Psychiatric–Medical Comorbidity1Antipsychotic prophylaxis in surgical patients modestly decreases delirium incidence — but not duration — in high-incidence samples: A meta-analysis☆,
Introduction
Delirium, an acute change in mental status marked by impairment of attention, remains a common and serious medical complication among hospitalized patients. The full syndrome of delirium often involves hallucinations, agitation, sleep disturbance, affective symptoms and other disruptions in cognition, causing patients risk of injury as well as subjective distress.
In the elderly, the prevalence of delirium in the hospital ranges between 14% and 56% and at least doubles the likelihood of mortality over the subsequent year [1], [2], [3]. One particularly vulnerable period for developing delirium is in the days following surgery, where rates as high as 70% have been reported [4]. Reviews of delirium in patients following orthopedic or cardiac surgeries have found heterogeneous incidence rates ranging from 3.6% to 53.3% and 13.5% to 41.7%, respectively [5], [6].
Differences in the patient population, surgical procedure, anesthesia and method of neuropsychiatric assessment all likely contribute to this variation, though it is clear that delirium remains a significant problem and not solely in the immediate postoperative period. A large prospective study of patients undergoing coronary artery bypass grafting revealed that delirium was a significant, independent predictor of hospitalization for stroke and all-cause mortality over the subsequent 5 years [7]. In patients with dementia at baseline, evidence suggests that episodes of postoperative delirium are even more likely, last longer and accelerate the rate of cognitive decline [7], [8], [9], [10], [11].
With an aging population and an increasing number of elderly patients undergoing surgery, there is a growing need to understand the risk factors associated with delirium as well as potential interventions to prevent it [12]. Multidisciplinary interventions such as the Hospital Elder Life Program (HELP), which involves baseline screening of patients and management of hospital-associated risk factors, led to a reduction in delirium incidence (9.9% versus 15.0%) and duration (105 versus 161 total days), but not severity [13].
Similar reductions were found in other studies employing nonpharmacologic interventions such as staff education, systematic monitoring of mental status, attention to nutrition and other risk factor reduction [14], [15]. A recent study in patients undergoing elective abdominal surgery employed a modified, proactive HELP program consisting of early mobilization, attention to nutritional needs and cognitive activities, which led to a significantly lower rate of delirium (0%) compared to the usual care group (16.7%) [16]. A proactive, structured consultation with a geriatrician reduced delirium incidence by about one third among elderly patients undergoing surgical repair of hip fracture, though this study was not powered to demonstrate which specific recommendations were effective for prevention [17]. Variability in the findings of these studies suggests that patient population and other factors are significantly influencing delirium incidence as well, leading to a limited consensus over which interventions are most preventive in routine practice.
The notion that medications alone can serve as prophylaxis against delirium remains under investigation. Drawing on the observation that decreased acetylcholine was associated with delirium, there was initial hope for the role of cholinesterase inhibitors in prevention [18]. Trials of donepezil and rivastigmine failed to yield significant, positive results in brief perioperative courses, though these studies had relatively low incidence rates and were generally underpowered to demonstrate small treatment effects [19], [20], [21]. In the case of Sampson et al., a trend towards lower incidence and shorter hospital stay was seen with donepezil, though only 33 patients completed the study, and the overall delirium incidence rate (21.2%) was lower than anticipated by the authors. The timing and duration of treatment may also be important, however; over a 24-month study period, standing rivastigmine decreased the incidence and severity of delirium in patients with vascular dementia [22].
A small pilot study of gabapentin 900 mg daily given before and after surgery showed a significant decrease in delirium incidence compared to placebo, with a trend towards lower opiate requirements in the gabapentin arm [23]. Rubino et al. found that a postoperative bolus and subsequent infusion of clonidine reduced delirium severity — though not incidence — in 30 intensive-care patients following aortic dissection repair [24]. A preliminary trial using melatonin to prevent delirium has shown promise, and a larger study has been proposed [25], [26].
While antipsychotics, primarily haloperidol, are routinely used to treat the symptoms of delirium — such as agitation, anxiety, sleep disturbance and hallucinations — there are few studies examining their potential role in actually preventing it [27], [28], [29]. The present meta-analysis reviews the available randomized placebo-controlled trials conducted to date that address this question.
Section snippets
Search strategy and selection of studies
The PubMed, Cochrane Library and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched for studies published between 1984 and 2012 with the following key words: “delirium,” “prevention” and “trial.” Of these results, studies were included if they employed a randomized controlled trial design, comparing delirium incidence in surgical patients given prophylactic antipsychotic or placebo. All patients had to be nondelirious at baseline and subject to a discrete
Study characteristics
Five randomized placebo-controlled trials comprising a total of 1413 patients were eligible for inclusion (Table 1). In the first published study of its kind, Kaneko et al. randomized 78 patients undergoing gastrointestinal surgery to placebo or haloperidol 5 mg iv each night for five nights. During the study period, 10.5% of the experimental arm became delirious compared to 32.5% in the placebo group (P< .05), and no significant adverse events were reported [31].
Kalisvaart et al. randomized
Discussion
This meta-analysis demonstrates that prophylactic antipsychotic administration has a modest benefit in preventing postsurgical delirium. Based on the risk reduction calculation, eight patients would require antipsychotic treatment to prevent one case of delirium, though the NNT varied substantially among the studies. In the pooled analyses of studies reporting these data, these interventions did not change the length of hospital stay, nor did it consistently impact the duration and severity of
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The authors have no conflicts of interest to report.
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The Psychiatric–Medical Comorbidity section will focus on the prevalence and impact of psychiatric disorders in patients with chronic medical illness as well as the prevalence and impact of medical disorders in patients with chronic psychiatric illness.