Cholinesterase inhibitors for the treatment of delirium in non‐ICU settings

Ailan Yu; Shanshan Wu; Zongwang Zhang; Tom Dening; Sai Zhao; Gillian Pinner; Jun Xia; Daogui Yang

doi:10.1002/14651858.CD012494.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Study	Interventions	N	MD	95% CI	P value
Overshott 2010	Cholinesterase inhibitors (rivastigmine) versus placebo	15	‐3.6	‐15.6 to 8.4	0.5

Analysis 1.1

Comparison 1 Cholinesterase inhibitors (rivastigmine) versus placebo, Outcome 1 Duration of delirium (days).

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Analysis 1.2

Comparison 1 Cholinesterase inhibitors (rivastigmine) versus placebo, Outcome 2 Adverse events (nausea).

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Analysis 1.3

Comparison 1 Cholinesterase inhibitors (rivastigmine) versus placebo, Outcome 3 Use of rescue medications.

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Analysis 1.4

Comparison 1 Cholinesterase inhibitors (rivastigmine) versus placebo, Outcome 4 Mortality.

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Analysis 1.5

Comparison 1 Cholinesterase inhibitors (rivastigmine) versus placebo, Outcome 5 Leaving the study early.

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Summary of findings for the main comparison. Cholinesterase inhibitors (rivastigmine) compared to placebo for the treatment of delirium in non‐ICU settings

Cholinesterase inhibitors (rivastigmine) compared to placebo for the treatment of delirium in non‐ICU settings
Patient or population: people with delirium Settings: non‐ICU Intervention: cholinesterase inhibitors (rivastigmine)* Comparison: placebo
Outcomes	Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Cholinesterase inhibitors (rivastigmine)
Duration of delirium days Follow‐up: 42 days	The mean duration was 9.9 days	The mean duration was 3.6 days lower (15.6 lower to 8.4 higher)	Not estimable	15 (1 study)	⊕⊕⊝⊝ Low¹	The data were reported by Overshott 2010. The study was grossly underpowered, and the data were skewed.
Severity of delirium CAM negative Follow‐up: 28 days	See comment	See comment	See comment	See comment	See comment	No study reported this outcome.
Adverse events nausea Follow‐up: 42 days	143 per 1000	43 per 1000 (1 to 899)	RR 0.3 (0.01 to 6.29)	15 (1 study)	⊕⊕⊝⊝ Low¹
Persistent cognitive impairment	See comment	See comment	See comment	See comment	See comment	No study reported this outcome.
Length of hospitalisation	See comment	See comment	See comment	See comment	See comment	No study reported this outcome.
Mortality Follow‐up: 42 days	571 per 1000	57 per 1000 (6 to 891)	RR 0.1 (0.01 to 1.56)	15 (1 study)	⊕⊕⊝⊝ Low¹
Cost of intervention	See comment	See comment	See comment	See comment	See comment	No study reported this outcome.
The dose of intervention: 1.5 mg once a day increasing to 1.5 mg twice a day after 7 days. The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CAM: Confusion Assessment Method; CI: confidence interval; ICU: intensive care unit; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Downgraded twice for imprecision due to very small sample size.

Summary of findings for the main comparison. Cholinesterase inhibitors (rivastigmine) compared to placebo for the treatment of delirium in non‐ICU settings

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Comparison 1. Cholinesterase inhibitors (rivastigmine) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Duration of delirium (days) Show forest plot			Other data	No numeric data

2 Adverse events (nausea) Show forest plot	1	15	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.01, 6.29]

3 Use of rescue medications Show forest plot	1	15	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.01, 2.10]

4 Mortality Show forest plot	1	15	Risk Ratio (M‐H, Random, 95% CI)	0.10 [0.01, 1.56]

5 Leaving the study early Show forest plot	1	15	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.07, 11.54]

Comparison 1. Cholinesterase inhibitors (rivastigmine) versus placebo

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