Pharmacological Management of Delirium in Hospitalized Adults – A Systematic Evidence Review

Department of Pharmacy, Wishard Health Services, Indianapolis, IN, USA.
Journal of General Internal Medicine (Impact Factor: 3.42). 05/2009; 24(7):848-53. DOI: 10.1007/s11606-009-0996-7
Source: PubMed


Despite 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.
We 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.
Three reviewers independently extracted the data for participants, interventions and outcome measures, and critically appraised each study using the JADAD scale.
We 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.
The 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.

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Available from: Malaz Boustani, Jan 06, 2014
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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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    • "Studies by Devlin et al. [63,64] and Skrobik et al. [65] also found a positive role of quetiapine and olanzapine in treating delirium in critically ill patients. Campbell et al. [66] found no superiority for second-generation antipsychotics over haloperidol in managing delirium. Devlin et al. [67] had critically reviewed six studies [54,65,68-71] which used haloperidol to prevent or treat delirium in noncritically or critically ill patients. "
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    ABSTRACT: Introduction The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. Methods The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from 'Google Scholar'. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. Results We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16 to 0.95). Both typical (three RCTs with 965 patients, RR = 0.71; 95% CI = 0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR = 0.36; 95% CI = 0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR = 0.71; 95% CI = 0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR = 0.99; 95% CI = 0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR = 0.93; 95% CI = 0.61 to 1.43) or acetylcholinesterase inhibitors and placebo (four RCTs with 242 patients, RR = 0.95; 95% CI = 0.63 to 1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1,636 patients, pooled SMD (standard mean difference) = -0.06; 95% CI = -0.16 to 0.04). Conclusions The included studies showed great inconsistencies in definition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.
    Full-text · Article · Mar 2013 · Critical care (London, England)
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    • "e more conservative mea - sures have failed . If medications are required to treat patients with symptoms of delirium , the use of low dose typical antipsychotics such as haloper - idol as well as atypical antipsychotics such as ola - nazapine are suggested in the literature , each equally effective for the management of the delir - ious patient ( Campbell et al . , 2009 ) . However , cau - tion should be exercised when prescribing these medications as they may be fail to manage the symptoms of delirium in patients with the hypoac - tive subtype . Flinn et al . ( 2009 ) suggested that patients with delirium - associated agitation are best managed by administering intra - venous haloperidol in 0 . 25 – 0"
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    ABSTRACT: Background A high prevalence for the development of delirium after hip fracture was found in the group of geriatric patients. The National Institute for Health and Clinical Excellence has introduced a guideline for the management delirium (NICE, 2010). Protocols composed of detection, prevention and management of post-operative delirium required some adaptation to meet the needs of local nurses. Aim A protocol with a nursing care plan referenced from an international guideline and other literature was developed to predict, prevent and manage post-operative delirium for geriatric patients with hip fracture. Methods The literature suggests numerous risk factors are associated with post-operative delirium and its preventive interventions were adopted to develop the protocol and nursing care plan. Findings Six major risk categories included mental and behavioural influence, sensory impairment, physiological influence, immobility influence, electrolyte disturbance and infection influence. These were used for screening patients, accompanied by various preventive interventions. A protocol was developed to strive for the best management of geriatric patients receiving hip fracture surgery from admission to discharge. Conclusions The protocol incorporated with the Risk Assessment for Management of Postoperative delirium (RAMP) care plan was adapted for staff to implement in their local clinical area. Further study is required to determine its effectiveness on the prevention of the development of post operative delirium (POD) in the future.
    Full-text · Article · Jan 2013 · International Journal of Orthopaedic and Trauma Nursing
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