Nada S. Al-Qadheeb

Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short-term mortality: a systematic review and meta-analysis.

Objectives:We reviewed randomized trials of adult ICU patients of interventions hypothesized to reduce delirium burden to determine whether interventions that are more effective at reducing delirium duration are associated with a reduction in short-term mortality. Data Sources:We searched CINHAHL, EMBASE, MEDLINE, and the Cochrane databases from 2001 to 2012. Study Selection:Citations were screened for randomized trials that enrolled critically ill adults, evaluated delirium at least daily, compared a drug or nondrug intervention hypothesized to reduce delirium burden with standard care (or control), and reported delirium duration and/or short-term mortality (⩽ 45 d). Data Extraction:In duplicate, we abstracted trial characteristics and results and evaluated quality using the Cochrane risk of bias tool. We performed random effects model meta-analyses and meta-regressions. Data Synthesis:We included 17 trials enrolling 2,849 patients which evaluated a pharmacologic intervention (n = 13) (dexmedetomidine [n = 6], an antipsychotic [n = 4], rivastigmine [n = 2], and clonidine [n = 1]), a multimodal intervention (n = 2) (spontaneous awakening [n = 2]), or a nonpharmacologic intervention (n = 2) (early mobilization [n = 1] and increased perfusion [n = 1]). Overall, average delirium duration was lower in the intervention groups (difference = –0.64 d; 95% CI, –1.15 to –0.13; p = 0.01) being reduced by more than or equal to 3 days in three studies, 0.1 to less than 3 days in six studies, 0 day in seven studies, and less than 0 day in one study. Across interventions, for 13 studies where short-term mortality was reported, short-term mortality was not reduced (risk ratio = 0.90; 95% CI, 0.76–1.06; p = 0.19). Across 13 studies that reported mortality, meta-regression revealed that delirium duration was not associated with reduced short-term mortality (p = 0.11). Conclusions:A review of current evidence fails to support that ICU interventions that reduce delirium duration reduce short-term mortality. Larger controlled studies are needed to establish this relationship.

Efficacy and Safety of Early Dexmedetomidine During Noninvasive Ventilation for Patients With Acute Respiratory Failure: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

BACKGROUND Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear. METHODS Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 μg/kg/h titrated every 30 min to 0.7 μg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 μg, respectively, at a minimum interval of every 3 h. RESULTS The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar. CONCLUSIONS Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.

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.

Optimising the recognition of delirium in the intensive care unit.

Delirium affects up to 80% of critically ill patients and negatively influences patient outcome. Consensus guidelines advocate that a validated screening tool like the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) be used to identify delirium rather than a subjective approach. The CAM-ICU and ICDSC have the most rigorous psychometric data to support their use. The differences between these two instruments are far less important to the outcome of patients than the regular and reliable use of either in routine ICU care. Implementation of a large-scale delirium screening effort is both feasible and sustainable and should be accompanied by both didactic and bedside education. An ICU clinical road map should be used on a daily basis that promotes delirium assessment, establishes a targeted sedation goal and defines the analgesic/sedative regimen that is best suited to maintain patient comfort, prevent delirium and promote wakefulness.

Impact of Enteral Methadone on the Ability to Wean off Continuously Infused Opioids in Critically Ill, Mechanically Ventilated Adults: A Case-Control Study

BACKGROUND: Continuously infused opioids are frequently used to optimize patient comfort in the intensive care unit (ICU). However, concerns about rebound pain and opioid withdrawal may delay efforts to discontinue this therapy. OBJECTIVE: To measure the association between use of scheduled enteral methadone according to a protocol in mechanically ventilated, medical critically ill adults receiving prolonged continuously infused fentanyl and the time to discontinue continuously infused fentanyl therapy. METHODS: This case-control study included 20 consecutive mechanically ventilated adults in a medical ICU, without a history of chronic opioid use, who received 72 or more hours of continuously infused fentanyl and were prescribed scheduled enteral methadone as part of a protocol medical ICU strategy to wean off continuously infused fentanyl. Patients were matched in a 1:2 fashion, by duration of mechanical ventilation, to 40 consecutive preprotocol medical ICU patients meeting the same criteria but who were never given methadone. Duration of continuously infused fentanyl was compared between the 2 groups by constructing Kaplan-Meier plots and estimating the likelihood that methadone use was associated with a decrease in continuously infused fentanyl requirements over time, using a Cox proportional hazards model. RESULTS: The groups were well matched except the methadone patients were older (p = 0.04). Time (median [interquartile range]) to continuously infused fentanyl discontinuation was shorter in the methadone group (4.5 [3.9-5.8] vs 7.0 [4.9-11.5] days; p = 0.002). Continuously infused fentanyl was more likely to be discontinued 2 days after methadone was first initiated (hazard ratio 9.1; p = 0.0004). The proportion of patients who experienced 1 or more episodes of either QTc interval prolongation (p = 0.79) or unarousability (p = 0.47) was similar between the groups. CONCLUSIONS: Enterally administered methadone is associated with earlier cessation of continuously infused fentanyl in mechanically ventilated adults without a history of opioid dependence admitted to a medical ICU. Prospective, controlled studies are needed to further evaluate the safety and efficacy of methadone as a strategy to wean off continuously infused fentanyl in different ICU populations.

Agitation During Prolonged Mechanical Ventilation at a Long-Term Acute Care Hospital Risk Factors, Treatments, and Outcomes

Introduction: The prevalence, risk factors, treatment practices, and outcomes of agitation in patients undergoing prolonged mechanical ventilation (PMV) in the long-term acute care hospital (LTACH) setting are not well understood. We compared agitation risk factors, management strategies, and outcomes between patients who developed agitation and those who did not, in LTACH patients undergoing PMV. Methods: Patients admitted to an LTACH for PMV over a 1-year period were categorized into agitated and nonagitated groups. The presence of agitation risk factors, management strategies, and relevant outcomes were extracted and compared between the 2 groups. Results: A total of 80 patients were included, 41% (33) with agitation and 59% (47) without. Compared to the nonagitated group, the agitated group had a lower Sequential Organ Failure Assessment score (P < .0006), a greater transfer rate from an academic center (P = .05), a greater delirium frequency at both baseline (P = .04) and during admission (P < .001), and a greater rate of benzodiazepine discontinuation (P = .02). Although the use of scheduled antipsychotic (P = .0005) or restraint (P = .002) therapy was more common in the agitated group, use of benzodiazepines (P = .16), opioids (P = .11), or psychiatric evaluation (P = .90) was not. Weaning success, duration of LTACH stay, and daily costs were similar. Conclusion: Agitation among the LTACH patients undergoing PMV is associated with greater delirium and use of antipsychotics and restraints but does not influence weaning success or LTACH stay. Strategies focused on agitation prevention and treatment in this population need to be developed and formally evaluated.

Agreement Between ICU Clinicians and Electrophysiology Cardiologists on the Decision to Initiate a QTc‐interval Prolonging Medication in Critically Ill Patients with Potential Risk Factors for Torsade de Pointes: A Comparative, Case‐Based Evaluation

To measure concordance between different intensive care unit (ICU) clinicians and a consensus group of electrophysiology (EP) cardiologists for use of a common rate‐corrected QT interval (QTc)‐prolonging medication in cases containing different potential risk factor(s) for torsade de pointes (TdP).

Antipsychotic Prescribing Patterns, and the Factors and Outcomes Associated with Their Use, among Patients Requiring Prolonged Mechanical Ventilation in the Long-Term Acute Care Hospital Setting

BACKGROUND: Administration of scheduled antipsychotic therapy to mechanically ventilated patients to prevent or treat delirium is common, despite the lack of evidence to support its use. Among long-term acute care hospital (LTACH) patients requiring prolonged mechanical ventilation (PMV), the frequency of scheduled antipsychotic therapy use, and the factors and outcomes associated with it, have not been described. OBJECTIVE: To identify scheduled antipsychotic therapy prescribing practices, and the factors and outcomes associated with the use of antipsychotics, among LTACH patients requiring PMV. METHODS: Consecutive patients without major psychiatric disorders or dementia who were admitted to an LTACH for PMV over 1 year were categorized as those receiving scheduled antipsychotic therapy (≥24 hours of use) and those not receiving scheduled antipsychotic therapy. Presence of delirium, use of psychiatric evaluation, nonscheduled antipsychotic therapy, and scheduled antipsychotic therapy—related adverse effects were extracted and compared between the 2 groups and when significant (p ≤ 0.05), were entered into a regression analysis using generalized estimating equation techniques. RESULTS: Among 80 patients included, 39% (31) received scheduled antipsychotic therapy and 61% (49) did not. Baseline characteristics, including age, sex, illness severity, and medical history, were similar between the 2 groups. Scheduled antipsychotic therapy was administered on 52% of LTACH days for a median (interquartile range [IQR]) of 25 (6–38) days and, in the antipsychotic group, was initiated at an outside hospital (45%) or on day 2 (1–6; median [IQR]) of the LTACH stay (55%). Quetiapine was the most frequently administered scheduled antipsychotic (77%; median dose 50 [37–72] mg/day). Use of scheduled antipsychotic therapy was associated with a greater incidence of psychiatric evaluation (OR 5.7; p = 0.01), delirium (OR 2.4; p = 0.05), as-needed antipsychotic use (OR 4.1; p = 0.005) and 1:1 sitter use (OR 7.3; p = 0.001), but not benzodiazepine use (p = 0.19). CONCLUSIONS: Among LTACH patients requiring PMV, scheduled antipsychotic therapy is used frequently and is associated with a greater incidence of psychiatric evaluation, delirium, as-needed psychotic use, and sitter use. Although scheduled antipsychotic therapy—related adverse effects are uncommon, these effects are infrequently monitored.

Sedation, nighttime, icebergs, and the Titanic.

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