E. Wesley Ely

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002. Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks® database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (–) an intervention. A strong recommendation (either for or against) indicated that the intervention’s desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase “We recommend …” is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase “We suggest …” is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. Conclusion:These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial.

BACKGROUND Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)-ie, daily interruption of sedatives-with spontaneous breathing trials (SBTs). METHODS In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630. FINDINGS One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14.7 days vs 11.6 days; mean difference 3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were discharged from intensive care (median time in intensive care 9.1 days vs 12.9 days; p=0.01) and the hospital earlier (median time in the hospital 14.9 days vs 19.2 days; p=0.04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6.0% difference, 95% CI 0.6% to 11.8%; p=0.03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1.2% difference, 95% CI -5.2% to 2.5%; p=0.47), as were total reintubation rates (13.8%vs 12.5%; 1.3% difference, 95% CI -8.6% to 6.1%; p=0.73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0.68, 95% CI 0.50 to 0.92; p=0.01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7.4, 95% CI 4.2 to 35.5). INTERPRETATION Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Evaluation of delirium in critically ill patients: Validation of the Confusion Assessment Method for the Intensive Care Unit (cam-icu)

ObjectiveTo develop and validate an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation. DesignProspective cohort study. SettingThe adult medical and coronary intensive care units of a tertiary care, university-based medical center. PatientsThirty-eight patients admitted to the intensive care units. Measurements and Main Results We designed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU. Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference standard, a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders (fourth edition). A total of 293 daily, paired evaluations were completed, with reference standard diagnoses of delirium in 42% and coma in 27% of all observations. To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days, we used only the first-alert or lethargic comparison evaluation in each patient. Thirty-three of 38 patients (87%) developed delirium during their intensive care unit stay, mean duration of 4.2 ± 1.7 days. Excluding evaluations of comatose patients because of lack of characteristic delirium features, the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84, 0.79, and 0.95, respectively (p < .001). The two nurses’ and intensivist’s sensitivities when using the CAM-ICU compared with the reference standard were 95%, 96%, and 100%, respectively, whereas their specificities were 93%, 93%, and 89%, respectively. ConclusionsThe CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients. The CAM-ICU may be a useful instrument for both clinical and research purposes to monitor delirium in this challenging patient population.

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).

Lorazepam Is an Independent Risk Factor for Transitioning to Delirium in Intensive Care Unit Patients

Background:Delirium has recently been shown as a predictor of death, increased cost, and longer duration of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain but may contribute to patients’ transitioning into delirium. Methods:In this cohort study, the authors designed a priori an investigation to determine whether sedative and analgesic medications independently increased the probability of daily transition to delirium. Markov regression modeling (adjusting for 11 covariates) was used in the evaluation of 198 mechanically ventilated patients to determine the probability of daily transition to delirium as a function of sedative and analgesic dose administration during the previous 24 h. Results:Lorazepam was an independent risk factor for daily transition to delirium (odds ratio, 1.2 [95% confidence interval, 1.1–1.4]; P = 0.003), whereas fentanyl, morphine, and propofol were associated with higher but not statistically significant odds ratios. Increasing age and Acute Physiology and Chronic Health Evaluation II scores were also independent predictors of transitioning to delirium (multivariable P values < 0.05). Conclusions:Lorazepam administration is an important and potentially modifiable risk factor for transitioning into delirium even after adjusting for relevant covariates.

Costs associated with delirium in mechanically ventilated patients.

ObjectiveTo determine the costs associated with delirium in mechanically ventilated medical intensive care unit patients. DesignProspective cohort study. SettingA tertiary care academic hospital. PatientsPatients were 275 consecutive mechanically ventilated medical intensive care unit patients. InterventionsWe prospectively examined patients for delirium using the Confusion Assessment Method for the Intensive Care Unit. Measurements and Main ResultsDelirium was categorized as “ever vs. never” and by a cumulative delirium severity index. Costs were determined from individual ledger-level patient charges using cost-center-specific cost-to-charge ratios and were reported in year 2001 U.S. dollars. Fifty-one of 275 patients (18.5%) had persistent coma and died in the hospital and were excluded from further analysis. Of the remaining 224 patients, delirium developed in 183 (81.7%) and lasted a median of 2.1 (interquartile range, 1–3) days. Baseline demographics were similar between those with and without delirium. Intensive care unit costs (median, interquartile range) were significantly higher for those with at least one episode of delirium (

Delirium as a predictor of long-term cognitive impairment in survivors of critical illness

22,346,

Delirium in the Intensive Care Unit: Occurrence and Clinical Course in Older Patients

15,083–

Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients

35,521) vs. those with no delirium (

Delirium and Its Motoric Subtypes: A Study of 614 Critically Ill Patients

13,332,