Article

Haloperidol Prophylaxis for Elderly Hip-Surgery Patients at Risk for Delirium: A Randomized Placebo-Controlled Study

Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Utrecht, Utrecht, Netherlands
Journal of the American Geriatrics Society (Impact Factor: 4.57). 10/2005; 53(10):1658-66. DOI: 10.1111/j.1532-5415.2005.53503.x
Source: PubMed

ABSTRACT

To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium.
Randomized, double-blind, placebo-controlled trial.
Large medical school-affiliated general hospital in Alkmaar, The Netherlands.
A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium.
Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.
The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay.
The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted.
Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.

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    • "To assess risk factors for delirium instead of markers of delirium, all patients with preoperative delirium were subsequently excluded from analysis. Because all participants were at high risk of delirium, they all received routine care with prophylactic treatment of 0.5 mg haloperidol , three times daily from admission until postoperative day three, unless contraindications were present [13]. "
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    ABSTRACT: Background: A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. Methods: Patients (≥. 75. years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. Results: In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. Conclusion: Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. General significance: This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
    Full-text · Article · Oct 2015 · Biochimica et Biophysica Acta - Clinical
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    • "A meta-analysis stated that preoperative , low-dose, and short-term administration of haloperidol or risperidone may modestly decrease delirium incidence—but not duration—in high-incidence samples who require intensive care unit (ICU) support (Gilmore and Wolfe 2013). Some other studies have not demonstrated a decrease in the incidence of cognitive dysfunction in patients receiving pharmacologic prophylactic (such as haloperidol, donepezil (Sampson et al. 2007), citicoline (Bcpp et al. 2009), and rivastigmine) (Gamberini et al. 2009; Kalisvaart et al. 2005; Pisani et al. 2010). "

    Full-text · Article · Jul 2015
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    • "A meta-analysis stated that preoperative , low-dose, and short-term administration of haloperidol or risperidone may modestly decrease delirium incidence—but not duration—in high-incidence samples who require intensive care unit (ICU) support (Gilmore and Wolfe 2013). Some other studies have not demonstrated a decrease in the incidence of cognitive dysfunction in patients receiving pharmacologic prophylactic (such as haloperidol, donepezil (Sampson et al. 2007), citicoline (Bcpp et al. 2009), and rivastigmine) (Gamberini et al. 2009; Kalisvaart et al. 2005; Pisani et al. 2010). "
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    ABSTRACT: Coronary artery bypass graft (CABG) surgery is one of the most commonly performed invasive procedures worldwide [1, 2]. Since the introduction of cardiopulmonary bypass (CPB), the neurological consequence of CABG surgery has been an important subject [2]. Delirium is a major problem after CABG surgery with the approximate reported incidence rate of 20-80% [2]. This complication is associated with increased mortality, longer hospital stay, increased hospital costs, and long-term care [2-4]. Regarding the high incidence of delirium in patients undergoing CABG surgery, prophylactic treatment is preferable. Hence, pharmacological neuroprotective strategies have been developed for these patients [3, 4]. A meta-analysis indicated that preoperative low-dose and short-term administration of haloperidol or risperidone may modestly reduce delirium occurrence in high-risk patients that need intensive care unit (ICU) [4]. Other clinical trials have not reported any decreases in the incidence rate of delirium in patients receiving pharmacologic prophylactic (haloperidol, donepezil [5], citicoline [6], and rivastigmine) [7-9]. Acute inflammation and reduced serotonin neurotransmitter are the most important causes of delirium in these patients [10, 11]. In a meta-analysis, Peng et al. [12] showed the role of peripheral inflammatory markers, such as interleukin-6 and S-100 beta, in postoperative delirium [13]. Although some studies indicated that use of compounds with brain protective activities (such as propofol, aprotininand lidocaine) can prevent delirium after CABG surgery, no sufficient evidence was presented to make a change in standard clinical practice.
    Full-text · Article · Dec 2014 · Forschende Komplementärmedizin / Research in Complementary Medicine
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