The pharmacotherapeutic management of postoperative delirium: an expert update

ABSTRACT

Introduction

Postoperative delirium is a common sequela in older adults in the peri-operative period leading to poor outcomes with a complex pathophysiology which has led to a variety of different pharmacologic agents employed in attempts to prevent and treat this syndrome. No pharmacologic agent has been approved to treat this disorder, but this review discusses the pharmacologic strategies which have been tried based on the hypotheses of the causation of the syndrome including neurotransmitter imbalance, inflammation, and oxidative stress.

Areas covered

Systematic reviews and meta-analyses of randomized clinical trials (RCTs) were included via search of electronic databases specifically for the terms postoperative delirium and pharmacologic treatments. With this approach, the recurrent topics of analgesia and sedation, antipsychotics, acetylcholinesterase inhibitors (AchE-Is), inflammation, and melatonin were emphasized and provided the outline for this review.

Expert opinion

Research evidence does not support any particular agent in any of the pharmacologic classes reviewed. However, there is some potential benefit with dexmedetomidine, melatonin, and the monitoring of anesthetic agents all of which need further clinical trials to validate these conclusions. Exploration of ways to improve studies and the application of novel pharmacologic agents may offer future benefit.

KEYWORDS:

• Antipsychotics
• bispectral index (BIS)
• delirium
• dexmedetomidine
• melatonin
• pharmacology
• postoperative
• treatment

Article Highlights

• Postoperative delirium is a common sequela particularly in elderly surgical patients which is marked by an acute change in cognitive status and includes disturbances in attention, awareness, memory and perceptual misinterpretations.

• Various pharmacologic modalities have been used to treat or attempt to prevent this syndrome based on pathophysiologic mechanisms such as neurotransmitter disruption, inflammation, sleep disturbances and effects of anesthesia and sedation. The agents utilized include antipsychotics, melatonin, and dexmedetomidine and monitoring depth of anesthesia but studies do not support a universal recommendation for any of them.

• Clinical guidelines for the treatment of postoperative delirium strongly recommend non-pharmacologic interventions to address this syndrome.

• Future research should focus on improved study design with more homogeneous populations and consideration for genetic approaches as well as novel agents which can target putative pathophysiologic mechanisms that can be tailored to the particular individual’s risk factors to achieve better outcomes.

This box summarizes key points contained in the article.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.