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High-dose pralidoxime for organophosphorus poisoning
Correspondence
Kirti S Pawar and colleagues (Dec 16, p 2136)1 report that a highdose regimen of pralidoxime reduces morbidity and mortality in moderately severe cases of acute organophosphorus pesticide poisoning. We have some concerns. First, owing to repeated drought in rural India and dowries for daughters’ marriages, farmers are in heavy debt and many are committing suicide by consuming readily available organophosphorus compounds. The total cost of successful treatment of one patient with high-dose pralidoxime is US$400—ie, 3 years’ salary for a poor farmer. Thus this regimen is not at all practicable to rural India. Second, that severely intoxicated villagers in Pawar and colleagues’ study were excluded and admitted to government hospitals with no intensive-care facilities instead is demoralising and unethical. Third, we were surprised to note that Pawar and colleagues did not find any cardiovascular abnormalities, including shock, irrespective of severity.2,3 Finally, good nursing care, close monitoring of pneumonia and its rapid treatment, and prolonged ventilator use might be a more worthy management strategy than expensive pralidoxime therapy. M K Inamdar, in the same district as Pawar and colleagues, treated 68 patients with organophosphorus poisoning without pralidoxime; 28 required a ventilator for 6 days and three died (personal communication). In conclusion, there is a need to devise a practicable management strategy for organophosphorus poisoning in rural India, perhaps including development of newer antidotes with oximes such as obidoxime.4 Additionally, restriction of access to highly toxic pesticides and use of safer alternatives should result in fewer deaths.5 www.thelancet.com Vol 369 April 28, 2007
We declare that we have no conflict of interest.
*H S Bawaskar, Shashank R Joshi himmatbawaskar@rediffmail.com Bawaskar Hospital and Research Center, Mahad Raigad, Maharashtra 4012301, India (HSB); No 006 and 007, Turf Estate, Dr E Moses Road, Mumbai, India (SRJ) 1
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3
4
5
Pawer KS, Bhoite RR , Pillay CP, Chavan S, Malshikare DS, Garad MS. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006; 368: 2136–41. Cherian MA, Roshini C, Peter JV, Cherian AM. Oximes in organophosphorus poisoning. Ind J Crit Med 2005; 9: 155–63. Eddleston ME, Eyer P, Mohamed F, et al. Difference between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–59. Bawaskar HS, Joshi SR. Organophosphorus poisoning in agricultural India: status in 2005. J Assoc Physician India 2005; 53: 422–24. Eddleston M, Karalliedde L, Buckley N, et al. Pesticide poisoning in the developing world: a minimum pesticides list. Lancet 2002; 360: 1163–67.
Kirti Pawar and colleagues compare two pralidoxime regimens in 200 patients with moderately severe organophosphorous poisoning in an open-label randomised trial.1 The patients receiving the higher dose had less morbidity, pneumonia, and need of atropine or ventilatory support, and a shorter duration of intubation than those on the regular dose. Although the effectiveness of oximes is yet to be established,2–4 a control group was not included in the design. It is unclear how moderately severe illness was defined (two-thirds of the patients required ventilatory support) and which relative of the poisoned patients consented to participation. That those not satisfying inclusion criteria were shifted to a nearby government hospital poses a strong ethical concern. The very low atropine requirement in the study group is confusing and suggests that the study group had milder or dissimilar illness.5 A 1·8 mg unit dose given every 15 min should exceed the quoted median dose within the first 2 h when the dose of atropine would be the same in the two groups. It is surprising that without any external funding, all patients were able
to afford pralidoxime for the entire period of administration and that there were no dropouts for this reason. That Pawar and colleagues were able to determine the amount of pesticide ingested is also interesting because it proves challenging in clinical practice. We declare that we have no conflict of interest.
The printed journal includes an image merely for illustration
*Ashish Goel, Praveen Aggarwal, Sanjeev Bhoi, Vineet Gupta
Still Pictures
High-dose pralidoxime for organophosphorus poisoning
[email protected] Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India 1
2
3
4
5
Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006; 368: 2136–41. de Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet 1992; 339: 1136–38. Johnson S, Peter JV, Thomas K, Jeyaseelan L, Cherian AM. Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J Assoc Physicians India 1996; 44: 529–31. Cherian MA, Roshini C, Visalakshi J, Jeyaseelan L, Cherian AM. Biochemical and clinical profile after organophosphorus poisoning—a placebo-controlled trial using pralidoxime. J Assoc Physicians India 2005; 53: 427–31. Eddleston M, Eyer P, Worek F, et al. Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–59.
The Article on oxime therapy in acute organophosphate poisoning by Kirti Pawar and colleagues1 supports our hypothesis that the time of administration of the antidote might be a crucial factor in determining response to therapy.2 However, several concerns need to be addressed. Surprisingly, no patients with mild intoxication nor many patients presenting between 2·5 h and 24 h of ingestion were recorded. The resuscitation intubation rate was relatively high (66%). Given comparable initial treatment and disparate “resuscitation” group intubation rates, time to intubation (not provided) could have potentially confounded treatment efficacy. Although study group relative risk seemed extremely favourable, the
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
1425
Kirti S Pawar and colleagues (Dec 16, p 2136)1 report that a highdose regimen of pralidoxime reduces morbidity and mortality in moderately severe cases of acute organophosphorus pesticide poisoning. We have some concerns. First, owing to repeated drought in rural India and dowries for daughters’ marriages, farmers are in heavy debt and many are committing suicide by consuming readily available organophosphorus compounds. The total cost of successful treatment of one patient with high-dose pralidoxime is US$400—ie, 3 years’ salary for a poor farmer. Thus this regimen is not at all practicable to rural India. Second, that severely intoxicated villagers in Pawar and colleagues’ study were excluded and admitted to government hospitals with no intensive-care facilities instead is demoralising and unethical. Third, we were surprised to note that Pawar and colleagues did not find any cardiovascular abnormalities, including shock, irrespective of severity.2,3 Finally, good nursing care, close monitoring of pneumonia and its rapid treatment, and prolonged ventilator use might be a more worthy management strategy than expensive pralidoxime therapy. M K Inamdar, in the same district as Pawar and colleagues, treated 68 patients with organophosphorus poisoning without pralidoxime; 28 required a ventilator for 6 days and three died (personal communication). In conclusion, there is a need to devise a practicable management strategy for organophosphorus poisoning in rural India, perhaps including development of newer antidotes with oximes such as obidoxime.4 Additionally, restriction of access to highly toxic pesticides and use of safer alternatives should result in fewer deaths.5 www.thelancet.com Vol 369 April 28, 2007
We declare that we have no conflict of interest.
*H S Bawaskar, Shashank R Joshi himmatbawaskar@rediffmail.com Bawaskar Hospital and Research Center, Mahad Raigad, Maharashtra 4012301, India (HSB); No 006 and 007, Turf Estate, Dr E Moses Road, Mumbai, India (SRJ) 1
2
3
4
5
Pawer KS, Bhoite RR , Pillay CP, Chavan S, Malshikare DS, Garad MS. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006; 368: 2136–41. Cherian MA, Roshini C, Peter JV, Cherian AM. Oximes in organophosphorus poisoning. Ind J Crit Med 2005; 9: 155–63. Eddleston ME, Eyer P, Mohamed F, et al. Difference between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–59. Bawaskar HS, Joshi SR. Organophosphorus poisoning in agricultural India: status in 2005. J Assoc Physician India 2005; 53: 422–24. Eddleston M, Karalliedde L, Buckley N, et al. Pesticide poisoning in the developing world: a minimum pesticides list. Lancet 2002; 360: 1163–67.
Kirti Pawar and colleagues compare two pralidoxime regimens in 200 patients with moderately severe organophosphorous poisoning in an open-label randomised trial.1 The patients receiving the higher dose had less morbidity, pneumonia, and need of atropine or ventilatory support, and a shorter duration of intubation than those on the regular dose. Although the effectiveness of oximes is yet to be established,2–4 a control group was not included in the design. It is unclear how moderately severe illness was defined (two-thirds of the patients required ventilatory support) and which relative of the poisoned patients consented to participation. That those not satisfying inclusion criteria were shifted to a nearby government hospital poses a strong ethical concern. The very low atropine requirement in the study group is confusing and suggests that the study group had milder or dissimilar illness.5 A 1·8 mg unit dose given every 15 min should exceed the quoted median dose within the first 2 h when the dose of atropine would be the same in the two groups. It is surprising that without any external funding, all patients were able
to afford pralidoxime for the entire period of administration and that there were no dropouts for this reason. That Pawar and colleagues were able to determine the amount of pesticide ingested is also interesting because it proves challenging in clinical practice. We declare that we have no conflict of interest.
The printed journal includes an image merely for illustration
*Ashish Goel, Praveen Aggarwal, Sanjeev Bhoi, Vineet Gupta
Still Pictures
High-dose pralidoxime for organophosphorus poisoning
[email protected] Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India 1
2
3
4
5
Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006; 368: 2136–41. de Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet 1992; 339: 1136–38. Johnson S, Peter JV, Thomas K, Jeyaseelan L, Cherian AM. Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J Assoc Physicians India 1996; 44: 529–31. Cherian MA, Roshini C, Visalakshi J, Jeyaseelan L, Cherian AM. Biochemical and clinical profile after organophosphorus poisoning—a placebo-controlled trial using pralidoxime. J Assoc Physicians India 2005; 53: 427–31. Eddleston M, Eyer P, Worek F, et al. Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–59.
The Article on oxime therapy in acute organophosphate poisoning by Kirti Pawar and colleagues1 supports our hypothesis that the time of administration of the antidote might be a crucial factor in determining response to therapy.2 However, several concerns need to be addressed. Surprisingly, no patients with mild intoxication nor many patients presenting between 2·5 h and 24 h of ingestion were recorded. The resuscitation intubation rate was relatively high (66%). Given comparable initial treatment and disparate “resuscitation” group intubation rates, time to intubation (not provided) could have potentially confounded treatment efficacy. Although study group relative risk seemed extremely favourable, the
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
1425