Pedro A. Mendez-Tellez

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Design Prospective cohort study. Setting 13 intensive care units at four hospitals in Baltimore, Maryland, USA. Participants 485 consecutive mechanically ventilated patients with acute lung injury. Main outcome measure Two year survival after onset of acute lung injury. Results 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Conclusions Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Trial registration Clinicaltrials.gov NCT00300248.

Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

Objective:Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. Design:A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Setting:Thirteen ICUs from four academic teaching hospitals. Patients:Two hundred twenty-two survivors of acute lung injury. Interventions:None. Measurements and Main Results:At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. Conclusions:Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

Timing of Low Tidal Volume Ventilation and Intensive Care Unit Mortality in Acute Respiratory Distress Syndrome. A Prospective Cohort Study

RATIONALE Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood. OBJECTIVES To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time. METHODS Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors. MEASUREMENTS AND MAIN RESULTS An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier. CONCLUSIONS Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).

Patient and intensive care unit organizational factors associated with low tidal volume ventilation in acute lung injury.

Background:Barriers to evidence-based practice are not well understood. Within the intensive care unit (ICU) setting, low tidal volume ventilation (LTVV) in patients with acute lung injury (ALI) significantly decreases mortality. However, LTVV has not achieved widespread adoption. Objectives:To evaluate patient demographic and clinical factors, and ICU organizational factors associated with its use. Design, Setting and Patients:Prospective cohort study of 250 patients with ALI in 9 ICUs at 3 teaching hospitals in Baltimore, MD. Measurements:Use of LTVV the day after ALI onset and association of patients’ demographic and clinical factors and ICU organizational factors with LTVV using a multivariable logistic regression model adjusted for clustering of patients within ICUs. Results:On the day after ALI onset, 46% and 81% of patients received a tidal volume ≤6.5 and ≤8.5 mL/kg predicted body weight (PBW), respectively, with no significant changes at 3 and 5 days after ALI. Using a strict definition of LTVV (≤6.5 mL/kg PBW), no patient demographic factors were independently associated with LTVV; however, two patient clinical and ICU organizational factors (odds ratio, 95% confidence interval) were independently associated: serum HCO3 level (<22: .3, .1–.9, and >26: .6, .1–3.5, versus 22–26) and use of a written protocol for LTVV (6.0, 1.3 – 27.2). In a sensitivity analysis using tidal volume ≤8.5 mL/kg PBW, use of a written protocol remained significantly associated with LTVV. Conclusions:Patient demographic factors were not associated with LTVV. Given its strong association with LTVV, ICUs should use a written protocol for ventilation of ALI patients to help translate this evidence-based therapy into practice.

Corticosteroids and Transition to Delirium in Patients With Acute Lung Injury

Objective:Delirium is common in mechanically ventilated patients in the ICU and associated with short- and long-term morbidity and mortality. The use of systemic corticosteroids is also common in the ICU. Outside the ICU setting, corticosteroids are a recognized risk factor for delirium, but their relationship with delirium in critically ill patients has not been fully evaluated. We hypothesized that systemic corticosteroid administration would be associated with a transition to delirium in mechanically ventilated patients with acute lung injury. Design:Prospective cohort study. Setting:Thirteen ICUs in four hospitals in Baltimore, MD. Patients:Five hundred twenty mechanically ventilated adult patients with acute lung injury. Interventions:None. Measurements and Main Results:Delirium evaluation was performed by trained research staff using the validated Confusion Assessment Method for the ICU screening tool. A total of 330 of the 520 patients (64%) had at least two consecutive ICU days of observation in which delirium was assessable (e.g., patient was noncomatose), with a total of 2,286 days of observation and a median (interquartile range) of 15 (9, 28) observation days per patient. These 330 patients had 99 transitions into delirium from a prior nondelirious, noncomatose state. The probability of transitioning into delirium on any given day was 14%. Using multivariable Markov models with robust variance estimates, the following factors (adjusted odds ratio; 95% CI) were independently associated with transition to delirium: older age (compared to < 40 years old, 40–60 yr [1.81; 1.26–2.62], and ≥ 60 yr [2.52; 1.65–3.87]) and administration of any systemic corticosteroid in the prior 24 hours (1.52; 1.05–2.21). Conclusions:After adjusting for other risk factors, systemic corticosteroid administration is significantly associated with transitioning to delirium from a nondelirious state. The risk of delirium should be considered when deciding about the use of systemic corticosteroids in critically ill patients with acute lung injury.

Are intensive care factors associated with depressive symptoms 6 months after acute lung injury

Objective:To evaluate intensive care–related factors as predictors of depressive symptoms 6 months after acute lung injury (ALI). Design:Prospective cohort study. Setting:Thirteen intensive care units (ICUs) in four hospitals in Baltimore, MD. Patients:Consecutive ALI survivors (n = 160; 71% from medical ICUs) screened for depressive symptoms at 6 months post-ALI. Interventions:None. Measurements and Main Results:We prospectively measured 12 features of critical illness and ICU care and used multivariable regression to evaluate associations with depressive symptoms as measured by the Hospital Anxiety and Depression Score. The prevalence of a positive screening for depression (score ≥8) at 6 months post-ALI was 26%. Depressive symptoms were significantly associated with surgical (vs. medical or trauma) ICU admission (relative risk [RR] 2.2, 95% confidence interval [CI] 1.1–4.2), maximum daily Sequential Organ Failure Assessment Score of >10 (RR 2.1, 95% CI 1.1–3.5), and mean daily ICU benzodiazepine dose of ≥75 mg of midazolam equivalent (RR 2.1, 95% CI 1.1–3.5). Conclusions:Depressive symptoms at 6 months post-ALI are common and potentially associated with ICU-related factors. Mechanisms by which critical illness and intensive care management associate with depressive symptoms merit further investigation.

Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury

Objective:To evaluate the association between intensive care unit blood glucose levels and depression after acute lung injury. Design:Prospective cohort study. Setting:Twelve intensive care units in four hospitals in Baltimore, MD. Patients:Consecutive acute lung injury survivors (n = 104) monitored during 1717 intensive care unit patient-days and screened for depression at 3 months after acute lung injury. Interventions:None. Measurements and Main Results:The prevalence of a positive screening test for depression (Hospital Anxiety and Depression subscale score ≥8) at follow-up was 28%. After adjustment for confounders, patients with a mean daily minimum intensive care unit glucose level <100 mg/dL had significant increases in mean depression score (2.1 points, 95% confidence interval 0.6–3.7) and in the likelihood of a positive depression screening test (relative risk 2.6, 95% confidence interval 1.2–4.2). Patients with documented hypoglycemia <60 mg/dL during their intensive care unit stay also had greater symptoms of depression (2.0 points, 95% confidence interval 0.5–3.5; relative risk 3.6, 95% confidence interval 1.8–5.1). Other factors independently associated with a positive depression screening test included body mass index >40 kg/m2 (relative risk 3.3, 95% confidence interval 1.2–4.2), baseline depression/anxiety (relative risk 3.9, 95% confidence interval 1.5–6.5), and mean daily intensive care unit benzodiazepine dose >100 mg of midazolam-equivalent agent (relative risk 2.4, 95% confidence interval 1.1–3.8). Conclusions:Hypoglycemia in the intensive care unit is associated with an increased risk of positive screening for depression during early recovery from acute lung injury. Baseline depressive symptoms, morbid obesity, and intensive care unit benzodiazepine dose were also associated with postacute lung injury depressive symptoms. These findings warrant increased glucose monitoring for intensive care unit patients at risk for hypoglycemia and further research on how patient and intensive care unit management factors may contribute to postintensive care unit depression.

Mortality in sepsis versus non-sepsis induced acute lung injury.

IntroductionSepsis-induced acute lung injury (ALI) has been reported to have a higher case fatality rate than other causes of ALI. However, differences in the severity of illness in septic vs. non-septic ALI patients might explain this finding.Methods520 patients enrolled in the Improving Care of ALI Patients Study (ICAP) were prospectively characterized as having sepsis or non sepsis-induced ALI. Biologically plausible risk factors for in-hospital death were considered in multiple logistic regression models to evaluate the independent association of sepsis vs. non-sepsis ALI risk factors with mortality.ResultsPatients with sepsis-induced ALI had greater illness severity and organ dysfunction (APACHE II and SOFA scores) at ALI diagnosis and higher crude in-hospital mortality rates compared with non-sepsis ALI patients. Patients with sepsis-induced ALI received similar tidal volumes, but higher levels of positive end expiratory pressure, and had a more positive net fluid balance in the first week after ALI diagnosis. In multivariable analysis, the following variables (odds ratio, 95% confidence interval) were significantly associated with hospital mortality: age (1.04, 1.02 to 1.05), admission to a medical intensive care unit (ICU) (2.76, 1.42 to 5.36), ICU length of stay prior to ALI diagnosis (1.15, 1.03 to 1.29), APACHE II (1.05, 1.02 to 1.08), SOFA at ALI diagnosis (1.17, 1.09 to 1.25), Lung Injury Score (2.33, 1.74 to 3.12) and net fluid balance in liters in the first week after ALI diagnosis (1.06, 1.03 to 1.09). Sepsis did not have a significant, independent association with mortality (1.02, 0.59 to 1.76).ConclusionsGreater severity of illness contributes to the higher case fatality rate observed in sepsis-induced ALI. Sepsis was not independently associated with mortality in our study.

Studying outcomes of intensive care unit survivors: measuring exposures and outcomes

BackgroundMeasurement of long-term outcomes and the patient and intensive care unit (ICU) factors predicting them present investigators with unique challenges. There is little systematic guidance for measuring these outcomes and exposures within the ICU setting. As a result measurement methods are often variable and noncomparable across studies.MethodsWe use examples from the critical care literature to describe measurement as it relates to three key elements of clinical studies: subjects, outcomes and exposures, and time. Using this framework we review the principles and challenges of measurement and make recommendations for long-term outcomes research in the field of critical care medicine.DiscussionRelevant challenges discussed include: (a) selection bias and heterogeneity of ICU research subjects, (b) appropriate selection and measurement of outcome and exposure variables, and (c) accounting for the effect of time in the exposure-outcome relationship, including measurement of baseline data and time-varying variables.ConclusionsAddressing these methodological challenges will advance research aimed at improving the long-term outcomes of ICU survivors.

Early Physical Rehabilitation in the ICU and Ventilator Liberation

Critically ill patients requiring mechanical ventilation are frequently subjected to long periods of physical inactivity, leading to skeletal muscle atrophy and muscle weakness. Disuse muscle atrophy is the result of complex mechanisms, including altered protein turnover and disturbed redox signaling. These ICU-acquired complications are associated with longer duration of mechanical ventilation, prolonged ICU and hospital stays, and poorer functional status at hospital discharge. Similarly, there is growing evidence that continuous mandatory ventilation alters diaphragmatic structure and contractile function and promotes oxidative injury, resulting in a rapid-onset diaphragmatic atrophy and weakness, which most likely delays discontinuing mechanical ventilation. Physical rehabilitation, when started at the onset of mechanical ventilation, has been associated with shorter periods of mechanical ventilation, decreased ICU and hospital stay, and improved physical function at hospital discharge. This review summarizes the impact of both physical inactivity and mechanical ventilation on skeletal and diaphragmatic muscles structure and function. Also reviewed is the growing evidence demonstrating the feasibility and safety of early physical rehabilitation interventions for mechanically ventilated patients, as well as their benefit on patient outcomes.