Preventing Postoperative Delirium

The abstracted set of recommendations presented here provides essential guidance both on the prevention of postoperative delirium in older patients at risk of delirium and on the treatment of older surgical patients with delirium, and is based on the 2014 American Geriatrics Society (AGS) Guideline. The full version of the guideline, American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults is available at the website of the AGS. The overall aims of the study were twofold: first, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the prevention of postoperative delirium in older adults; and second, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the treatment of postoperative delirium in older adults. Prevention recommendations focused on primary prevention (i.e., preventing delirium before it occurs) in patients who are at risk for postoperative delirium (e.g., those identified as moderate-to-high risk based on previous risk stratification models such as the National Institute for Health and Care Excellence (NICE) guidelines, Delirium: Diagnosis, Prevention and Management. Clinical Guideline 103; London (UK): 2010 July 29). For management of delirium, the goals of this guideline are to decrease delirium severity and duration, ensure patient safety and improve outcomes.

Postoperative delirium (POD) is the most common serious postoperative complication in older adults. It has uncertain aetiology, limited preventative strategies, and poor long-term outcomes. This updated systematic review and meta-analysis aimed to estimate the effect of processed electroencephalography (pEEG)-guided general anaesthesia during surgery on POD incidence. We performed a systematic review and meta-analysis by searching OVID MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. Studies of adult patients having general anaesthesia for any surgery where pEEG was used and POD was an outcome measure were included. Full-text reports of RCTs published from database inception until August 28, 2021, were included. Trials were excluded if sedation rather than general anaesthesia was administered, or the setting was intensive care. The primary outcome was POD assessed by validated tools. The study was prospectively registered with PROSPERO. Nine studies, which included 4648 eligible subjects, were identified. The incidence of POD in the pEEG-guided general anaesthesia or lighter pEEG target group was 19.0% (440/2310) compared with 23.3% (545/2338) in the usual care or deeper pEEG target group (pooled odds ratio=0.78; 95% confidence interval, 0.60-1.00; P=0.054). Significant heterogeneity was detected (I2=53%). Our primary analysis demonstrated a highly sensitive result with a pooled analysis of trials in which the intervention group adhered to manufacturer's recommended guidelines, showing reduced incidence of POD with pEEG guidance. High clinical heterogeneity limits inferences from this and any future meta-analyses. CRD42020199404 (PROSPERO).

Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective &#x3b1;2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0&#xb7;1 &#x3bc;g/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802. Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0&#xb7;35, 95% CI 0&#xb7;22-0&#xb7;54; p<0&#xb7;0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0&#xb7;50, 0&#xb7;32-0&#xb7;78; p=0&#xb7;002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0&#xb7;44, 0&#xb7;26-0&#xb7;75; p=0&#xb7;002). Occurrence of hypotension and bradycardia did not differ between groups. For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

Dexmedetomidine can attenuate delirium in patients who are critically ill, but evidence with regards to its preventive effect on postoperative delirium remains equivocal. We hypothesised that the risk of delirium after intra-operative dexmedetomidine administration varies depending on the dose administered and aimed to identify the optimum dose to mitigate delirium. We included 114,786 adults undergoing general anaesthesia for non-cardiac, non-transplant surgery. Primary exposure was intra-operative dexmedetomidine dose in cumulative &#x3bc;g.kg-1 body weight, dichotomised into high vs. low dose based on the cohort median (0.49&#x2009;&#x3bc;g.kg-1). Primary outcome was delirium within 7&#x2009;days, identified from discharge notes, Confusion Assessment Method assessments and diagnostic codes. A total of 4804 (4.2%) patients received dexmedetomidine, with a median (IQR [range]) cumulative dose of 0.49 (0.28-0.84 [0.01-2.50])&#x2009;&#x3bc;g.kg-1. Postoperative delirium occurred in 3227 (2.8%) patients. Compared with no dexmedetomidine, the risk of delirium was lower in patients receiving low doses (&#x2264;&#x2009;0.49&#x2009;&#x3bc;g.kg-1) of dexmedetomidine (adjusted odds ratio 0.61, 95%CI 0.44-0.85, p&#x2009;=&#x2009;0.004), but not among those receiving high doses (>&#x2009;0.49&#x2009;&#x3bc;g.kg-1) (adjusted odds ratio 1.06, 95%CI 0.84-1.34, p&#x2009;=&#x2009;0.62). Fractional polynomial regression analyses suggested that doses between 0.25&#x2009;&#x3bc;g.kg-1 and 0.35&#x2009;&#x3bc;g.kg-1 were associated with the lowest delirium risk. Threshold regression and restricted cubic splines confirmed these findings. Low, but not high, dose dexmedetomidine administration was associated with lower risks of delirium, with optimal doses ranging between 0.25&#x2009;&#x3bc;g.kg-1 and 0.35&#x2009;&#x3bc;g.kg-1. We studied medical records from over 100,000 adults who underwent general anaesthesia for surgery. We looked at people who were given a medicine called dexmedetomidine during their operation and compared them with people who were not given this medicine. We also compared people who got a low dose with people who got a high dose. Some patients become confused or mixed up after surgery. This is called delirium. Dexmedetomidine may help prevent this confusion, but doctors are not sure what dose works best. We wanted to find out if the amount of medicine given changes the risk of delirium after surgery. We found that patients who were given a low dose of dexmedetomidine were less likely to become confused after surgery. Patients who were given a high dose did not have less confusion than patients who were not given the medicine at all. The safest and most helpful dose was a small amount, between 0.25 and 0.35 micrograms per kilogram of body weight. This means that giving a small dose of dexmedetomidine during surgery may help reduce confusion afterwards but giving more than this does not seem to help.

This editorial highlights the findings of the Balanced Anaesthesia Delirium study, a 515-patient substudy of the 6644 patient Balanced Anaesthesia trial, which found that targeting deep anaesthesia in patients undergoing major noncardiac surgery was not associated with significantly increased postoperative death or major morbidity. The substudy found that using bispectral index (BIS) guidance with the intention of deliberately achieving deep volatile agent-based anaesthesia (target BIS reading 35 vs 50) significantly increased delirium incidence (28% vs 19%), although not subsyndromal delirium incidence (45% vs 49%). We discuss the implications of these findings for anaesthetic practice, and address whether the BIS should be used as a guide to deliver precision anaesthesia for delirium prevention. We posit that subpopulation-based differences within this multicentre substudy could have affected delirium occurrence, since the findings appeared to rest on outcomes in patients from East Asia. We conclude that questions of whether and for whom deep anaesthesia is deliriogenic remain unanswered.

Postoperative delirium (POD) among the elderly population that undergoes noncardiac surgery is significantly associated with adverse clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of dexmedetomidine for the prophylaxis of POD among the elderly population after noncardiac surgery. We searched Embase, PubMed, and the Cochrane Library from inception date to March 2019 for randomized controlled trials (RCTs) that compared dexmedetomidine and placebo for the prevention of POD and evaluated the major cardiovascular outcomes among elderly people after noncardiac surgery. Two authors independently screened the studies and extracted data from the published articles. The main outcome was the incidence of POD. The secondary outcomes included the occurrence of bradycardia, hypotension, hypertension, tachycardia, myocardial infarction, stroke, hypoxaemia, and all-cause mortality. A total of 6 RCTs with 2102 participants were included. Compared with placebo, dexmedetomidine significantly reduced the prevalence of POD (RR = 0.61, 95% CI 0.34-0.76, P = 0.001, I2 = 66%), and the risk of tachycardia (RR = 0.48, 95% CI 0.30-0.76, P = 0.002, I2 = 0%), hypertension (RR = 0.59, 95% CI 0.44-0.79, P < 0.001, I2 = 20%), stroke (RR = 0.22, 95% CI 0.06-0.76, P = 0.02, I2 = 0%), and hypoxaemia (RR = 0.50, 95% CI 0.32-0.78, P = 0.002, I2 = 0%) in elderly patients who underwent noncardiac surgery. However, dexmedetomidine accelerated the occurrence of bradycardia (RR = 1.36, 95% CI 1.11-1.67, P = 0.003, I2 = 0%). Furthermore, no significant differences were observed in the incidence of hypotension, myocardial infarction, and all-cause mortality between the dexmedetomidine and placebo groups. Among elderly patients after noncardiac surgery, the prophylactic use of dexmedetomidine, compared with the use of placebo, was related to a decline in the incidence of POD.