Rapid atropinization in organophosphate overdose

July 28, 2012, 6:48 pm

★★★½☆

Open-Label Randomized Clinical Trial of Atropine Bolus Injection Versus Incremental Boluses Plus Infusion for Organophosphate Poisoning in Bangladesh. Abedin MJ et al. J Med Toxicol 2012;8:108-117.

Abstract

The primary cause of death after anticholinesterase poisoning is respiratory failure with subsequent hypoxemia. This results from muscarinic effects on the cardiovascular and pulmonary systems (bronchospasm, bronchorrhea, aspiration, bradydysrhythmias, or hypotension), nicotinic effects on skeletal muscles (weakness and paralysis), loss of central respiratory drive, and rarely seizures. Therefore, initial treatment for a patient exposed to OPs is directed at ensuring an adequate airway and ventilation, and at stabilizing cardiorespiratory function by reversing excessive muscarinic effects. [Goldfrank’s Toxicologic Emergencies, 9th edition 2011]

Since rapid reversal of muscarinic stimulation is crucial when treating organophosphate toxicity, administering adequate amounts of atropine as soon as possible is a key to achieving a good clinical outcome. In the past, the recommended dose of atropine in these cases was something like  1 – 5 mg every  IV every 10 minutes until bronchial secretions and wheezing resolved. This regimen may not achieve muscarinic reversal for a long time. Many toxicologists now recommend that a starting (adult) dose of 1 -5 mg atropine be followed by a dose that doubles every 5 minutes until there is adequate response.

This paper supports the double-dose-every-five-minutes approach. 156 patients with organophosphate poisoning were randomized to receive: Group A — 2 – 5 mg atropine IV initially, repeated every 10-15 minutes until response, or Group B — 1.8 – 3.0 mg atropine IV, doubled every 5 minutes until response. The authors found that the second (doubling) approach resulted in reduced short term mortality, intermediate syndrome, as well as lower incidences of atropine toxicity and intermediate syndrome.

This in  generally a well done paper, and I am convinced that rapid atropinization with the double dose regimen is the way to go in these cases. However, I wish the study design had allowed for a more fair comparison by allowing the same dosing interval in each arm. In addition, Table 3 contains I believe an important mistake. It indicates that the mean time to atropinization was 152 hours in Group A and 24 hours in Group B. Surely this should be minutes. This is an important paper, a crucial error such as this raises doubts about the care with which both the authors and the editors prepared the manuscript.

 

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