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

Date Published: July 15, 2008

Publisher: Public Library of Science

Author(s): Pradeepa Jayawardane, Andrew H Dawson, Vajira Weerasinghe, Lakshman Karalliedde, Nicholas A Buckley, Nimal Senanayake, Nick Bateman

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.

Partial Text: Organophosphate (OP) poisoning is a major global health problem [1,2] with hundreds of thousands of deaths every year [3,4]. OP poisoning leads to three main syndromes: (1) acute cholinergic syndrome, (2) intermediate syndrome (IMS), and (3) OP-induced delayed polyneuropathy (OPIDPN). IMS remains a major contributor to the high morbidity and mortality in OP poisoning, an important and expensive medical problem in the under-resourced developing world [5].

A prospective observational study of symptomatic OP poisoned patients was carried out in the Central Province of Sri Lanka with the approval of the Ethics Committees of the University of Peradeniya, Sri Lanka and the Australian National University, Canberra, Australia. Patients were recruited from Nuwara Eliya General Hospital, Nuwara Eliya from May 2005 to April 2005 and from Teaching Hospital, Peradeniya from May 2006 to December 2006.

Of a total of 91 patients recruited, serial clinical and electrophysiological assessments could be successfully completed in 78 (65 males). In 13 patients serial electrophysiological studies were not successful (withdrawal of consent, four; unable to perform due to restlessness/delirium, seven; technical difficulties, two). The OP ingested was chlorpyrifos in 59 of 78 patients. Two patients have ingested dimethoate:1 phenthoate:1 diazinon. In four patients, either the OP was not detected (n = 2), or the type of OP was not confirmed. Blood samples were not available or were not assayed for OP levels in 11 patients. Depression of RBC AChE to <50% of the lower limit of the normal range and/or toxicologically significant concentrations of OP was detected in 69 of 78. We found characteristic abnormalities on RNS associated with the development and resolution of muscle weakness in IMS. These clinical and electrophysiological changes varied in severity, presumably representing a continuum through which patients progress over time (Table 2). Source: http://doi.org/10.1371/journal.pmed.0050147

 

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