NIH Funds SCCM Discovery Study on the Use of Sepsis Bundles in the Emergency Department

In funding a five-year prospective multicenter study to determine the safest and most effective approach to sepsis intervention, the National Heart, Lung, and Blood Institute (NHLBI) is recognizing the significant accomplishments of the Surviving Sepsis Campaign (SSC) and the Society of Critical Care Medicine (SCCM) to improve outcomes in patients with sepsis.

More than 1.7 million Americans develop sepsis every year, and 270,000 die from it. It is the most expensive condition to treat, costing $23.6 billion a year.¹ Thanks to a $3.275 million grant from the NHLBI, the Assessment of Implementation of Methods in Sepsis and Respiratory Failure (AIMS) study will attempt to determine whether the SSC’s Hour-1 Bundle or 3-Hour Bundle is most effective when implemented in emergency departments.

Implemented on diagnosis of sepsis or septic shock, each bundle comprises the same steps: measuring the lactate level, obtaining blood cultures before administering antibiotics, administering broad-spectrum antibiotics, beginning rapid administration of crystalloids for hypotension or lactate level of 4 mmol/L or greater, and applying vasopressors for hypotension during or after fluid resuscitation.

The steps of the 3-Hour Bundle should be completed within three hours. The Hour-1 Bundle differs from the 3-Hour Bundle in that the steps should be started within the first hour, rather than completed within a certain amount of time, a challenge in busy emergency departments. The bundles are evidence-based and were developed from the SSC clinical practice guidelines. They have evolved over time with new science. With each iteration of the guidelines, the SSC leadership evaluates the bundles to determine whether they should be updated. The most recent guideline update stimulated a time change that will be tested by the AIMS study.

The study will be conducted at 18 centers, including community and academic hospitals, and will ultimately include about 10,000 patients who will be randomized to receive either the Hour-1 or the 3-Hour Bundle. SCCM will serve as the data and clinical coordinating center via Discovery, the Critical Care Research Network.

“We all appreciate that, especially in septic shock, the faster you do things, the better,” said Mitchell Levy, MD, MCCM, principal Investigator and chief of the Division of Pulmonary, Critical Care and Sleep Medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, USA. “The question is: Is it feasible and realistic to start all of these things in one hour?”

Some clinicians have expressed concern about the Hour-1 Bundle. For instance, they question the rationale for administering antibiotics to every patient with suspected sepsis and administering fluids to patients who may have congestive heart failure (CHF) or end-stage renal disease (ESRD). Dr. Levy notes that the literature demonstrates that the Hour-1 Bundle is safe and beneficial even for patients with CHF or ESRD,² but AIMS will be the first rigorous randomized trial to address the issue and will help determine the best approach.

Although the science points toward the benefit of starting these interventions within the first hour, the Hour-1 and 3-Hour Bundles have never been compared head to head, Dr. Levy notes. The goal is to either validate the Centers for Medicaid and Medicare’s mandate of implementing the 3-Hour Bundle or determine that the Hour-1 Bundle is better.

In addition to SCCM support, AIMS also has the support of the American College of Emergency Physicians (ACEP) since about 80% of patients with sepsis and septic shock admitted to the intensive care unit (ICU) first presented to the emergency department.³

The primary outcome will be hospital mortality. Secondary outcomes will include respiratory failure, the need for mechanical ventilation, hospital length of stay, and discharge status (e.g., to home, rehabilitation, or a skilled nursing facility). Researchers also will look at which bundle is most appropriate for various phenotypes.⁴

The NIH funding is for a T3 translational research grant awarded to Rhode Island Hospital, which seeks to ensure that evidence-based preventive interventions and treatments are delivered effectively. Staff in both the Hour-1 and 3-Hour Bundle arms will be trained in techniques for enhancing implementation of either bundle. Both bundles are highly nurse-driven since nurses perform the bulk of the work in sepsis care.

“Through the years, we haven’t moved the needle very far to improve outcomes, and the promise of this well-designed study is to provide conclusive evidence of the best approach,” said Brian Delmonaco, MD, FACEP, medical director of pulmonology and critical care medicine at Good Samaritan Regional Medical Center in Corvallis, Oregon, USA, a participating site lead physician research investigator. “This study permits the sites to implement the protocol within their own local practices and features implementation science, including collaboration, surveys, education, and training to share best practices,” he said.

Although the research will be conducted in emergency departments, the findings are important for the ICU. “The treatment sepsis patients receive in the emergency department is key to their survival,” said Dr. Levy. “There is a close partnership between the emergency department and critical care, and we’re hopeful that the study will increase compliance with the sepsis bundles in addition to shedding light on the best approach to effective sepsis care.”
 

References

1. Buchman TG, Simpson SQ, Sciarretta KL, et al. Sepsis among Medicare beneficiaries: the burdens of sepsis, 2012-2018. Crit Care Med. 2020 Mar;48(3):276-288. doi: 10.1097/CCM.0000000000004224.
2. Liu VX, Fielding-Singh V, Greene JD, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017 Oct 1;196(7):856-863. doi: 10.1164/rccm.201609-1848OC.
3. Yealy DM, Mohr NM, Shapiro NI, Venkatesh A, Jones AE, Self WH. Early care of adults with suspected sepsis in the emergency department and out-of-hospital environment: a consensus-based task force report. Ann Emerg Med. 2021 Jul;78(1):1-19. doi: 10.1016/j.annemergmed.2021.02.006. Erratum in: [No authors listed]. Corrigendum. Ann Emerg Med. 2021 Sep;78(3):464. doi: 10.1016/j.annemergmed.2021.07.117.
4. Seymour C, Kennedy J, Wang S, et al. Derivation, validation and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003-2017. doi:10.1001/jama.2019.5791