Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. [Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly. A randomized controlled trial]. Reducing delirium after hip fracture: a randomized trial. Efficacy of a comprehensive geriatric intervention in older patients hospitalized for hip fracture: a randomized, controlled trial. Donepezil in the prevention and treatment of post-surgical delirium. Prevention of thromboembolism in hip-fracture patients. Comparison of low-dose heparin and low-molecular-weight heparin combined with dihydroergotamine. A double-blind trial of risperidone and haloperidol for the treatment of delirium. Preventing venous thromboembolism in elderly patients with hip fractures: studies of low-dose heparin, dipyridamole, aspirin, and flurbiprofen. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia.
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. 40 to 50% of elderly with hip fracture present delirium. The morbimortality increase in patients whose presented delirium.
                To study the use of citicoline (CDP choline) in the prevention of delirium in elderly under hip fracture surgery.
                A randomized control trial. The patients with hip fracture without dementia or an other organic brain illness. The medication were administered 24 hours before and during 4 days after surgery. The doses was 1.2 g/day. The primary outcome measure was percentage of patients with delirium measured with Abbreviated Mental Test (AMT) and Confusion Assessment Method (CAM). The Mini Mental State (MMS) was used before and 4 days after surgery. All treatment comparation was considered statistically significant at p< 0.05 calculating chi square and Wilcoxon test.
                The sample size was 81 patients (46 placebo and 35 citicoline). The mean age was 79.45 for tested group and 79.97 for placebo. There was no statistically significant difference between groups with respect to ASA class of anesthesia. The incidence of delirium was 17.39% in placebo and 11.76% in citicoline group (p= 0.6). CAM and AMT at 1, 2, 3, 4 days post surgery was not significant in placebo and citicoline group (p= 0.8 and p= 0.34).
                In the present study the citicoline did not prevent or reduce the incidence of delirium in hip fracture surgery in elderly. Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture.
                Prospective, randomized, blinded.
                Inpatient academic tertiary medical center.
                126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture.
                Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or "usual care." A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm.
                The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment.
                Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients. To evaluate whether an early multidisciplinary geriatric intervention in elderly patients with hip fracture reduced length of stay, morbidity, and mortality and improved functional evolution.
                Randomized, controlled intervention trial.
                Orthopedic ward in a university hospital.
                Three hundred nineteen patients aged 65 and older hospitalized for hip fracture surgery.
                Participants were randomly assigned to a daily multidisciplinary geriatric intervention (n=155) or usual care (n=164) during hospitalization in the acute phase of hip fracture.
                Primary endpoints were in-hospital length of stay and incidence of death or major medical complications. Secondary endpoints were the rate of recovery of previous activities of daily living and ambulation ability at 3, 6, and 12 months.
                Median length of stay was 16 days in the geriatric intervention group and 18 days in the usual care group (P=.06). Patients assigned to the geriatric intervention showed a lower in-hospital mortality (0.6% vs 5.8%, P=.03) and major medical complications rate (45.2% vs 61.7%, P=.003). After adjustment for confounding variables, geriatric intervention was associated with a 45% lower probability of death or major complications (95% confidence interval=7-68%). More patients in the geriatric intervention group achieved a partial recovery at 3 months (57% vs 44%, P=.03), but there were no differences between the groups at 6 and 12 months.
                Early multidisciplinary daily geriatric care reduces in-hospital mortality and medical complications in elderly patients with hip fracture, but there is not a significant effect on length of hospital stay or long-term functional recovery. Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery.
                A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant.
                Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility.
                This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population. In a prospective, double-blind, controlled study, we compared the antithrombotic efficacy of low-dose heparin with dihydroergotamine (A), low-molecular-weight heparin with dihydroergotamine (B), and placebo (C). Two hundred and thirteen patients surgically treated for fractures of the hip were randomly divided into three groups. One hundred and sixty-one patients were analyzed. All thrombi were verified by ascending phlebography. Nine patients died within 1 month after operation. A and B proved to be equally safe but failed to provide any protection against deep-vein thrombosis, although B showed a tendency to reduce the incidence. Mortality within 1 month of operation was unaffected by the type of prophylaxis. To compare the clinical efficacy of haloperidol and risperidone for the treatment of delirium, the authors performed a double-blind comparative study. Twenty-eight patients with delirium were recruited and randomly assigned to receive a flexible-dose regimen of haloperidol or risperidone over 7 days. The severity of delirium was assessed by using Memorial Delirium Assessment Scale scores. Scores for each group decreased significantly over the study period. However, no significant differences in mean Memorial Delirium Assessment Scale scores between groups were found. The group-by-time effect was not significant. In addition, there was no significant difference in the frequency of response to the drugs between the two groups. One patient in the haloperidol group experienced mild akathisia, but no other patients reported clinically significant side effects. These data show no significant difference in the efficacy or response rate between haloperidol and risperidone in the treatment of delirium. Low-dose heparin, dipyridamole (alone and in combination with aspirin), and flurbiprofen were evaluated as potential prophylactic agents against deep venous thrombosis in elderly patients with hip fractures. None of the agents that modify platelet behaviour could reduct the frequency of isotopically diagnosed venous thrombosis. Low-dose heparin reduced the overall frequency of venous thrombosis and its extent as judged by the frequency of bilaterally abnormal scans, but this reduction did not achieve statistical significance. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder.
                In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year.
                Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group.
                Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.
Research evidence on effectiveness of interventions to prevent delirium is sparse. Based on a single study, a programme of proactive geriatric consultation may reduce delirium incidence and severity in patients undergoing surgery for hip fracture. Prophylactic low dose haloperidol may reduce severity and duration of delirium episodes and shorten length of hospital admission in hip surgery. Further studies of delirium prevention are needed.