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.

Assessing glycemic variability in critically ill patients: A prospective cohort study comparing insulin infusion therapy with insulin sliding scale.

Glycemic variability (GV) has been associated with an increased mortality rate among critically ill patients. The clinical outcomes of having less GV even with slight hyperglycemia are better than those having tight glycemic control but higher GV. Insulin infusion remains the preferred method to control stress hyperglycemia in critically ill patients. However, its impacts on GV and clinical outcomes in critically ill patients still need further investigation. This study intended to evaluate the impact of insulin infusion therapy (IIT) compared to the insulin sliding scale (ISS) on the extent of GV and explore its impact on the clinical outcomes for critically ill patients. A prospective, single-center observational cohort study was conducted at a tertiary academic hospital in Saudi Arabia between March 2021 and November 2021. The study included adult patients admitted to ICUs who received insulin for stress hyperglycemia management. Patients were categorized into two groups based on the regimen of insulin therapy during ICU stay (IIT versus ISS). The primary outcome was the GV between the two groups. Secondary outcomes were ICU mortality, the incidence of hypoglycemia, and ICU length of stay (LOS). A total of 381 patients were screened; out of them, eighty patients met the eligibility criteria. The distribution of patients having diabetes and a history of insulin use was similar between the two groups. The GV was lower in the IIT group compared to the ISS group using CONGA (- 0.65, 95% CI [- 1.16, - 0.14], p-value = 0.01). Compared with ISS, patients who received IIT had a lower incidence of hypoglycemia that required correction (6.8% vs 2.77%; p-value = 0.38). In contrast, there were no significant differences in ICU LOS and ICU mortality between the two groups. Our study demonstrated that the IIT is associated with decreased GV significantly in critically ill patients without increasing the incidence of severe hypoglycemia. There is no survival benefit with the use of the IIT. Further studies with larger sample size are required to confirm our findings and elaborate on IIT's potential effect in reducing ICU complications in critically ill patients.

Effect of sacubitril/valsartan on hospital readmissions in heart failure with reduced ejection fraction in Saudi Arabia: A multicenter retrospective cohort study.

Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that has been shown in multiple clinical trials to have clinical benefits and is recommended by major clinical management guidelines as a first-line treatment for heart failure with reduced ejection fraction (HFrEF). The most significant benefit that was observed in clinical trials is its effect in reducing hospital readmissions. However, little evidence supports its effectiveness in practice, especially in Saudi Arabia. A multicenter retrospective cohort study was conducted using the patient medical records at 2 tertiary hospitals in Saudi Arabia. Eligible patients were adults (≥18 years old) with a confirmed diagnosis of HFrEF who were discharged on either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) in addition to the other recommended therapy for HFrEF. The primary endpoint was the all-cause 30-day readmission rate. The secondary endpoints included all-cause readmissions at 60-day, 90-day, and 12 months. Additionally, 30-day, 60-day, and 90-day readmissions due to HF were evaluated. A total of 398 patients were included in our analysis; 199 (50.0%) received sacubitril/valsartan (group 1), and 199 (50.0%) received ACEI/ARB (group 2). Our results showed that all-cause 30-day readmissions in group 1 were significantly lower than in group 2 (7% vs 25.0%, RR 0.28, 95% Cl 0.16-0.49; P < .001). Additionally, the secondary outcomes showed significantly fewer 60-day, 90-day, and 12-month all-cause readmissions were identified in group 1 compared to group 2 (11% vs 30.7%, RR 0.36, 95% CI 0.23-0.56; P < .001), (11.6%. vs 32.6%, RR 0.35, 95% CI 0.23-0.55; P < .001) and (23.6% vs 51.2%, RR 0.46, 95% CI 0.35-0.62; P < .001), respectively. Furthermore, HF readmissions at 30-day, 60-day, and 90-day in group 1 were significantly lower than in group 2 (P < .05). Sacubitril/valsartan for the treatment of HFrEF is associated with a significantly lower rate of all-cause readmission as well as HF readmissions compared to ACEI/ARB. These benefits extend up to 12 months post-discharge.

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

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.