Comparison of two commonly practiced atropinization regimens in acute organophosphorus and carbamate poisoning,doubling doses vs. ad hoc: a prospective observational study

Abstract

There is a wide variation and lack of evidence in current recommendations for atropine dosing schedules leading to subsequent variation in clinical practice. Therefore, we sought to examine the safety and effectiveness of a titrated vs. ad hoc atropine treatment regimen in a cohort of patients with acute cholinesterase inhibitor pesticide poisoning. A prospective cohort study was conducted in three district secondary referral hospitals in Sri Lanka using a structured data collection form that collected details of clinical symptoms and outcomes of cholinesterase inhibitor pesticide poisoning, atropine doses, and signs of atropinization. We compared two hospitals that used a titrated dosing protocol based on a structured monitoring sheet for atropine infusion with another hospital using an ad hoc regime. During the study, 272 symptomatic patients with anticholinesterase poisoning requiring atropine were admitted to the three hospitals. Outcomes of death and ventilation were analyzed for all patients, 226 patients were prospectively assessed for atropine toxicity. At baseline, patients in the titrated dose cohort had clinical signs consistent with greater toxicity. This in part may be due to ingestion of more toxic organophosphates. They received less pralidoxime and atropine, and were less likely to develop features of atropine toxicity, such as delirium (1% vs. 17%), hallucinations (1% vs. 35%), or either (1% vs. 35%) and need for patient restraint (3% vs. 48%) compared with the ad hoc dose regime. After adjusting for the pesticides ingested, there was no difference in mortality and ventilatory rates between protocols. Ad hoc high dose atropine regimens are associated with more frequent atropine toxicity without any obvious improvement in patient outcome compared with doses titrated to clinical effect. Atropine doses should be titrated against response and toxicity. Further education and the use of a structured monitoring sheet may assist in more appropriate atropine use in anticholinesterase pesticide poisoning.

Keywords

atropine toxicity atropinization protocols organophosphorous poisoning

References

1 Eddleston M . Patterns and problems of deliberate self-poisoning in the developing world. QJM 2000; 93: 715–731.

2 Bajgar J . Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 2004; 38: 151–216.

3 Eddleston M Buckley NA Checketts H Senarathna L Mohamed F Sheriff MH . Speed of initial atropinisation in significant organophosphorus pesticide poisoning – a systematic comparison of recommended regimens. J Toxicol 2004; 42: 865–875.

4 Bird SB Gaspari RJ Dickson EW . Early death due to severe organophosphate poisoning is a centrally mediated process. Acad Emerg Med 2003; 10: 295–298.

5 Eddleston M Dawson A Karalliedde L Dissanayake W Hittarage A Azher S . Early management after self-poisoning with an organophosphorus or carbamate pesticide – a treatment protocol for junior doctors. Crit Care 2004; 8: R391–R397.

6 Eddleston M Eyer P Worek F Mohamed F Senarathna L von Meyer L . Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–1459.

7 Buckley NA Eddleston M Szinicz L . Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev 2005; XXX: CD005085.

8 Association AP . Practice guidelines for the treatment of patients with delirium. Am J Psychiatry 1999; 156: 1–20.

9 Meanger D . Delirium: optimizing management. BMJ 2001; 322: 144–149.

10.

10 Ely EW Siegel MD Inouye SK . Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction. Semin Respir Crit Care Med 2001; 22: 115–126.

11.

11 Ely EW Gautam S Margolin R Francis J May L Speroff T . The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001; 27: 1892–1900.

12.

12 Inouye SK van Dyck CH Alessi CA Balkin S Siegal AP Horwitz RI . Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113: 941–948.