C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Butler CC, Gillespie D, White P, et al. N Engl J Med. 2019 Jul 11;381(2):111-120. [CrossRef] [PubMed]

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce use of antibiotics in patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). The authors performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The authors conclude that CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.

Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial

Subirà C, Hernández G, Vázquez A. et al. JAMA. 2019;321(22):2175-2182. [CrossRef]

Daily spontaneous breathing trials (SBTs) are the best approach to determine whether patients are ready for disconnection from mechanical ventilation, but mode and duration of SBT remain controversial. The authors randomized patients to undergo a 2-hour T-piece SBT (n = 578) or a 30-minute SBT with 8-cm H2O pressure support ventilation (n = 557). Among 1153 patients who were randomized successful extubation occurred in 473 patients (82.3%) in the pressure support ventilation group and 428 patients (74.0%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13.0%; P = .001). Reintubation, median intensive care unit length of, and median hospital length of stay did not differ but hospital mortality was lower for pressure support (10.4% vs 14.9%, P = .02) as was 90-day mortality was (13.2% vs 17.3%, P = .04). The authors conclude that among patients receiving mechanical ventilation, a spontaneous breathing trial consisting of 30 minutes of pressure support ventilation, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for spontaneous breathing trials.

Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis

Seymour CW, Kennedy JN, Wang S, et al. JAMA. 2019 May 19. [CrossRef] [PubMed]

Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. The authors derived sepsis phenotypes from 20,189 total who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients), in a prospective cohort study of sepsis due to pneumonia. Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. The 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). This study shows that older sicker patients with sepsis are more likely to die. The authors conclude that further research is needed to determine the utility of these phenotypes in clinical care.  

Association of Unrecognized Obstructive Sleep Apnea with Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery

Chan MTV, Wang CY, Seet E, et al. JAMA. 2019 May 14;321(18):1788-98. [CrossRef] [PubMed]

Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. This prospective cohort study enrolled adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate or mild OSA (P > .05). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

CPAP Adherence May Slow 1-Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea

Richards KC, Gooneratne N, Dicicco B, et al. J Am Geriatr Soc. 2019 Mar;67(3):558-64. [CrossRef] [PubMed]

Obstructive sleep apnea (OSA) has been linked to an increased risk for Alzheimer's disease (AD), but little prospective evidence exists on the effects of OSA treatment in preclinical AD. The objective was to determine if continuous positive airway pressure (CPAP) treatment adherence, controlling for baseline differences, predicts cognitive and everyday function after 1 year in older adults with mild cognitive impairment (MCI) and to determine effect sizes for a larger trial. Older adults, aged 55 to 89 years, with an apnea-hypopnea index of 10 or higher participated: (1) MCI, OSA, and CPAP adherent (MCI +CPAP), n = 29; and (2) MCI, OSA, CPAP nonadherent (MCI -CPAP), n = 25. The primary cognitive outcome was memory (Hopkins Verbal Learning Test-Revised), and the secondary cognitive outcome was psychomotor/cognitive processing speed (Digit Symbol subtest from the Wechsler Adult Intelligence Scale Substitution Test). Secondary function and progression measures were the Everyday Cognition, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale, and Clinical Dementia Rating. Statistically significant improvements in psychomotor/cognitive processing speed in the MCI +CPAP group vs the MCI -CPAP group were observed at 1 year after adjustment for age, race, and marital status (parameter estimate = 1.68; standard error = 0.47; 95% confidence interval = 0.73-2.62), with a 6-month effect size (ES) of 0.46 and a 1-year ES of 1.25. There were small to moderate ESs for memory (ES 0.20, 6 mo), attention (ES 0.25, 1 y), daytime sleepiness (ES 0.33, 6 mo and ES 0.22, 1 y), and everyday function (ES 0.50, 6 mo) favoring the MCI +CPAP group vs the MCI -CPAP group. The authors conclude that after controlling for baseline differences, 1 year of CPAP adherence in MCI +OSA significantly improved cognition and may slow the trajectory of cognitive decline.