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.
ABSTRACT
Introduction: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID19) but its use in COVID19-related acute respiratory distress syndrome (ARDS) is not well-established. Research Question or Hypothesis: Is IVIG therapy associated with lower mortality in COVID19-related ARDS? Study Design: Retrospective cohort Methods: We included adult COVID19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-severe ARDS were divided into two groups based on whether they received IVIG therapy. Primary outcome was all-cause ICU mortality. Secondary outcomes were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders. The primary outcome was compared using competing-risks survival analysis. Statistical analysis was conducted using Stata MP 16.0. P values of less than 0.05 was considered significant. Results: Among 590 patients included in the study, 400 received routine care and 190 received IVIG therapy in addition to routine care. One-hundred eighteen pairs were created after propensity score matching with no differences between the groups. The median time from ICU admission to initiation of IVIG therapy was 6.3 days (interquartile range [IQR] 2.1-11.9 days) and the median cumulative dose of IVIG received was 150 grams (IQR 105-235 grams). ICU mortality was 27.1% overall and 25.8% in the matched cohort. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%;sub-distribution hazard ratio[sHR] 3.5;95% CI 1.98-6.19;P<0.001). Ventilator-free days and ICU-free days at day-28 were lower (P<0.001 for both), and incidence of acute kidney injury was higher in the IVIG group (85.6% vs. 67.8%;P=0.001). Conclusion: IVIG therapy in patients with COVID19-related moderate-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to further confirm this observation.