Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study

Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) COVID-19 patients. Adult critically ill patients with COVID-19were included in a multicenter retrospective-prospective retrospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 h of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): −0.26 (−0.45, −0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 h after the start of ketamine treatment compared to the pre-treatment period (6 h) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): −1.55 (−2.42, −0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill COVID-19 patients. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative on critically ill adult patients.