Polymyxin B and the Pulmonary Peril: A Case Series of Acute Respiratory Failure

The neurotoxicity potential of polymyxin B is underrecognized.

Four critically ill patients treated with polymyxin B for suspected or confirmed nosocomial Gram-negative infections developed acute hypercapnic respiratory failure temporally associated with polymyxin B administration. Respiratory support escalated from room air or low-flow oxygen to noninvasive or invasive mechanical ventilation after one, two, five, and seven doses of polymyxin. No alternative explanation for the abrupt deterioration was identified after clinical evaluation. Following cessation of polymyxin (n = 3) or dose reduction (n = 1), all patients were liberated from ventilation within 60 h. Measured polymyxin concentrations were above the therapeutic range in all patients; however, the delayed timing of sampling, measured at variable intervals after the respiratory events, limits conclusions regarding causality and dose-dependent toxicity.

Polymyxin B should be considered as a potential cause of acute hypercapnic respiratory failure in critically ill patients when no alternative explanation is apparent. Both idiosyncratic susceptibility and drug accumulation may contribute, although the delayed timing of drug concentration measurements precludes firm conclusions regarding dose-dependent toxicity. Further prospective studies are required to define the mechanisms and risk factors.