Article, 2024
Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis
EClinicalMedicine,
ISSN
2589-5370,
Volume 71,
Page 102569,
10.1016/j.eclinm.2024.102569
Contributors
Ceric, Ameldina
0000-0001-6846-5961
(Corresponding author)
[1]
[2]
Holgersson, Johan
0000-0003-1858-2371
[2]
May, Teresa L
0000-0002-9130-8013
[3]
Skrifvars, Markus Benedikt
[4]
Hästbacka, Johanna R
0000-0002-3613-7231
[5]
Saxena, Manoj K
0000-0002-0385-6731
[6]
[7]
Aneman, Anders E M
0000-0003-2096-5304
[8]
Delaney, Anthony P
0000-0002-1015-7146
[7]
Reade, Michael Charles
0000-0003-1570-0707
[9]
Delcourt, Candice
0000-0003-2257-4286
[10]
[11]
Jakobsen, Janus Christian
0000-0002-3642-2120
[12]
[13]
Nielsen, Niklas
0000-0002-6013-126X
[2]
Affiliations
- [1]
Skåne University Hospital
[NORA names:
Sweden; Europe, EU; Nordic; OECD];
- [2]
Lund University
[NORA names:
Sweden; Europe, EU; Nordic; OECD];
- [3]
Maine Medical Center
[NORA names:
United States; America, North; OECD];
- [4]
University of Helsinki
[NORA names:
Finland; Europe, EU; Nordic; OECD];
- [5]
Tampere University
[NORA names:
Finland; Europe, EU; Nordic; OECD];
(... more)
- [6]
St George Hospital
[NORA names:
Australia; Oceania; OECD];
- [7]
George Institute for Global Health
[NORA names:
Australia; Oceania; OECD];
- [8]
Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District, South Western Sydney Clinical School, University of New South Wales, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia
[NORA names:
Australia; Oceania; OECD];
- [9]
University of Queensland
[NORA names:
Australia; Oceania; OECD];
- [10]
Macquarie University
[NORA names:
Australia; Oceania; OECD];
- [11]
UNSW Sydney
[NORA names:
Australia; Oceania; OECD];
- [12]
Rigshospitalet
[NORA names:
Capital Region of Denmark;
Hospital; Denmark; Europe, EU; Nordic; OECD];
- [13]
University of Southern Denmark
[NORA names:
SDU University of Southern Denmark;
University; Denmark; Europe, EU; Nordic; OECD]
(less)
Abstract
Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults.
Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960.
Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected.
Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor.
Funding: None.
Keywords
Central,
Cochrane,
Cochrane risk,
Cochrane risk of bias tool,
Embase,
Grading of Recommendations,
LILACS,
MEDLINE,
PROSPERO,
Web,
Web of Science,
administered to critically ill patients,
adult patients,
adults,
adverse events,
aggregate data,
alleviate anxiety,
analysis,
anxiety,
assess mortality,
assessment,
asynchrony,
bias,
bias tool,
care,
care unit,
certainty,
certainty of evidence,
clinical trials,
compare interventions,
critically ill adult patients,
critically ill adults,
critically ill patients,
criticism,
data,
death,
deep sedation,
delirium,
development,
different levels,
discomfort,
effect,
effects of different levels,
evaluation,
events,
evidence,
grade,
high risk of bias,
ill adult patients,
ill adults,
ill patients,
inception,
intensive care,
intensive care unit,
intervention,
level of sedation,
levels,
meta-analyses,
meta-analysis,
methodological rigor,
mortality,
outcomes,
patient-ventilator asynchrony,
patients,
primary outcome,
prolonged intensive care,
randomised clinical trials,
recommendations,
reduction,
relative risk reduction,
review,
review of clinical trials,
rigor,
risk,
risk of bias,
risk of bias tool,
risk of death,
risk reduction,
science,
sedation,
sequential analysis,
serious adverse events,
study,
systematic review,
systematic review of clinical trials,
tools,
trial sequential analysis,
trials,
units
Funders
Data Provider: Digital Science