Victor D. Dinglas

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.

Depressive Symptoms and Impaired Physical Function after Acute Lung Injury: a 2-Year Longitudinal Study

RATIONALEnSurvivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear.nnnOBJECTIVESnTo evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions.nnnMETHODSnThis prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (depressive symptoms) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (impaired physical function) in patients without baseline impairment.nnnMEASUREMENTS AND MAIN RESULTSnDuring 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms.nnnCONCLUSIONSnIncident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors long-term outcomes.

One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial

Objective To evaluate the effect of initial low energy permissive underfeeding (“trophic feeding”) versus full energy enteral feeding (“full feeding”) on physical function and secondary outcomes in patients with acute lung injury. Design Prospective longitudinal follow-up evaluation of the NHLBI ARDS Clinical Trials Network’s EDEN trial Setting 41hospitals in the United States. Participants 525 patients with acute lung injury. Interventions Randomised assignment to trophic or full feeding for up to six days; thereafter, all patients still receiving mechanical ventilation received full feeding. Measurements Blinded assessment of the age and sex adjusted physical function domain of the SF-36 instrument at 12 months after acute lung injury. Secondary outcome measures included survival; physical, psychological, and cognitive functioning; quality of life; and employment status at six and 12 months. Results After acute lung injury, patients had substantial physical, psychological, and cognitive impairments, reduced quality of life, and impaired return to work. Initial trophic versus full feeding did not affect mean SF-36 physical function at 12 months (55 (SD 33) v 55 (31), P=0.54), survival to 12 months (65% v 63%, P=0.63), or nearly all of the secondary outcomes. Conclusion In survivors of acute lung injury, there was no difference in physical function, survival, or multiple secondary outcomes at 6 and 12 month follow-up after initial trophic or full enteral feeding. Trial Registration NCT No 00719446

Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding EDEN Trial follow-up

RATIONALEnWe hypothesized that providing patients with acute lung injury two different protein/calorie nutritional strategies in the intensive care unit may affect longer-term physical and cognitive performance.nnnOBJECTIVESnTo assess physical and cognitive performance 6 and 12 months after acute lung injury, and to evaluate the effect of trophic versus full enteral feeding, provided for the first 6 days of mechanical ventilation, on 6-minute-walk distance, cognitive impairment, and secondary outcomes.nnnMETHODSnA prospective, longitudinal ancillary study of the ARDS Network EDEN trial evaluating 174 consecutive survivors from 5 of 12 centers. Blinded assessments of patients arm anthropometrics, strength, pulmonary function, 6-minute-walk distance, and cognitive status (executive function, language, memory, verbal reasoning/concept formation, and attention) were performed.nnnMEASUREMENTS AND MAIN RESULTSnAt 6 and 12 months, respectively, the mean (SD) percent predicted for 6-minute-walk distance was 64% (22%) and 66% (25%) (P = 0.011 for difference between assessments), and 36 and 25% of survivors had cognitive impairment (P = 0.001). Patients performed below predicted values for secondary physical tests with small improvement from 6 to 12 months. There was no significant effect of initial trophic versus full feeding for the first 6 days after randomization on survivors percent predicted for 6-minute-walk distance, cognitive impairment status, and all secondary outcomes.nnnCONCLUSIONSnEDEN trial survivors performed below predicted values for physical and cognitive performance at 6 and 12 months, with some improvement over time. Initial trophic versus full enteral feeding for the first 6 days after randomization did not affect physical and cognitive performance.

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

RATIONALEnReducing 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.nnnOBJECTIVESnTo evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.nnnMETHODSnMultivariable, 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.nnnMEASUREMENTS AND MAIN RESULTSnAn 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; Pu2009=u20090.008). 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; Pu2009=u20090.019). 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.nnnCONCLUSIONSnHigher 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).

Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study

RATIONALEnExisting studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size.nnnOBJECTIVESnTo evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization.nnnMETHODSnA prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status.nnnMEASUREMENTS AND MAIN RESULTSnAt 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes.nnnCONCLUSIONSnPatients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors physical outcomes.

Safety of physical therapy interventions in critically ill patients: A single-center prospective evaluation of 1110 intensive care unit admissions ☆

PURPOSEnCritical illness survivors commonly have impaired physical functioning. Physical therapy interventions delivered in the intensive care unit can reduce these impairments, but the safety of such interventions within routine clinical practice requires greater investigation.nnnMATERIALS AND METHODSnWe conducted a prospective observational study of routine physical therapy from July 2009 through December 2011 in the Johns Hopkins Hospital Medical Intensive Care Unit in Baltimore, MD. The incidence of 12 types of physiological abnormalities and potential safety events associated with physical therapy were monitored and evaluated for any additional treatment, cost, or length of stay.nnnRESULTSnOf 1787 admissions of at least 24 hours, 1110 (62%) participated in 5267 physical therapy sessions conducted by 10 different physical therapists on 4580 patient-days. A total of 34 (0.6%) sessions had a physiological abnormality or potential safety event, with the most common being arrhythmia (10 occurrences, 0.2%) and mean arterial pressure greater than 140 mm Hg (8 occurrences; 0.2%) and less than 55 mm Hg (5 occurrences; 0.1%). Only 4 occurrences (0.1%) required minimal additional treatment or cost, without additional length of stay.nnnCONCLUSIONSnIn this large, single-center study, routine care physical therapy interventions were safe for critically ill patients.

Reducing Deep Sedation and Delirium in Acute Lung Injury Patients: A Quality Improvement Project*

Objective:Deep sedation and delirium are common in the ICU. Mechanically ventilated patients with acute lung injury are at especially high risk for deep sedation, delirium, and associated long-term physical and neuropsychiatric impairments. We undertook an ICU-wide structured quality improvement project to decrease sedation and delirium. Design:Prospective quality improvement project in comparison with a retrospective acute lung injury control group. Setting:Sixteen-bed medical ICU in an academic teaching hospital with pre-existing use of goal-directed sedation with daily interruption of sedative infusions. Patients:Consecutive acute lung injury patients. Intervention:A “4Es” framework (engage, educate, execute, evaluate) was used as part of the quality improvement process. A new sedation protocol was created and implemented, which recommends a target Richmond Agitation Sedation Scale score of 0 (alert and calm) and requires failure of intermittent sedative dosing prior to starting continuous infusions. In addition, twice-daily delirium screening using the Confusion Assessment Method for the ICU was introduced into routine practice. Measurements and Main Results:Sedative use and delirium status in acute lung injury patients after implementation of the quality improvement project (n = 82) were compared with a historical control group (n = 120). During the quality improvement vs. control periods, use of narcotic and benzodiazepine infusions were substantially lower (median proportion of medical ICU days per patient: 33% vs. 74%, and 22% vs. 70%, respectively, both p < 0.001). Further, wakefulness increased (median Richmond Agitation Sedation Scale score per patient: −1.5 vs. −4.0, p < 0.001), and days awake and not delirious increased (median proportion of medical ICU days per patient: 19% vs. 0%, p < 0.001). Conclusion:Through a structured quality improvement process, use of sedative infusions can be substantially decreased and days awake without delirium significantly increased, even in severely ill, mechanically ventilated patients with acute lung injury.

Baseline quality of life before intensive care: A comparison of patient versus proxy responses

Objective:To compare acute lung injury patients self-reported, retrospective baseline quality of life before their intensive care hospitalization with population norms and retrospective proxy estimates. Design:Prospective cohort study using the Short Form 36 quality-of-life survey. Setting:Thirteen intensive care units at four teaching hospitals in Baltimore, Maryland. Patients:One hundred thirty-six acute lung injury survivors and their designated proxies. Interventions:Both patients and proxies were asked to estimate patient baseline quality of life before hospital admission using the Short Form 36 survey. Measurements and Main Results:Compared with population norms, quality-of-life scores were lower in acute lung injury patients across all eight domains, but the difference was significantly greater than the minimum clinically important difference in only two of eight domains (Physical Role and General Health). The mean paired difference between patient and proxy responses revealed no clinically important difference. However, &kgr; statistics demonstrated only fair to moderate agreement for all domains. Bland-Altman analysis revealed that, for all domains, proxies tended to overestimate quality of life when patient scores were low and underestimate the quality of life when patient scores were high. Conclusion:Retrospective assessment of quality of life before hospitalization revealed that acute lung injury patients scores were consistently lower than population norms, but the magnitude of this difference may not be clinically important. Proxy assessments had only fair to moderate agreement with patient assessments. Across all eight Short Form 36 quality-of-life domains, proxy responses represented an attenuation of patient quality-of-life estimates.

Depressive Symptoms After Critical Illness: A Systematic Review and Meta-analysis

Objectives: To synthesize data on prevalence, natural history, risk factors, and post-ICU interventions for depressive symptoms in ICU survivors. Data Sources: PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, and Cochrane Controlled Trials Registry (1970–2015). Study Selection: Studies measuring depression after hospital discharge using a validated instrument in more than 20 adults from non-specialty ICUs. Data Extraction: Duplicate independent review and data abstraction. Data Synthesis: The search identified 27,334 titles, with 42 eligible articles on 38 unique studies (n = 4,113). The Hospital Anxiety and Depression Scale-Depression subscale was used most commonly (58%). The pooled Hospital Anxiety and Depression Scale-Depression subscale prevalence (95% CI) of depressive symptoms at a threshold score greater than or equal to 8 was 29% (22–36%) at 2–3 months (12 studies; n = 1,078), 34% (24–43%) at 6 months (seven studies; n = 760), and 29% (23–34%) at 12–14 months (six studies; n = 1,041). The prevalence of suprathreshold depressive symptoms (compatible with Hospital Anxiety and Depression Scale-Depression subscale, ≥ 8) across all studies, using all instruments, was between 29% and 30% at all three time points. The pooled change in prevalence (95% CI) from 2–3 to 6 months (four studies; n = 387) was 5% (–1% to +12%), and from 6 to 12 months (three studies; n = 412) was 1% (–6% to +7%). Risk factors included pre-ICU psychologic morbidity and presence of in-ICU psychologic distress symptoms. We did not identify any post-ICU intervention with strong evidence of improvement in depressive symptoms. Conclusions: Clinically important depressive symptoms occurred in approximately one-third of ICU survivors and were persistent through 12-month follow-up. Greater research into treatment is needed for this common and persistent post-ICU morbidity.