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.

Clinical sedation scores as indicators of sedative and analgesic drug exposure in intensive care unit patients.

BACKGROUND: It is unclear how best to measure sedative/analgesic drug exposure in the clinical care of critically ill patients. Large doses and prolonged use of sedatives and analgesics in the intensive care unit (ICU) may lead to oversedation and adverse effects, including delirium and long-term cognitive impairment. These issues are of particular concern in elderly patients (aged > or =65 years), who account for at least half of all ICU admissions and nearly two thirds of ICU days. OBJECTIVE: This pilot study explored the relationships between clinical sedation scores, sedative/analgesic drug doses, and plasma drug concentrations in critically ill patients, the majority of whom were elderly. METHODS: This was a prospective, observational study conducted in a 500-bed, tertiary care community hospital. Study patients included a cohort of mechanically ventilated, medical ICU patients who were admitted to the hospital between April and June 2004 who required use of fentanyl, lorazepam, or propofol. Sedative/analgesic medications were administered according to clinical guidelines. Patients' sedation levels were measured twice daily using the Richmond Agitation-Sedation Scale (RASS). Dosing of fentanyl, lorazepam, and propofol was recorded. Blood was sampled twice daily for up to 5 days to analyze plasma drug concentrations. To specifically evaluate the effects of acute, extended (rather than chronic) sedative and analgesic exposure, the study focused on an ICU population receiving these agents for at least 48 hours but <2 weeks. RESULTS: Eighteen medical ICU patients (11 females, 7 males; mean [SD] age, 66.1 [18.1] years) on mechanical ventilation comprised the study cohort. Fifteen patients were aged >62 years, and 11 of those were aged > or =71 years. Plasma drug concentrations (median and interquartile range) were as follows: fentanyl--2.1 ng/mL, 0.9-3.4 ng/mL; lorazepam--266 ng/mL, 112-412 ng/mL; and propofol--845 ng/mL, 334-1342 ng/mL. Maximum concentrations were 3- to 12-fold higher than medians (fentanyl, 7.3 ng/mL; lorazepam, 3108 ng/mL; propofol, 10,000 ng/mL). Medication doses were only moderately correlated with RASS scores (Spearman rho): fentanyl--rho = -0.39, P = 0.002; lorazepam--rho = -0.28, P = 0.001; and propofol--rho = -0.46, P < 0.001. Plasma drug concentrations of fentanyl and lorazepam demonstrated moderate correlations with sedation scores (fentanyl--rho = -0.46, P = 0.002; lorazepam: rho = -0.49, P < 0.001), while propofol concentrations correlated poorly with sedation scores (rho = -0.18, P = 0.07). Associations between interval drug doses and plasma concentrations were as follows: fentanyl, rho = 0.84; lorazepam, rho = 0.76; and propofol, rho = 0.61 (all, P < 0.001). Instructive examples of discrepant dose versus plasma concentration profiles and drug interactions are provided, including 3 cases with patients aged > or =64 years. CONCLUSIONS: Elderly patients are commonly encountered in the ICU setting. Only moderate correlations existed between clinical sedation levels and dose or plasma concentration of sedative/analgesic medications in this study population. Further work is needed to understand appropriate and feasible measures of exposure to sedatives/analgesics relating to clinical outcomes.

The sedation of critically ill adults: Part 1: Assessment. The first in a two-part series focuses on assessing sedated patients in the ICU.

The prevention or treatment of pain, anxiety, and delirium in the ICU is an important goal. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry serious risks. In 2002 the Society of Critical Care Medicine, along with the American Society of Health-System Pharmacists, updated recommendations in its clinical practice guidelines for the sustained use of sedatives and analgesics in adults. This two-part series examines those recommendations that relate to sedation assessment and management, as well as the current literature. This month Part 1 also reviews pertinent recommendations concerning pain and delirium and discusses tools for assessing pain, delirium, and sedation. In August Part 2 will explore pharmacologic and nonpharmacologic management of anxiety and agitation in critically ill patients. The prevention or treatment of pain, anxiety, and delirium in the ICU is an important goal. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry serious risks. In 2002 the Society of Critical Care Medicine, along with the American Society of Health-System Pharmacists, updated recommendations in its clinical practice guidelines for the sustained use of sedatives and analgesics in adults. This two-part series examines those recommendations that relate to sedation assessment and management, as well as the current literature. This month Part 1 also reviews pertinent recommendations concerning pain and delirium and discusses tools for assessing pain, delirium, and sedation. In August Part 2 will explore pharmacologic and nonpharmacologic management of anxiety and agitation in critically ill patients.

The sedation of critically ill adults: part 2: management.

The prevention and treatment of pain, anxiety, and delirium in the ICU are important goals. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry grave risks. Without having an agreed-upon end point for sedation, different providers will likely have disparate treatment goals, increasing the risk of iatrogenic complications and possibly impeding recovery. In 2002 the Society of Critical Care Medicine, along with the American Society of Health-System Pharmacists, updated recommendations in its clinical practice guidelines for the sustained use of sedatives and analgesics in adults. This two-part series examines those recommendations concerning sedation assessment and management, as well as the current literature. Last month, Part 1 reviewed pertinent recommendations concerning pain and delirium and discussed tools for assessing pain, delirium, and sedation. This month, Part 2 explores pharmacologic and nonpharmacologic management of anxiety and agitation in the ICU. The second in a two-part series focuses on the pharmacologic and nonpharmacologic management of anxiety and agitation in the ICU.