Brendan J. Clark

Pulmonary Vascular Dysfunction Is Associated with Poor Outcomes in Patients with Acute Lung Injury

RATIONALE Despite the recognition that acute lung injury (ALI) can elevate pulmonary artery (PA) pressure and right ventricular afterload, the impact of pulmonary vascular dysfunction on outcomes of these patients is not well defined. OBJECTIVES To investigate the impact of pulmonary vascular dysfunction in patients with acute lung injury. METHODS Secondary analysis of the Fluid and Catheter Treatment Trial. A total of 501 patients who received a PA catheter were evaluated for associations between increases in transpulmonary gradient (TPG) (PA mean pressure - PA occlusion pressure) or pulmonary vascular resistance index (PVRi) and 60-day mortality, ventilator-, intensive care unit (ICU)-, and cardiovascular-free days (days with mean arterial pressure ≥ 60 mm Hg off vasopressor support). MEASUREMENTS AND MAIN RESULTS We were able to measure the TPG in 475 (95%) and the PVRi in 470 (92%) patients. Patients with an elevated baseline TPG had an increased 60-day mortality (30 versus 19%; P = 0.02), and lower numbers of median ventilator- [25-75% quartiles] (15 [0-22] versus 19 [7-24]; P = 0.005), ICU- (14 [0-21] versus 18 [5-22]; P = 0.005), and cardiovascular-free days (23 [12-27] versus 25 [18-27]; P = 0.03). The median PVRi (305 [204-431] dyne s/cm⁵/m²) was elevated early in the course of ALI. PVRi was statistically higher in patients who died (326 [209-518] versus 299 [199-416]; P = 0.01). In individual multivariate models, TPG and PVRi remained independent risk factors for 60-day mortality and decrease in the number of ventilator-, ICU-, and cardiovascular-free days. CONCLUSIONS Pulmonary vascular dysfunction is common in ALI, and is independently associated with poor outcomes. Future trials targeting pulmonary vascular dysfunction may be indicated.

Postextubation dysphagia is persistent and associated with poor outcomes in survivors of critical illness

IntroductionDysphagia is common among survivors of critical illness who required mechanical ventilation during treatment. The risk factors associated with the development of postextubation dysphagia, and the effects of dysphagia on patient outcomes, have been relatively unexplored.MethodsWe conducted a retrospective, observational cohort study from 2008 to 2010 of all patients over 17 years of age admitted to a university hospital ICU who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech pathologist.ResultsA BSE was performed after mechanical ventilation in 25% (630 of 2,484) of all patients. After we excluded patients with stroke and/or neuromuscular disease, our study sample size was 446 patients. We found that dysphagia was present in 84% of patients (n = 374) and classified dysphagia as absent, mild, moderate or severe in 16% (n = 72), 44% (n = 195), 23% (n = 103) and 17% (n = 76), respectively. In univariate analyses, we found that statistically significant risk factors for severe dysphagia included long duration of mechanical ventilation and reintubation. In multivariate analysis, after adjusting for age, gender and severity of illness, we found that mechanical ventilation for more than seven days remained independently associated with moderate or severe dysphagia (adjusted odds ratio (AOR) = 2.84 [interquartile range (IQR) = 1.78 to 4.56]; P < 0.01). The presence of severe postextubation dysphagia was significantly associated with poor patient outcomes, including pneumonia, reintubation, in-hospital mortality, hospital length of stay, discharge status and surgical placement of feeding tubes. In multivariate analysis, we found that the presence of moderate or severe dysphagia was independently associated with the composite outcome of pneumonia, reintubation and death (AOR = 3.31 [IQR = 1.89 to 5.90]; P < 0.01).ConclusionsIn a large cohort of critically ill patients, long duration of mechanical ventilation was independently associated with postextubation dysphagia, and the development of postextubation dysphagia was independently associated with poor patient outcomes.

Post-extubation dysphagia is associated with longer hospitalization in survivors of critical illness with neurologic impairment

IntroductionCritically ill patients can develop acute respiratory failure requiring endotracheal intubation. Swallowing dysfunction after liberation from mechanical ventilation, also known as post-extubation dysphagia, is common and deleterious among patients without neurologic disease. However, the risk factors associated with the development of post-extubation dysphagia and its effect on hospital lengthofstay in critically ill patients with neurologic disorders remains relatively unexplored.MethodsWe conducted a retrospective, observational cohort study from 2008 to 2010 of patients with neurologic impairment who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech-language pathologist.ResultsA BSE was performed after mechanical ventilation in 25% (630/2,484) of all patients. In the 184 patients with neurologic impairment, post-extubation dysphagia was present in 93% (171/184), and was classified as mild, moderate, or severe in 34% (62/184), 26% (48/184), and 33% (61/184), respectively. In univariate analyses, statistically significant risk factors for moderate/severe dysphagia included longer durations of mechanical ventilation and the presence of a tracheostomy. In multivariate analysis, adjusting for age, tracheostomy, cerebrovascular disease, and severity of illness, mechanical ventilation for >7 days remained independently associated with moderate/severe dysphagia (adjusted odds ratio = 4.48 (95%confidence interval = 2.14 to 9.81), P<0.01). The presence of moderate/severe dysphagia was also significantly associated with prolonged hospital lengthofstay, discharge status, and surgical placement of feeding tubes. When adjusting for age, severity of illness, and tracheostomy, patients with moderate/severe dysphagia stayed in the hospital 4.32 days longer after their initial BSE than patients with none/mild dysphagia (95% confidence interval = 3.04 to 5.60 days, P <0.01).ConclusionIn a cohort of critically ill patients with neurologic impairment, longer duration of mechanical ventilation is independently associated with post-extubation dysphagia, and the development of post-extubation dysphagia is independently associated with a longer hospital length of stay after the initial BSE.

Diagnosis and treatment of post-extubation dysphagia: Results from a national survey

PURPOSE This study sought to determine the utilization of speech-language pathologist (SLPs) for the diagnosis and treatment of post-extubation dysphagia in survivors of mechanical ventilation. METHODS We designed, validated, and mailed a survey to 1,966 inpatient SLPs who routinely evaluate patients for post-extubation dysphagia. RESULTS Most SLP diagnostic evaluations (60%; 95% CI, 59%-62%) were performed using clinical techniques with uncertain accuracy. Instrumental diagnostic tests (such as fluoroscopy and endoscopy) are more likely to be available at university than community hospitals. After adjusting for hospital size and academic affiliation, instrumental test use varied significantly by geographical region. Treatments for post-extubation dysphagia usually involved dietary adjustment (76%; 95% CI, 73-79%) and postural changes/compensatory maneuvers (86%; 95% CI, 84-88%), rather than on interventions aimed to improve swallowing function (24%; 95% CI, 21-27%). CONCLUSIONS SLPs frequently evaluate acute respiratory failure survivors. However, diagnostic evaluations rely mainly upon bedside techniques with uncertain accuracy. The use of instrumental tests varies by geographic location and university affiliation. Current diagnostic practices and feeding decisions for critically ill patients should be viewed with caution until further studies determine the accuracy of bedside detection methods.

Secondary prevention in the intensive care unit: Does intensive care unit admission represent a teachable moment?

Objectives: Cigarette smoking and unhealthy alcohol use are common causes of preventable morbidity and mortality that frequently result in admission to an intensive care unit. Understanding how to identify and intervene in these conditions is important because critical illness may provide a “teachable moment.” Furthermore, the Joint Commission recently proposed screening and receipt of an intervention for tobacco use and unhealthy alcohol use as candidate performance measures for all hospitalized patients. Understanding the efficacy of these interventions may help drive evidence-based institution of programs, if deemed appropriate. Data Sources: A summary of the published medical literature on interventions for unhealthy alcohol use and smoking obtained through a PubMed search. Summary: Interventions focusing on behavioral counseling for cigarette smoking in hospitalized patients have been extensively studied. Several studies include or focus on critically ill patients. The evidence demonstrates that behavioral counseling leads to increased rates of smoking cessation but the effect depends on the intensity of the intervention. The identification of unhealthy alcohol use can lead to brief interventions. These interventions are particularly effective in trauma patients with unhealthy alcohol use. However, the current literature would not support routine delivery of brief interventions for unhealthy alcohol use in the medical intensive care unit population. Conclusions: Intensive care unit admission represents a “teachable moment” for smokers and some patients with unhealthy alcohol use. Future studies should assess the efficacy of brief interventions for unhealthy alcohol use in medical intensive care unit patients. In addition, identification of the timing and optimal individual to conduct the intervention will be necessary.

Alcohol screening scores and 90-day outcomes in patients with acute lung injury

Objectives:The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test that correspond to past-year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with acute lung injury. Design:Secondary analysis. Setting:The Acute Respiratory Distress Syndrome Network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in patients with acute lung injury. Subjects:Patients meeting consensus criteria for acute lung injury enrolled in one of three recent Acute Respiratory Distress Syndrome Network clinical trials. Interventions:None. Measurements and Main Results:Of 1,133 patients enrolled in one of three Acute Respiratory Distress Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders Identification Test score available for analysis. Alcohol misuse was common with 70 (7%) of patients having Alcohol Use Disorders Identification Test scores in zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between validated Alcohol Use Disorders Identification Test zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients having Alcohol Use Disorders Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio 1.70; 95% confidence interval 1.00, 2.87; p = 0.048). Conclusions:Severe but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in acute lung injury patients.

Healthcare Utilization in Medical Intensive Care Unit Survivors with Alcohol Withdrawal

BACKGROUND Rehospitalization is an important and costly outcome that occurs commonly in several diseases encountered in the medical intensive care unit (ICU). Although alcohol use disorders are present in 40% of ICU survivors and alcohol withdrawal is the most common alcohol-related reason for admission to an ICU, rates and predictors of rehospitalization have not been previously reported in this population. METHODS We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using 2 administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source. RESULTS Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (hazard ratio 2.23, 95% CI 1.57, 3.34, p < 0.001), anxiety disorder (hazard ratio 2.04, 95% CI 1.30, 3.32, p < 0.01), depression (hazard ratio 1.62, 95% CI 1.05, 2.40, p = 0.03), and Deyo comorbidity score ≥3 (hazard ratio 1.43, 95% CI 1.09, 1.89, p = 0.01) were significant predictors of time to death or first rehospitalization. Bipolar disorder was associated with time to first emergency department or urgent care clinic visit (hazard ratio 2.03, 95% CI 1.24, 3.62, p < 0.01) in the 656 patients who were alive and not rehospitalized within 1 year. CONCLUSIONS The presence of a psychiatric comorbidity is a significant predictor of multiple measures of unplanned healthcare utilization in medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal. This finding highlights the potential importance of targeting longitudinal multidisciplinary care to patients with a dual diagnosis.

Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use

BACKGROUND Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. METHODS We performed a cross-sectional observational study of current regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low-risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patients acute illness was assessed by calculating the Acute Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. RESULTS Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHE II score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). CONCLUSIONS Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers.

Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study

IntroductionWe sought to determine whether higher levels of the novel biomarker growth differentiation factor-15 (GDF-15) are associated with poor outcomes and the presence of pulmonary vascular dysfunction (PVD) in patients with acute respiratory distress syndrome (ARDS).MethodsWe conducted a retrospective cohort study in patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment (FACT) Trial. Patients enrolled in the FACT Trial who received a pulmonary artery catheter (PAC), had plasma available from the same study day and sufficient hemodynamic data to determine the presence of PVD were included. Logistic regression was used to determine the association between GDF-15 level and 60-day mortality.ResultsOf the 513 patients enrolled in the FACT Trial assigned to receive a PAC, 400 were included in this analysis. Mortality at 60 days was significantly higher in patients whose GDF-15 levels were in the third (28%) or fourth (49%) quartile when compared to patients with GDF-15 levels in the first quartile (12%) (P <0.001). Adjusting for severity of illness measured by APACHE III score, the odds of death for patients with GDF-15 levels in the fourth quartile when compared to the first quartile was 4.26 (95% CI 2.18, 10.92, P <0.001). When added to APACHE III alone for prediction of 60-day mortality, GDF-15 levels increased the area under the receiver operating characteristic curve from 0.72 to 0.77. At an optimal cutoff of 8,103 pg/mL, the sensitivity and specificity of GDF-15 for predicting 60-day mortality were 62% (95% CI 53%, 71%) and 76% (95% CI 71%, 81%), respectively. Levels of GDF-15 were not useful in identifying the presence of PVD, as defined by hemodynamic measurements obtained by a PAC.ConclusionsIn patients with ARDS, higher levels of GDF-15 are significantly associated with poor outcome but not PVD.

Smoking cessation and the risk of hospitalization for pneumonia

BACKGROUND Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. METHODS We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). RESULTS Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% CI 0.31-0.74), while former smokers had no difference in (adjusted HR 0.83, 95% CI 0.63-1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% CI 0.45-0.95). However, this lower risk was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41-0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. CONCLUSIONS Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD.