Yahya Shehabi

Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial

CONTEXT Gamma-aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the alpha(2) agonist dexmedetomidine may have distinct advantages. OBJECTIVE To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients. DESIGN, SETTING, AND PATIENTS Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU. INTERVENTIONS Dexmedetomidine (0.2-1.4 microg/kg per hour [n = 244]) or midazolam (0.02-0.1 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between -2 and +1) from enrollment until extubation or 30 days. MAIN OUTCOME MEASURES Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events. RESULTS There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, -3.2% to 7.5%]; P = .18). The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 76.6% (n = 93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P < .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P = .01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P = .24). Dexmedetomidine-treated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P < .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P = .07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P < .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P = .02). CONCLUSIONS There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00216190 Published online February 2, 2009 (doi:10.1001/jama.2009.56).

Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients*

Objectives:To determine the relationship between the number of delirium days experienced by intensive care patients and mortality, ventilation time, and intensive care unit stay. Design:Prospective cohort analysis. Setting:Patients from 68 intensive care units in five countries. Patients:Three hundred fifty-four medical and surgical intensive care patients enrolled in the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) trial received a sedative study drug and completed at least one delirium assessment. Interventions:Sedative drug interruption and/or titration to maintain light sedation with daily arousal and delirium assessments up to 30 days of mechanical ventilation. Measurements and Main Results:The primary outcome was all-cause 30-day mortality. Multivariable analysis using Cox regression incorporating delirium duration as a time-dependent variable and adjusting for eight relevant baseline covariates was conducted to quantify the relationship between number of delirium days and the three main outcomes. Overall, delirium was diagnosed in 228 of 354 patients (64.4%). Mortality was significantly lower in patients without delirium compared to those with delirium (15 of 126 [11.9%] vs. 69 of 228 [30.3%]; p < .001). Similarly, the median time to extubation and intensive care unit discharge were significantly shorter among nondelirious patients (3.6 vs. 10.7 days [p < .001] and 4 vs. 16 days [p < .001], respectively). In multivariable analysis, the duration of delirium exhibited a nonlinear relationship with mortality (p = .02), with the strongest association observed in the early days of delirium. In comparison to 0 days of delirium, an independent dose-response increase in mortality was observed, which increased from 1 day of delirium (hazard ratio, 1.70; 95% confidence interval, 1.27–2.29; p < .001), 2 days of delirium (hazard ratio, 2.69; confidence interval, 1.58–4.57; p < .001), and ≥3 days of delirium (hazard ratio, 3.37; confidence interval, 1.92–7.23; p < .001). Similar independent relationships were observed between delirium duration and ventilation time and intensive care length of stay. Conclusions:In ventilated and lightly sedated intensive care unit patients, the duration of delirium was the strongest independent predictor of death, ventilation time, and intensive care unit stay after adjusting for relevant covariates.

Prevalence of Delirium with Dexmedetomidine Compared with Morphine Based Therapy after Cardiac Surgery A Randomized Controlled Trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study)

Background:Commonly used sedatives/analgesics can increase the risk of postoperative complications, including delirium. This double-blinded study assessed the neurobehavioral, hemodynamic, and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia. Methods:A total of 306 patients at least 60 yr old were randomized to receive dexmedetomidine (0.1–0.7 &mgr;g · kg−1 · h−1) or morphine (10-70 &mgr;g · kg−1 · h−1) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2–4. Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. Secondary outcomes included ventilation time, additional sedation/analgesia, and hemodynamic and adverse effects. Results:Of all sedation assessments, 75.2% of dexmedetomidine and 79.6% (P = 0.516) of morphine treatment were in the target range. Delirium incidence was comparable between dexmedetomidine 13 (8.6%) and morphine 22 (15.0%) (relative risk 0.571, 95% confidence interval [CI] 0.256–1.099, P = 0.088), however, dexmedetomidine-managed patients spent 3 fewer days (2 [1–7] versus 5 [2–12]) in delirium (95% CI 1.09–6.67, P = 0.0317). The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine (3 of 20 [15%] versus 9 of 25 [36%]) (relative risk 0.416, 95% CI 0.152–0.637, P = 0.001). Dexmedetomidine-treated patients were more likely to be extubated earlier (relative risk 1.27, 95% CI 1.01–1.60, P = 0.040, log-rank P = 0.036), experienced less systolic hypotension (23% versus 38.1%, P = 0.006), required less norepinephrine (P < 0.001), but had more bradycardia (16.45% versus 6.12%, P = 0.006) than morphine treatment. Conclusion:Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation, less hypotension, less vasopressor requirement, and more bradycardia versus morphine regimen.

A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit*

Objective: To compare the intensive care unit costs and determine factors influencing these costs in mechanically ventilated patients randomized to dexmedetomidine or midazolam by continuous infusion. Design: Cost minimization analysis of a double-blind, multicenter clinical trial randomizing patients 2:1 to receive dexmedetomidine or midazolam from the institutional perspective. Setting: Sixty-eight intensive care units in the United States, Australia, New Zealand, Brazil, and Argentina. Patients: A total of 366 intubated intensive care unit patients anticipated to require sedation for >24 hrs. Measurements and Main Results: Intensive care unit resource use was compared within the two treatment arms, using the U.S. representative costs for these resources. The analyses characterized patient costs from start of study drug until intensive care unit discharge including costs associated with the intensive care unit stay, costs during mechanical ventilation, study drug acquisition cost, and costs of treating adverse drug reactions probably or possibly related to study drugs. Blinded to treatment group, costs were calculated using Medicare reimbursement schedules, average IMS drug costs, expert opinion, and peer-reviewed literature. Censored lengths of intensive care unit stay and mechanical ventilation were imputed, using a nonparametric adjustment algorithm. Crude and multivariate median regressions were performed to relate intensive care unit cost and treatment. Including drug acquisition cost, sedation with dexmedetomidine was associated with a median total intensive care unit cost savings of

Procalcitonin Algorithm in Critically Ill Adults with Undifferentiated Infection or Suspected Sepsis A Randomized Controlled Trial

9679 (confidence interval,

Comfort and patient-centred care without excessive sedation: the eCASH concept

2314–

Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study*.

17,045) compared with midazolam. The primary cost drivers were reduced costs of intensive care unit stay (median savings,

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

6584, 95% confidence interval,

Pro/Con debate: is procalcitonin useful for guiding antibiotic decision making in critically ill patients?

727–

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle.

12,440) and reduced costs of mechanical ventilation (median savings,