Delirium‐associated medication in people at risk: A systematic update review, meta‐analyses, and GRADE‐profiles

Abstract

Background: Drug-associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium-associated medication is uncertain due to a lack of highquality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium.Methods: A systematic update review and meta-analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug-delirium associations were pooled in meta-analyses using the random-effects model. Quality of evidence was assessed using the GRADEapproach. This study is preregistered with OSF (DOI https://doi.org.10.17605/ OSF.IO/4PUHY). Results:The 31 eligible studies, presenting results for 24 medication classes were identified. Meta-analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72-1.28; high-quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15-0.40), Ketamine (OR: 0.72, 95% CI 0.35-1.46) or corticosteroids (OR: 0.69, 95% CI 0.32-1.50; moderate quality evidence, respectively). Low-level evidence suggests a three-fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04-9.26). Opioids, benzodiazepines, H 1 -antihistamines, and antidepressants did not reach reliable evidence levels in our analyses. Conclusion:We investigated the retrievable body of evidence for deliriumassociated medication. The results of this systematic review were then interpreted in conjunction with other evidence-based works and guidelines providing conclusions for clinical decision-making.

Is there an anticholinergic effect of drugs beyond polypharmacy? A simulation study on death, dementia, and delirium in UK Biobank

“…The absolute difference between the cumulative prescribing of anticholinergic drugs and of general medications without putative anticholinergic effects was 0.03 to 0.05 (OR), depending on the outcome. If the effect of polypharmacy, instead of a null effect, is considered the reference value, the effect of anticholinergic use is thus much smaller than what was previously reported in studies that did not control for polypharmacy in this way 1,3,[28][29][30] .…”

“…The sum of an individual's values yields a weighted burden score -the anticholinergic burden -that can be used by clinicians or researchers to identify patients or populations vulnerable to adverse side effects. Anticholinergic burden has been associated with adverse long-term health outcomes, including all-cause mortality 1 , dementia 2 , and delirium 3 .…”

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol

“…A meta-analysis of randomized controlled trials that used perioperative ketamine to prevent POD and neurocognitive impairment showed that ketamine did not significantly affect the incidence of POD compared with a placebo (Hovaguimian et al, 2018;Souad et al, 2023;Viderman et al, 2023). But to be clear, ketamine did not increase the risk of POD (Reisinger et al, 2023). The negative results of these prior clinical trials are in stark contrast to the relatively solid theoretical support for the efficacy of ketamine in the prevention of POD.…”