Daniel J. Pallin, MD, MPH and Rory Spiegel, MD
A new 1-hour sepsis care bundle was ill conceived and may have unintended negative consequences.
In April 2018, the Surviving Sepsis Campaign (SSC) — an initiative sponsored by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine — issued guidelines that promote adherence to an “Hour-1 Bundle” for patients with suspected sepsis (Intensive Care Med 2018; 44:925). The bundle consists of five interventions to be initiated within 1 hour of the “time of triage in the emergency department or, if referred from another care location, from the earliest chart annotation consistent with all elements of sepsis (formerly severe sepsis) or septic shock ascertained through chart review.” The interventions are as follows:
Measure the lactate level; remeasure if >2 mmol/L.
- Obtain blood cultures before giving antibiotics.
- Administer antibiotics.
- Give 30 mg/kg crystalloid for hypotension or lactate ≥4 mmol/L.
- Give vasopressors if patient remains hypotensive despite fluid resuscitation.
The new guidelines have provoked controversy within the critical care and emergency medicine communities, and dismay over foreseeable unintended consequences has led to a counter-campaign. Detractors highlight the low quality of evidence supporting the bundle, the risks of overtesting and overtreating patients with low probability of sepsis, and the diversion of attention away from more evidence-based time-sensitive tasks.
Before we discuss these tradeoffs, a brief digression on the SSC’s history is in order. The SSC was established in 2002 and funded primarily by the drug company Eli Lilly. Lilly manufactured Xigris (recombinant activated protein C), an expensive medication that showed initial promise as a therapy for sepsis; it was FDA-approved in 2001 based on a single trial. According to one analysis of Lilly’s involvement in SSC, the company hoped to promote widespread use of its drug through guidelines elaborated by representatives of critical care organizations (N Engl J Med 2006; 355:1640). Xigris failed in subsequent trials and was removed from the market, but SSC survives. It has published several iterations of sepsis guidelines since 2003; this latest “Hour-1 Bundle” reduces the time window for implementing the prescribed interventions from 3 hours to 1 hour. Prior SSC recommendations were adopted as core measures by the National Quality Forum and the Centers for Medicare and Medicaid Services. As a result, physicians are penalized for failing to follow SSC guidelines. We worry that the same chain of events could unfold again.
Our concerns are fourfold. First, the quality of evidence for bundle elements ranges from low to moderate — as the bundle creators themselves acknowledge. Moreover, the general idea that a protocol (or “bundle”) should be used for sepsis at all is not well supported by evidence. On the contrary, high-quality evidence suggests that protocolized care for sepsis increases utilization of resources without benefiting patients (Intensive Care Med 2015; 41:1549).
Second, based on the parameters defining the 1-hour window (quoted in the first paragraph, above), we infer that compliance with the 1-hour standard would be applied retrospectively to patients ultimately diagnosed with sepsis. Retrospectively, the diagnosis is simple — when a patient has positive blood cultures and has progressed to hemodynamic collapse. But prospectively, at time of presentation, the diagnosis is far more elusive. Any regulatory mandate should use the time of recognition that sepsis is present as time zero. And, the evidence supporting a 1-hour deadline is not strong — it is based on inference from observational studies rather than direct evidence from trials (PLoS One 2015; 10:e0125827). A guideline that could be enforced with penalties for nonadherence should be based on the highest-quality evidence.
Third, we believe that widespread adherence to the bundle would harm some targeted patients. SSC does not consider the realities of caring for a mixed group of patients with noninfectious conditions, sepsis mimics, occult sepsis, and overt sepsis. The only way to achieve compliance within 1 hour is to target any patient who may end up having sepsis ascertained eventually through chart review. But blood cultures are time-consuming and have higher false-positive rates when drawn hastily in emergency settings. The dangers of overuse of broad-spectrum antibiotics are well known. And some targeted patients, such as those with congestive heart failure, may be harmed by large volumes of intravenous crystalloid (Ann Intern Med 2018; 168:558).
Finally, a 1-hour mandate would unjustly divert attention from other patients, particularly in busy emergency departments. Evidence supporting time-sensitive management of other conditions (e.g., myocardial infarction and stroke) is much stronger than the evidence supporting the new sepsis bundle. And many other patients — for example, those in extreme pain or those exsanguinating from trauma — also have time-sensitive needs.
Nobody would argue against aggressive and timely resuscitation of patients with overt sepsis. But this ill-founded guideline will subject many other patients to needlessly aggressive treatment, while drawing attention away from patients who need care immediately but don’t have a “campaign” to champion their cause. The “Hour-1 Bundle” should be rescinded and should not be adopted as a standard by third-party payors or other authorities.