Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation.

OBJECTIVE: To review clinical data on idarucizumab for the reversal of dabigatran-associated anticoagulation. DATA SOURCES: Articles for this review were identified via PubMed using the MeSH term dabigatran combined with the keyword idarucizumab Additional online searches via PubMed and Google Scholar were conducted for both prescribing and cost information. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials published between 1946 and May 2016 were included for review. Bibliographies of selected articles were also manually reviewed for relevant publications that focused on reversal strategies for dabigatran-associated anticoagulation. DATA SYNTHESIS: The safety and tolerability of idarucizumab has been evaluated in 3 phase I clinical trials. The use of idarucizumab for reversing dabigatran-associated anticoagulation is also being evaluated in the phase III RE-VERSE AD study. Interim results of the RE-VERSE AD study have been published. CONCLUSIONS: Idarucizumab rapidly neutralizes the anticoagulant effect of dabigatran in healthy volunteers, in patients with life-threatening bleeding, and in patients requiring urgent surgery that cannot be delayed. These observations are largely based on laboratory assessments rather than clinical outcomes. Idarucizumab is well tolerated, and it does not appear to induce procoagulant or immunogenic adverse effects.

Interprofessional education with a community fall prevention event.

Implementation of interprofessional education (IPE) among multiple professional degree programs has many challenges. Students from four health science programs: pharmacy; nursing; physician assistant studies and physical therapy participated in an interprofessional community fall prevention event. This paper briefly describes the development of this IPE opportunity and the assessment of changes on students' attitudes about IPE after participation in the event. Differing views on teamwork and professional roles are reported by professions. Positive attitudes towards interprofessional teamwork were observed after participation in the event. Based on these data, it appears that an interprofessional community service event offers a useful approach forward for incorporating IPE into the curricula of different health care programs.

Sofosbuvir: A Nucleotide NS5B Inhibitor for the Treatment of Chronic Hepatitis C Infection.

OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..

Clinical outcomes with ertapenem as a first-line treatment option of infections caused by extended-spectrum ß-lactamase producing gram-negative bacteria.

BACKGROUND: Infections caused by extended-spectrum ß-lactamase (ESBL)-producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem). OBJECTIVE: To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organisms. METHODS: This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem. RESULTS: Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50). There were no significant differences in clinical or microbiologic cure rates across important subgroups. CONCLUSIONS: Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.

Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study.

INTRODUCTION: We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium. METHODS: Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤ 0.10 for this exploratory study. RESULTS: Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17]. CONCLUSIONS: Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.

Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Three academic medical centers. PATIENTS: Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition. INTERVENTIONS: Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > or = 10 days, or intensive care unit discharge. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p =.006)], and less agitation (Sedation-Agitation Scale score > or = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66). CONCLUSIONS: Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study.

INTRODUCTION: While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. METHODS: Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>or=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS. RESULTS: Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>or=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar. CONCLUSIONS: Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.

Assessment of delirium in the intensive care unit: nursing practices and perceptions.

BACKGROUND: Despite practice guidelines promoting delirium assessment in intensive care, few data exist regarding current delirium assessment practices among nurses and how these practices compare with those for sedation assessment. OBJECTIVES: To identify current practices and perceptions of intensive care nurses regarding delirium assessment and to compare practices for assessing delirium with practices for assessing sedation. METHODS: A paper/Web-based survey was administered to 601 staff nurses working in 16 intensive care units at 5 acute care hospitals with sedation guidelines specifying delirium assessment in the Boston, Massachusetts area. RESULTS: Overall, 331 nurses (55%) responded. Only 3% ranked delirium as the most important condition to evaluate, compared with altered level of consciousness (44%), presence of pain (23%), or improper placement of an invasive device (21%). Delirium assessment was less common than sedation assessment (47% vs 98%, P < .001) and was more common among nurses who worked in medical intensive care units (55% vs 40%, P = .03) and at academic centers (53% vs 13%, P < .001). Preferred methods for assessing delirium included assessing ability to follow commands (78%), checking for agitation-related events (71%), the Confusion Assessment Method for the Intensive Care Unit (36%), the Intensive Care Delirium Screening Checklist (11%), and psychiatric consultation (9%). Barriers to assessment included intubation (38%), complexity of the tool for assessing delirium (34%), and sedation level (13%). CONCLUSIONS: Practice and perceptions of delirium assessment vary widely among critical care nurses despite the presence of institutional sedation guidelines that promote delirium assessment.

Predictors of mortality in patients with suspected propofol infusion syndrome.

OBJECTIVES: To identify predictors of mortality in patients with suspected propofol infusion syndrome and to develop a simple scoring system to identify patients with suspected propofol infusion syndrome who are most at risk of death. DESIGN: Retrospective, database analysis. SETTING: MEDWATCH system. PARTICIPANTS: Reports (1989-2005) where propofol was associated with > or = 1 of 24 published propofol infusion syndrome clinical manifestations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After comparison of demographic and clinical manifestations between survivors and nonsurvivors, a multivariate logistic regression model was built through a stepwise selection process and then used to develop a simplified mortality scoring system. Of 1139 patients with suspected propofol infusion syndrome, 342 (30%) were fatal. Death was more likely if patients were < or = 18 yrs (odds ratio [95% confidence interval], 2.3 [1.7-3.2]), male (1.3 [1.1-1.7]), received a vasopressor (1.8 [1.3-2.5)]), or had the following clinical manifestations: cardiac (3.8 [2.88-4.91]), metabolic acidosis (3.7 [2.7-5.0]), renal failure (1.9 [1.4-2.6]), hypotension (1.8 [1.3-2.3]), rhabdomyolysis (1.8 [1.3-2.3]), or dyslipidemia (2.0 [1.2-3.4]). The multivariable modeling process found that cardiac symptoms, rhabdomyolosis, hypotension, metabolic acidosis, renal failure, and age each affected survival, although significant interactions existed between some of these factors. Based on the combination of the presence or absence of the six factors in the multivariate model, a propofol infusion syndrome mortality risk score of 0 to 4 resulted in a predicted %/observed % mortality for each score of 0 (10%/10%), 1 (24%/24%), 2 (47%/44%), 3 (72%/81%), and 4 (89%/83%). CONCLUSIONS: A number of characteristics are independently associated with higher mortality in patients with suspected propofol infusion syndrome, only some of which are currently reflected in the package insert. Further research should focus on prospectively evaluating the mortality scoring system in patients with suspected propofol infusion syndrome.

Impact of an institution-specific hospital-acquired pneumonia protocol on the appropriateness of antibiotic therapy and patient outcomes.

STUDY OBJECTIVE: To evaluate the impact of a hospital-acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay. DESIGN: Before- and after-study of protocol implementation. SETTING: A 450-bed, academic medical center. PATIENTS: One hundred consecutive patients with proven or suspected HAP. INTERVENTION: Implementation of an HAP protocol that was based on the 2005 American Thoracic Society-Infectious Diseases Society of America guidelines and included extensive education of clinicians and monitoring by pharmacists. MEASUREMENTS AND MAIN RESULTS: Before protocol implementation, 50 patients with HAP were evaluated against protocol criteria. After protocol implementation, a second cohort of 50 patients with HAP was evaluated. Compared with the preprotocol group, implementation of the protocol led to an increase in both the proportion of patients who received appropriate empiric antibiotic coverage (17 [34%] vs 31 [62%] patients, p=0.005) and appropriate antibiotic deescalation (21 [42%] vs 36 [72%] patients, p=0.002) according to protocol recommendations but did not affect the appropriateness of empiric antibiotic therapy based on final lung culture data (34 [68%] vs 41 [82%] patients, p=0.11). Compared with the preprotocol group, use of the protocol decreased the duration of intravenous antibiotic therapy (median [range] 9 [2-21] vs 7 [1-16] days, p=0.024), was associated with a trend for a shorter duration of stay in the intensive care unit (median [range] 19 [2-57] vs 11 [3-76] days, p=0.065), and did not significantly affect mortality (5 [10%] vs 8 [16%] patients, p=0.37). Pharmacists performed 59 interventions to support the protocol in 29 patients in the postprotocol group, of which 48% were accepted. CONCLUSIONS: Implementation of an HAP protocol improved appropriate empiric antibiotic use and decreased the duration of antibiotic therapy without adversely affecting patient outcomes.

Combined didactic and scenario-based education improves the ability of intensive care unit staff to recognize delirium at the bedside.

BACKGROUND: While nurses play a key role in identifying delirium, several authors have noted variability in their ability to recognize delirium. We sought to measure the impact of a simple educational intervention on the ability of intensive care unit (ICU) nurses to clinically identify delirium and to use a standardized delirium scale correctly. METHODS: Fifty ICU nurses from two different hospitals (university medical and community teaching) evaluated an ICU patient for pain, level of sedation and presence of delirium before and after an educational intervention. The same patient was concomitantly, but independently, evaluated by a validated judge (rho = 0.98) who acted as the reference standard in all cases. The education consisted of two script concordance case scenarios, a slide presentation regarding scale-based delirium assessment, and two further cases. RESULTS: Nurses' clinical recognition of delirium was poor in the before-education period as only 24% of nurses reported the presence or absence of delirium and only 16% were correct compared with the judge. After education, the number of nurses able to evaluate delirium using any scale (12% vs 82%, P < 0.0005) and use it correctly (8% vs 62%, P < 0.0005) increased significantly. While judge-nurse agreement (Spearman rho) for the presence of delirium was relatively high for both the before-education period (r = 0.74, P = 0.262) and after-education period (r = 0.71, P < 0.0005), the low number of nurses evaluating delirium before education lead to statistical significance only after education. Education did not alter nurses' self-reported evaluation of delirium (before 76% vs after 100%, P = 0.125). CONCLUSION: A simple composite educational intervention incorporating script concordance theory improves the capacity for ICU nurses to screen for delirium nearly as well as experts. Self-reporting by nurses of completion of delirium screening may not constitute an adequate quality assurance process.

Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients.

OBJECTIVE: Although medical intensive care unit nurses at our institution routinely use the Intensive Care Delirium Screening Checklist (ICDSC) to identify delirium, physicians rely on traditional diagnostic methods. We sought to measure the effect of physicians' use of the ICDSC on their ability to detect delirium. DESIGN: Before-after study. SETTING: Medical intensive care unit of an academic medical center. PATIENTS AND PARTICIPANTS: A total of 25 physicians with >or=1 month of clinical experience in the medical intensive care unit conducted 300 delirium assessments in 100 medical intensive care unit patients. MEASUREMENTS AND MAIN RESULTS: Physicians sequentially evaluated two patients for delirium using whatever diagnostic method preferred. Following standardized education regarding ICDSC use, each physician evaluated two different patients for delirium using the ICDSC. Each physician assessment was preceded by consecutive, but independent, evaluations for delirium by the patient's nurse and then a validated judge using the ICDSC. Before (PRE) physician ICDSC use, the validated judge identified delirium in five patients; the physicians and nurses identified delirium in zero and four of these patients, respectively. The physicians incorrectly identified delirium in four additional patients. After (POST) physician ICDSC use, the validated judge identified delirium in 11 patients; the physicians and nurses identified delirium in eight and ten of these patients, respectively. The physicians incorrectly identified delirium in one patient. After physician ICDSC use, agreement improved between both the physicians and validated judge (PRE kappa = -0.14 [95% confidence interval {CI} = -0.27 to -0.02] to POST kappa = 0.67 [95% CI = 0.38 to 0.96]) and physicians and nurses (PRE kappa = -0.15 [95% CI = -0.29 to -0.02] to POST kappa = 0.58 [95% CI = 0.25 to 0.91]). Nurses vs. validated judge agreement was strong in both periods (PRE kappa = 0.65 [95% CI = 0.29 to 1.00] and POST kappa = 0.92 [95% CI = 0.76 to 1.00]). CONCLUSIONS: Use of the ICDSC, along with education supporting its use, improves the ability of physicians to detect delirium in the medical intensive care unit.

Propofol associated with a shorter duration of mechanical ventilation than scheduled intermittent lorazepam: a database analysis using Project IMPACT.

BACKGROUND: While one prospective controlled study in medical intensive care unit (ICU) patients demonstrated that sedation with propofol leads to a shorter duration of mechanical ventilation compared with scheduled intermittent intravenous lorazepam, its conclusions may not be applicable to surgical ICU patients and institutions not using daily sedation interruption. OBJECTIVE: To compare the duration of mechanical ventilation between medical and surgical ICU patients receiving propofol versus scheduled intermittent lorazepam in routine clinical practice. METHODS: Retrospective data (January 2001-December 2005) were obtained from the Project IMPACT database for medical and surgical ICU patients at Tufts-New England Medical Center, a 450 bed academic hospital. These patients had been mechanically ventilated for 24 hours or more and had received 24 hours or more of either propofol or scheduled intermittent lorazepam as the sole sedative. Clinically relevant variables were identified a priori, and their influence on duration of mechanical ventilation was evaluated. Differences in these variables between propofol and scheduled intermittent lorazepam groups within the ICU cohorts were then measured. RESULTS: Of 4608 database patients, 287 met criteria. Factors associated with a prolonged duration of mechanical ventilation for the medical ICU cohort included sedation use for 5 or more days (OR 13.8; 95% CI 8.3 to 19.4), narcotic use (OR 7.6; 95% CI 2.3 to 13), and scheduled intermittent lorazepam use (OR 7.0; 95% CI 0.4 to 13.7). For the surgical ICU cohort, these factors included sedation use for 5 or more days (OR 15; 95% CI 11.4 to 19.4), APACHE II (Acute Physiology and Chronic Health Evaluation II) score equal to or greater than 18 (OR 4.1; 95% CI 0.4 to 7.8), and scheduled intermittent lorazepam use (OR 4.0; 95% CI 0.2 to 7.7). Duration of mechanical ventilation was the only variable that differed significantly between propofol and scheduled intermittent lorazepam in both the medical ICU, with a median (range) of 6 (3-12) versus 11 (5-25; p = 0.03), and surgical ICU, with a median of 4 (2-15) versus 9 (4-20; p = 0.001), groups. CONCLUSIONS: Sedation with propofol in the naturalistic setting appears to be associated with a shorter duration of mechanical ventilation compared with scheduled intermittent lorazepam in both medial and surgical ICU patients when only one sedative drug is used. Data from this uncontrolled observational study are consistent with findings from a randomized clinical trial.

Survey of sedation practices during noninvasive positive-pressure ventilation to treat acute respiratory failure.

OBJECTIVES: Noninvasive positive-pressure ventilation (NPPV) is increasingly used in patients with acute respiratory failure, but few data exist regarding current sedation practices during NPPV. We sought to characterize current practices and attitudes regarding sedation during NPPV. DESIGN: Cross-sectional Web-based survey. SETTING: Medical institutions. PARTICIPANTS: Physician members of the American College of Chest Physician's Critical Care Network (n = 2,656) and the European Respiratory Society's Assembly of Critical Care (n = 339). INTERVENTIONS: Survey. MEASUREMENTS AND MAIN RESULTS: Of the 790 of 2,985 (27%) of physicians who responded, 15%, 6%, and 28% never used sedation, analgesia, or hand restraints any of the time for NPPV patients, respectively, and the large majority reported using these interventions in < or =25% of patients. Sedation, analgesia, and hand restraints were more commonly used by North Americans than Europeans (41% vs. 24% for sedation, 48% vs. 35% for analgesia, and 27% vs. 16% for hand restraints, all p < .01) and critical care vs. noncritical care physicians (42% vs. 24% for sedation and 50% vs. 34% for analgesia, all p < .01). A benzodiazepine alone was the most preferred (33%), followed by an opioid alone (29%). Europeans were less likely to use a benzodiazepine alone (25% vs. 39%, p < .001) but more likely to use an opioid alone (37% vs. 26%, p < .009). Sedation was usually administered as an intermittent intravenous bolus, outside of a protocol, and was assessed by nurses using clinical end points rather than a sedation scale. CONCLUSIONS: Most physicians infrequently use sedation and analgesic therapy for NPPV to treat acute respiratory failure, but practices vary widely within and between specialties and geographic regions.

Factors influencing variability in compliance rates and clinical outcomes among three different severe sepsis bundles.

BACKGROUND: While 3 different quality indicator bundles are either approved (Voluntary Hospitals of America [VHA], Institute for Healthcare Improvement [IHI]) or proposed (Joint Commission on Accreditation of Healthcare Organizations [JCAHO]) to rate clinical practices in treatment of severe sepsis, it is suspected that differences in the quality indicators among these bundles may lead to discrepant benchmarking data. OBJECTIVE: To compare bundle compliance and patient factors associated with it among the IHI, JCAHO, and VHA severe sepsis bundles and explore possible reasons for any observed variability. METHODS: Using a retrospective, noninterventional design, we evaluated 50 adults (APACHE II score 25 +/- 6, organ failure 2 +/- 1, and shock 52%) with severe sepsis who were admitted consecutively to an intensive care unit at a 450 bed university-affiliated hospital. RESULTS: Few patients met 100% (IHI 6%, JCAHO 0%, VHA 6%) or 75% or greater (IHI 22%, JCAHO 6%, VHA 22%) of the quality indicators in each bundle. The number of patients who met 50% or more of the quality indicators varied significantly between JCAHO (28%) and both IHI (66%; p < 0.001) and VHA (60%; p < 0.001), but not between IHI and VHA (p = 0.53). Compliance with 50% or more of the quality indicators was more likely to occur when patients had shock (IHI, JCAHO, VHA), an APACHE II score greater than or equal to 25 (VHA), 2 or more organ failures (VHA), or survived hospitalization (IHI). We identified a number of factors that may help explain these differences. CONCLUSIONS: Differences among the IHI, JCAHO, and VHA severe sepsis bundles lead to variability in bundle compliance rates and the patient factors associated with the variability and may lead to confusion when benchmarking practices among institutions. Future efforts should focus on developing a single valid and reliable bundle that allows providers to improve the quality of sepsis care.

Delirium assessment in the critically ill.

OBJECTIVE: To compare available instruments for assessing delirium in critically ill adults that have undergone validity testing and provide clinicians with strategies to incorporate these instruments into clinical practice. DESIGN: Medline (1966-September 2006) was searched using the key words: delirium, cognitive dysfunction, assessment, intensive care unit, and critical illness to identify assessment tools that have been used to evaluate delirium in critically ill adults. A special emphasis was placed on delirium assessment tools that have been properly validated. Data on how these tools have been adopted into clinical practice as well as strategies for clinicians to improve delirium assessment in the ICU are highlighted. MEASUREMENTS AND RESULTS: Six delirium assessment instruments including the Cognitive Test for Delirium (CTD), abbreviated CTD, Confusion Assessment Method-ICU, Intensive Care Delirium Screening Checklist, NEECHAM scale, and the Delirium Detection Score were identified. While each of these scales have undergone validation in critically ill adults, substantial differences exist among the scales in terms of the quality and extent of the validation effort, the specific components of the delirium syndrome each address, their ability to identify hypoactive delirium, their use in patients with a compromised level of consciousness, and their ease of use. CONCLUSIONS: Incorporation of delirium assessment into clinical practice in the intensive care unit using a validated tool may improve patient care. Clinicians can adopt a number of different strategies to overcome the many barriers associated with routine delirium assessment in the ICU.

Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients.

Delirium is common in acutely ill patients and can result in substantial morbidity if left untreated. Atypical antipsychotics have been postulated to be safer and more effective than haloperidol for treatment of this condition. To evaluate the role of atypical antipsychotics versus haloperidol for treatment of delirium in hospitalized acutely ill adults, we searched MEDLINE (1977-September 2006) and International Pharmaceutical Abstracts (1997-September 2006) for English-language publications of clinical trials that compared atypical antipsychotics and haloperidol. Four comparative studies were identified: one double-blind, randomized study (risperidone vs haloperidol), one single-blind, randomized study (olanzapine vs haloperidol), and two retrospective studies (olanzapine vs haloperidol and quetiapine vs haloperidol). These studies demonstrated that atypical antipsychotics are as efficacious as haloperidol. In addition, they appear to be associated with a lower frequency of extrapyramidal effects, and thus are safer than haloperidol. However, these conclusions are based on a limited number of studies; larger comparative trials are needed to elucidate the role of atypical antipsychotics for treating delirium in this population.

NXY-059: review of neuroprotective potential for acute stroke.

OBJECTIVE: To review available literature on the pharmacology, pharmacokinetics, efficacy, and tolerability of NXY-059, an investigational agent with a potential role in the treatment of acute stroke. DATA SOURCES: Information was obtained from a MEDLINE search (1966-February 2006) of English-language literature utilizing the following search terms: NXY-059, cerovive, nitrones, neuroprotection, free radical trapper, and secondary neurologic injury. STUDY SELECTION AND DATA EXTRACTION: Data from animal and human trials were evaluated to summarize the mechanism of action, efficacy, and safety of NXY-059. All published and unpublished trials and abstracts citing NXY-059 were selected. DATA SYNTHESIS: NXY-059 is an intravenous, nitrone-based, free radical trapping agent in Phase III trials for treatment of acute stroke. In various animal models, NXY-059 has shown reductions in infarct volume and neurologic deficits. Pharmacokinetic studies indicate that NXY-059 displays a predictable pharmacokinetic profile and primarily undergoes renal elimination. Results from 2 Phase II clinical trials showed favorable results for the safety and tolerability of the drug. A recent analysis of one of the Phase III trials showed a statistically significant reduction in the primary outcome of disability after acute stroke in patients who received NXY-059 compared with placebo. CONCLUSIONS: NXY-059 is a novel agent undergoing worldwide Phase III trials. Initial safety and efficacy data have not revealed any serious adverse events requiring special monitoring and/or precautions, with the exception of drug accumulation in patients with renal insufficiency. The potential benefit of this agent can change the current management algorithm for acute stroke and may represent significant advancement for the care of these patients.