Critically ill patients with severe acute respiratory syndrome

Context  Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease capable of causing severe respiratory failure. Objective  To determine the epidemiological features, course, and outcomes of patients with SARS-related critical illness. Design, Setting, and Patients  Retrospective case series of 38 adult patients with SARS-related critical illness admitted to 13 intensive care units (ICUs) in the Toronto area between the onset of the outbreak and April 15, 2003. Data were collected daily during the first 7 days in the ICUs, and patients were followed up for 28 days. Main Outcome Measures  The primary outcome was mortality at 28 days after ICU admission. Secondary outcomes included rate of SARS-related critical illness, number of tertiary care ICUs and staff placed under quarantine, and number of health care workers (HCWs) contracting SARS secondary to ICU-acquired transmission. Results  Of 196 patients with SARS, 38 (19%) became critically ill, 7 (18%) of whom were HCWs. The median (interquartile range [IQR]) age of the 38 patients was 57.4 (39.0-69.6) years. The median (IQR) duration between initial symptoms and admission to the ICU was 8 (5-10) days. Twenty-nine (76%) required mechanical ventilation and 10 of these (34%) experienced barotrauma. Mortality at 28 days was 13 (34%) of 38 patients and for those requiring mechanical ventilation, mortality was 13 (45%) of 29. Six patients (16%) remained mechanically ventilated at 28 days. Two of these patients had died by 8 weeks' follow-up. Patients who died were more often older, had preexisting diabetes mellitus, and on admission to hospital were more likely to have bilateral radiographic infiltrates. Transmission of SARS in 6 study ICUs led to closure of 73 medical-surgical ICU beds. In 2 university ICUs, 164 HCWs were quarantined and 16 (10%) developed SARS. Conclusions  Critical illness was common among patients with SARS. Affected patients had primarily single-organ respiratory failure, and half of mechanically ventilated patients died. The SARS outbreak greatly strained regional critical care resources.      

Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study

Context  Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed. Objective  To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS. Design, Setting, and Patients  Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003. Interventions  Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1. Main Outcome Measures  Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results. Results  Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P = .001), had better oxygen saturation (P = .02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P = .02), had less of an increase in creatine kinase levels (P = .03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone. Conclusions  In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.      

Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure

Context  The association between systolic blood pressure (SBP) at admission, clinical characteristics, and outcomes in patients hospitalized for heart failure who have reduced or relatively preserved systolic function has not been well studied. Objective  To evaluate the relationship between SBP at admission, clinical profile, and outcomes in patients hospitalized for acute heart failure. Design, Setting, and Patients  Cohort study using data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry and performance-improvement program for patients hospitalized with heart failure at 259 US hospitals between March 2003 and December 2004. Patients were divided into quartiles by SBP at hospital admission (<120, 120-139, 140-161, and >161 mm Hg). In-hospital outcomes were based on 48 612 patients aged 18 years or older with heart failure. Of the 41 267 patients with left ventricular function assessed, 21 149 (51%) had preserved left ventricular function. Postdischarge outcomes were based on a prespecified subgroup (n = 5791, 10% of patients) with follow-up data assessed between 60 and 90 days. Main Outcome Measures  In-hospital and postdischarge mortality. Results  Patients with higher SBP were more likely to be female and black and to have preserved systolic function. Fifty percent of the patients had SBP higher than 140 mm Hg at admission. Patients with lower SBP at admission had higher in-hospital and postdischarge mortality rates. Higher SBP at admission was associated with lower in-hospital mortality rates: 7.2% (<120 mm Hg), 3.6% (120-139 mm Hg), 2.5% (140-161 mm Hg), and 1.7% (>161 mm Hg) (P<.001 for overall difference). Postdischarge mortality rates in the follow-up cohort by SBP at admission were 14.0%, 8.4%, 6.0%, and 5.4%, respectively (P<.001 for overall difference). Conclusions  Systolic hypertension is common in patients hospitalized for heart failure. Systolic blood pressure is an independent predictor of morbidity and mortality in patients with heart failure with either reduced or relatively preserved systolic function. Low SBP (<120 mm Hg) at hospital admission identifies patients who have a poor prognosis despite medical therapy. These findings may have important therapeutic implications because characteristics and outcomes differ greatly among patients with heart failure with varying SBP.      

Diabetes and mortality following acute coronary syndromes

Context  The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain. Objective  To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS. Design, Setting, and Patients  A subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62 036 patients (46 577 with ST-segment elevation myocardial infarction [STEMI] and 15 459 with unstable angina/non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event. Main Outcome Measures  Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes. Results  Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI (2.1% vs 1.1%, P < .001) and STEMI (8.5% vs 5.4%, P < .001). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with higher 30-day mortality after UA/NSTEMI (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.24-2.56) or STEMI (OR, 1.40; 95% CI, 1.24-1.57). Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI (hazard ratio [HR], 1.65; 95% CI, 1.30-2.10) or STEMI (HR, 1.22; 95% CI, 1.08-1.38). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2% vs 8.1%). Conclusion  Despite modern therapies for ACS, diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease.      

Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome

Context  Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%. Objective  To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness. Design, Setting, and Patients  Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003. Main Outcome Measures  The primary outcome measure was 28-day mortality after symptom onset. Results  Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (=" BORDER="0">7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO₂ to fraction of inspired oxygen were associated with earlier recovery. Conclusions  Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.      

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.      

Primary care outcomes in patients treated by nurse practitioners or physicians: a randomized trial

Context  Studies have suggested that the quality of primary care delivered by nurse practitioners is equal to that of physicians. However, these studies did not measure nurse practitioner practices that had the same degree of independence as the comparison physician practices, nor did previous studies provide direct comparison of outcomes for patients with nurse practitioner or physician providers. Objective  To compare outcomes for patients randomly assigned to nurse practitioners or physicians for primary care follow-up and ongoing care after an emergency department or urgent care visit. Design  Randomized trial conducted between August 1995 and October 1997, with patient interviews at 6 months after initial appointment and health services utilization data recorded at 6 months and 1 year after initial appointment. Setting  Four community-based primary care clinics (17 physicians) and 1 primary care clinic (7 nurse practitioners) at an urban academic medical center. Patients  Of 3397 adults originally screened, 1316 patients (mean age, 45.9 years; 76.8% female; 90.3% Hispanic) who had no regular source of care and kept their initial primary care appointment were enrolled and randomized with either a nurse practitioner (n = 806) or physician (n = 510). Main Outcome Measures  Patient satisfaction after initial appointment (based on 15-item questionnaire); health status (Medical Outcomes Study Short-Form 36), satisfaction, and physiologic test results 6 months later; and service utilization (obtained from computer records) for 1 year after initial appointment, compared by type of provider. Results  No significant differences were found in patients' health status (nurse practitioners vs physicians) at 6 months (P = .92). Physiologic test results for patients with diabetes (P = .82) or asthma (P = .77) were not different. For patients with hypertension, the diastolic value was statistically significantly lower for nurse practitioner patients (82 vs 85 mm Hg; P = .04). No significant differences were found in health services utilization after either 6 months or 1 year. There were no differences in satisfaction ratings following the initial appointment (P = .88 for overall satisfaction). Satisfaction ratings at 6 months differed for 1 of 4 dimensions measured (provider attributes), with physicians rated higher (4.2 vs 4.1 on a scale where 5 = excellent; P = .05). Conclusions  In an ambulatory care situation in which patients were randomly assigned to either nurse practitioners or physicians, and where nurse practitioners had the same authority, responsibilities, productivity and administrative requirements, and patient population as primary care physicians, patients' outcomes were comparable.      

Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema

Context  Randomized controlled trials have shown that the use of noninvasive ventilation (NIV) reduces the need for endotracheal intubation and invasive mechanical ventilation and reduces complication rates and mortality in selected groups of patients. But whether these benefits translate to a clinical setting is unclear. Objective  To evaluate longitudinally the routine implementation of NIV and its effect on patients admitted to the intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease (COPD) or severe cardiogenic pulmonary edema (CPE). Design  Retrospective, observational cohort study using prospectively collected data from January 1, 1994, through December 31, 2001. Setting  A 26-bed medical intensive care unit (ICU) of a French university referral hospital. Participants  A cohort of 479 consecutive patients ventilated for acute exacerbation of COPD or CPE. Main Outcome Measures  The ICU mortality and incidence rates of ICU-acquired infections. Results  A significant increase in NIV use and a concomitant decrease in mortality and ICU-acquired infection rates were observed over the study years. With adjustment for relevant covariates and propensity scores, NIV was identified as an independent factor linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.78), whereas a high severity score on admission (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR, 3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU-acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P = .04). Conclusion  Implementing routine use of NIV in critically ill patients with acute exacerbation of COPD or severe CPE was associated with improved survival and reduction of nosocomial infections.      

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.      

Characteristics and Outcomes in Adult Patients Receiving Mechanical Ventilation: A 28-Day International Study

Context  The outcome of patients receiving mechanical ventilation for particular indications has been studied, but the outcome in a large number of unselected, heterogeneous patients has not been reported. Objective  To determine the survival of patients receiving mechanical ventilation and the relative importance of factors influencing survival. Design, Setting, and Subjects  Prospective cohort of consecutive adult patients admitted to 361 intensive care units who received mechanical ventilation for more than 12 hours between March 1, 1998, and March 31, 1998. Data were collected on each patient at initiation of mechanical ventilation and daily throughout the course of mechanical ventilation for up to 28 days. Main Outcome Measure  All-cause mortality during intensive care unit stay. Results  Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H₂O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO₂ to fraction of inspired oxygen <100). Conclusion  Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit.