Exploring Ketamine Analgosedation Use and Its Effect on Incident Delirium in Critically Ill Adults

Ketamine is increasingly being used for analgosedation, but its effect on delirium remains unclear. We compared delirium risk variables and ketamine analgosedation use between adults who developed incident delirium and those who did not, evaluated whether ketamine analgosedation increases delirium risk, and compared ICU delirium characteristics, treatments, and outcomes between ketamine and nonketamine patients with delirium.

Design: Secondary, subgroup analysis of a cohort study.

Setting: Single, 36-bed mixed medical-surgical ICU in the Netherlands from July 2016 to February 2020.

Patients: Consecutive adults were included. Patients admitted after elective surgery, not expected to survive greater than or equal to 48 hours, admitted with delirium, or where delirium occurred prior to ketamine use were excluded.

Intervention: None.

Measurements and main results: Trained ICU nurses evaluated patients without coma (Richmond Agitation Sedation Scale. -4/-5) every 8 hours with the Confusion Assessment Method ICU; a delirium day was defined by greater than or equal to1 + Confusion Assessment Method ICU and/or scheduled antipsychotic use. Among 11 variables compared between the delirium and nondelirium groups (Baseline: age, Charlson Comorbidity score, cognitive impairment, admission type, and Acute Physiology and Chronic Health Evaluation-IV score, daily ICU [until delirium occurrence or discharge]: Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) and total ICU days, 7 (age, Charlson score, Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) were significantly different and were entered, along with delirium occurrence, in a logistic regression model. A total of 332 of 925 of patients (36%) developed delirium. Ketamine use was greater in patients with delirium (54 [16%] vs 4 [0.7%]; p < 0.01). Ketamine use (adjusted odds ratio, 5.60; 95% CI, 1.09-29.15), age (adjusted odds ratio, 1.03; 95% CI, 1.01-1.06), coma (adjusted odds ratio, 2.10; 95% CI, 1.15-3.78), opioid use (adjusted odds ratio, 171.17; 95% CI, 66.45-553.68), and benzodiazepine use (adjusted odds ratio, 34.07; 95% CI, 8.12-235.34) were each independently and significantly associated with increased delirium. Delirium duration, motoric subtype, delirium treatments, and outcomes were not different between the ketamine and nonketamine groups.

Conclusions: Ketamine analgosedation may contribute to increased ICU delirium. The characteristics of ketamine and nonketamine delirium are similar. Further prospective research is required to evaluate the magnitude of risk for delirium with ketamine use.