dr
Natu can be avoided by simultaneous administration of scorpion antivenom
and prazosin( 1). Since advent of prazosin , the fatality is reduced to
<1% , confirmed its importance in antagonizing the venom action (
9,10 ). Prazosin is a cheap drug available universally even in
peripheral primary health centers and almost every chemists shop (1).
While scorpion antivenom is not easily available and moreover it is
expensive. It is our humble appeal to Dr Natu with strong political
background should force the government of Maharashtra that scorpion
antivenom should be freely available and administered free of cost to a
victim of scorpion sting admitted in private or government hospitals.
References
1-Bawakar HS and Bawakar PH. Efficacy and safety of scorpion antivenom
plus prazosin compared with prazoisn alone for venomous scorpion
(Mesobuthus Tamulus) sting: randomized open label clinical trial. BMJ
2010;341:c7136.
2- Bawakar HS and Bawakar PH. Doagnostic cardiac premonitory signs and
symptoms of red scorpion sting. Lancet 1982;II:552-54
3- Bawakar HS and Bawakar PH.Vasodilators : scorpion envenoming and the
heart (an Indian experience) Toxicon 1994;32:1031-40.
4-Bawakar HS and bawakar PH. Prazosin therapy and scorpion envenomation.
J.Assc.Phys.India. 2000;48:1175-1180.
5-Mill EJ and Ford N- Research into scorpion stings. (Editorial ) BMJ
2011;342:115
6- Treatment for scorpion sting in rural India .Research BMJ
2011;342:152.
7- Bawaskar HS and Bawakar PH.Management of the cardiovascular
manifestations of poisoning by the Indian red scorpion(Mesobuthus
tamulus). British Heart J. 1992;68:478-80.
8-Gupta V. Prazosin:A Pharmacological antidote for scorpin envenomation.
J.Trop.peditr. 2006;52:150-51
9-Bawaskar HS and Bawakar PH. Prazosin in the management of
cardiovascular manifestations of scorpion sting. Lancet 1986;II:510-11.
10-Thirunavukkarasu AB, Chandrasekaran V. Efficacy of antivenom serum
over prazosin in severe scorpion envenomation:Is the current evidence
enough? J.Postgrad.Medicine ( Epub ahead of print) 2011 Jan 24
http://www.jpgmonline.com/preprintarticle..asp?
Competing interests: No competing interests
We read the article "Efficacy and safety of scorpion antivenom plus
prazosin compared with prazosin alone for venomous scorpion (Mesobuthus
tamulus) sting: randomized open label clinical trial" by Bawaskar HS(1)
with interest.
We would like to share with the readers that we already have
published the RCT (done in 2006-2007) comparing the usefulness of Scorpion
antivenom, Scorpion antivenom + prazosin as against prazosin alone in
severe scorpion sting.(2)
Dr. Bawaskar has confirmed our findings in the current article, that
the administration of antivenom + prazosin is superior to prazosin alone
for recovery time.
The study by Dr. Bawaskar has removed the earlier doubts that they
had expressed regarding the efficacy of Scorpion antivenom in 2007.(3)
In fact the dose of scorpion antivenom is the only changed component
which has hastened the recovery.
It is mentioned in the current article citing our study that in severe
scorpion envenomation the dose of antivenom required is much higher. The
adequate additional doses as suggested by Ismail M(4) would have shortened
the recovery time further as seen in our study.(2)
Depending upon the severity of scorpion envenomation the dose of
antivenin will vary and increase. This was not adequately studied in prior
studies which were inconclusive for the efficacy of scorpion antivenin.
Principle findings of our study(2) were as follows,
1. In patients with scorpion antivenin or the combination were
evident after 1 hour of therapy, while in the prazosin treated group
recovery signs were seen only after 8 hours.
2.The mean time for complete recovery was 4.14(+-) 1.6 h in the
patients treated with scorpion antivenom, 3.46(+-)1.10 h in the patients
treated with the combined regime of scorpion antivenom + prazosin and
19.28(+-) 5.03 h in the patients treated with prazosin.
3. Depending upon the severity of envenomation the dose of scorpion
antivenom should vary. (2 to 8 vials in our study.)
4. Prazosin should be reserved for patients presenting with
hypertension and pulmonary edema. In these patients too, scorpion
antivenom should be administered to neutralize the venom and achieve
clinical recovery faster. Only one dose of prazosin suffices when given
with scorpion antivenom, as complete recovery would be seen when the next
dose is due.
References:
1 Bawaskar HS, Bawaskar PH. Efficacy and safety of scorpion antivenom plus
prazosin compared with prazosin alone for venomous scorpion (Mesobuthus
tamulus) sting: randomized open label clinical trial. BMJ 2010;341:c7136
2 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.
3 Bawaskar HS, Bawaskar PH. Utility of scorpion antivenin vs prazosin
in the management of severe mesobuthus tamulus (an Indian red scorpion)
envenoming at rural setting. J Assoc Physicians India 2007;55:14-21.
4 Ismail M. The scorpion envenoming syndrome. Review article. Toxicon
1995;33:825-58.
Competing interests: No competing interests
The report by Bawaskar and Bawaskar, raises major concerns regarding
the methodology used and the results' interpretation1.
First, the sample size calculation was surprisingly based on the time
required for recovery after scorpion sting rather than on the primary end
point, that is the proportion in each group of patients achieving complete
resolution of the grade 2 clinical syndrome by the end of 10 hours. In
addition, the choice of the 10 hour-limit as a censory time is far from
being clinically relevant especially when in their previous publication,
the same authors recorded an average recovery time of 54 hours in patients
treated with SAV and 30 hours in patients treated with prazosin only2. Why
therefore the censory limit of 10 hours and the objective of reducing this
recovery time form 14 hours to 10 hours?
Second, the chosen endpoint does not seem the most appropriate to the
particular envenomation due to the Indian scorpion Mesobuthus tamulus.
Reducing the duration of clinical manifestations may be a reasonable goal
with the Arizona scorpion (which does not expose to the risk of
mortality), but this could be debatable for the case of Old World
scorpions which carry a significant potential of lethality3. If one
analyses the study conclusion, what is the clinical relevance of a
recovery hastening from scorpion sting by 8 hours in a condition that
might actually evoke patients' demise? In this setting, patient-centered
outcomes should be preferred. These could be either prevention of life-
threatening events in patients with systemic envenomation, or reversal of
acute heart failure features when present (curative effects of
antivenom)4.
Third, Bawaskar's study relied on a clinical gradation that hampered
an accurate interpretation of the actual effects of antivenom. According
to this gradation, patients with tachycardia and/or cold extremities could
be graded 2 or 3 as well. Hence, a patient with tachycardia and cold
extremities at inclusion (Grade 2) and who still had tachycardia and cold
extremities 8 or 12 hours later, could be classified either Grade 2 or
even Grade 3 (treatment failure). Moreover, almost all included patients
in the current report (97% and 100% in both study arms, respectively) had
cold extremities. These patients have been graded 2 (and hence included in
the study). They could have been graded 3 as well, and excluded from the
study according to exclusion criteria. In an unblinded RCT, this lack of
precision might also alter the objective classification of patients when
evaluated at different points of time. A gradation system should ideally
be discriminant (ability to identify patients with different severity
levels) and calibrated (ability to predict the outcome). The one used in
this study is very weak regarding the two aspects.
Fekri Abroug, Fahmi Dachraoui, Islem Ouanes, Souheil Elatrous, Lamia
Ouanes-Besbes.
CHU F.Bourguiba. University of Monastir. 5000 Tunisia
References
1. 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;342:c7136.
2. Bawaskar HS, Bawaskar PH. Utility of scorpion antivenin vs prazosin in
the management of severe Mesobuthus tamulus (Indian red scorpion)
envenoming at rural setting. J Assoc Physicians India 2007;55:14-21.
3. Boyer LV, Theodorou AA, Berg RA, Mallie J, Chavez-Mendez A, Garcia-
Ubbelohde W, et al. Antivenom for critically ill children with
neurotoxicity from scorpion stings. N Engl J Med 2009;360(20):2090-8.
4. Abroug F, ElAtrous S, Nouira S, Haguiga H, Touzi N, Bouchoucha S.
Serotherapy in scorpion envenomation: a randomised controlled trial.
Lancet 1999;354(9182):906-9.
Competing interests: No competing interests
Re: Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial
I read with interest about the efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for enomous scorpion ( mesobuthus tamulus) sting; randomized open label clinical trial in BMJ;2011(342):153.
Scorpion sting is a life threatning accident which is common in western Maharastra. Most of the victims are poor farmers and labourers. Working as a medical officer in a rural area we get to see many cases of severe scorpion sting.
Before the advent of scorpion antivenom , prazosin was used as non specific treatment. While treating cases with prazosin the patient needs close monitering till the time of recovery
Prazosin, by blocking alfa receptors, corrects the abnormal hemodyanamic, metabolic effect of circulating catecholamine. It took 10 to 24 hrs to recover. By that time the patient looks exhausted.
We used anti scorpion venom to treat severe scorpion bite presenting with autonomic strom. We found that it is useful if the patient comes within six hours of a bite, as it binds to free circulating scorpion venom rather than to already tissue bound venom. It takes on average 8 hours to recover. We have also seen that patient treated with antiscorpion venom alone went into pulmonary oedema. The number was high in case of antiscorpion venome compared to prazosin. They needed further refferal service at a tertiary care center. Antiscorpion treatment is monospecfic.
We used both antidote for severe scorpion sting presenting with autonomic strom, recovery time was significantly reduced to average 4 hrs. No life threating complication like pulmonary oedema.
References
1)BawaskarHSand BawaskarPH.Prazosin for vasodilator treatment of acute pulmonary edema due to scorpion sting.annal.tro.med.parsitol.1987;81;719-23
2)Efficay and safety of sorpion antivenom plus prazosin compared with prazosinn alone for venomousscorpion(mesobuthus tamulus) sting.randomised open label clinical trial .Bawaskar H.S bawaskar P. H.BMJ;2011(342):153
3)Efficacy of anti-scorpion venom serum over prazosin in the managementent of severe scorpion envenomation.VS natu,SB kamerkar,K Vdya, v natu, s sane, r khuste, s thatte,DA uchil,NN rege.
all three author given conset to publish.
Competing interests: No competing interests