Ketamine-based sedation use in mechanically ventilated critically ill patients with COVID-19: A multicenter cohort study

Backgrounds: 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) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective 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 hours 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. Results: 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 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (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. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients

Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: A multicenter cohort study

Background: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. Methods: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. Results: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). Conclusion: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs

The association between tocilizumab therapy and the development of thrombosis in critically ill patients with COVID-19: a multicenter, cohort study

Abstract The use of tocilizumab for the management of COVID-19 emerged since it modulates inflammatory markers by blocking interleukin 6 receptors. Concerns regarding higher thrombosis risk while using tocilizumab were raised in the literature. The aim of this study is to investigate the association between tocilizumab therapy and the development of thromboembolic events in critically ill COVID-19 patients. A propensity score-matched, multicenter cohort study for critically ill adult patients with COVID-19. Eligible patients admitted to ICU between March 2020 and July 2021 were categorized into two sub-cohorts based on tocilizumab use within 24 h of ICU admission. The primary endpoint was to assess the incidence of all thrombosis cases during ICU stay. The secondary endpoints were 30-day mortality, in-hospital mortality, and the highest coagulation parameters follow-up (i.e., D-dimer, Fibrinogen) during the stay. Propensity score matching (1:2 ratio) was based on nine matching covariates. Among a total of 867 eligible patients, 453 patients were matched (1:2 ratio) using propensity scores. The thrombosis events were not statistically different between the two groups in crude analysis (6.8% vs. 7.7%; p-value = 0.71) and regression analysis [OR 0.83, 95% CI (0.385, 1.786)]. Peak D-dimer levels did not change significantly when the patient received tocilizumab (beta coefficient (95% CI): 0.19 (− 0.08, 0.47)), while there was a significant reduction in fibrinogen levels during ICU stay (beta coefficient (95% CI): − 0.15 (− 0.28, − 0.02)). On the other hand, the 30-day and in-hospital mortality were significantly lower in tocilizumab-treated patients (HR 0.57, 95% CI (0.37, 0.87), [HR 0.67, 95% CI (0.46, 0.98), respectively). The use of tocilizumab in critically ill patients with COVID-19 was not associated with higher thrombosis events or peak D-dimer levels. On the other hand, fibrinogen levels, 30-day and in-hospital mortality were significantly lower in the tocilizumab group. Further randomized controlled trials are needed to confirm our findings