Prognostication in sepsis is limited by disease heterogeneity, and measures to risk-stratify patients in the proximal phases of care lack simplicity and accuracy. Hyperlactatemia and vasopressor dependence are easily identifiable risk factors for poor outcomes. This study compares incidence and hospital outcomes in sepsis based on initial serum lactate level and vasopressor use in the emergency department (ED). In a retrospective analysis of a prospectively identified dual-center ED registry, patients with sepsis were categorized by ED vasopressor use and initial serum lactate level. Vasopressor-dependent patients were categorized as dysoxic shock (lactate >4.0 mmol/L) and vasoplegic shock (≤4.0 mmol/L). Patients not requiring vasopressors were categorized as cryptic shock major (lactate >4.0 mmol/L), cryptic shock minor (>2.0 and ≤4.0 mmol/L), and sepsis without lactate elevation (≤2.0 mmol/L). Of 446 patients included, 4.9% (n = 22) presented in dysoxic shock, 11.7% (n = 52) in vasoplegic shock, 12.1% (n = 54) in cryptic shock major, 30.9% (n = 138) in cryptic shock minor, and 40.4% (n = 180) in sepsis without lactate elevation. Group mortality rates at 28 days were 50.0, 21.1, 18.5, 12.3, and 7.2%, respectively. After adjusting for potential confounders, odds ratios for mortality at 28 days were 15.1 for dysoxic shock, 3.6 for vasoplegic shock, 3.8 for cryptic shock major, and 1.9 for cryptic shock minor, when compared to sepsis without lactate elevation. Lactate elevation is associated with increased mortality in both vasopressor dependent and normotensive infected patients presenting to the emergency department (ED). Cryptic shock mortality (normotension + lactate >4 mmol/L) is equivalent to vasoplegic shock mortality (vasopressor requirement + lactate <4 mmol/L) in our population. The odds of normotensive, infected patients decompensating is three to fourfold higher with hyperlactemia. The proposed Sepsis-3 definitions exclude an entire group of high-risk ED patients. A simple classification in the ED by vasopressor requirement and initial lactate level may identify high-risk subgroups of sepsis. This study may inform prognostication and triage decisions in the proximal phases of care.
Sepsis Severe sepsis Septic shock Cryptic shock Lactate Vasopressor
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We wish to acknowledge Drs. Sundeep R. Bhat, Mellisa Wollan, and Martina T. Sanders-Spight for their assistance in the formulation and maintenance of the sepsis registry utilized in this study. We also acknowledge the generous funding support from the G.D. Hsiung Research Fellowship through the Yale School of Medicine.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of human and animal rights
Study approved by the Yale Investigational Review Committee.
Informed consent was not required for the study.
This study was funded by the G.D. Hsiung Research Fellowship, Yale School of Medicine, 2014.
Elixhauser A, Friedman B, Stranges E (2006) Septicemia in U.S. hospitals (2009) statistical brief #122, in healthcare cost and utilization project (HCUP) statistical briefs. Agency for Health Care Policy and Research (US), RockvilleGoogle Scholar
Ranzani OT, Monteiro MB, Ferreira EM, Santos SR, Machado FR, Noritomi DT (2013) Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock. Rev Bras Terapia Intensiv 25(4):270–278. doi:10.5935/0103-507x.20130047Google Scholar
Thomas-Rueddel DO, Poidinger B, Weiss M et al (2015) Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock. J Crit Care 30(2):439e1–e6. doi:10.1016/j.jcrc.2014.10.027
Arnold RC, Sherwin R, Shapiro NI et al (2013) Multicenter observational study of the development of progressive organ dysfunction and therapeutic interventions in normotensive sepsis patients in the emergency department. Acad Emerg Med 20(5):433–440. doi:10.1111/acem.12137CrossRefPubMedGoogle Scholar
Hernandez G, Bruhn A, Castro R et al (2012) Persistent sepsis-induced hypotension without hyperlactatemia: a distinct clinical and physiological profile within the spectrum of septic shock. Crit Care Res Pract. doi:10.1155/2012/536852PubMedPubMedCentralGoogle Scholar
Dugas AF, Mackenhauer J, Salciccioli JD, Cocchi MN, Gautam S, Donnino MW (2012) Prevalence and characteristics of nonlactate and lactate expressors in septic shock. J Crit Care 27(4):344–350. doi:10.1016/j.jcrc.2012.01.005
Donnino MW, Nguyen B, Jacobsen G, Tomlanovich M, Rivers EP (2003). Cryptic septic shock: a sub-analysis of early, goal-directed therapy. Chest 124(4 meeting abstracts):90S-bGoogle Scholar
Wira CR, Francis MW, Bhat S, Ehrman R, Conner D, Siegel M (2014) The shock index as a predictor of vasopressor use in emergency department patients with severe sepsis. Western J Emerg Med 15(1):60CrossRefGoogle Scholar