Current Sepsis Mandates Are Overly Prescriptive, and Some Aspects May Be Harmful

There is no debate that sepsis is a major public health problem that merits the vigorous attention of the medical and public health community. We strongly support efforts to increase sepsis awareness and to operationalize best practices in all hospitals. We are concerned, however, that some aspects of the Centers for Medicare and Medicaid Services’(CMS) Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) mandatory reporting requirement and similar state-based mandates may paradoxically harm some patients by pressuring clinicians to provide aggressive, rapid, rigid, and reflexive care that is not suitable for all patients. The complexity and subjectivity of sepsis diagnosis make forced, fixed treatment rules dangerous and data collection onerous yet unreliable. We believe patients will be better served by allowing clinicians more discretion to determine which patients need sepsis care, requiring a narrower set of more evidence-based interventions, and incentivizing objective measurement strategies so that hospitals and policy makers can reliably assess the impact of their efforts. SEP-1 and most state-based mandates are modeled upon Surviving Sepsis Campaign guidelines (1). Clinicians are required to check lactate levels, draw blood cultures, administer broad-spectrum antibiotics for all patients, and infuse greater than or equal to 30 cc/kg of crystalloid fluids for patients that are hypotensive or have lactate levels greater than or equal to 4 mmol/L, all within 3 hours of time zero. Clinicians must also start vasopressors for patients with persistent hypotension, reassess volume status, and recheck lactate if the initial level was elevated, all within 6 hours of time zero. Time zero is defined as the first moment when the patient has documentation of suspected sepsis, or suspected infection plus greater than or equal to 2 systemic inflammatory response syndrome criteria and evidence of organ dysfunction within a 6-hour window. This bundle includes a mix of measures that are well supported by data and others that are not. Timely antibiotics have repeatedly been associated with better outcomes in critically ill patients with serious infections. Retrospective analyses of almost 50,000 patients treated for sepsis in New York State and 35,000 patients treated for sepsis in Northern California, for example, reported strong associations between time-to-antibiotics and in-hospital mortality (2, 3). A Bayesian hierarchical analysis of 37 studies of early goal-directed therapy found that the only aspects of goal-directed therapy associated with lower mortality were the timing and appropriateness of antibiotics (4). The data on lactate and volume resuscitation, however, are more equivocal (5). Lactate levels and lactate clearance rates correlate well with outcomes, but an elevated lactate level is not specific for sepsis, and there are very little data indicating that checking lactate levels (particularly serial levels) improves outcomes (6–9). Of greater concern, large volume infusions may be harmful to patients who are hypervolemic or euvolemic at presentation, as well as to patients with cardiomyopathy, renal dysfunction, limited pulmonary reserve, or malnutrition. Notably, the New York State analysis found no association between timeto-completion of the initial 30 cc/kg fluid bolus and mortality in patients with hypotension or lactate greater than or equal to 4 mmol/L (2). More concerningly, a growing body of literature associates larger volume resuscitation and positive daily fluid balances with higher mortality rates (10–14). Even the data on time to antibiotics, however, are more nuanced than SEP-1 allows (15). Timely antibiotics appear to matter most for patients with septic shock. The association between time-to-antibiotics and mortality in New York State and Northern California was clearest only in the subset of patients who required vasopressors (2, 3). A randomized trial of prehospital antibiotics versus antibiotics in the emergency department in a population of patients without shock found no difference in mortality rates despite a 90-minute difference in time-to-antibiotics (16). Over and above the strengths and limitations of each SEP-1 component, it is unclear whether the bundle as a whole leads 1 Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA. 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. Dr. Klompas’ institution received funding from Centers for Disease Control and Prevention and the Massachusetts Department of Public Health. Dr. Rhee’s institution received funding from Agency for Healthcare Research and Quality (AHRQ) (K08HS025008), and he received support for article research from AHRQ. For information regarding this article, E-mail: mklompas@bwh.harvard.edu Current Sepsis Mandates Are Overly Prescriptive, and Some Aspects May Be Harmful