Impact of an Alcohol Withdrawal Treatment Pathway on Hospital Length of Stay: A Retrospective Observational Study Comparing Pre and Post Pathway Implementation.

OBJECTIVE: To determine if the implementation of a hospital-specific alcohol withdrawal treatment pathway used in a medical-surgical patient population decreased hospital length of stay (LOS) compared with the standard of care. METHODS: This retrospective observational study, conducted in a large academic tertiary care hospital, involved 582 subjects who met criteria for study inclusion, with 275 subjects in the 2010 cohort and 307 in the 2012 cohort. The Alcohol Withdrawal Project Team was formed with the goal of creating a standardized approach to the recognition and treatment of alcohol withdrawal at Duke University Hospital. The group created a computerized physician order entry alcohol withdrawal treatment pathway with 4 possible treatment paths chosen on the basis of current withdrawal symptoms, vital signs, and alcohol withdrawal history. The 4 treatment paths are 1 prophylaxis; 2 mild-to-moderate withdrawal; 3 moderate-to-severe withdrawal, and 4 severe withdrawal/alcohol withdrawal delirium. Each treatment path corresponds to a different lorazepam dose and dose schedule and symptom assessment. This pathway was implemented in the hospital at the end of 2011. RESULTS: Using a Cox proportional hazards model and adjusting for covariates, there was a 1 day [95% confidence interval (CI), 1-2 d] reduction in median hospital LOS between the 2010 and 2012 cohorts, 5 versus 4 days, respectively. The average ratio in hospital LOS between the 2 cohorts was 1.25 (95% CI, 1.25-1.67). The CI was estimated by bootstrapping and indicated a significantly longer LOS in the 2010 cohort compared with the 2012 cohort. Nonsignificant changes were found in the proportion of subjects admitted to the intensive care unit (24% in 2010 vs. 29.3% in 2012), LOS in the intensive care unit (7.1±8 d in 2010 vs. 5.6±6.9 d in 2012), and proportion of patients discharged with a diagnosis of delirium tremens (17.8% in 2010 vs. 15.3% in 2012). CONCLUSIONS: This study demonstrates the successful implementation of an alcohol withdrawal treatment pathway in a medical-surgical population hospitalized in a large tertiary care facility with significant impact on hospital LOS.

Depressive symptoms and early mortality following lung transplantation: A pilot study.

BACKGROUND: Impaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pretransplant depression, quality of life (QoL), and post-transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short-term mortality in a consecutive series of lung transplant recipients. METHODS: Depression (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR=1.6]) and again approximately 2 weeks following transplantation (median=0.5 months [IQR=0.5]), in a series of 66 patients transplanted between March 2013 and April 2014. The association between psychiatric diagnoses from participants' comprehensive pretransplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality. RESULTS: During a median follow-up of 2.8 years (range 0.4-3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR=2.17 [1.01, 4.67], P=.048), and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pretransplant depression, history of depression, nor QoL was associated with mortality. CONCLUSIONS: Greater post-transplant depressive symptoms are independently associated with mortality among lung transplant recipients.

Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.

Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (-2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate with DRS-R98 scores for delirium severity. In conclusion, we report no evidence of association between serum IGF-I levels and incidence of POD, although the sample size was inadequate for a conclusive study. Further efforts to investigate IGF-I as a delirium risk factor in elderly should address comorbidities and confounders that influence IGF-I levels.

Reduced Cerebral Perfusion Pressure during Lung Transplant Surgery Is Associated with Risk, Duration, and Severity of Postoperative Delirium.

RATIONALE: Delirium is common following lung transplant and is associated with poorer clinical outcomes. The extent to which intraoperative hemodynamic alterations may contribute to postoperative delirium among lung transplant recipients has not been examined. OBJECTIVES: To examine the impact of intraoperative hemodynamic changes on neurobehavioral outcomes among lung transplant recipients. METHODS: Intraoperative hemodynamic function during lung transplant was assessed in a consecutive series of patients between March and November 2013. Intraoperative cerebral perfusion pressure was assessed every minute in all patients. Following lung transplant, patients were monitored for the presence and severity of delirium using the Confusion Assessment Method and the Delirium Rating Scale until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Sixty-three patients received lung transplants, of whom 23 (37%) subsequently developed delirium. Lower cerebral perfusion pressure was associated with increased risk of delirium (odds ratio [OR], 2.08 per 10-mm Hg decrease; 95% confidence interval [CI], 1.02-4.24; P = 0.043), longer duration of delirium (OR, 1.7 d longer per 10-mm Hg decrease; 95% CI, 1.1-2.7; P = 0.022), and greater delirium severity (b = -0.81; 95% CI, -1.47 to -0.15; P = 0.017). CONCLUSIONS: Poorer cerebral perfusion pressure during lung transplant is associated with greater risk for delirium following transplant, as well as greater duration and severity of delirium, independent of demographic and medical predictors.

Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review.

Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor, possesses pharmacologic properties that may confer utility for the treatment of alcohol dependence. Research suggests that not only can it be useful in promoting maintenance of alcohol abstinence but also it may play a key role in decreasing alcohol cravings and anxiety often associated with alcohol dependence. To assess the benefit of baclofen for alcohol dependence, a review of the literature was conducted to identify published data investigating this off-label treatment. Four randomized controlled trials to date have been published and were included in this review. Although primary outcomes differ between studies, patients randomized to baclofen experience higher rates of abstinence from alcohol than those taking placebo in two of the trials. Secondary analyses indicate that baclofen is safe in patients with alcohol dependence, including those with moderate to severe liver cirrhosis, and may provide beneficial anxiolytic effects. Despite some positive data, the largest available randomized controlled trial failed to find any differences between baclofen and placebo. In all studies, individuals with severe medical comorbidities, seizure disorders, and psychiatric disorders were excluded from trials, which may limit external validity. In summary, there may be beneficial effects from using baclofen for the treatment of alcohol dependence; however, limited conclusions can be drawn from the small number of studies currently available for review. Larger well-designed trials are needed to further define baclofen's role for the treatment of alcohol dependence.

A computerized physician order entry set designed to improve safety of intravenous haloperidol utilization: a retrospective study in agitated hospitalized patients.

BACKGROUND: Intravenous haloperidol can increase the risk for corrected QT (QTc) interval prolongation, torsades de pointes (TdP) and sudden death. OBJECTIVE: The purpose of this study was to examine the effects of implementation of a computerized physician order entry (CPOE) set on adherence to monitoring parameters, maximum and cumulative doses, and identification or mitigation of risk factors for QTc prolongation in patients prescribed intravenous haloperidol. METHODS: A retrospective cohort study of medically ill hospitalized inpatients prescribed intravenous haloperidol was conducted. Data were collected for two distinct 1-year time periods: the pre-CPOE set period (30 June 2007 through 30 June 2008) and the post-CPOE set period (1 January 2009 through 1 January 2010). The CPOE set was implemented on 1 October 2008. RESULTS: A total of 151 subjects were included; 84 subjects were in the pre-CPOE set group and 67 subjects were in the post-CPOE set group. Following CPOE set implementation, subjects in the post-CPOE group, compared with the pre-CPOE group, were more likely to receive a 24-hour cumulative dose of intravenous haloperidol <2 mg (Fisher's exact test; p < 0.048), have a baseline ECG (Fisher's exact test; p = 0.045), have a follow-up ECG within 24 hours of intravenous haloperidol administration (Fisher's exact test; p = 0.009) and have a magnesium value assessed at the time of intravenous haloperidol administration (Fisher's exact test; p = 0.004). CONCLUSION: This study reports on the successful implementation of a CPOE set designed to improve the safety of intravenous haloperidol administration in medically ill patients.

Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly.

BACKGROUND: Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied. METHODS: Patients 65 yr or older undergoing elective knee arthroplasty were prospectively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium. Exclusion criteria included dementia, mini-mental state exam score less than 24, delirium, clinically significant central nervous system/neurologic disorder, current alcoholism, or any serious psychiatric disorder. Delirium was assessed on postoperative days 2 and 3 using standardized scales. Patients' preexisting medical conditions were obtained from medical charts. The occurrence of obstructive sleep apnea was confirmed by contacting patients to check their polysomnography records. Data were analyzed using Pearson chi-square or Wilcoxon rank sum tests and multiple logistic regressions adjusted for effects of covariates. RESULTS: Of 106 enrolled patients, 27 (25%) developed postoperative delirium. Of the 15 patients with obstructive sleep apnea, eight (53%) experienced postoperative delirium, compared with 19 (20%) of the patients without obstructive sleep apnea (P = 0.0123, odds ratio: 4.3). Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses. CONCLUSIONS: This is the first prospective study employing validated measures of delirium to identify an association between preexisting obstructive sleep apnea and postoperative delirium.

Defining the role of baclofen for the treatment of alcohol dependence: a systematic review of the evidence.

The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.

Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.

OBJECTIVES: The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo. BACKGROUND: Depression is common among HF patients. It is associated with increased hospitalization and mortality. METHODS: The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks. RESULTS: A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78). CONCLUSIONS: Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Depression and ischemic heart disease: what have we learned from clinical trials?

PURPOSE OF REVIEW: Discuss the interplay of depression and ischemic heart disease. Studies demonstrate high prevalence of depression and its negative impact among patients with ischemic heart disease. RECENT FINDINGS: Results extend previous findings among men, demonstrating a significant increase in mortality and cardiovascular events among depressed women. Sertraline, citalopram and mitrazapine have been shown to be safe and well tolerated in patients with ischemic heart disease. Sertraline and citalopram have demonstrated efficacy for treating depression in such patients. Mirtazapine did not have significant efficacy on post-myocardial infarction depression. Cognitive-behavioral therapy and interpersonal therapy have not been found to have a significant treatment effect. Treating depression may have an impact on cardiovascular morbidity and mortality, but this has not yet been adequately studied. Studies to date lack sufficient statistical power to fully examine the impact of interventions for depression on cardiovascular outcomes. SUMMARY: Cardiologists encounter depression among 25-30% of their patients with ischemic heart disease. Depression is an independent risk factor for poor prognosis among ischemic heart disease patients, at a level comparable to several conventional cardiac risk factors. Adequate treatment of depression may improve the poor prognosis of depressed patients with ischemic heart disease.

A randomized trial of sertraline as a cessation aid for smokers with a history of major depression.

OBJECTIVE: Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated. METHOD: The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits. RESULTS: Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed. CONCLUSIONS: Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.