Comorbid Septic Shock, HFrEF Linked to Lack of Guideline-Recommended Treatment

There was less of a chance of patients with heart failure with reduced ejection fraction (HFrEF) in septic shock to receive guideline-directed intravenous (IV) fluids, according to a new study that evaluated potential relationships between 30-mL/kg IV fluid administration, in-hospital mortality, intensive care unit admission, rate of invasive mechanical ventilation, and vasoactive medication administration.

Findings were published recently in JAMA Network Open, and the study was conducted among 5278 patients with community-onset sepsis—of whom 884 had preexisting HFrEF—who were hospitalized at the University of Pittsburgh Medical Center between January 1, 2013, and December 31, 2015. Follow-up was conducted through July 1, 2016. Multivariable models adjusted for patient factors and sepsis severity. The median (QR) overall patient age was 70 (60-81) years, 82% were White, and 51% were male; the median Sequential Organ Failure Assessment score was 4 (3-5), and 43% met the criteria for septic shock.

“There is increasing concern about the downstream harms of fluid overload,” the study authors wrote. “A greater understanding of the epidemiology of preexisting HFrEF prior to sepsis and its association with outcomes is needed to balance the pros and cons of fluid resuscitation for these patients at high risk.”

There was a similar rate of in-hospital mortality seen in the patients with septic shock and HFrEF, as well as those with septic shock but no HFrEF: 12% and 13%, respectively (P = .83). However, the patients with both conditions were 48% less likely to receive guideline-directed IV fluid therapy compared with those in septic shock only: 25% vs 37% (P < .001).

Multivariate adjustment produced similar results. Patients with HFrEF were 37% less likely to receive the recommended 30-mL/kg IV fluid treatment (adjusted OR [aOR], 0.63; 95% CI, 0.69-1.24; P = .59) in the first 6 hours after sepsis onset. Thirty-five percent of all patients with septic shock received at least 30 mL/kg of IV fluids in the 6 hours of sepsis onset. Higher odds of receiving IV fluids within that 6-hour window were seen among patients who were female (men had a 29% less chance for an aOR of 0.71; 95% CI, 0.58-0.87; P = .001), had a lower Elixhauser Comorbidity Index (aOR, 0.91; 95% CI, 0.87-0.95; P < .001), were younger (aOR, 0.98; 95% CI, 0.98-0.99; P < .001), and had a higher presenting Sequential Organ Failure Assessment score (aOR, 1.09; 95% CI, 1.01-1.18; P = .03).

Risk-adjusted mortality, meanwhile, did not differ by much (aOR, 0.92; 95% CI, 0.69-1.24; P = .59) compared with that seen among patients who did not have HFrEF. Further, there was no correlation seen when considering IV fluid volume (aOR, 1.00; 95% CI, 0.98-1.03; P = .72). An overall 9% of patients died during hospitalization.

Additional patient data show that the patients with HFrEF and sepsis vs no HFrEF were typically male (64.1% vs 47.9%, respectively) and Black (20% vs 14.9%), and they had elevated median serum creatinine (1.7 [1.2-2.9] vs 1.4 [0.9-2.3] mg/dL).

Compared with patients with a normal ejection fraction, those with HFrEF were also shown to have more right ventricular dysfunction and severe mitral valve regurgitation at baseline: 18% vs 6% (P < .001) for both.

The study authors note that controversy surrounds the use of early IV fluid administration for septic shock. While some observational studies show a benefit, there are no data on benefit from randomized clinical trials on a specific fluid volume or resuscitation strategy, and “excess fluid administration can lead to adverse outcomes, including mechanical ventilation and mortality.”

However, they also stress that their findings are important because they “expand on existing knowledge by showing that patients with preexisting HFrEF are less likely to receive guideline-recommended IV fluids, despite showing no differences in markers of illness severity or completion rates of other guideline-recommended care.”

Reference

Powell RE, Kennedy JN, Senussi MH, Barbash IJ, Seymour CW. Association between preexisting heart failure with reduced ejection fraction and fluid administration among patients with sepsis. JAMA Netw Open. Published online October 7, 2022. doi:10.1001/jamanetworkopen.2022.35331