Ketamine infusion as a sedative-analgesic in severe ARDS (KISS)

Abstract

RationaleKetamine has been used as a sedative analgesic in trauma setting, but data regarding its efficacy and safety is lacking in severe ARDS. This retrospective study aims to determine if Ketamine is safer as a sedative agent in mechanically ventilated patients. During the COVID pandemic, as there was a shortage of sedative agents, Ketamine was used. ObjectivesThe primary objective was to compare the safety of ketamine to other sedatives. The secondary objective was to compare the effect of ketamine to other sedatives regarding the need for vasopressor, incidence of delirium, infectious complications, acute kidney injury, hospital length of stay, and length of ventilator days. MethodsA retrospective, observational cohort study was conducted. Measurements and Main ResultsOne hundred and twenty-four patients (63 men and 61 women) were included. Thirty-four patients received ketamine, while 90 patients received other traditionally used sedatives such as propofol and midazolam. The patients' median age was 64 years in the ketamine group and 68 years in the non-ketamine group. Seventeen patients in the ketamine group (50%) and 65 patients (72%) in the non-ketamine group had mortality (p < 0.02). The hospital length of stay was 22.85 days (± 16.36) in the ketamine group and 15.62 days (± 14.63) in the non-ketamine group (p < 0.02). There was no statistically significant difference among the outcomes of the need for vasopressor, the incidence of delirium, infectious complications, and acute kidney injury. ConclusionsKetamine as a sedative-analgesic agent in COVID-19 patients with severe acute respiratory distress syndrome demonstrated safety with reduced mortality. The ketamine group had a higher hospital length of stay, but a similar complication profile compared to the non-ketamine group. Further prospective randomized controlled trials are warranted to confirm these findings.

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

“…Similar to our finding, Pata ( Pata et al, 2021 ) and his colleagues found that patients who were sedated with ketamine had a lower incidence of hospital-acquired infection. This can be explained by the immunomodulatory activity of ketamine; it has been shown to antagonize inflammatory responses and reduce proinflammatory cytokine production, such as reduced IL-6 and TNFα production ( Yuhas et al, 2015 ).…”

“…Another factor that might have contributed to our findings of shorter length of hospital stay could be related to reduced incidence of delirium with low doses of ketamine ( Perbet et al, 2018 ). These results were inconsistent with the results of the Pata et al ( Pata et al, 2021 ) study, which reported that patients in the ketamine group had longer hospital stays due to neurocognitive perturbation.…”

“…Notably, ketamine use had no effect on 30 days mortality or hospital mortality, which was comparable to previous findings reported by Chan ( Chan et al, 2022 ) et al However, these results conflict with Pata et al ( Pata et al, 2021 ) previous findings as patients in the ketamine group had lower mortality with unexplained mechanisms. Our study was likely underpowered to detect a statistically significant mortality difference between patients receiving ketamine and controls.…”

“…A single center retrospective study that assessed the impact of ketamine as an adjunct sedative in patients with respiratory failure due to COVID-19 pneumonia found that patients who received ketamine had reduced propofol and vasopressor requirements, whereas the need for opioid infusion was increased ( Garner et al, 2021 ). In contrast, another retrospective observational study has demonstrated that the administration of ketamine is associated with higher hospital length of stay among mechanically ventilated patients with COVID-19 ( Pata et al, 2021 ). Up to this point, the evidence that supports the use of ketamine in mechanically ventilated critically ill patients with COVID-19 is insufficient and uncertain.…”

Observational study of the effect of ketamine infusions on sedation depth, inflammation, and clinical outcomes in mechanically ventilated patients with SARS-CoV-2

“…Pata et al, in their retrospective cohort study, recognised that these sedation challenges exist and demonstrated safety and reduced mortality with ketamine in severe ARDS COVID patients. 24 Our study cohort represents a historic population of COVID-19 critically ill patients with data obtained during the early period of the pandemic, prior to immunisation and established therapies being validated; thus, the severity of respiratory failure and ARDS along with the disease burden was high. In our enterprise, ketamine was added when the sedation and analgesia requirements exceeded what was possible with maximal doses of other agents.…”