Association of low-dose ketamine with hallucinations in critically ill patients: a target trial emulation.
Ary Serpa Neto, Marcus Young, Jian Wen Chan, Natasha E Holmes, Kartik Kishore, Dinesh Pandey, Hossein Jahanabadi, Andrew Casamento, Rinaldo Bellomo
Intensive care medicine May 5, 2025 DOI: 10.1007/s00134-025-07926-w via PubMed
Summary
AI-generated from the abstractLow-dose ketamine given to critically ill patients in the intensive care unit is strongly associated with a higher risk of hallucinations. In a retrospective study of 7514 patients, 8% received low-dose ketamine. Among those treated, 26% experienced hallucinations within 30 days of ICU admission, compared to 7% of untreated patients. The first hallucination also occurred earlier in ketamine-treated patients. After adjusting for other factors, low-dose ketamine increased the odds of hallucinations more than sixfold. The authors caution that the observational design means residual confounding could influence these results.
Study at a glance
| Characteristics | Retrospective cohort study with target trial emulation Peer reviewed |
|---|---|
| Sample size | 7,514 |
| Population | Critically ill patients in the intensive care unit |
| Intervention | low-dose ketamine |
| Dose | 0.11 (0.08-0.15) mg/kg/h |
| Duration | 30-day follow-up from ICU admission |
| Topics | Ketamine |
| Keywords | Delirium Hallucination Ketamine side effects Intensive care medicine Pain management |
| Citations | 9 |
| Key finding | Low-dose ketamine was associated with a significantly higher risk of hallucinations within 30 days of ICU admission (OR, 6.46 [95% CI 5.17-8.07]). |
Abstract
Ketamine use is a potentially modifiable risk factor for hallucinations. We aimed to use target trial emulation to investigate the association between low-dose ketamine and development of hallucinations in critically ill patients in the intensive care unit (ICU). Retrospective study using data from a university affiliated ICU in Melbourne, Australia. Application of marginal structural models and parametric g-formulas to assess the impact of low-dose ketamine on the development of hallucinations. We studied 7514 patients from June 2016 to April 2021. Of these, 625 patients (8%) received low-dose ketamine, beginning at a median of 0 (0-1) days from ICU admission and at a mean daily dose of 0.11 (0.08-0.15) mg/kg/h. Low-dose ketamine treated patients had a higher rate of hallucinations within 30 days of ICU admission (26% vs. 7%; p < 0.001) and the first episode of hallucination occurred earlier than in unexposed patient (2 [1-3] vs. 3 [1-7] days from ICU admission; p < 0.001). After adjustment for baseline and time-dependent confounders, low-dose ketamine was associated with a higher risk of hallucinations within 30 days (OR, 6.46 [95% CI 5.17-8.07]; p < 0.001). These findings were confirmed with parametric g-formulas. In ICU patients, low-dose ketamine was strongly associated with an increased risk of hallucinations. However, these findings should be interpreted with caution due to the observational nature of the study and the risk of residual confounding.