Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.