Early Treatment with Risperidone for Subsyndromal Delirium after On-pump Cardiac Surgery in the Elderly (original) (raw)

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery—A randomized controlled trial*

Critical Care Medicine, 2009

ostoperative delirium is an acute, fluctuating disorder of attention and cognition that is associated with prolonged hospitalization, late cognitive deficits, increased 1-year mortality, and higher costs (1). Postoperative delirium is a common problem after cardiac surgery. Reported rates vary widely, with some authors describing rates as high as 70%, depending on the type of cardiac surgery, the assessment methods, and the defini-Objective: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery.

Delirium in the Postoperative Cardiac Patient: A Review

Journal of Cardiac Surgery, 2005

Background and aim of review: Cardiac surgery is increasingly common and relatively safe, but there are frequent reports of neuropsychiatric sequelae occurring in the postoperative period. One of the most common neuropsychiatric presentations of cardiac surgery is delirium, also called postcardiotomy delirium (PCD). Despite the vast numbers of cardiac surgeries performed today, there is a paucity of data on risk factors and management options of PCD available to the clinician. This review aims to summarize available information, increase clinicians' awareness of PCD and suggest effective management of this illness. Methods: Our literature search was completed using the databases Medline and CINAHL; it was limited to human and English language studies from 1964 to the present. Search terms included "delirium," "agitation," "postoperative," "cardiac," "neuropsychiatric," "neuroleptics," "psychosis," "surgery," "treatment," "postcardiotomy," and "pharmacotherapy." Results: Our review of the literature revealed several risk factors for PCD, as well as various options for its pharmacological management. Conclusions: A multifactorial model should be applied when considering risk stratification for and prevention of delirium postoperatively. Pharmacologically, conventional antipsychotic agents, such as haloperidol, have long been used to manage delirium. In light of haloperidol's side effects, particularly those applicable to the cardiac patient, further research is required into the role of second generation antipsychotics. These agents are common in clinical use, and may be the preferred medications.

Pharmacological Risk Factors for Delirium after Cardiac Surgery: A Review

Current Neuropharmacology, 2012

The objective of this review is to evaluate the literature on medications associated with delirium after cardiac surgery and potential prophylactic agents for preventing it. Source: Articles were searched in MEDLINE, Cumulative Index to Nursing and Allied Health, and EMBASE with the MeSH headings: delirium, cardiac surgical procedures, and risk factors, and the keywords: delirium, cardiac surgery, risk factors, and drugs. Principle inclusion criteria include having patient samples receiving cardiac procedures on cardiopulmonary bypass, and using DSM-IV-TR criteria or a standardized tool for the diagnosis of delirium. Principal Findings: Fifteen studies were reviewed. Two single drugs (intraoperative fentanyl and ketamine), and two classes of drugs (preoperative antipsychotics and postoperative inotropes) were identified in the literature as being independently associated with delirium after cardiac surgery. Another seven classes of drugs (preoperative antihypertensives, anticholinergics, antidepressants, benzodiazepines, opioids, and statins, and postoperative opioids) and three single drugs (intraoperative diazepam, and postoperative dexmedetomidine and rivastigmine) have mixed findings. One drug (risperidone) has been shown to prevent delirium when taken immediately upon awakening from cardiac surgery. None of these findings was replicated in the studies reviewed. Conclusion: These studies have shown that drugs taken perioperatively by cardiac surgery patients need to be considered in delirium risk management strategies. While medications with direct neurological actions are clearly important, this review has shown that specific cardiovascular drugs may also require attention. Future studies that are methodologically consistent are required to further validate these findings and improve their utility.

Efficacy and safety of haloperidol prophylaxis for delirium prevention in older medical and surgical at-risk patients acutely admitted to hospital through the emergency department: study protocol of a multicenter, randomised, double-blind, placebo-controlled clinical trial

BMC Geriatrics, 2014

Background: Delirium is associated with substantial morbidity and mortality rates in elderly hospitalised patients, and a growing problem due to increase in life expectancy. Implementation of standardised non-pharmacological delirium prevention strategies is challenging and adherence remains low. Pharmacological delirium prevention with haloperidol, currently the drug of choice for delirium, seems promising. However, the generalisability of randomised controlled trial results is questionable since studies have only been performed in selected postoperative hip-surgery and intensive care unit patient populations. We therefore present the design of the multicenter, randomised, double-blind, placebo-controlled clinical trial on early pharmacological intervention to prevent delirium: haloperidol prophylaxis in older emergency department patients (The HARPOON study). Methods/Design: In six Dutch hospitals, at-risk patients aged 70 years or older acutely admitted through the emergency department for general medicine and surgical specialties are randomised (n = 390) for treatment with prophylactic haloperidol 1 mg or placebo twice daily for a maximum of seven consecutive days. Primary outcome measure is the incidence of in-hospital delirium within seven days of start of the study intervention, diagnosed with the Confusion Assessment Method, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for delirium. Secondary outcome measures include delirium severity and duration assessed with the Delirium Rating Scale Revised 98; number of delirium-free days; adverse events; hospital length-of-stay; all-cause mortality; new institutionalisation; (Instrumental) Activities of Daily Living assessed with the Katz Index of ADL, and Lawton IADL scale; cognitive function assessed with the Six-item Cognitive Impairment Test, and the Dutch short form Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be contacted by telephone three and six months post-discharge to collect data on cognitive-and physical function, home residency, all-cause hospital admissions, and all-cause mortality.

Elderly patient with delirium after myocardial infarction

Journal of the National Medical Association, 2006

Delirium is a transient global disorder of cognition. Almost any medical illness or medication can cause delirium. Here, we report a 71-year-old male who presented to the emergency department with a sudden change in mental status, which later resolved. An electrocardiogram was consistent with acute myocardial infarction. The patient later developed symptoms of delirium, and haloperidol was administered. The symptoms did not resolve, and risperidone was initiated instead. The patient subsequently became hypotensive, and treatment was again changed to olanzapine. He returned to full consciousness with olanzapine treatment. When the potential hypotensive effects of haloperidol and risperidone are taken into consideration, in patients with high cardiac risk, olanzapine may provide a better option for the treatment of delirium.

Haloperidol and risperidone in the treatment of delirium and its subtypes

European Journal of Psychiatry

Background and Objectives: To compare the safety and efficacy of haloperidol and risperidone in the treatment of delirium and its subtypes Methods: We collected sociodemographic data and medical variables in addition to systematically rating all patients with delirium with the Memorial Delirium Assessment Scale (MDAS), Karnofsky Performance Status Scale (KPS) and abbreviated Udvalg for Kliniske Undersogelser (UKU) at baseline (T1), 2-3 days (T2) and 4-7 days (T3) and created an IRB-approved delirium database. For this secondary analysis we extracted all data containing haloperidol (HAL) and risperidone (RIS). Results: We were able to retrieve 32 patients treated with haloperidol (HAL) and risperidone (RIS) each. Both samples did not significantly differ in respect to age, cancer diagnoses or etiologies. The MDAS scores at baseline were higher in HAL treated subjects (20.2) compared to RIS treated subjects (17.7). The treatment results between HAL and RIS were not significantly different: Over the course of treatment MDAS scores improved from 20.2 to 8.3 (HAL) and 17.7 to 7.5 in (RIS), delirium resolution rates were 68.8% (HAL) and 84.4% (RIS). In hypoactive delirium the MDAS scores improved from 18.5 to 9.3 (HAL) and from 15.3 to 6.6 (RIS), delirium resolution rates were 64.3% (HAL) and 91.3% (RIS). In hyperactive delirium the MDAS scores improved from 22.5 to 6.6 (HAL) and 20.1 to 8.4 (RIS), delirium resolution rates were 72.2% (HAL) and 75% (RIS). There were no significant differences in KPS scores at all observation times. Treatment with HAL caused more EPS. Conclusions: Both haloperidol and risperidone may be equally effective in the treatment of delirium and its subtypes. Treatment with haloperidol resulted in more side effects.

Early delirium after cardiac surgery: an analysis of incidence and risk factors in elderly (≥65 years) and very elderly (≥80 years) patients

Clinical Interventions in Aging, 2018

Introduction: Postoperative delirium is a common complication of cardiac surgery associated with increased mortality, morbidity, and long-term cognitive dysfunction. The aim of this study was to identify incidence and risk factors of delirium in elderly ($65 years) and very elderly ($80 years) patients undergoing major cardiac surgery. Materials and methods: We performed a retrospective cohort analysis of prospectively collected data from a register of the cardiac surgery department of a tertiary referral university hospital between 2014 and 2016. Analysis was performed in two groups, 65yearsand65 years and 65yearsand80 years. Results: We analyzed 1,797 patients 65years,including230(7.2465 years, including 230 (7.24%) patients 65years,including230(7.2480 years. Delirium was diagnosed in 21.4% (384/1,797) of patients above 65 years, and in 33.5% (77/230) of octogenarians. Early mortality did not differ between patients with and without delirium. Intensive care unit (ICU) stay (p,0.001), hospital stay (p,0.001), and intubation time (p=0.002) were significantly longer in patients undergoing cardiac surgery 65yearswithdelirium.Accordingtomultivariableanalysis,65 years with delirium. According to multivariable analysis, 65yearswithdelirium.Accordingtomultivariableanalysis,65 years, age (odds ratio [OR] 1.036, p=0.002), low ejection fraction (OR 1.634, p=0.035), diabetes (1.346, p=0.019), and extracardiac arteriopathy (OR 1.564, p=0.007) were found to be independent predictors of post-cardiac surgery delirium. Postoperative risk factors for developing delirium $65 years were atrial fibrillation (1.563, p=0.001), postoperative pneumonia (OR 1.896, p=0.022), elevated postoperative creatinine (OR 1.384, p=0.004), and prolonged hospitalization (OR 1.019, p=0.009). Conclusion: Patients above 65 years of age with postoperative delirium have poorer outcome and are more likely to have prolonged hospitalization and ICU stay, and longer intubation times, but 30-day mortality is not increased. In our study, eight independent risk factors for development of post-cardiac surgery delirium were age, low ejection fraction, diabetes, extracardiac arteriopathy, postoperative atrial fibrillation, pneumonia, elevated creatinine, and prolonged hospitalization time.

Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium

Journal of Psychosomatic Research 2011; 71: 277 -281. , 2011

Objective: The objective of the study was to assess the efficacy and safety of second-generation antipsychotics olanzapine and risperidone vs. haloperidol in patients of delirium admitted to medical and surgical wards. Methods: Prospective follow-up single-blind randomized controlled trials were performed. Consecutive patients with delirium referred to the consultation–liaison psychiatry team were eligible for the study. The study sample comprised 64 patients, with 20 subjects in the haloperidol group, 21 subjects in the risperidone group and 23 subjects in the olanzapine group. A flexible dose regimen (haloperidol −0.25 to 10 mg; risperidone −0.25 to 4 mg; olanzapine −1.25 to 20 mg) was used. Delirium Rating Scale-Revised-98 (DRSR98) was used as the primary efficacy measure, and mini mental status examination (MMSE) was used as a secondary efficacy measure. Results: There was no significant difference in mean baseline DRS-R98 severity scores and MMSE scores between the three groups. However, there were a significant reduction in DRS-R98 severity scores and a significant improvement in MMSE scores over the period of 6 days, but there was no difference between the three groups. Four patients in the haloperidol group, six subjects in the risperidone group and two subjects in the olanzapine group experienced some side effects. Conclusions: Risperidone and olanzapine are as efficacious as haloperidol in the treatment of delirium.

Pharmacological management of delirium in hospitalized adults–a systematic evidence review

Journal of general …, 2009

BACKGROUND AND OBJECTIVESDespite the significant burden of delirium among hospitalized adults, there is no approved pharmacologic intervention for delirium. This systematic review evaluates the efficacy and safety of pharmacologic interventions targeting either prevention or management of delirium.DATA SOURCESWe searched Medline, PubMed, the Cochrane Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) information systems from January 1966 to October 2008. We included randomized, controlled trials comparing pharmacologic compounds either to each other or placebo. We excluded non-comparison trials, studies with patients aged < 18 years, a history of an Axis I psychiatric disorder, and patients with alcohol-related delirium.REVIEW METHODSThree reviewers independently extracted the data for participants, interventions and outcome measures, and critically appraised each study using the JADAD scale.RESULTSWe identified 13 studies that met our inclusion criteria and evaluated 15 compounds: second-generation antipsychotics, first-generation antipsychotics, cholinergic enhancers, an antiepileptic agent, an inhaled anesthetic, injectable sedatives, and a benzodiazepine. Four trials evaluated delirium treatment and suggested no differences in efficacy or safety among the evaluated treatment methods (first and second generation antipsychotics). Neither cholinesterase inhibitors nor procholinergic drugs were effective in preventing delirium. Multiple studies, however, suggest either shorter severity and duration, or prevention of delirium with the use of haloperidol, risperidone, gabapentin, or a mixture of sedatives in patients undergoing elective or emergent surgical procedures.CONCLUSIONThe existing limited data indicates no superiority for second-generation antipsychotics over haloperidol in managing delirium. Although preliminary results suggest delirium prevention may be accomplished through various mechanisms, further studies are necessary to prove effectiveness.