Pulmonary rehab, thiamine for sepsis, and more

Recent summaries from ACP Hospitalist Weekly.

Pulmonary rehabilitation within 90 days of discharge for COPD linked to lower mortality

Initiating pulmonary rehabilitation within 90 days of discharge may improve one-year survival in older patients with chronic obstructive pulmonary disease (COPD), a retrospective cohort study found.

Researchers used claims data from Medicare fee-for-service beneficiaries hospitalized for COPD in 2014 at 4,446 U.S. hospitals, with follow-up through Dec. 31, 2015. The primary outcome was all-cause mortality at one year. The researchers modeled time from discharge to death using Cox regression with time-varying exposure to pulmonary rehabilitation, adjusting for mortality and for unbalanced characteristics and propensity to initiate pulmonary rehabilitation. In additional analyses, they evaluated the associations between mortality and timing of pulmonary rehabilitation and number of sessions completed. Results were published by JAMA on May 12.

Image by Getty Images
Image by Getty Images

Of 197,376 patients (mean age, 76.9 years; 58.6% women), 2,721 (1.5%) initiated pulmonary rehabilitation within 90 days of discharge and completed a median of nine sessions (interquartile range, 4 to 14) during that time. Overall, 38,302 (19.4%) patients died within one year of discharge, including 198 (7.3%) patients who initiated pulmonary rehabilitation within 90 days and 38,104 (19.6%) patients who started after 90 days or not at all. Initiation within 90 days was associated with lower risk of death over one year (absolute risk difference, −6.7% [95% CI, −7.9% to −5.6%]; hazard ratio [HR], 0.63 [95% CI, 0.57 to 0.69]; P<0.001) compared to initiation after 90 days or none at all. Early pulmonary rehabilitation initiation was associated with lower mortality across start dates, ranging from 30 days or fewer (absolute risk difference, −4.6% [95% CI, −5.9% to −3.2%]; HR, 0.74 [95% CI, 0.67 to 0.82]; P<0.001) to 61 to 90 days after discharge (absolute risk difference, −11.1% [95% CI, −13.2% to −8.4%]; HR, 0.40 [95% CI, 0.30 to 0.54]; P<0.001). For 31 to 60 days, the absolute risk difference was −10.6% (95% CI, −12.4% to −8.4%), and the HR was 0.43 (95% CI, 0.34 to 0.54) (P<0.001). In the first 90 days, every three additional sessions (a suggested weekly dose) was associated with lower risk of death (HR, 0.91 [95% CI, 0.85 to 0.98]; P=0.01).

Among other limitations, treatment assignment was not random, and information about the individual components of pulmonary rehabilitation (e.g., education, exercise training, nutrition counseling, smoking cessation) were unavailable in the claims data, the study authors noted. “These findings support current guideline recommendations for pulmonary rehabilitation after hospitalization for COPD, although the potential for residual confounding exists and further research is needed,” they concluded.

Despite the benefits and recommendations for its use, pulmonary rehabilitation is underutilized for many reasons, including a dearth of referrals from health care professionals, an accompanying editorial noted. “In the US, there are no health care system-driven incentives for physicians to refer patients to pulmonary rehabilitation, no relevant required national care quality metrics, and financial reimbursement of clinicians does not depend on whether their patients undertake pulmonary rehabilitation,” the editorialists wrote.

The study findings should encourage health systems to increase funding for and use of pulmonary rehabilitation services, as well as encourage CMS and other payers to require referrals of suitable patients as part of national care quality metrics, they added. “It is time that one of the most effective treatments for patients with COPD and other chronic respiratory diseases be used routinely and proactively,” they wrote.

Thiamine not associated with improved mortality in septic shock

Patients who receive thiamine soon after admission for septic shock do not appear to have improved survival at 28 days, according to a recent study.

Researchers in Japan performed a retrospective observational cohort study at over 1,000 acute care hospitals to determine whether thiamine affected mortality in patients with septic shock who required norepinephrine within two days of admission. Data from July 2010 to March 2017 were analyzed. Patients were included in the thiamine group if they received at least 100 mg of thiamine within two days of admission. The primary outcome was 28-day mortality. Study results were published May 11 by Critical Care Medicine and appeared in the August issue.

Overall, 68,571 patients were eligible for the study. Of these, 18,780 received thiamine within two days of admission and 49,791 did not. Among those receiving thiamine, 10,143 (54.0%) received 100 mg/d and 7,679 (40.9%) received 200 mg/d. Twenty-eight day mortality rates were 19.2% in the thiamine group and 17.8% in the no-thiamine group. The researchers adjusted for confounders by inverse probability of treatment weighting and found no significant differences between the thiamine and no-thiamine groups (risk difference, 0.2%; 95% CI, −0.5% to 0.9%), between the 100-mg thiamine group and the no-thiamine group (risk difference, 0.6%; 95% CI, −0.3% to 1.4%), or between the 200-mg thiamine group and the no-thiamine group (risk difference, −0.3%; 95% CI, −1.3% to 0.8%).

The researchers noted that their study was observational, that data on serum thiamine levels were not included, and that differences in norepinephrine doses could not be assessed. They concluded that their study indicated no benefit of early thiamine administration among patients with septic shock who required norepinephrine. However, they wrote, “Further studies are warranted to evaluate the efficacy of thiamine administration to patients with septic shock, especially using doses higher than those used in our cohort.”

Readmissions for heart failure within 90 days linked to long-term mortality risk

Patients readmitted to the hospital within 90 days of their index admission for heart failure may be at higher risk for long-term mortality, a recent study found.

Researchers in Japan analyzed registry data on patients who were hospitalized with heart failure to examine the incidence, distribution, predictors, and prognostic impact of early versus mid-range readmission. Early readmission was defined as 0 to 30 days, and mid-range readmission was defined as 31 to 90 days. Patients were admitted to three university hospitals and three tertiary referral hospitals in the metropolitan Tokyo area between 2006 and 2017 and were followed after discharge for a median of 2.0 years. The primary outcomes of the study were all-cause death and heart failure readmission. Results were published May 7 by the Journal of the American Heart Association and appeared in the May 18 issue.

Data from 3,592 consecutive patients hospitalized with heart failure and subsequently discharged in stable condition were included in the study. A total of 39.6% were women, and the mean age was 73.9 years. Overall, 397 patients (11.1%) were readmitted for heart failure within 90 days of the index admission. Of those, 171 (43.1%) had early readmissions and 226 (56.9%) had mid-range readmissions. During follow-up, 122 (30.7%) of the patients who were readmitted within 90 days died versus 461 (14.4%) of those who were not readmitted.

In multivariate analysis, previous heart failure admission, older age, lower systolic blood pressure, lower hemoglobin level, lower left ventricular ejection fraction, and nonuse of renin-angiotensin system (RAS) inhibitors were independent determinants of 90-day readmission. Independent determinants of 30-day readmission were similar: previous heart failure admission, older age, lower left ventricular ejection fraction, nonuse of RAS inhibitors, and nonuse of mineralocorticoid receptor antagonists. After adjustment, heart failure readmission any time within 90 days after the index admission was an independent predictor of subsequent all-cause death (hazard ratio, 2.36; P<0.001), but risk did not differ by readmission timing.

The authors noted among other factors that their study was retrospective and used registry data and that the results may not be generalizable outside of Japan. They concluded that approximately 60% of 90-day readmissions for heart failure in their study occurred after 30 days and that patients readmitted within a 90-day timeframe were at higher risk for long-term mortality regardless of proximity to the index admission. “Despite [its] limitations, this study highlights the continuous [heart failure] readmission beyond 30 days and its poor prognosis, which underlines the universal characteristics of patients readmitted with [heart failure] and challenges the current excessive focus on 30-day readmission bringing unintended consequence,” they wrote.

Early RRT did not affect survival in critically ill patients with severe acute kidney injury

Mortality does not significantly differ according to when renal replacement therapy (RRT) is initiated in critically ill patients with severe acute kidney injury (AKI) when severe complications are not present, a systematic review and meta-analysis found.

Researchers identified 10 studies with a total of 2,143 patients that compared a strategy of early (usually 2 to 8 h after randomization) versus delayed RRT initiation (from 25 to 57 h after randomization) in critically ill patients with severe AKI (defined as Kidney Disease: Improving Global Outcomes [KDIGO] AKI stage 2 or 3 or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). Individual patient data were available for nine studies with 1,879 patients with severe AKI.

The included trials randomly allocated patients to either early RRT (n=933) or delayed RRT (n=946). The meta-analysis was restricted to trials involving patients treated in the past 10 years to reflect only those exposed to contemporary care. The primary outcome of the analysis was all-cause mortality at day 28 after randomization. Results were published online on April 23 by The Lancet.

Of 929 patients allocated to the delayed RRT group who had available data, 390 (42%) never received RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 [44%] of 837 patients) and the early RRT group (355 [43%] of 827 patients; risk ratio, 1.01 [95% CI, 0.91 to 1.13]; P=0.80), corresponding to an overall risk difference of 0.01 (95% CI, −0.04 to 0.06). There was no heterogeneity across studies, and most studies had a low risk of bias.

Among other limitations of the analysis, the included trials had different definitions for what constituted early and delayed RRT initiation strategies, the study authors noted. They added that while previous observational studies and meta-analyses of them suggested a benefit from early RRT, such studies were likely to be biased because they generally only included patients who actually received RRT without considering those with severe AKI who recovered kidney function without receiving RRT.

“The deliberate delay of RRT initiation under close patient supervision, and the initiation only when a clinical indication emerges, appears to be an acceptable approach, with the potential for resource savings,” they concluded.