By Kathryn Radigan, MD, MSc

Attending Physician, Division of Pulmonary and Critical Care, Stroger Hospital of Cook County, Chicago

Dr. Radigan reports no financial relationships relevant to this field of study.

SYNOPSIS: When the Severe Sepsis and Septic Shock Early Management Bundle was used to identify patients with severe sepsis or patients in septic shock, delays in lactate measurements for patients with abnormal lactate levels were associated with delayed initiation of antibiotic therapy and increased mortality.

SOURCE: Han X, Edelson DP, Snyder A, et al. Implications of Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Early Management Bundle and initial lactate measurement on the management of sepsis. Chest 2018;154:302-308.

Sepsis remains the top cause of in-hospital death. Early recognition and timely treatment of sepsis through care bundles has become a priority. The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) in October 2015. SEP-1 pinpoints patients with “severe sepsis” by selecting patients who meet two of four systemic inflammatory response syndrome (SIRS) criteria, demonstrate a documented suspicion of infection within a six-hour period, and exhibit one new organ dysfunction. Compliance with the bundle is measured by obtaining blood cultures, initiating antibiotics, and checking serum lactate between six hours before and three hours after presentation with a repeat lactate six hours later if elevated on initial draw. To characterize those who were affected and to analyze the implications of SEP-1 on patient care and outcomes, Han et al conducted a retrospective trial including 5,762 adult patients admitted to the University of Chicago from November 2008 through January 2016. All patients met one of the International Classification of Diseases, Ninth Revision (ICD-9) codes specified by SEP-1. Time to lactate draw, along with antibiotic and IV fluid administration, were measured. Additionally, researchers assessed in-hospital mortality.

Lactates were checked within the appropriate period 32% of the time on the ward (n = 505), 55% in the ICU (n = 818), and 79% in the ED (n = 2,144). Mortality increased with higher initial lactate levels across all locations. If lactate measurement was delayed, these patients exhibited the highest in-hospital mortality (29%) and were associated with an increased time to antibiotic administration (median time, 3.9 vs. 2.0 hours). The odds of death increased with every additional hour delay in lactate measurement for patients with initial lactate > 2.0 mmol/L (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.0003-1.05; P = 0.04). Delays in initial lactate measurement that were found to be elevated were associated with delayed fluid administration, delayed antibiotics, and increased mortality.


Severe sepsis accounts for almost 10% of all deaths.1 Sepsis bundles have been implemented to decrease mortality. Despite the SEP-1 criteria, little is known regarding the consequences of delayed lactate measurement, especially in areas of the hospital outside the ED.

Interestingly, the Han et al study revealed that lactate measurement may make a significant difference for patients with sepsis and septic shock. This is not surprising, as lactate clearance has remained a fundamental goal in sepsis management. Patients with elevated values often receive more aggressive and timely resuscitation. Delayed lactate measurement not only affects length of stay (LOS), but more importantly it affects overall mortality.

Patients who underwent a lactate draw within the SEP-1 window experienced the shortest LOS (median, 11 days; interquartile range [IQR], 7-19 days; P < 0.01). LOS was longest for patients who never received a lactate measurement (median, 18 days; IQR, 11-32 days), followed by those patients who experienced a delay in lactate measurement (median, 15 days; IQR, 9-26 days). As for mortality, patients with delayed lactates demonstrated the highest in-hospital mortality (29%), followed by those with lactate samples drawn within the CMS window (27%) and those without a lactate sample (23%; P < 0.01).

Although the authors did not address it specifically, it is interesting to note that there was a significant decrease in mortality and longer LOS for patients who never underwent a lactate draw. As opposed to the patients who underwent a lactate draw early and those with delayed lactate, one may infer that the severity of illness for patients who never underwent a lactate draw was less. Since these patients experienced decreased mortality, they are not dying early and, therefore, are in the hospital longer. The longer LOS also may be related to the fact that most of these patients were identified on the wards. Many of the events could have occurred later in the hospital stay.

Although the importance of early and appropriate antibiotics is known, many often forget that every hour delay in antimicrobial administration is associated with a 7.6% average decrease in survival.2 Within this study, there was a significant increase in mortality for every hour of delay in initial lactate draw > 2.0 mmol/L, which was associated with a 2% increase in the odds of death in an adjusted analysis (OR, 1.02; 95% CI, 1.0003-1.05; P = 0.04). When these numbers were adjusted for time to antibiotics and IV fluids, the association no longer was significant (P = 0.51). There was a two-hour delay in receiving antibiotics and 1.3-hour delay for IV fluid bolus for those who received lactate measurement within the time frame. This, compared to 3.9 hours to antibiotics and 4.8 hours for IV fluid bolus for those who were measured later. Based on these data, the difference in mortality was associated with earlier interventions that included antibiotics, fluids, and source control.

Critically, clinicians need to give special attention to patients already admitted to the hospital. This study demonstrates that many patients develop sepsis on the wards. It is time to broaden our focus outside the ED. Although not addressed in this study, the identification of sepsis is paramount. Often, doctors and nurses on general medicine floors and in the ICU miss sepsis. Even though 60% of patients with severe sepsis underwent serum lactate measurements within the mandated period, timelines varied based on location of patient. For instance, 32% of patients met the standard SEP-1 timeline on the wards, compared with 55% in the ICU and 79% in the ED.

Regarding the patients who did not receive lactate within the mandated time frame, 14% received delayed lactates (between three and 24 hours after the time of first suspicion of sepsis). More than one-quarter had no lactate measurements at all. Since patients with initial lactate levels > 2.0 mmol/L were at an increased odds of death by 2% for each hour in lactate delay, it is important that recognition of sepsis and lactate measurements improve.

Systematic, timely lactate measurements in sepsis patients may be useful in prompting earlier, potentially life-saving interventions, including IV fluids and antibiotics. Clinicians also should focus on early resuscitation efforts that include lactate measurements in those populations in which there often is delay, especially those on the wards and ICU.

Despite the obvious benefits, researchers also were concerned that mandating lactate measurements for all sepsis patients may lead to many unwarranted lactate measurements and excessive resource use. More studies are needed to further improve patient outcomes.


  1. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-1310.
  2. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-1596.