Risk of serotonin syndrome in critically ill COVID-19 patients receiving linezolid and opioids concomitantly: A retrospective cohort study

ABSTRACT

Introduction: Linezolid is an oxazolidinone antibiotic characterized by a reversible, non-selective monoamine oxidase inhibitory (MAOI) effect. Combining linezolid with MAOIs may increase serotonin syndrome (SS) risk. Secondary to its high lung tissue penetration, linezolid is recommended in patients with suspected or confirmed resistant gram-positive bacterial pneumonia, especially if vancomycin cannot be used. Opioids are required for sedation and analgesia in patients with respiratory failure requiring invasive mechanical ventilation. However, it remains unclear whether co-administration of linezolid with opioids should be avoided due to the risk of Serotonin syndrome. Research Question or Hypothesis: Whether combing linezolid with opioids will increase the incidence of SS in coronavirus disease 2019 (COVID-19) critically ill patients. Study Design: Retrospective observational study. Methods: All adult patients admitted to the intensive care units with COVID-19 pneumonia who received linezolid between March 2020 and September 2020 were included in the study. The primary outcome is the prevalence of SS defined by Hunter's criteria. SS was confirmed if the patient had spontaneous clonus;inducible clonus plus agitation or diaphoresis;ocular clonus plus agitation or diaphoresis;tremor plus hyperreflexia;or hypertonia plus fever plus ocular clonus or inducible clonus. Descriptive statistical analysis was done using SPSS version25. Results: We included 106 patients, most of the patients were males (91.5%). Approximately half of the patients had hypertension and diabetes (51.9%, and 44.3%, respectively). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most commonly prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one incident of SS (1.6%) manifested as spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made the association with the linezolid-opioids combination doubtful. Conclusion: In this study, the incidence of SS was low in COVID-19 patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.