Anesth Pain Med.  2021 Jan;16(1):28-48. 10.17085/apm.20079.

Pharmacological strategies to prevent postoperative delirium: a systematic review and network meta-analysis

• Lee JM
• Cho YJ
• Ahn EJ
• Choi GJ
• Kang H

• KMID: 2512280
• DOI: http://doi.org/10.17085/apm.20079

Abstract

Background
Postoperative delirium (POD) is a condition of cerebral dysfunction and a common complication after surgery. This study aimed to compare and determine the relative efficacy of pharmacological interventions for preventing POD using a network meta-analysis (NMA).
Methods
We performed a systematic and comprehensive search to identify and analyze all randomized controlled trials until June 29, 2020, comparing two or more pharmacological interventions, including placebo, to prevent or reduce POD. The primary outcome was the incidence of POD. We performed a network meta-analysis and used the surface under the cumulative ranking curve (SUCRA) values and rankograms to present the hierarchy of the pharmacological interventions evaluated.
Results
According to the SUCRA value, the incidence of POD decreased in the following order: the combination of propofol and acetaminophen (86.1%), combination of ketamine and dexmedetomidine (86.0%), combination of diazepam, flunitrazepam, and pethidine (84.8%), and olanzapine (75.6%) after all types of anesthesia; combination of propofol and acetaminophen (85.9%), combination of ketamine and dexmedetomidine (83.2%), gabapentin (82.2%), and combination of diazepam, flunitrazepam, and pethidine (79.7%) after general anesthesia; and ketamine (87.1%), combination of propofol and acetaminophen (86.0%), and combination of dexmedetomidine and acetaminophen (66.3%) after cardiac surgery. However, only the dexmedetomidine group showed a lower incidence of POD than the control group after all types of anesthesia and after general anesthesia.
Conclusions
Dexmedetomidine reduced POD compared with the control group. The combination of propofol and acetaminophen and the combination of ketamine and dexmedetomidine seemed to be effective in preventing POD. However, further studies are needed to determine the optimal pharmacological intervention to prevent POD.

Keyword

Delirium; Network meta-analysis; Pharmacology; Surgical procedures, operative

Figure

• 

  Fig. 1. PRISMA flowchart of included and excluded trials. PRISMA: preferred reporting requirements for systematic review and meta-analysis, NMA: network meta-analysis.

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  Fig. 2. Network plot of included studies comparing different pharmacological interventions. The nodes show a comparison of pharmacological interventions to prevent postoperative delirium, and the edges show the available direct comparisons among the pharmacological interventions. The nodes and edges are weighed on the basis of the weights applied in the network meta-analysis and the inverse of the standard error of effect. (A) All types of anesthesia, (B) general anesthesia, (C) cardiac surgery.

• 

  Fig. 3. Inconsistency plot between the direct and indirect effect estimates for the same comparison. Inconsistency factor (IF) as the absolute difference with 95% confidence interval (CI) between the direct and indirect estimates for each paired comparison is presented. IF values close to 0 indicate that the two sources are in agreement. (A) All type of anesthesia, (B) general anesthesia, (C) cardiac surgery.

• 

  Fig. 4. Predictive interval plots between each management modality and placebo group. Diamond shape represents the mean summary effects. Black line represents the 95% confidence interval (CI), and red line represents the predictive interval (PrI). PrIs provide an interval that is expected to encompass the estimate of a future study. (A) All type of anesthesia, (B) general anesthesia, (C) cardiac surgery.

• 

  Fig. 5. Rankogram. Profiles indicate the probabilities for treatments to assume any of the possible ranks. It is the probability that a given treatment ranks first, second, third, and so on, among all of the treatments evaluated in the NMA. (A) All type of anesthesia, (B) general anesthesia, (C) cardiac surgery. NMA: network meta-analysis.

• 

  Fig. 6. Cumulative ranking curve plot. The profile indicates the sum of the probabilities from those ranked first, second, third, and so on. A higher cumulative ranking curve (surface of under cumulative ranking curve [SUCRA]) value is regarded as an improved result for an individual’s intervention. When ranking treatments, the closer the SUCRA value is to 100%, the higher the treatment ranking is relative to all other treatments. (A) All type of anesthesia, (B) general anesthesia, (C) cardiac surgery.

• 

  Fig. 7. Expected mean ranking and surface of under cumulative ranking curve (SUCRA) values. X-axis corresponds to expected mean ranking based on SUCRA value, and Y-axis corresponds to SUCRA value. (A) All type of anesthesia, (B) general anesthesia, (C) cardiac surgery.

• 

  Fig. 8. Comparison-adjusted funnel plot.

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