Naeem A. Ali

Acquired Weakness, Handgrip Strength, and Mortality in Critically Ill Patients

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).

Glucose variability and mortality in patients with sepsis

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.

A framework for diagnosing and classifying intensive care unit-acquired weakness

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.

Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury

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.

Alcohol dependence is independently associated with sepsis, septic shock, and hospital mortality among adult intensive care unit patients.

Objective: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. Design:Retrospective cohort study. Setting:Two ICUs in an urban hospital. Patients:Patients included 11,651 adult admissions to Denver Health Medical Center from January 1, 1999, to December 31, 2004, with ≥1 ICU day. Interventions:None. Measurements and Main Results: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. Conclusions: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.

Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality

Hyperglycemia is often observed in medically ill patients. Previous studies have shown that patients with hyperglycemia during induction therapy for acute lymphoblastic leukemia develop more infections and have shorter disease‐free survival. The authors hypothesized that hyperglycemia may be associated with adverse outcomes in patients with acute myeloid leukemia (AML) and sought to determine whether this association exists in this population.

Psychiatric Diagnoses and Psychoactive Medication Use Among Nonsurgical Critically Ill Patients Receiving Mechanical Ventilation

IMPORTANCE The relationship between critical illness and psychiatric illness is unclear. OBJECTIVE To assess psychiatric diagnoses and medication prescriptions before and after critical illness. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study in Denmark of critically ill patients in 2006-2008 with follow-up through 2009, and 2 matched comparison cohorts from hospitalized patients and from the general population. EXPOSURES Critical illness defined as intensive care unit admission with mechanical ventilation. MAIN OUTCOMES AND MEASURES Adjusted prevalence ratios (PRs) of psychiatrist-diagnosed psychiatric illnesses and prescriptions for psychoactive medications in the 5 years before critical illness. For patients with no psychiatric history, quarterly cumulative incidence (risk) and adjusted hazard ratios (HRs) for diagnoses and medications in the following year, using Cox regression. RESULTS Among 24,179 critically ill patients, 6.2% had 1 or more psychiatric diagnoses in the prior 5 years vs 5.4% for hospitalized patients (adjusted PR, 1.31; 95% CI, 1.22-1.42; P<.001) and 2.4% for the general population (adjusted PR, 2.57; 95% CI, 2.41-2.73; P<.001). Five-year preadmission psychoactive prescription rates were similar to hospitalized patients: 48.7% vs 48.8% (adjusted PR, 0.97; 95% CI, 0.95-0.99; P<.001) but were higher than the general population (33.2%; adjusted PR, 1.40; 95% CI, 1.38-1.42; P<.001). Among the 9912 critical illness survivors with no psychiatric history, the absolute risk of new psychiatric diagnoses was low but higher than hospitalized patients: 0.5% vs 0.2% over the first 3 months (adjusted HR, 3.42; 95% CI, 1.96-5.99; P <.001), and the general population cohort (0.02%; adjusted HR, 21.77; 95% CI, 9.23-51.36; P<.001). Risk of new psychoactive medication prescriptions was also increased in the first 3 months: 12.7% vs 5.0% for the hospital cohort (adjusted HR, 2.45; 95% CI, 2.19-2.74; P<.001) and 0.7% for the general population (adjusted HR, 21.09; 95% CI, 17.92-24.82; P<.001). These differences had largely resolved by 9 to 12 months after discharge. CONCLUSIONS AND RELEVANCE Prior psychiatric diagnoses are more common in critically ill patients than in hospital and general population cohorts. Among survivors of critical illness, new psychiatric diagnoses and psychoactive medication use is increased in the months after discharge. Our data suggest both a possible role of psychiatric disease in predisposing patients to critical illness and an increased but transient risk of new psychiatric diagnoses and treatment after critical illness.

Continuity of care in intensive care units: a cluster-randomized trial of intensivist staffing.

RATIONALE Little is known about the consequences of intensivists’ work schedules, or intensivist continuity of care. OBJECTIVES To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work–home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.

The association between body mass index, processes of care, and outcomes from mechanical ventilation: a prospective cohort study.

Objective: To determine the association between excess weight and processes of care and outcomes for critically ill adults. Design: Prospective cohort study. Setting: Three medical intensive care units at two hospitals. Patients: Five hundred eighty mechanically ventilated adult patients admitted between February 1, 2006 and January 31, 2008. Interventions: None. Measurements and Main Results: After adjusting weight based on the recorded fluid balance before enrollment, 21.9% of subjects were categorized into different body mass index categories than without this adjustment. We used a competing risk analysis with events of interest considered death during hospitalization and successful liberation from mechanical ventilation. We found no statistically significant difference between body mass index categories (<25 kg/m2 vs. 25 to <30 kg/m2 vs. ≥30 kg/m2) in the competing risks analyses when the results were unadjusted or adjusted for severity of illness and comorbidities. When the analyses were adjusted for the use of continuous infusions of opioids and/or sedatives and ventilator parameters (tidal volume per ideal body weight, positive end-expiratory pressure, and airway pressure), subjects with an overweight fluid-balance–adjusted body mass index had significantly lower hazard ratios for dying while hospitalized (adjusted hazard ratio 0.68 [95% confidence interval 0.47–0.99], p = .044), and those with an obese fluid-adjusted body mass index had significantly higher hazard ratios for successful extubation (adjusted hazard ratio 1.53 [95% confidence interval 1.14–2.06], p = .005). An analysis of longer-term mortality found lower adjusted hazard ratios for subjects with overweight (adjusted hazard ratio 0.74 [95% confidence interval 0.56–0.96]) and obese (adjusted hazard ratio 0.74 [95% confidence interval 0.59–0.94]) fluid-balance–adjusted body mass indices. Conclusions: Processes of provided care may affect the observed association between excess weight and outcomes for critically ill adults and should be considered when making inferences about observed results. It is unknown if disparities in processes of care are due to clinically justified reasons for variation, bias against heavier patients, or other reasons.

Results from the national sepsis practice survey: predictions about mortality and morbidity and recommendations for limitation of care orders

IntroductionCritically ill patients and families rely upon physicians to provide estimates of prognosis and recommendations for care. Little is known about patient and clinician factors which influence these predictions. The association between these predictions and recommendations for continued aggressive care is also understudied.MethodsWe administered a mail-based survey with simulated clinical vignettes to a random sample of the Critical Care Assembly of the American Thoracic Society. Vignettes represented a patient with septic shock with multi-organ failure with identical APACHE II scores and sepsis-associated organ failures. Vignettes varied by age (50 or 70 years old), body mass index (BMI) (normal or obese) and co-morbidities (none or recently diagnosed stage IIA lung cancer). All subjects received the vignettes with the highest and lowest mortality predictions from pilot testing and two additional, randomly selected vignettes. Respondents estimated outcomes and selected care for each hypothetical patient.ResultsDespite identical severity of illness, the range of estimates for hospital mortality (5th to 95th percentile range, 17% to 78%) and for problems with self-care (5th to 95th percentile range, 2% to 74%) was wide. Similar variation was observed when clinical factors (age, BMI, and co-morbidities) were identical. Estimates of hospital mortality and problems with self-care among survivors were significantly higher in vignettes with obese BMIs (4.3% and 5.3% higher, respectively), older age (8.2% and 11.6% higher, respectively), and cancer diagnosis (5.9% and 6.9% higher, respectively). Higher estimates of mortality (adjusted odds ratio 1.29 per 10% increase in predicted mortality), perceived problems with self-care (adjusted odds ratio 1.26 per 10% increase in predicted problems with self-care), and early-stage lung cancer (adjusted odds ratio 5.82) were independently associated with recommendations to limit care.ConclusionsThe studied clinical factors were consistently associated with poorer outcome predictions but did not explain the variation in prognoses offered by experienced physicians. These observations raise concern that provided information and the resulting decisions about continued aggressive care may be influenced by individual physician perception. To provide more reliable and accurate estimates of outcomes, tools are needed which incorporate patient characteristics and preferences with physician predictions and practices.