Association of Frailty and Cardiopulmonary Resuscitation Outcomes in Older U.S. Veterans.

Objectives: Determine the association between frailty and immediate survival of cardiopulmonary resuscitation (CPR) in older Veterans. Secondary outcomes: compare in-hospital mortality, duration of resuscitation efforts, hospital and intensive care unit (ICU) length of stay, neurologic outcomes, and discharge disposition between frail and non-frail Veterans. Methods: Retrospective cohort study including Veterans 50 years and older, who were "Full Code" and had in-hospital cardiac arrest between 7/1/2017 and 6/30/2020, at the Miami VAMC. Frailty Index for the VA (VA-FI) was used to determine frailty status. Immediate Survival was determined by return of spontaneous circulation (ROSC) and in-hospital mortality was determined by all-cause mortality. We compared outcomes between frail and non-frail Veterans using chi-square test. After adjusting for age, gender, race, and previous hospitalizations, we used multivariate binomial logistic regression with 95% confidence intervals to analyze the relationship between immediate survival and frailty, and in-hospital mortality and frailty. Results: 91% Veterans were non-Hispanic, 49% Caucasian, 96% male, mean age 70.7 ± 8.5 years, 73% frail and 27% non-frail. Seventy-six (65.5%) Veterans had ROSC, without difference by frailty status (P = .891). There was no difference based on frailty status of in-hospital mortality, discharge disposition, or neurologic outcomes. Frail and non-frail Veterans had resuscitation efforts lasting the same amount of time. Conclusions and Implications: CPR outcomes were not different depending on frailty status in our Veteran population. With these results, we cannot use frailty - as measured by the VA-FI - as a prognosticator of CPR outcomes in Veterans.

A comparison of microbiology and demographics among patients with healthcare-associated, hospital-acquired, and ventilator-associated pneumonia: a retrospective analysis of 1184 patients from a large, international study.

BACKGROUND: Acceptance of healthcare-associated pneumonia (HCAP) as an entity and the associated risk of infection by potentially multidrug-resistant (MDR) organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas and Acinetobacter have been debated. We therefore compared patients with HCAP, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) enrolled in a trial comparing linezolid with vancomycin for treatment of pneumonia. METHODS: The analysis included all patients who received study drug. HCAP was defined as pneumonia occurring < 48 hours into hospitalization and acquired in a long-term care, subacute, or intermediate health care facility; following recent hospitalization; or after chronic dialysis. RESULTS: Data from 1184 patients (HCAP = 199, HAP = 379, VAP = 606) were analyzed. Compared with HAP and VAP patients, those with HCAP were older, had slightly higher severity scores, and were more likely to have comorbidities. Pseudomonas aeruginosa was the most common gram-negative organism isolated in all pneumonia classes [HCAP, 22/199 (11.1%); HAP, 28/379 (7.4%); VAP, 57/606 (9.4%); p = 0.311]. Acinetobacter spp. were also found with similar frequencies across pneumonia groups. To address potential enrollment bias toward patients with MRSA pneumonia, we grouped patients by presence or absence of MRSA and found little difference in frequencies of Pseudomonas and Acinetobacter. CONCLUSIONS: In this population of pneumonia patients, the frequencies of MDR gram-negative pathogens were similar among patients with HCAP, HAP, or VAP. Our data support inclusion of HCAP within nosocomial pneumonia guidelines and the recommendation that empiric antibiotic regimens for HCAP should be similar to those for HAP and VAP.

Candidemia in the critically ill: initial therapy and outcome in mechanically ventilated patients.

BACKGROUND: Mortality among critically ill patients with candidemia is very high. We sought to determine whether the choice of initial antifungal therapy is associated with survival among these patients, using need for mechanical ventilatory support as a marker of critical illness. METHODS: Cohort analysis of outcomes among mechanically ventilated patients with candidemia from the 24 North American academic medical centers contributing to the Prospective Antifungal Therapy (PATH) Alliance registry. Patients were included if they received either fluconazole or an echinocandin as initial monotherapy. RESULTS: Of 5272 patients in the PATH registry at the time of data abstraction, 1014 were ventilated and concomitantly had candidemia, with 689 eligible for analysis. 28-day survival was higher among the 374 patients treated initially with fluconazole than among the 315 treated with an echinocandin (66% versus 51%, P < .001). Initial fluconazole therapy remained associated with improved survival after adjusting for non-treatment factors in the overall population (hazard ratio .75, 95% CI .59-.96), and also among patients with albicans infection (hazard ratio .62, 95% CI .44-.88). While not statistically significant, fluconazole appeared to be associated with higher mortality among patients infected with glabrata (HR 1.13, 95% CI .70-1.84). CONCLUSIONS: Among ventilated patients with candidemia, those receiving fluconazole as initial monotherapy were significantly more likely to survive than those treated with an echinocandin. This difference persisted after adjustment for non-treatment factors.

Risk of contrast induced nephropathy in the critically ill: a prospective, case matched study.

INTRODUCTION: Computerized tomography is frequently employed in the critically ill, often using intravenous radiocontrast material. Many of these patients have clinical features that are considered risk factors for contrast induced nephropathy, but are simultaneously at risk for renal injury from other factors related to their acute illnesses. The attributable risk for renal dysfunction from radiocontrast exposure has not been well quantified in this population. METHODS: A prospective matched cohort study was conducted of patients scanned with or without radiocontrast enhancement while receiving intensive care in a Veterans Affairs Medical Center. Patients were matched for pre-scan measured creatinine clearance, diabetes, mechanical ventilation, and vasopressor use. Measured clearance was followed for three days after scanning. Evolution of nephropathy, as determined by change in measured clearance, was compared within matched pairs. RESULTS: Fifty-three pairs of patients satisfied matching criteria. Unmatched characteristics were similar among the pairs, including serum creatinine variability during the week preceding scanning (67 ± 85% among contrast recipients, 63 ± 62% among others) and clinical risk factors for renal failure. In 29 pairs, pre-scan measured clearances were less than 60 mL/minute/1.73 m2. Following scanning, measured clearance declined by at least 33% in 14 contrast and 19 non-contrast patients (95% confidence interval for contrast associated difference in nephropathy rates -27% to 9%), while a 50% reduction in clearance persisted three days after scanning in three contrast and nine non-contrast patients (95% confidence interval for difference in rates -25% to 2%). CONCLUSIONS: Among established intensive care unit patients declines in glomerular filtration following contrast-enhanced scanning are common, but these changes are far more likely to be attributable to factors other than the contrast exposure itself. The upper bound for the incidence of contrast induced renal injury lasting even three days was 2% in the population studied.

Use of intensive care, mechanical ventilation, both, or neither by patients with acute lung injury.

OBJECTIVE: Reports of acute lung injury and acute respiratory distress syndrome have generally been restricted to mechanically ventilated intensive care unit patients, creating an incomplete picture of the epidemiologies of the syndromes. We sought to determine the incidence and outcomes of acute lung injury and acute respiratory distress syndromes throughout an entire hospital population. DESIGN: Retrospective cohort study. SETTING: A Department of Veterans Affairs medical center. PATIENTS: All patients satisfying criteria for acute lung injury or acute respiratory distress syndrome during a 2-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 11,465 acute medical and surgical admissions during the study period; 156 patients had acute lung injury or acute respiratory distress syndrome. Only 74 (47%) were invasively ventilated in an intensive care unit for acute lung injury. Another 15 (10%) patients were ventilated for other reasons, 41 (26%) were admitted to an intensive care unit at approximately the time of acute lung injury onset but were not invasively ventilated, and 26 (17%) were managed with neither invasive ventilation nor admission to an intensive care unit. Four-week mortality differed by group (p = .023), ranging from 22% among those managed in an intensive care unit without invasive ventilation to 50% among those ventilated for acute lung injury or acute respiratory distress syndrome. By 2 yrs, differences in survival between groups were no longer significant. Notably, only 53 (34%) patients would have been eligible for widely cited acute lung injury intervention trials. Ten patients had a second episode of acute lung injury during the study period, equating to a 16%-per-year risk of recurrence. CONCLUSIONS: Acute lung injury and acute respiratory distress syndrome studies restricted to patients mechanically ventilated in intensive care units substantially underestimate the incidence of the syndromes. Nonventilated patients and those cared for outside of intensive care units may still be at substantial risk for death. Further characterization of previously overlooked acute lung injury and acute respiratory distress syndrome patients may suggest new therapeutic opportunities.

Feasibility of shortening respiratory isolation with a single sputum nucleic acid amplification test.

RATIONALE: Serial smear analysis to guide respiratory isolation (RI) of patients with suspected tuberculosis (TB), the majority of whom will be found not to have TB, leads to expensive and unnecessary isolation, and may potentially result in decreased vigilance of subjects with respiratory compromise. OBJECTIVES: To compare the performance of a single first-sputum, Mycobacterium tuberculosis-specific nucleic acid amplification (NAA) test with three sputum smears for assessing the need for RI. METHODS: Prospective evaluation of 493 patients with suspected TB (74% HIV positive) admitted to RI in a major county hospital in the United States, who had at least three sputum smears and material available from the first sample for additional NAA testing. MEASUREMENTS AND MAIN RESULTS: Accuracy of the first sputum NAA result and serial smears for identifying patients with potentially infectious TB who truly require RI was determined. Forty-six patients (9.3%) had TB confirmed by culture. First-sputum NAA test detected all patients with TB who had a positive smear (n = 35), even when the first of the three specimens was smear negative. In addition, when compared with serial smears, the first-sputum NAA had a higher sensitivity (0.87; 95% confidence interval [CI], 0.74-0.95) and specificity (1.0) in the detection of subjects with positive M. tuberculosis cultures (smear sensitivity, 0.76; 95% CI, 0.61-0.87; and specificity, 0.96; 95% CI, 0.94-0.98). CONCLUSIONS: A single first-sputum NAA testing can rapidly and accurately identify the subset of patients with suspected TB who require RI according to serial sputum smears. Its potential use to shorten RI time does not preclude the need to obtain subsequent specimens for culture.

Influence of critical illness on physicians' prognoses for underlying disease: a randomized study using simulated cases.

OBJECTIVE: During critical illness, physicians often provide estimates of the severity of underlying disease to aid patients and families when formulating care directives. We sought to determine whether factors such as the superimposed acute illness, the prognoses of other patients cared for by the same physician, or the phrasing of inquiry influence these assessments of underlying disease. DESIGN, SETTING, AND SUBJECTS: Internal medicine attending and resident physicians participated in a computerized, Web-available survey that described two case vignettes, one with cardiomyopathy and the other with lung cancer as underlying diseases. Using random assignment, each respondent was presented one case as having septic shock, and the other as an uneventful clinic visit. Respondents were explicitly asked to ignore the context and to assess the severity of the underlying disease alone to predict survival time and quality of life. The order in which subjects encountered the cases and phrasing of the survival question also were varied through randomization. MEASUREMENTS AND MAIN RESULTS: Mortality predictions for the cardiomyopathy case at 5 yrs were sensitive to both context (predicted survival, 39% +/- 23% when presented as septic vs. 52% +/- 24% when presented as a clinic patient; p < .001) and to whether a lung cancer case was presented before it (39% +/- 23% when presented after lung cancer vs. 52% +/- 24% when presented before; p < .001). These effects were independent and led to mean predicted 5-yr survival probabilities ranging from 31% to 59%. Predicted 1-yr survival from lung cancer was sensitive to phrasing (p < .05) but not to context. Quality of life predictions were also sensitive to context and case order. CONCLUSIONS: Physician appraisal of underlying disease severity is potentially vulnerable to a number of biases that may be relevant in the critical care setting. These biases appear to vary with the nature of the underlying disease.

Increasing Non-tuberculous Mycobacteria Infections in Veterans With COPD and Association With Increased Risk of Mortality.

Background: There are limited data on the epidemiology of Non-tuberculous mycobacteria (NTM) infections among patients with COPD, particularly in the veteran population. This study examined the prevalence, incidence, and mortality of pulmonary NTM infections among veterans with COPD population in the United States. Methods: We analyzed nationwide data from Veterans Affairs Hospitals from 2001 to 2015. First, we determined the incidence and prevalence rates and geographic distribution of NTM infections among veterans with COPD and then we evaluated the association between NTM infections with mortality among veterans with COPD. Pulmonary NTM and COPD diagnosis were defined based on charting claims for each condition on ≥2 occasions and ≥30 days apart. COPD diagnoses had to precede diagnosis of NTM. Cox Proportional-Hazards Regression was performed to determine the dependency of survival time of COPD patients with NTM. Results: The incidence and prevalence rates of NTM rose over the study period, with a sharp rise in incidence after 2012. The areas with the highest NTM period prevalence were Puerto Rico (370), followed by Florida (351) and District of Columbia (309) in 100,000 COPD population. Mortality registered for those patients with COPD Patients and NTM infection was 1.43 times higher compared to those that were uninfected. Conclusions: NTM rates have been increasing in veterans with COPD since 2012. NTM infection is associated with increased risk of mortality. This highlights the importance of identifying preventable risk factors associated with NTM infections in subjects with COPD.

Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis.

PURPOSE: Critically ill patients, among whom acute kidney injury is common, are often considered particularly vulnerable to iodinated contrast medium nephrotoxicity. However, the attributable incidence remains uncertain given the paucity of observational studies including a control group. This study assessed acute kidney injury incidence attributable to iodinated contrast media in critically ill patients based on new data accounting for sample and effect size and including a control group. METHODS: Systematic review of studies measuring incidence of acute kidney injury in critically ill patients following contrast medium exposure compared to matched unexposed patients. Patient-level meta-analysis implementing a Bayesian nested mixed effects multiple logistic regression model. RESULTS: Ten studies were identified; only four took into account the baseline acute kidney injury risk, three by patient matching (560 patients). Objective meta-analysis of these three studies (vague and impartial a priori hypothesis concerning attributable acute kidney injury risk) did not find that iodinated contrast media increased the incidence of acute kidney injury (odds ratio 0.95, 95% highest posterior density interval 0.45-1.62). Bayesian analysis demonstrated that, to conclude in favor of a statistically significant incidence of acute kidney injury attributable to contrast media despite this observed lack of association, one's a priori belief would have to be very strongly biased, assigning to previous uncontrolled reports 3-12 times the weight of evidence strength provided by the matched studies including a control group. CONCLUSIONS: Meta-analysis of matched cohort studies of iodinated contrast medium exposure does not support a significant incidence of acute kidney injury attributable to iodinated contrast media in critically ill patients.

Relationship of baseline glucose homeostasis to hyperglycemia during medical critical illness.

STUDY OBJECTIVE: To elucidate the relationship of baseline glucose control and acute stimuli with hyperglycemia during medical critical illness. DESIGN: Prospective cohort study. SETTING: Medical ICU (MICU) of a university affiliated hospital. PATIENTS: Convenience sample of 100 medical patients meeting criteria for severity of illness and anticipated length of stay and not admitted to the hospital for diabetic ketoacidosis or a hyperglycemic hyperosmolar state. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized as having normal, abnormal, or unevaluable baseline glucose control based on history and glycosylated hemoglobin (HbA1c). Data collection included blood glucose measurements within 120 h of MICU admission, and dosing of norepinephrine, corticosteroids, propofol, and carbohydrates. Average blood glucose and times over glycemic thresholds were calculated using linear interpolation. Hyperglycemia (glucose > 110 mg/dL) was pervasive in all groups. Among the 51 patients with normal baseline glucose control, HbA1c was correlated with hyperglycemic time (p < 0.01, R(2) = 0.15). Multiple regression found HbA1c, age, corticosteroid dose, and carbohydrate administration independently associated with hyperglycemic time (p < 0.05 for each, total R(2) = 0.49) in these patients, while body mass index, APACHE (acute physiology and chronic health evaluation) II, norepinephrine dose, propofol dose, gender, and sepsis were not associated with time > 110 mg/dL. Among normal subjects, HbA1c was independently predictive of peak and average glucose, and the fraction of time glucose was > 150 mg/dL and > 200 mg/dL (p < 0.05 for each). Patients with abnormal baseline glucose control had significantly more hyperglycemia than patients with normal baseline control. CONCLUSIONS: Even in patients without evidence of abnormal glucose homeostasis at baseline, hyperglycemia is common during critical illness. Time exposure to hyperglycemia is correlated with acute stressors and baseline glucose regulation, as characterized by HbA1c. Patients with low HbA1c levels are less disposed to hyperglycemia during severe illness than patients with higher, but still normal, HbA1c.

Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study.

BACKGROUND: The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. METHODS: We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. FINDINGS: 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. INTERPRETATION: Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. FUNDING: Pfizer, US Medical.

Acute lung injury outside of the ICU: incidence in respiratory isolation on a general ward.

BACKGROUND: Epidemiologic investigations of acute lung injury (ALI) and ARDS have focused on mechanically ventilated patients in ICUs, and have reported high mortality rates. We sought to determine the incidence and lethality of these syndromes in the respiratory isolation areas of general wards, a non-ICU setting that often serves patients with acute lung processes. METHODS: We prospectively studied all patients who were admitted to respiratory isolation rooms on the general wards of a large tertiary care hospital over a 1-year period. Patients were classified as having ALI or ARDS if they met consensus definitions for the syndromes. Characteristics and outcomes were compared to those of other patients who had been admitted to a respiratory isolation room with infiltrating lung disease but lacking bilateral infiltrates, hypoxemia, or both. RESULTS: Of 715 patients admitted to respiratory isolation rooms on general wards, 474 (66%) had acute infiltrates. ALI criteria were met by 9% of patients (62 of 715 patients), with 2% of patients (15 of 715) satisfying the criteria for ARDS. Respiratory distress was present in 71% of ALI patients (44 of 62 patients) and 32% of patients (130 of 412 patients) with acute infiltrates who did not have ALI (p < 0.001). However, the 90-day survival rates (ALI patients, 88%; patients with acute infiltrates who did not have ALI, 90%) was similar between the two groups (p > 0.50). CONCLUSIONS: ALI and ARDS may be frequent among patients who are admitted to respiratory isolation beds outside of ICUs. Mortality rates are substantially lower than those typically reported from surveys of ventilated ICU patients with ALI and ARDS.

Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients.

OBJECTIVE: To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. DESIGN: A noninferiority analysis was used to compare rates of clinically significant upper gastrointestinal bleeding in a prospective, phase 3, double-blind trial with parallel omeprazole suspension and cimetidine treatment groups. SETTING: A total of 47 intensive care units in the United States. PATIENTS: A total of 359 critically ill patients who required mechanical ventilation for > or =48 hrs, had an Acute Physiology and Chronic Health Evaluation score of > or =11 at baseline, had an intact stomach with a nasogastric or orogastric tube in place, and had at least one additional risk factor for upper gastrointestinal bleeding. INTERVENTIONS: Patients were randomized to treatment with omeprazole suspension (two 40-mg doses on day 1, via orogastric or nasogastric tube, and 40 mg each day thereafter) or intravenous cimetidine (300-mg bolus and 50 mg/hr thereafter) for up to 14 days. Gastric aspirates were sampled for bleeding and pH. Medication doses were doubled for failure of pH control (two successive aspirates with pH < or = 4). MEASUREMENTS AND MAIN RESULTS: Clinically significant upper gastrointestinal bleeding (bright red blood not clearing after 5-10 mins of lavage or persistent Gastroccult-positive "coffee-grounds" material for 8 hrs on days 1-2 or for 2-4 hrs on days 3-14 and not clearing with > or =100 mL of lavage) was the primary end point of the trial. The rate of clinically significant bleeding in the per-protocol population was 4.5% with omeprazole suspension and 6.8% with cimetidine, meeting the criteria for the noninferiority of omeprazole suspension. Median gastric pH was > or =6 on all trial days with omeprazole suspension treatment and on 50% of days with cimetidine treatment (p < .001, all trial days). In the omeprazole suspension group, median gastric pH was >4 on each trial day in 95% of patients. CONCLUSIONS: Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding and more effective than intravenous cimetidine in maintaining gastric pH of >4 in critically ill patients.

An epidemiologic study of early renal replacement therapy after orthotopic liver transplantation.

The preoperative impairment of renal function is associated with the need for postoperative renal replacement therapy (RRT) in patients undergoing liver transplantation. The principal goal of this investigation was to identify other factors apparent before or during transplant that were independently associated with the need for RRT in the early posttransplant period. A total of 260 consecutive adult patients who received a primary liver transplant were studied. Twenty-eight patients required early RRT (RRT initiated within 1 wk of transplant); 23 for control of volume overload. Preoperative blood urea nitrogen (odds ratio [95% CI], 1.52 [1.15 to 2.01] per 10 mg/dl), serum creatinine (1.91 [1.06 to 3.44] per 1 mg/dl), and urine output (0.12 [0.03 to 0.44] L/d) were independently predictive of the need for early RRT and in combination formed a parsimonious model that discriminated well (area under the receiver operating characteristic curve, 0.877) and had excellent fit (P = 0.699 to reject model fit). No other potential predictors meaningfully improved predictions of which patients would require early RRT. Patients requiring early RRT consumed more healthcare resources than patients who did not require early RRT, spending more time in intensive care (15 +/- 13 d versus 7 +/- 11 d; P < 0.001) and in the hospital (34 +/- 27 d versus 19 +/- 20 d; P < 0.001). The need for early RRT was strongly associated with death before hospital discharge (29% mortality versus 4% mortality among all others; P < 0.001). The data demonstrate that dependency on RRT in the first week after orthotopic liver transplantation stems almost entirely from preoperative renal dysfunction.