The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka

Pradeepa Jayawardane,Andrew H Dawson,Nimal Senanayake,Vajira Weerasinghe,Lakshman Karalliedde,Nicholas A Buckley,Nick Bateman

doi:10.1371/journal.pmed.0050147

Abstract

BackgroundIntermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research.Methods and FindingsSeventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements.ConclusionsCharacteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.

Highlights

Organophosphate (OP) poisoning is a major global health problem [1,2] with hundreds of thousands of deaths every year [3,4]
The forme fruste Intermediate syndrome (IMS) with the characteristic early changes on repetitive nerve stimulation (RNS) indicates that IMS is a spectrum disorder
Our findings suggest that IMS is a spectrum disorder in which the initial pathological process starts with acute cholinergic state, which may or may not progress through a series of electrophysiological changes leading to respiratory failure and progressive decrement on RNS

Summary

Introduction

Organophosphate (OP) poisoning is a major global health problem [1,2] with hundreds of thousands of deaths every year [3,4]. Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. These highly toxic compounds, which are widely used in agriculture, in developing countries, disrupt the transmission of messages from the brain to the body in insect pests and in people. This is used in the part of the nervous system that controls breathing and other automatic vital functions, at neuromuscular junctions, and in parts of the central nervous system. Acetylcholine is quickly broken down after it has delivered its message, but organophosphates disrupt this process and, affect nerve transmission to muscles. The intermediate syndrome (IMS), which results in muscle weakness in the limbs, neck, and throat, develops in some patients 24– 96 hours after poisoning. Long-term nerve damage sometimes develops 2–3 weeks after poisoning

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