The Impact of Ketamine on Outcomes in Critically Ill Patients: a Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Controlled Trials

Overview

Journal Acute Crit Care

Specialty Critical Care

Date 2024 Mar 13

PMID 38476062

Authors

Yerkin Abdildin

Karina Tapinova

Assel Nemerenova

Dmitriy Viderman

Affiliations

Soon will be listed here.

Abstract

Background: This meta-analysis aims to evaluate the effects of ketamine in critically ill intensive care unit (ICU) patients.

Methods: We searched for randomized controlled trials (RCTs) in PubMed, Scopus, and the Cochrane Library; the search was performed initially in January but was repeated in December of 2023. We focused on ICU patients of any age. We included studies that compared ketamine with other traditional agents used in the ICU. We synthesized evidence using RevMan v5.4 and presented the results as forest plots. We also used trial sequential analysis (TSA) software v. 0.9.5.10 Beta and presented results as TSA plots. For synthesizing results, we used a random-effects model and reported differences in outcomes of two groups in terms of mean difference (MD), standardized MD, and risk ratio with 95% confidence interval. We assessed the risk of bias using the Cochrane RoB tool for RCTs. Our outcomes were mortality, pain, opioid and midazolam requirements, delirium rates, and ICU length of stay.

Results: Twelve RCTs involving 805 ICU patients (ketamine group, n=398; control group, n=407) were included in the meta-analysis. The ketamine group was not superior to the control group in terms of mortality (in five studies with 318 patients), pain (two studies with 129 patients), mean and cumulative opioid consumption (six studies with 494 patients), midazolam consumption (six studies with 304 patients), and ICU length of stay (three studies with 270 patients). However, the model favored the ketamine group over the control group in delirium rate (four studies with 358 patients). This result is significant in terms of conventional boundaries (alpha=5%) but is not robust in sequential analysis. The applicability of the findings is limited by the small number of patients pooled for each outcome.

Conclusions: Our meta-analysis did not demonstrate differences between ketamine and control groups regarding any outcome except delirium rate, where the model favored the ketamine group over the control group. However, this result is not robust as sensitivity analysis and trial sequential analysis suggest that more RCTs should be conducted in the future.

Citing Articles

Opioid-Free Using Ketamine versus Opioid-Sparing Anesthesia during the Intraoperative Period in Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.

Choi H, Huh J, Kim M, Moon S, Kim K, Hwang W J Pers Med. 2024; 14(8).

PMID: 39202072 PMC: 11355072. DOI: 10.3390/jpm14080881.

Ketamine sedation in critically ill patients: Past, present and future.

Sharif S, Prakash J, Rochwerg B Indian J Anaesth. 2024; 68(8):674-676.

PMID: 39176115 PMC: 11338373. DOI: 10.4103/ija.ija_519_24.

References

Anwar S, Cooper J, Rahman J, Sharma C, Langford R . Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology. 2019; 131(1):119-131. DOI: 10.1097/ALN.0000000000002751. View

Kang H . Trial sequential analysis: novel approach for meta-analysis. Anesth Pain Med (Seoul). 2021; 16(2):138-150. PMC: 8107247. DOI: 10.17085/apm.21038. View

Castellini G, Bruschettini M, Gianola S, Gluud C, Moja L . Assessing imprecision in Cochrane systematic reviews: a comparison of GRADE and Trial Sequential Analysis. Syst Rev. 2018; 7(1):110. PMC: 6064621. DOI: 10.1186/s13643-018-0770-1. View

Christ G, Mundigler G, Merhaut C, Zehetgruber M, Kratochwill C, Heinz G . Adverse cardiovascular effects of ketamine infusion in patients with catecholamine-dependent heart failure. Anaesth Intensive Care. 1997; 25(3):255-9. DOI: 10.1177/0310057X9702500308. View

Bourgoin A, Albanese J, Wereszczynski N, Charbit M, Vialet R, Martin C . Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003; 31(3):711-7. DOI: 10.1097/01.CCM.0000044505.24727.16. View

Manasco A, Stephens R, Yaeger L, Roberts B, Fuller B . Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis. J Crit Care. 2019; 56:80-88. DOI: 10.1016/j.jcrc.2019.12.004. View

Brinck E, Tiippana E, Heesen M, Bell R, Straube S, Moore R . Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018; 12:CD012033. PMC: 6360925. DOI: 10.1002/14651858.CD012033.pub4. View

Erstad B, Patanwala A . Ketamine for analgosedation in critically ill patients. J Crit Care. 2016; 35:145-9. DOI: 10.1016/j.jcrc.2016.05.016. View

von der Brelie C, Seifert M, Rot S, Tittel A, Sanft C, Meier U . Sedation of Patients with Acute Aneurysmal Subarachnoid Hemorrhage with Ketamine Is Safe and Might Influence the Occurrence of Cerebral Infarctions Associated with Delayed Cerebral Ischemia. World Neurosurg. 2016; 97:374-382. DOI: 10.1016/j.wneu.2016.09.121. View

10.

Hudetz J, Patterson K, Iqbal Z, Gandhi S, Byrne A, Hudetz A . Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009; 23(5):651-7. DOI: 10.1053/j.jvca.2008.12.021. View

11.

Viderman D, Nabidollayeva F, Aubakirova M, Yessimova D, Badenes R, Abdildin Y . Postoperative Delirium and Cognitive Dysfunction after General and Regional Anesthesia: A Systematic Review and Meta-Analysis. J Clin Med. 2023; 12(10). PMC: 10219265. DOI: 10.3390/jcm12103549. View

12.

Hovaguimian F, Tschopp C, Beck-Schimmer B, Puhan M . Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta-analysis. Acta Anaesthesiol Scand. 2018; 62(9):1182-1193. DOI: 10.1111/aas.13168. View

13.

Wetterslev J, Thorlund K, Brok J, Gluud C . Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2007; 61(1):64-75. DOI: 10.1016/j.jclinepi.2007.03.013. View

14.

Perbet S, Godet T, Constantin J . Ketamine infusion for sedation in ICU, response to Dr Mion. Anaesth Crit Care Pain Med. 2019; 38(4):399. DOI: 10.1016/j.accpm.2019.02.012. View

15.

Perbet S, Verdonk F, Godet T, Jabaudon M, Chartier C, Cayot S . Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients: A randomised double-blind control trial. Anaesth Crit Care Pain Med. 2018; 37(6):589-595. DOI: 10.1016/j.accpm.2018.09.006. View

16.

Luo D, Wan X, Liu J, Tong T . Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2016; 27(6):1785-1805. DOI: 10.1177/0962280216669183. View

17.

Viderman D, Aubakirova M, Nabidollayeva F, Yegembayeva N, Bilotta F, Badenes R . Effect of Ketamine on Postoperative Neurocognitive Disorders: A Systematic Review and Meta-Analysis. J Clin Med. 2023; 12(13). PMC: 10342373. DOI: 10.3390/jcm12134314. View

18.

Amer M, Maghrabi K, Bawazeer M, Alshaikh K, Shaban M, Rizwan M . Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial. J Intensive Care. 2021; 9(1):54. PMC: 8404029. DOI: 10.1186/s40560-021-00569-1. View

19.

Wan X, Wang W, Liu J, Tong T . Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014; 14:135. PMC: 4383202. DOI: 10.1186/1471-2288-14-135. View

20.

Knack S, Prekker M, Moore J, Klein L, Atkins A, Miner J . The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial. J Emerg Med. 2023; 65(5):e371-e382. DOI: 10.1016/j.jemermed.2023.06.009. View