Critical illness polyneuropathy: Clinical findings and cell culture assay of neurotoxicity assessed by a prospective study

Abstract

Objective: First, to evaluate the role of typical intensive care-related conditions like sepsis, prolonged ventilation, drug effects and metabolic disorders in the pathogenesis of critical illness polyneuropathy (CIP); second, to investigate the possible significance of patient serum neurotoxicity assessed by an in vitro cytotoxicity assay with respect to CIP development. Design: Prospective study. Setting: Neurological intensive care unit. Patients and participants: Twenty-eight patients who were on mechanical respiratory support for at least 4 days during a 21-month study period. Results: Diagnosis of CIP was established by clinical and electrophysiological examination in 16 (57%) of 28 patients. Patients were investigated on days 4, 8 and 14 of mechanical ventilation. Two of 16 CIP patients had clinical signs of polyneuropathy at initial examination. Factors that correlated significantly with the development of CIP were: the multiple organ failure score on day 8 of ventilation, the total duration of respiratory support, the presence of weaning problems and the manifestation of complicating sepsis and/or lung failure. The in vitro toxicity assay showed serum neurotoxicity in 12 of 16 CIP patients. Electrophysiological investigations yielded false positive results of the toxicity assay in six patients (not developing CIP) and false negative results in four patients (developing clinical and electrophysiological signs of CIP). Statistical analysis did not reveal a significant correlation between the diagnosis of CIP sand the finding serum neurotoxicity. Conclusion: The results support the hypothesis of a multi-factorial aetiopathogenesis of CIP. We observed serum neurotoxicity in the majority of CIP patients, indicating the possible involvement of a so far unknown, low-molecular-weight neurotoxic agent in CIP pathogenesis.