Sodium excretion, postop antibiotics, and more

Summaries from ACP Hospitalist Weekly.

Urine sodium excretion associated with six-month mortality in hospitalized heart failure patients

Urine sodium excretion was strongly associated with mortality in hospitalized heart failure patients whereas the traditional metrics of urine output and weight change were not, a recent study found.

The post hoc analysis included 316 patients from the Renal Optimization Strategies Evaluation-Acute Heart Failure (ROSE-AHF) trial. All were hospitalized with acute decompensated heart failure, were treated with protocol-driven high-dose loop diuretic therapy, and had their 24-hour urine sodium excretion measured. Results were published in the May JACC: Heart Failure.

Image by Getty Images
Image by Getty Images

The patients' sodium excretion in the first 24 hours was highly variable (range, 0.12 to 19.8 g; median, 3.63 g; interquartile range, 1.85 to 6.02 g). It was not correlated with diuretic agent dose (P=0.27). A univariate model found that greater sodium excretion was associated with reduced six-month mortality (hazard ratio [HR], 0.80 per doubling of sodium excretion; 95% CI, 0.66 to 0.95; P=0.01), while gross urine output (P=0.43), net fluid balance (P=0.87), and weight change (P=0.11) were not. The study defined sodium excretion of less than 2 g per day as a poor natriuretic response, and this was associated with higher mortality, even in patients with a negative net fluid balance (HR, 2.02; 95% CI, 1.17 to 3.46; P=0.01).

The study shows that sodium excretion varies significantly within and across heart failure patients and that it is a “critical variable” in treating acute decompensations, the study authors said. However, they noted that 24-hour urine collection to measure sodium excretion may not be feasible in usual clinical practice. To resolve this problem, the study authors have developed and are currently validating a sodium prediction equation. “Much in the way that 24-h creatinine collections have largely been supplanted by [estimated glomerular filtration rate] derived from an equation and a spot serum creatinine value, we have developed a formula that can estimate the amount of sodium excretion from a dose of loop diuretic agent by using a spot urine sodium and creatinine level,” they said.

Limitations of the study include that the ROSE-AHF trial was not designed to study these questions and that it primarily comprised white men, all of whom had estimated glomerular filtration rates under 60 mL/min/1.73 m2. Thus, the results should be considered hypothesis generating, the study authors said.

According to an accompanying editorial comment, the study's results “support the collection of urine samples and measurement of urinary sodium excretion on a daily basis during an acute heart failure hospital admission to assess response to loop diuretics.” Ongoing research should provide more evidence of the benefits of urinary measurements, the editorialists said.

Antibiotic prophylaxis more than 24 hours after surgery increased harms without reducing infections

Longer durations of postoperative antimicrobial prophylaxis increased the incidence of acute kidney injury (AKI) and Clostridium difficile infection without reducing surgical-site infections (SSIs), a multicenter retrospective study found.

Participants were patients within the Veterans Affairs health care system who had cardiac, orthopedic total joint replacement, colorectal, and vascular procedures from Oct. 1, 2008, through Sept. 30, 2013. A trained nurse reviewer manually reviewed records for type and duration of surgical prophylaxis and for SSIs and other postoperative outcomes. Researchers compared type and duration of antimicrobial prophylaxis with 30-day SSI, seven-day incidence of AKI, and 90-day incidence of C. difficile infection. Duration of postoperative antimicrobial prophylaxis was categorized as less than 24 hours, 24 to less than 48 hours, 48 to less than 72 hours, and 72 hours or more. Results were published on April 24 by JAMA Surgery.

A total of 79,058 patients (mean age, 64.8 years; 96.3% men) were included. All procedures had SSI and C. difficile outcome data available, and 90.2% had AKI outcome data. After stratification by type of surgery and adjustments for various confounders (including age, sex, race, and diabetes), SSI was not associated with duration of prophylaxis. The adjusted odds of AKI increased with each additional day of prophylaxis. For cardiac procedures, adjusted odds ratios (aORs) were 1.03 (95% CI, 0.95 to 1.12) for 24 to less than 48 hours, 1.22 (95% CI, 1.08 to 1.39) for 48 to less than 72 hours, and 1.82 (95% CI, 1.54 to 2.16) for 72 hours or more. For noncardiac procedures, the corresponding aORs were 1.31 (95% CI, 1.21 to 1.42), 1.72 (95% CI, 1.47 to 2.01), and 1.79 (95% CI, 1.27 to 2.53), respectively. There was a similar duration-dependent association for risk of postoperative C. difficile infection (aORs, 1.08 [95% CI, 0.89 to 1.31] for 24 to <48 h, 2.43 [95% CI, 1.80 to 3.27] for 48 to <72 h, and 3.65 [95% CI, 2.40 to 5.53] for ≥72 h).

For both AKI and C. difficile infection, the unadjusted numbers needed to harm (NNHs) decreased as antibiotic duration increased. For AKI, the NNH decreased from 9 patients with 24 to 48 hours of therapy to 6 with 48 to less than 72 hours of therapy to 4 with 72 hours of therapy or more. For C. difficile, the NNHs were 2,000, 90, and 50, respectively. Receipt of vancomycin appeared to drive antimicrobial-associated AKI, with an aOR of 1.17 (95% CI, 1.10 to 1.25) for cardiac procedures and an aOR of 1.21 (95% CI, 1.13 to 1.30) for noncardiac procedures.

Limitations of the study include its retrospective, observational nature and the potential lack of generalizability to women and other health care settings, the study authors noted.

These findings support the existing literature, which suggests that repeated antibiotic dosing after wound closure may increase risk of adverse events, an accompanying editorial commentary said. The data merit the implementation of real-time audit and feedback for postoperative antibiotic usage, which “could reduce antibiotic-associated complications without affecting SSI rates,” although prospective trials and continued refinement of surgical prophylaxis guidelines are needed, the editorialists said.

Restrictive or individualized fluid resuscitation may work for severe sepsis, studies find

A restrictive fluid resuscitation strategy for severe sepsis and septic shock was associated with similar outcomes to usual care, a small study found.

The trial included 109 patients with severe sepsis and septic shock admitted from the ED to the ICU at two U.S. hospitals from November 2016 to February 2018. They were randomly assigned to either a restrictive IV fluid resuscitation strategy in which they received no more than 60 mL/kg of IV fluid (n=55) or usual care (n=54) for the first 72 hours of care. The restrictive group received significantly less resuscitative IV fluid than the usual care group (47.1 vs. 61.1 mL/kg; P=0.01). By 30 days, there were 12 deaths in each group (21.8% vs. 22.2%; odds ratio, 1.02[95% CI, 0.41 to 2.53]). The rates of new organ failure, hospital and ICU lengths of stay, and serious adverse events were also similar between groups. Results were published by Critical Care Medicine on April 12 and appeared in the July issue.

This pilot study was too small to prove superiority or noninferiority of the restrictive strategy, but it does suggest that after initial resuscitation of 30 mL/kg, restricting fluid “may be appropriate,” the authors said. They noted that the usual care group in this trial received substantially less fluid compared to patients in the original early goal-directed therapy trials or to patients treated in the studied ICUs before the study started. “In effect, this created two study arms that tested fluid minimization, one more limited than the other, and notably, neither group produced high rates of organ dysfunction or serious adverse events,” the authors said. The results “contribute to the current state of clinical equipoise surrounding the use of IV fluids in sepsis,” which future research, including the ongoing CLOVERS trial, should shed more light on, they said.

Another recent sepsis study found that lactate and base excess may be useful to guide fluid resuscitation in sepsis. The post-hoc analysis of 1,741 septic patients compared baseline levels of central venous oxygen saturation (SCVO2), lactate, and base excess (BE), including alactic BE, which the authors defined as the sum of lactate and standard BE. SCVO2 was under 70% in 35% of patients. Mortality, organ dysfunction, and lactate were highest in patients with the highest and lowest SCVO2 levels. Lactate was associated with mortality, but it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dL), which the study found could be identified by a negative alactic BE. Results were published by the American Journal of Respiratory and Critical Care Medicine on April 15 and appeared in the Sept. 1 issue.

“We suggest that patients might be first stratified on the basis of SCVO2 to understand the origin of lactate production, and then on the basis of the alactic BE to better understand organ (i.e., kidney) perfusion and volemia. Changes in this simple parameter over time may facilitate early restoration of appropriate fluid balance and/or prompt the use of renal replacement therapy,” the authors said.

Functional mobility was strongest predictor of readmissions after MI in elderly

Adding functional mobility to the factors generally used to predict readmission risk may improve individual risk assessment for older patients hospitalized with acute myocardial infarction (MI), a study found.

The prospective cohort study included 3,006 patients ages 75 years or older who were hospitalized with MI at 94 U.S. hospitals and underwent in-hospital assessment of functional impairments including cognition, vision, hearing, and mobility. The patients' mean age was 81.5 years, 44.4% were women, and 10.5% were nonwhite. Researchers derived a model to predict 30-day readmissions in 2,004 of the patients and validated it in the other 1,002. Results were published in the May Circulation: Cardiovascular Quality and Outcomes.

Within 30 days, 18.2% of the patients had been readmitted. Readmitted patients were older, had more comorbidities, and were more likely to have functional impairments, including activities of daily living disability (17.0% vs. 13.0%; P=0.013) and impaired functional mobility (72.5% vs. 53.6%; P<0.001). Functional mobility was measured using the Timed Up and Go (TUG) test. The final validated model included eight variables that predicted readmission: worse functional mobility, lower ejection fraction, chronic obstructive pulmonary disease, arrhythmia, acute kidney injury, lower first diastolic blood pressure, no use of a P2Y12 inhibitor, and lower general health status. Significant impairment in functional mobility (TUG >25 s) was the strongest predictor of readmission (odds ratio compared to TUG <15 s, 1.86; 95% CI, 1.32 to 2.61).

The resulting model was well calibrated with moderate discrimination, the study authors concluded. “The modest discrimination indicates that much of the variability in readmission risk among this population remains unexplained by patient-level factors,” they wrote. To the authors' knowledge, this risk model is the first specifically developed and validated for use at the patient level in older patients with MI. It is based on a diverse patient population and practical for clinical use, they said. However, the study was limited by a number of factors, including that only about a third of eligible patients were enrolled and outcomes other than 30-day readmissions were not measured, both the study authors and an accompanying editorial noted.

“Apart from these issues, there are some surprises with respect to some of the variables in the model, raising concern that chance or serendipity may be playing a role,” added the editorial. For example, no previous research has identified an association between low diastolic blood pressure and readmissions. Additional study is needed to confirm these findings, but the study “does underscore the critical importance of assessing function in this population, and, even more importantly, to initiate cardiac rehabilitation during hospitalization, to the extent feasible, and to continue a structured rehabilitation program after discharge,” the editorialist said.