ORIGINAL RESEARCH Lactate, bicarbonate and anion gap for evaluation of patients presenting with sepsis to the emergency department: A prospective cohort study Biswadev MITRA , 1,2,3 Cristina ROMAN , 1,4 Kate E CHARTERS, 1 Gerard O’REILLY , 1,2,3 Dashiell GANTNER 2,5 and Peter A CAMERON 1,2,3 1 Emergency and Trauma Centre, The Alfred Hospital, Melbourne, Victoria, Australia, 2 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia, 3 National Trauma Research Institute, The Alfred Hospital, Melbourne, Victoria, Australia, 4 Department of Pharmacy, Alfred Health, Melbourne, Victoria, Australia, and 5 Department of Intensive Care, The Alfred Hospital, Melbourne, Victoria, Australia Abstract Objective:A serum lactate level >2 mmol/L has been chosen as the preferred cut-off value for screening of patients with suspected sepsis. In patients with suspected sepsis pre- senting to the ED, we aimed to deter- mine the outcomes of patients with initial lactate levels ≤2 mmoL/L, but abnormal bicarbonate or anion gaps (AGs). Methods: This prospective cohort study enrolled patients from an adult tertiary referral hospital who pres- ented with suspected sepsis. The pre- dictive value of lactate, bicarbonate and the AG for intensive care unit (ICU) admission and death at hospi- tal discharge were evaluated using area under the receiver operating characteristic curves (AUROC). Results: There were 441 patients with suspected sepsis enrolled from February 2016 to June 2017. There were 96 (22.0%) patients who were admitted to the ICU and at hospital discharge, 42 (9.6%) patients had died. There was no statistically sig- nificant difference between the AUROCs of lactate or bicarbonate level or AG to predict ICU admission (P = 0.17). There was no statistically significant difference between the AUROCs of lactate or bicarbonate level or AG to predict mortality at hospital discharge (P = 0.44). Among the 73 patients with normal lactate levels, but abnormal bicar- bonate or AG, there were seven (9.6%) deaths. Conclusions: A normal lactate level alone should not be used to exclude life-threatening sepsis. Patients with metabolic acidosis characterised by low bicarbonate or high AG levels, but with normal lactate levels, have high rates of ICU requirement and mortality and should also be consid- ered for early, aggressive therapy. Key words: emergency department, lactate, resuscitation, sepsis, severe sepsis. Introduction Sepsis is defined as life-threatening organ dysfunction caused by a dys- regulated host response to infection. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. 1 Early recognition and management have been associ- ated with improved outcomes. 2,3 While early recognition may be straightforward in severe sepsis or septic shock, it remains challenging for patients with early sepsis. 4 A serum lactate level >2 mmol/L has been chosen as the preferred cut- off value for prediction of severe sepsis by the International Sepsis Def- initions Task Force using a Delphi process to identify the lowest serum lactate level independently associated with a greater risk of death. 5 Although international guidelines rec- ommend obtaining a serum lactate measurement to assist in identifica- tion of a septic patient that is criti- cally ill, there are limitations to using lactate as a criterion in screening for severe sepsis. 6 Serum lactate measure- ments may not be readily avail- able, especially outside of a critical care setting or in resource-limited environments. In addition, practical Correspondence: Professor Biswadev Mitra, Emergency and Trauma Centre, The Alfred Hospital, 55 Commercial Road, Melbourne, VIC 3004, Australia. Email: biswadev.mitra@monash.edu Biswadev Mitra, MBBS, MHSM, PhD, FACEM, Emergency Physician; Cristina Roman, BPharm (Hons), MPP, Clinical Pharmacist; Kate E Charters, BMedSci (Hons), MBBS, Hospital Medical Officer; Gerard O’Reilly, MBBS, MPH, MBiostat, PhD, FACEM, Emergency Physician; Dashiell Gantner, MBBS, FCICM, Intensivist; Peter A Cameron, MBBS, MD, FACEM, Academic Director. Accepted 1 May 2019 Key findings • A normal lactate level on pre- sentation to the ED does not exclude life-threatening sepsis. • Low bicarbonate and/or high anion gap should be consid- ered in the assessment of sepsis. • Recognition of early sepsis remains challenging. © 2019 Australasian College for Emergency Medicine Emergency Medicine Australasia (2019) doi: 10.1111/1742-6723.13324