Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study.

OBJECTIVE: To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. PATIENTS: Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. INTERVENTIONS: Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. CONCLUSIONS: Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.

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.

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.

Sleep and mechanical ventilation.

Critically ill patients have severe sleep disruption and typically encounter loss of circadian sleep pattern, steep fragmentation, increasing proportions of transitional stages of sleep, and loss of slow wave and rapid eye movement sleep. Mechanical ventilation is associated with these same sleep abnormalities, but what is attributable to the intensive care unit environment versus mechanical ventilation itself may be difficult to discern. Recent studies have shown that the ventilator mode and inappropriate settings can contribute to sleep fragmentation, and it is important to avoid overventilation that can induce central apneas when using spontaneous breathing modes. Noninvasive ventilation in the acute setting seems to be associated with the same sleep abnormalities as invasive ventilation. Long-term noninvasive positive pressure ventilation assists ventilation nocturnally and improves for patients with chronic respiratory failure caused by restrictive thoracic disorders.

A survey of critical care nurses' practices and perceptions surrounding early intravenous antibiotic initiation during septic shock.

BACKGROUND: Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized. AIM: To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock. METHODS: A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition. RESULTS: Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%). CONCLUSIONS: Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts.

Severe Thrombocytopenia in Adults with Severe Acute Respiratory Distress Syndrome: Impact of Extracorporeal Membrane Oxygenation Use.

Extracorporeal membrane oxygenation (ECMO) use is perceived to cause thrombocytopenia (T), but the role of non-ECMO factors in the development of T remains unclear. We sought to evaluate the incidence and factors associated with severe T (platelet count ≤ 50,000/µl) in adults with severe acute respiratory distress syndrome (ARDS) managed with or without ECMO. The ECMO (n = 32) versus the non-ECMO (n = 53) groups had a similar baseline platelet count (214,000 vs. 179,000/µl), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.13), unfractionated heparin (UFH) exposure (p = 0.62), and severe T incidence (25 vs. 19%, p = 0.5). Although the APACHE II score (p = 0.01), presence of liver failure (p = 0.08), and platelet transfusion (p = 0.0009) were different between the severe T (18/85 [21%]) and non-severe T groups (67/85 [79%]), the incidence of septic shock (p = 0.64), heparin infusion use (p = 0.41), exposure to non-heparin T-causing medications (p = 0.77) and ECMO use (p = 0.5) were not. An adjusted multivariate linear regression model revealed that only the APACHE II score was independently associated with the development of severe T (p = 0.01) but use of ECMO was not (p = 0.32) ECMO use may not affect the incidence of severe T among adults with severe ARDS. Larger studies that are prospective in nature are required to confirm this finding.

Effect of Extracorporeal Membrane Oxygenation Use on Sedative Requirements in Patients with Severe Acute Respiratory Distress Syndrome.

STUDY OBJECTIVES: To compare sedative dose requirements during the 6-hour period when they are greatest in patients with severe acute respiratory distress syndrome (ARDS), as well as the time from severe ARDS onset to reach this maximum sedation exposure, between patients with severe ARDS who were managed either with or without extracorporeal membrane oxygenation (ECMO). Also, to explore factors other than ECMO use that may influence sedation requirements during this period of maximum sedation. DESIGN: Retrospective comparative cohort analysis. DATA SOURCES: Two academic centers, one with an adult ECMO program and one without. PATIENTS: Consecutive adults with severe ARDS who were receiving continuous-infusion sedative therapy for at least 48 hours from the time of severe ARDS diagnosis and who were managed with ECMO (34 patients) or without ECMO (60 patients) between 2009 and 2013. MEASUREMENTS AND MAIN RESULTS: Among patients managed with ECMO, the maximum median (interquartile range [IQR]) 6-hr sedative exposure (in midazolam equivalents) was nearly twice as high (118 [IQR 48-225] mg vs 60 [37-99] mg, p=0.004) and was reached, on average, 3 days later (4 [IQR 1-8] vs 1 [IQR 0.5-6] days, p=0.003) than patients not managed with ECMO. Patients managed with ECMO were younger, had a higher Sequential Organ Failure Assessment score, and, in the 24 hours prior to the period of maximum sedative exposure, had a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and were more likely to receive renal replacement and high-dose fentanyl (2000 µg or more/24 hrs) therapy. An adjusted multivariable linear regression model using the natural logarithmic value of the maximum sedative exposure in a 6-hour period revealed that patient age (p=0.04) and administration of high-dose fentanyl in the 24 hours prior to the 6-hour period of maximum sedative use (p<0.0001) were each independently associated with the maximum 6-hour sedative requirement reached, but the use of ECMO was not (p=0.52). CONCLUSION: Although the application of ECMO during severe ARDS resulted in a period of maximum sedation exposure that was both greater and took longer to reach, factors other than ECMO, particularly high-dose opioid administration, appeared more likely to account for this maximum sedation use. Further research surrounding sedative requirements, clearance, and patient response during ECMO is required.

Managing acute respiratory failure during exacerbation of chronic obstructive pulmonary disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major health problem, causing more than half a million hospital admissions per year in the United States. Although overall mortality is low, it is substantially higher with severe exacerbations that require intensive care and mechanical ventilation. The majority of COPD exacerbations result from infection, with typical bacterial organisms most commonly identified. Numerous randomized controlled trials and meta-analyses have documented the benefits of antibiotics, low-flow oxygen, and systemic corticosteroids, and the therapeutic equivalency of the major classes of bronchodilators (short-acting beta-agonist and anticholinergics). Randomized controlled trials also demonstrate that noninvasive ventilation can decrease the incidence of intubation, shorten stay, reduce infectious complications, and improve survival. Although patients who require intubation have the worst prognosis, the vast majority of them can be successfully liberated from mechanical ventilation. For invasively ventilated patients the clinical emphasis should be on improving patient-ventilator interaction and avoiding dynamic hyperinflation (intrinsic positive end-expiratory pressure).

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.