Metformin use and early lactate levels in critically ill patients according to chronic and acute renal impairment
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RESEARCH LETTER
Open Access
Metformin use and early lactate levels in critically ill patients according to chronic and acute renal impairment Rene A. Posma1,2* , Adam Hulman3 , Reimar W. Thomsen2 , Bente Jespersen4 , Maarten W. Nijsten1 Christian F. Christiansen2
and
Keywords: Metformin, Lactate, Acute kidney injury, Chronic kidney disease, Metformin-associated lactic acidosis, Critical care
Main text Metformin is the most widely used oral antihyperglycemic agent. Because it is eliminated unmodified in urine, patients with renal insufficiency can accumulate metformin and may develop lactic acidosis [1]. Recent guidelines only restrict the use of metformin in patients with severe chronic kidney disease (CKD) because the benefit is considered larger than the risk for lactic acidosis [2]. Lactate measurement has a central role in identifying and monitoring critical illness [3]. A better understanding of the impact of metformin on lactate levels could improve clinical assessment of the critically ill. Data were collected by combining data from Danish nationwide medical databases with laboratory data [4]. This multicenter cohort included all adults (≥ 18 years) hospitalized and surviving 24 h of intensive care unit (ICU) treatment in northern Denmark between January 2010 and August 2017. We required ≥ 3 lactate measurements between 6 h before until 24 h after ICU admission, with ≥ 12 h between first and last measurement. Patients receiving dialysis before ICU admission were excluded. Metformin use was defined as a filled prescription for metformin within 90 days before ICU admission [4]. CKD * Correspondence: [email protected] 1 Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 2 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Full list of author information is available at the end of the article
stage was assessed by the mean estimated glomerular filtration rate (eGFR) 365 days until 7 days before ICU admission [5]. Acute kidney injury (AKI) within 24 h after ICU admission was defined and staged according to the KDIGO creatinine criteria. Lactate trajectories over time for metformin users and nonusers were fitted by a mixed-effects model assuming unstructured covariance and including individuallevel random intercept and slope. Time was modeled as a natural cubic spline with knot locations at − 1 h, + 4 h, and + 12 h relative to ICU admission. Time-by-group interaction was entered as a covariate, and analyses were subsequently stratified by eGFR level or AKI stage. Differences in maximum lactate level with 95% confidence intervals between metformin users and nonusers were model-based. We studied 20,741 patients with a total of 209,394 lactate measurements, of whom 1905 (9%) patients used metformin (Table 1). Compared with nonusers, metformin users had a similar preadmission eGFR but had more often AKI stage 2 or 3. Metformin users had 0.61 (0.45–0.77) mmol/ L higher maximum lactate levels than nonusers (Fig. 1a). T
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