Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial

Context  Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. Objective  To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. Design and Setting  Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. Patients  Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. Interventions  Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). Main Outcome Measures  The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. Results  Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). Conclusion  Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.      

Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial

Context  A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival; however, whether those results hold true for patients with hypoxemic acute respiratory failure (ARF) is unclear. Objective  To determine whether prone positioning improves mortality in ARF patients. Design, Setting, and Patients  Prospective, unblinded, multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed randomization conducted from December 14, 1998, through December 31, 2002. To be included, patients had to be at least 18 years, hemodynamically stable, receiving mechanical ventilation, and intubated and had to have a partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FIO₂) ratio of 300 or less and no contraindications to lying prone. Interventions  Patients were randomly assigned to prone position placement (n = 413), applied as early as possible for at least 8 hours per day on standard beds, or to supine position placement (n = 378). Main Outcome Measures  The primary end point was 28-day mortality; secondary end points were 90-day mortality, duration of mechanical ventilation, incidence of ventilator-associated pneumonia (VAP), and oxygenation. Results  The 2 groups were comparable at randomization. The 28-day mortality rate was 32.4% for the prone group and 31.5% for the supine group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.79-1.19; P = .77). Ninety-day mortality for the prone group was 43.3% vs 42.2% for the supine group (RR, 0.98; 95% CI, 0.84-1.13; P = .74). The mean (SD) duration of mechanical ventilation was 13.7 (7.8) days for the prone group vs 14.1 (8.6) days for the supine group (P = .93) and the VAP incidence was 1.66 vs 2.14 episodes per 100-patients days of intubation, respectively (P = .045). The PaO₂/FIO₂ ratio was significantly higher in the prone group during the 28-day follow-up. However, pressure sores, selective intubation, and endotracheal tube obstruction incidences were higher in the prone group. Conclusions  This trial demonstrated no beneficial outcomes and some safety concerns associated with prone positioning. For patients with hypoxemic ARF, prone position placement may lower the incidence of VAP.      

Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial

Maureen O. Meade, MD, MSc; Deborah J. Cook, MD, MSc; Gordon H. Guyatt, MD, MSc; Arthur S. Slutsky, MD; Yaseen M. Arabi, MD; D. James Cooper, MD; Andrew R. Davies, MD; Lori E. Hand, RRT, CCRA; Qi Zhou, PhD; Lehana Thabane, PhD; Peggy Austin, CCRA; Stephen Lapinsky, MD; Alan Baxter, MD; James Russell, MD; Yoanna Skrobik, MD; Juan J. Ronco, MD; Thomas E. Stewart, MD; for the Lung Open Ventilation Study Investigators

JAMA. 2008;299(6):637-645.

Context  Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality.

Objective  To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end–expiratory pressure.

Design and Setting  Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.

Patients  Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250.

Interventions  The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H₂O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H₂O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475).

Main Outcome Measure  All-cause hospital mortality.

Results  Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H₂O in the experimental group vs 9.8 (SD, 2.7) cm H₂O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045).

Conclusions  For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies.

Trial Registration  clinicaltrials.gov Identifier: NCT00182195

     

Paresis acquired in the intensive care unit: a prospective multicenter study

Context  Although electrophysiologic and histologic neuromuscular abnormalities are common in intensive care unit (ICU) patients, the clinical incidence of ICU-acquired neuromuscular disorders in patients recovering from severe illness remains unknown. Objectives  To assess the clinical incidence, risk factors, and outcomes of ICU-acquired paresis (ICUAP) during recovery from critical illness in the ICU and to determine the electrophysiologic and histologic patterns in patients with ICUAP. Design  Prospective cohort study conducted from March 1999 to June 2000. Setting  Three medical and 2 surgical ICUs in 4 hospitals in France. Participants  All consecutive ICU patients without preexisting neuromuscular disease who underwent mechanical ventilation for 7 or more days were screened daily for awakening. The first day a patient was considered awake was day 1. Patients with severe muscle weakness on day 7 were considered to have ICUAP. Main Outcome Measures  Incidence and duration of ICUAP, risk factors for ICUAP, and comparative duration of mechanical ventilation between ICUAP and control patients. Results  Among the 95 patients who achieved satisfactory awakening, the incidence of ICUAP was 25.3% (95% confidence interval [CI], 16.9%-35.2%). All ICUAP patients had a sensorimotor axonopathy, and all patients who underwent a muscle biopsy had specific muscle involvement not related to nerve involvement. The median duration of ICUAP after day 1 was 21 days. Mean (SD) duration of mechanical ventilation after day 1 was significantly longer in patients with ICUAP compared with those without (18.2 [36.3] vs 7.6 [19.2] days; P = .03). Independent predictors of ICUAP were female sex (odds ratio [OR], 4.66; 95% CI, 1.19-18.30), the number of days with dysfunction of 2 or more organs (OR, 1.28; 95% CI, 1.11-1.49), duration of mechanical ventilation (OR, 1.10; 95% CI, 1.00-1.22), and administration of corticosteroids (OR, 14.90; 95% CI, 3.20-69.80) before day 1. Conclusions  Identified using simple bedside clinical criteria, ICUAP was frequent during recovery from critical illness and was associated with a prolonged duration of mechanical ventilation. Our findings suggest an important role of corticosteroids in the development of ICUAP.      

Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial

Context  Many physicians believe that the pulmonary artery catheter (PAC) is useful for the diagnosis and treatment of cardiopulmonary disturbances; however, observational studies suggest that its use may be harmful. Objective  To determine the effects on outcome of the early use of a PAC in patients with shock mainly of septic origin, acute respiratory distress syndrome (ARDS), or both. Design, Setting, and Patients  A multicenter randomized controlled study of 676 patients aged 18 years or older who fulfilled the standard criteria for shock, ARDS, or both conducted in 36 intensive care units in France from January 30, 1999, to June 29, 2001. Intervention  Patients were randomly assigned to either receive a PAC (n = 335) or not (n = 341). The treatment was left to the discretion of each individual physician. Main Outcome Measures  The primary end point was mortality at 28 days. The principal secondary end points were day 14 and 90 mortality; day 14 organ system, renal support, and vasoactive agents–free days; hospital, intensive care unit, and mechanical ventilation–free days at day 28. Results  The 2 groups were similar at baseline. There were no significant differences in mortality with or without the PAC at day 14: 49.9% vs 51.3% (mortality relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .70); day 28: 59.4% vs 61.0% (RR, 0.97; 95% CI, 0.86-1.10; P = .67); or day 90: 70.7% vs 72.0% (RR, 0.98; 95% CI, 0.89-1.08; P = .71). At day 14, the mean (SD) number of days free of organ system failures with or without the PAC (2.3 [3.6] vs 2.4 [3.5]), renal support (7.4 [6.0] vs 7.5 [5.9]), and vasoactive agents (3.8 [4.8] vs 3.9 [4.9]) did not differ. At day 28, mean (SD) days in hospital with or without the PAC (0.9 [3.6] vs 0.9 [3.3]), in the intensive care unit (3.4 [6.8] vs 3.3 [6.9]), or mechanical ventilation use (5.2 [8.5] vs 5.0 [8.5]) did not differ. Conclusion  Clinical management involving the early use of a PAC in patients with shock, ARDS, or both did not significantly affect mortality and morbidity.      

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial

Context  Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. Objective  To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. Design, Setting, and Participants  Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. Interventions  Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. Main Outcome Measures  Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA_1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. Results  Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R² = 0.46, P < .001) and lower baseline HbA_1c levels (combined R² = 0.52, P < .001). There were no serious complications in either group. Conclusions  Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. Trial Registration  actr.org Identifier: ACTRN012605000159651      

Delivery of preventive services to older adults by primary care physicians

Context  Rates of preventive services remain below national goals. Objective  To identify characteristics of physicians and their practices that are associated with the quality of preventive care their patients receive. Design  Cross-sectional analysis of data on US physician respondents to the 2000-2001 Community Tracking Study Physician Survey linked to claims data on Medicare beneficiaries they treated in 2001. Physician variables included training and qualifications and sex. Practice setting variables included practice type, size, sources of revenue, and access to information technology. Analyses were adjusted for patient demographics and comorbidity, as well as community characteristics. Setting and Participants  Primary care delivered by 3660 physicians providing usual care to 24 581 Medicare beneficiaries aged 65 years and older. Main Outcome Measures  Proportion of eligible beneficiaries receiving each of 6 preventive services: diabetic monitoring with hemoglobin A_1c measurement or eye examinations, screening for colon or breast cancer, and vaccination for influenza or pneumococcus in 2001. Results  Overall, the proportion of beneficiaries receiving services was below national goals. Physician and, more consistently, practice-level characteristics were both associated with differences in the delivery of services. The strongest associations were with practice type and the percentage of practice revenue derived from Medicaid. For instance, beneficiaries receiving usual care in practices with less than 6% of revenue from Medicaid were more likely than those with more than 15% of revenue derived from Medicaid to receive diabetic eye examinations (48.9% vs 43%; P = .02), hemoglobin A_1c monitoring (61.2% vs 48.4%; P<.001), mammograms (52.1% vs 38.9%; P<.001), colon cancer screening (10.0% vs 8.5%; P = .60), and influenza (50.2% vs 39.2%; P<.001) and pneumococcal (8.2% vs 6.4%; P<.001) vaccinations. Other variables associated with delivery of preventive services after adjustment for patient and geographic factors included obtaining usual health care from a physician who worked in group practices of 3 or more, who was a graduate of a US or Canadian medical school, or who reported availability of information technology to generate preventive care reminders or access treatment guidelines. Conclusions  Delivery of routine preventive services is suboptimal for Medicare beneficiaries. However, patients treated within particular practice settings and by particular subgroups of physicians are at particular risk of low-quality care. Profiling these practices may help develop tailored interventions that can be directed to sites where the opportunities for quality improvement are greatest.      

Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Context.— No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. Objective.— To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. Design.— Randomized, double-blind, placebo-controlled trial. Setting.— Medical intensive care units of 4 medical centers. Participants.— Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. Interventions.— Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. Main Outcome Measures.— Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. Results.— Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO₂ to fraction of inspired oxygen (FIO₂), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO₂ to FIO₂ (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. Conclusions.— In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.      

Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial

Context  Ventilator management protocols shorten the time required to wean adult patients from mechanical ventilation. The efficacy of such weaning protocols among children has not been studied. Objective  To evaluate whether weaning protocols are superior to standard care (no defined protocol) for infants and children with acute illnesses requiring mechanical ventilator support and whether a volume support weaning protocol using continuous automated adjustment of pressure support by the ventilator (ie, VSV) is superior to manual adjustment of pressure support by clinicians (ie, PSV). Design and Setting  Randomized controlled trial conducted in the pediatric intensive care units of 10 children's hospitals across North America from November 1999 through April 2001. Patients  One hundred eighty-two spontaneously breathing children (<18 years old) who had been receiving ventilator support for more than 24 hours and who failed a test for extubation readiness on minimal pressure support. Interventions  Patients were randomized to a PSV protocol (n = 62), VSV protocol (n = 60), or no protocol (n = 60). Main Outcome Measures  Duration of weaning time (from randomization to successful extubation); extubation failure (any invasive or noninvasive ventilator support within 48 hours of extubation). Results  Extubation failure rates were not significantly different for PSV (15%), VSV (24%), and no protocol (17%) (P = .44). Among weaning successes, median duration of weaning was not significantly different for PSV (1.6 days), VSV (1.8 days), and no protocol (2.0 days) (P = .75). Male children more frequently failed extubation (odds ratio, 7.86; 95% confidence interval, 2.36-26.2; P<.001). Increased sedative use in the first 24 hours of weaning predicted extubation failure (P = .04) and, among extubation successes, duration of weaning (P<.001). Conclusions  In contrast with adult patients, the majority of children are weaned from mechanical ventilator support in 2 days or less. Weaning protocols did not significantly shorten this brief duration of weaning.      

Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis

Context  In patients with acute cardiogenic pulmonary edema noninvasive ventilation may reduce intubation rate, but the impact on mortality and the superiority of one technique over another have not been clearly established. Objective  To systematically review and quantitatively synthesize the short-term effect of noninvasive ventilation on major clinical outcomes. Data Sources  MEDLINE and EMBASE (from inception to October 2005) and Cochrane databases (library issue 4, 2005) were searched to identify relevant randomized controlled trials and systematic reviews published from January 1, 1988, to October 31, 2005. Study Selection and Data Extraction  Included trials were all parallel studies comparing noninvasive ventilation to conventional oxygen therapy in patients with acute pulmonary edema. Comparisons of different techniques, either continuous positive airway pressure (CPAP) or bilevel noninvasive pressure support ventilation (NIPSV), were also included. Data Synthesis  Fifteen trials were selected. Overall, noninvasive ventilation significantly reduced the mortality rate by nearly 45% compared with conventional therapy (risk ratio [RR], 0.55; 95% confidence interval [CI], 0.40-0.78; P = .72 for heterogeneity). The results were significant for CPAP (RR, 0.53; 95% CI, 0.35-0.81; P = .44 for heterogeneity) but not for NIPSV (RR, 0.60; 95% CI, 0.34-1.05; P = .76 for heterogeneity), although there were fewer studies in the latter. Both modalities showed a significant decrease in the "need to intubate" rate compared with conventional therapy: CPAP (RR, 0.40; 95% CI, 0.27-0.58; P = .21 for heterogeneity), NIPSV (RR, 0.48; 95% CI, 0.30-0.76; P = .24 for heterogeneity), and together (RR, 0.43; 95% CI, 0.32-0.57; P = .20 for heterogeneity). There were no differences in intubation or mortality rates in the analysis of studies comparing the 2 techniques. Conclusions  Noninvasive ventilation reduces the need for intubation and mortality in patients with acute cardiogenic pulmonary edema. Although the level of evidence is higher for CPAP, there are no significant differences in clinical outcomes when comparing CPAP vs NIPSV.      

Acute renal failure in critically ill patients: a multinational, multicenter study

Context  Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. Objectives  To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. Design, Setting, and Patients  Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. Main Outcome Measures  Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. Results  Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). Conclusion  In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.      

Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS)

Context  Goal-directed delivery of sedative and analgesic medications is recommended as standard care in intensive care units (ICUs) because of the impact these medications have on ventilator weaning and ICU length of stay, but few of the available sedation scales have been appropriately tested for reliability and validity. Objective  To test the reliability and validity of the Richmond Agitation-Sedation Scale (RASS). Design  Prospective cohort study. Setting  Adult medical and coronary ICUs of a university-based medical center. Participants  Thirty-eight medical ICU patients enrolled for reliability testing (46% receiving mechanical ventilation) from July 21, 1999, to September 7, 1999, and an independent cohort of 275 patients receiving mechanical ventilation were enrolled for validity testing from February 1, 2000, to May 3, 2001. Main Outcome Measures  Interrater reliability of the RASS, Glasgow Coma Scale (GCS), and Ramsay Scale (RS); validity of the RASS correlated with reference standard ratings, assessments of content of consciousness, GCS scores, doses of sedatives and analgesics, and bispectral electroencephalography. Results  In 290-paired observations by nurses, results of both the RASS and RS demonstrated excellent interrater reliability (weighted , 0.91 and 0.94, respectively), which were both superior to the GCS (weighted , 0.64; P<.001 for both comparisons). Criterion validity was tested in 411-paired observations in the first 96 patients of the validation cohort, in whom the RASS showed significant differences between levels of consciousness (P<.001 for all) and correctly identified fluctuations within patients over time (P<.001). In addition, 5 methods were used to test the construct validity of the RASS, including correlation with an attention screening examination (r = 0.78, P<.001), GCS scores (r = 0.91, P<.001), quantity of different psychoactive medication dosages 8 hours prior to assessment (eg, lorazepam: r = - 0.31, P<.001), successful extubation (P = .07), and bispectral electroencephalography (r = 0.63, P<.001). Face validity was demonstrated via a survey of 26 critical care nurses, which the results showed that 92% agreed or strongly agreed with the RASS scoring scheme, and 81% agreed or strongly agreed that the instrument provided a consensus for goal-directed delivery of medications. Conclusions  The RASS demonstrated excellent interrater reliability and criterion, construct, and face validity. This is the first sedation scale to be validated for its ability to detect changes in sedation status over consecutive days of ICU care, against constructs of level of consciousness and delirium, and correlated with the administered dose of sedative and analgesic medications.      

Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit

Context  In the intensive care unit (ICU), delirium is a common yet underdiagnosed form of organ dysfunction, and its contribution to patient outcomes is unclear. Objective  To determine if delirium is an independent predictor of clinical outcomes, including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation. Design, Setting, and Participants  Prospective cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001. Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Main Outcome Measures  Primary outcomes included 6-month mortality, overall hospital length of stay, and length of stay in the post-ICU period. Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge. Results  Of 275 patients, 51 (18.5%) had persistent coma and died in the hospital. Among the remaining 224 patients, 183 (81.7%) developed delirium at some point during the ICU stay. Baseline demographics including age, comorbidity scores, dementia scores, activities of daily living, severity of illness, and admission diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month mortality rates (34% vs 15%, P = .03) and spent 10 days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age, severity of illness, comorbid conditions, coma, and use of sedatives or analgesic medications), delirium was independently associated with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P = .008), and longer hospital stay (adjusted HR, 2.0; 95% CI, 1.4-3.0; P<.001). Delirium in the ICU was also independently associated with a longer post-ICU stay (adjusted HR, 1.6; 95% CI, 1.2-2.3; P = .009), fewer median days alive and without mechanical ventilation (19 [interquartile range, 4-23] vs 24 [19-26]; adjusted P = .03), and a higher incidence of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P = .002). Conclusion  Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma, sedatives, and analgesics in patients receiving mechanical ventilation.      

Influence of patient literacy on the effectiveness of a primary care-based diabetes disease management program

Context  Low literacy is an important barrier for patients with diabetes, but interventions to address low literacy have not been well examined. Objective  To examine the role of literacy on the effectiveness of a comprehensive disease management program for patients with diabetes. Design, Setting, and Participants  Analysis of the influence of literacy on glycemic control and systolic blood pressure using data from a randomized controlled trial (conducted from February 2001 through April 2003) of a comprehensive diabetes management program. Participants were 217 patients aged 18 years or older with type 2 diabetes and poor glycemic control (glycosylated hemoglobin [HbA_1c] levels 8.0%) and presenting to a US academic general internal medicine practice. Interventions  All communication to patients was individualized and delivered to enhance comprehension among patients with low literacy. Intervention patients received intensive disease management from a multidisciplinary team. Control patients received an initial management session and continued with usual care. Main Outcome Measures  Achievement of goal HbA_1c levels and systolic blood pressure at 12-month follow-up for control and intervention patients stratified by literacy status. Results  Complete 12-month data were available for 193 patients (89%). Among patients with low literacy, intervention patients were more likely than control patients to achieve goal HbA_1c levels (7.0%) (42% vs 15%, respectively; adjusted odds ratio [OR], 4.6; 95% confidence interval [CI], 1.3 to 17.2; P = .02). Patients with higher literacy had similar odds of achieving goal HbA_1c levels regardless of intervention status (24% vs 23%; adjusted OR, 1.0; 95% CI, 0.4 to 2.5; P = .98). Improvements in systolic blood pressure were similar by literacy status. Conclusions  Literacy may be an important factor for predicting who will benefit from an intervention for diabetes management. A diabetes disease management program that addresses literacy may be particularly beneficial for patients with low literacy, and increasing access to such a program could help reduce health disparities.      

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model

Context  Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. Objective  To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. Design, Setting, and Participants  Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E^–/– (apoE^–/–) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 µm (PM_2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. Main Outcome Measures  Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. Results  In the high-fat chow group, the mean (SD) composite plaque area of PM_2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM_2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM_2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10^-8 vs 4.3 [0.1] x 10^-8, respectively; P = .04). Mice fed high-fat chow and exposed to PM_2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). Conclusion  In an apoE^–/– mouse model, long-term exposure to low concentration of PM_2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.      

Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial

Context  Few depressed older adults receive effective treatment in primary care settings. Objective  To determine the effectiveness of the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. Design  Randomized controlled trial with recruitment from July 1999 to August 2001. Setting  Eighteen primary care clinics from 8 health care organizations in 5 states. Participants  A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). Intervention  Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care. Main Outcome Measures  Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. Results  At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. Conclusion  The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.      

Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial

Context  Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury. Objective  To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury. Design and Setting  Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999. Patients  Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO₂ to FiO₂ of 250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization. Interventions  Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death. Main Outcome Measures  The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test. Results  An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P = .97; difference, –0.1 day [95% confidence interval, –2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO₂ that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P = .54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P = .54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P = .89). Conclusion  Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.      

Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial

Context  Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF. Objective  To determine if an association between azithromycin use and pulmonary function exists in patients with CF. Design and Setting  A multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States. Participants  Of the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV₁) of 30% or more. Participants were stratified by FEV₁ (=" BORDER="0">60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center. Intervention  The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight =" BORDER="0">40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets. Main Outcome Measures  Change in FEV₁ from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain. Results  The azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV₁ at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P = .009). Nausea occurred in 17% more participatns in the azithromycin group (P = .01), diarrhea in 15% more (P = .009), and wheezing in 13% more (P = .007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P = .03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P = .02). Conclusion  Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.      

Differences in Preferences for Neonatal Outcomes Among Health Care Professionals, Parents, and Adolescents

Context  In neonatal intensive care, parents make important clinical management decisions in conjunction with health care professionals. Yet little information is available on whether preferences of health care professionals and parents for the resulting health outcomes differ. Objective  To measure and compare preferences for selected health states from the perspectives of health care professionals (ie, neonatologists and neonatal nurses), parents of extremely low-birth-weight (ELBW) or normal birth-weight infants, and adolescents who were either ELBW or normal birth-weight infants. Design  Cross-sectional cohort study. Setting and Participants  A total of 742 participants were recruited and interviewed between 1993 and 1995, including 100 neonatologists from hospitals throughout Canada; 103 neonatal nurses from 3 regional neonatal intensive care units; 264 adolescents (aged 12-16 years), including 140 who were ELBW infants and 124 sociodemographically matched term controls; and 275 parents of the recruited adolescents. Main Outcome Measure  Preferences (utilities) for 4 to 5 hypothetical health states of children were obtained by direct interviews using the standard gamble method. Results  Overall, neonatologists and nurses had similar preferences for the 5 health states, and a similar proportion rated some health states as worse than death (59% of neonatologists and 68% of nurses;P=.20). Health care professionals rated the health states lower than did parents of ELBW and term infants (P<.001). Overall, 64% of health care professionals and 45% of parents rated 1 or more health states to be worse than death (P<.001). Differences in mean utility scores between health care professionals and parents and adolescent respondents were most pronounced for the 2 most severely disabled health states (P<.001). Conclusions  When asked to rate the health-related quality of life for the hypothetical conditions of children, health care professionals tend to provide lower utility scores than do adolescents and their parents. These findings have implications for decision making in the neonatal intensive care unit.      

Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network

Context  Three clinical studies have suggested that ketoconazole, a synthetic imidazole with anti-inflammatory activity, may prevent the development of acute respiratory distress syndrome (ARDS) in critically ill patients. However, the use of ketoconazole as treatment for acute lung injury (ALI) and ARDS has not been previously studied. Objective  To test the efficacy of ketoconazole in reducing mortality and morbidity in patients with ALI or ARDS. Design  Randomized, double-blind, placebo-controlled trial conducted from March 1996 to January 1997. Setting  Twenty-four hospitals associated with 10 network centers in the United States, constituting the ARDS Network. Patients  A total of 234 patients with ALI or ARDS. Intervention  Patients were randomly assigned to receive ketoconazole, 400 mg/d (n=117), or placebo (n=117), initiated within 36 hours of fulfilling study entry criteria and given enterally for up to 21 days. Main Outcome Measures  Primary outcome measures were the proportion of patients alive with unassisted breathing at hospital discharge and the number of days of unassisted breathing (ventilator-free days) during 28 days of follow-up. Secondary outcome measures included the proportion of patients achieving unassisted breathing for 48 hours or more, the number of organ failure–free days, and changes in plasma interleukin 6 (IL-6) and urinary thromboxane A₂ metabolites (thromboxane B₂ [TXB₂] and 11-dehydro-TXB₂). Results  In-hospital mortality (SE) was 34.1% (4.3%) for the placebo group and 35.2% (4.3%) for the ketoconazole group (P=.85). The median number of ventilator-free days within 28 days of randomization was 9 in the placebo group and 10 in the ketoconazole group (P=.89). There were no statistically significant differences in the number of organ failure–free days, pulmonary physiology, or adverse events between treatment groups. The median serum ketoconazole level was 1.25 µg/mL and serum levels greater than 0.5 µg/mL were detected in 96% of patients assayed. Plasma IL-6, urinary TXB₂, and 11-dehydro-TXB₂ levels were unaffected by ketoconazole. Conclusions  In these patients with ALI or ARDS, ketoconazole was safe and bioavailable but did not reduce mortality or duration of mechanical ventilation or improve lung function. These data do not support the use of ketoconazole for the early treatment of ALI or ARDS.