Rationale: ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this. Objectives: To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality. Methods: A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength. Measurements and Main Results: We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4–25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5–13.6; P = 0.007). Conclusions: ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Neuromuscular dysfunction is prevalent in critically ill patients, is associated with worse short-term outcomes, and is a determinant of long-term disability in intensive care unit survivors. Diagnosis is made with the help of clinical, electrophysiological, and morphological observations; however, the lack of a consistent nomenclature remains a barrier to research. We propose a simple framework for diagnosing and classifying neuromuscular disorders acquired in critical illness.

Rationale: Profound muscle weakness during and after critical illness is termed intensive care unit–acquired weakness (ICUAW). Objectives: To develop diagnostic recommendations for ICUAW. Methods: A multidisciplinary expert committee generated diagnostic questions. A systematic review was performed, and recommendations were developed using the Grading, Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Measurement and Main Results: Severe sepsis, difficult ventilator liberation, and prolonged mechanical ventilation are associated with ICUAW. Physical rehabilitation improves outcomes in heterogeneous populations of ICU patients. Because it may not be feasible to provide universal physical rehabilitation, an alternative approach is to identify patients most likely to benefit. Patients with ICUAW may be such a group. Our review identified only one case series of patients with ICUAW who received physical therapy. When compared with a case series of patients with ICUAW who did not receive structured physical therapy, evidence suggested those who receive physical rehabilitation were more frequently discharged home rather than to a rehabilitative facility, although confidence intervals included no difference. Other interventions show promise, but fewer data proving patient benefit existed, thus precluding specific comment. Additionally, prior comorbidity was insufficiently defined to determine its influence on outcome, treatment response, or patient preferences for diagnostic efforts. We recommend controlled clinical trials in patients with ICUAW that compare physical rehabilitation with usual care and further research in understanding risk and patient preferences. Conclusions: Research that identifies treatments that benefit patients with ICUAW is necessary to determine whether the benefits of diagnostic testing for ICUAW outweigh its burdens.

Objective: Treatment and prevention of hyperglycemia has been advocated for subjects with sepsis. Glucose variability, rather than the glucose level, has also been shown to be an important factor associated with in-hospital mortality, in general, critically ill patients. Our objective was to determine the association between glucose variability and hospital mortality in septic patients and the expression of glucose variability that best reflects this risk. Design: Retrospective, single-center cohort study. Setting: Academic, tertiary care hospital. Patients: Adult subjects hospitalized for >1 day, with a diagnosis of sepsis were included. Interventions: None. Measurements: Glucose variability was calculated for all subjects as the average and standard deviation of glucose, the mean amplitude of glycemic excursions, and the glycemic lability index. Hospital mortality was the primary outcome variable. Logistic regression was used to determine the odds of hospital death in relation to measures of glucose variability after adjustment for important covariates. Main results: Of the methods used to measure glucose variability, the glycemic lability index had the best discrimination for mortality (area under the curve = 0.67, p < 0.001). After adjustment for confounders, including the number of organ failures and the occurrence of hypoglycemia, there was a significant interaction between glycemic lability index and average glucose level, and the odds of hospital mortality. Higher glycemic lability index was not independently associated with mortality among subjects with average glucose levels above the median for the cohort. However, subjects with increased glycemic lability index, but lower average glucose values had almost five-fold increased odds of hospital mortality (odds ratio = 4.73, 95% confidence interval = 2.6-8.7) compared with those with lower glycemic lability index. Conclusions: Glucose variability is independently associated with hospital mortality in septic patients. Strategies to reduce glucose variability should be studied to determine whether they improve the outcomes of septic patients.

Objective: To determine the association between body mass index (BMI) and hospital mortality for critically ill adults. Design: Retrospective cohort study. Setting: One-hundred six intensive care units (ICUs) in 84 hospitals. Patients: Mechanically ventilated adults (n = 1,488) with acute lung injury (ALI) included in the Project IMPACT database between December 1995 and September 2001. Interventions: None. Measurements and Main Results: Over half of the cohort had a BMI above the normal range. Unadjusted analyses showed that BMI was higher among subjects who survived to hospital discharge vs. those who did not (p < .0001). ICU and hospital mortality rates were lower in higher BMI categories. After risk-adjustment, BMI was independently associated with hospital mortality (p < .0001) when modeled as a continuous variable. The adjusted odds were highest at the lowest BMIs and then declined to a minimum between 35 and 40 kg/m². Odds increased after the nadir but remained below those seen at low BMIs. With use of a categorical designation, BMI was also independently associated with hospital mortality (p = .0055). The adjusted odds were highest for the underweight BMI group (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05–3.60) relative to the normal BMI group. As in the analysis using the continuous BMI variable, the odds of hospital mortality were decreased for the groups with higher BMIs (overweight adjusted OR, 0.72; 95% CI, 0.51–1.02; obese adjusted OR, 0.67; 95% CI, 0.46–0.97; severely obese adjusted OR, 0.78; 95% CI, 0.44–1.38). Differences in the use of heparin prophylaxis mediated some of the protective effect of severe obesity. Conclusions: BMI was associated with risk-adjusted hospital mortality among mechanically ventilated adults with ALI. Lower BMIs were associated with higher odds of death, whereas overweight and obese BMIs were associated with lower odds.

To determine the association between alcohol dependence (alcoholism not in remission and/or alcohol withdrawal) and sepsis, septic shock, and hospital mortality among intensive care unit (ICU) patients. Retrospective cohort study. Two ICUs in an urban hospital. Patients included 11,651 adult admissions to Denver Health Medical Center from January 1, 1999, to December 31, 2004, with ≥1 ICU day. None. Of first admissions appearing in the data set (n = 9,981), 1,222 (12.2%) had a diagnosis consistent with alcohol dependence. These patients had higher rates of sepsis (12.9% vs. 7.6%, p < .001), organ failure (67.3% vs. 45.8%, p < .001), septic shock (3.6% vs. 2.1%, p = .001), and hospital mortality (9.4% vs. 7.5%, p = .022) on unadjusted analyses. Patients with alcohol dependence also had fewer hospital-free days. After adjustment for factors with known association with sepsis, alcohol dependence was associated with sepsis. This association was modified if the patient received (adjusted odds ratio, 0.92; 95% confidence interval, 0.65–1.31) or did not receive (adjusted odds ratio, 1.91; 95% confidence interval, 1.49–2.44) red cell transfusions. A general predisposition to infections mediated some, but not all, of this association. Results were similar when repeat admissions were included in the analysis. Alcohol dependence was also associated with septic shock and hospital mortality in multivariable analyses. Among those with liver disease and sepsis, alcohol dependence was associated with more than two-fold increased risk-adjusted odds of hospital mortality (adjusted odds ration, 2.31; 95% confidence interval, 1.26–4.24). Similarly, sepsis and liver disease carried higher odds of death for alcohol-dependent patients than for those without alcohol dependence. Alcohol dependence is independently associated with sepsis, septic shock, and hospital mortality among ICU patients. The underlying mechanisms of this association require exploration, as an increased rate of infections mediated some, but not all, of this association.