Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study
Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aim...
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Published in | Annals of intensive care Vol. 10; no. 1; p. 36 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Springer International Publishing
26.03.2020
Springer Nature B.V SpringerOpen |
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Abstract | Background
Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers.
Methods
This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model.
Results
Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users.
Conclusion
In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. |
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AbstractList | Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers.
This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model.
Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2-3.2) in metformin users and 1.6 (1.0-2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users.
In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. BackgroundLactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers.MethodsThis cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model.ResultsOf 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users.ConclusionIn this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. |
ArticleNumber | 36 |
Author | Frøslev, Trine Touw, Daan J. Nijsten, Maarten W. Posma, Rene A. Jespersen, Bente Christiansen, Christian F. van der Horst, Iwan C. C. Thomsen, Reimar W. |
Author_xml | – sequence: 1 givenname: Rene A. orcidid: 0000-0001-7599-1441 surname: Posma fullname: Posma, Rene A. email: r.a.posma@umcg.nl organization: Department of Critical Care, University of Groningen, University Medical Center Groningen, Department of Clinical Epidemiology, Aarhus University Hospital – sequence: 2 givenname: Trine surname: Frøslev fullname: Frøslev, Trine organization: Department of Clinical Epidemiology, Aarhus University Hospital – sequence: 3 givenname: Bente orcidid: 0000-0001-7196-2870 surname: Jespersen fullname: Jespersen, Bente organization: Department of Renal Medicine, Aarhus University Hospital – sequence: 4 givenname: Iwan C. C. orcidid: 0000-0003-3891-8522 surname: van der Horst fullname: van der Horst, Iwan C. C. organization: Department of Intensive Care, Maastricht University Medical Center+, Maastricht University – sequence: 5 givenname: Daan J. orcidid: 0000-0002-1429-4789 surname: Touw fullname: Touw, Daan J. organization: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen – sequence: 6 givenname: Reimar W. orcidid: 0000-0001-9135-3474 surname: Thomsen fullname: Thomsen, Reimar W. organization: Department of Clinical Epidemiology, Aarhus University Hospital – sequence: 7 givenname: Maarten W. orcidid: 0000-0002-0981-9392 surname: Nijsten fullname: Nijsten, Maarten W. organization: Department of Critical Care, University of Groningen, University Medical Center Groningen – sequence: 8 givenname: Christian F. orcidid: 0000-0002-0727-953X surname: Christiansen fullname: Christiansen, Christian F. organization: Department of Clinical Epidemiology, Aarhus University Hospital |
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Keywords | Effect modification Metformin Lactate Metabolism Diabetes mellitus |
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7 F Luo (652_CR49) 2019; 18 A Rhodes (652_CR29) 2017; 43 EM Alkozai (652_CR1) 2018; 56 C Meyer (652_CR10) 2003; 285 M Schmidt (652_CR23) 2014; 29 A Pottegard (652_CR31) 2017; 46 MHT Hartman (652_CR51) 2017; 106 RA Posma (652_CR13) 2016; 20 P Cummings (652_CR43) 2019 K Doenyas-Barak (652_CR15) 2016; 20 J Radziuk (652_CR6) 1997; 46 CF Christiansen (652_CR25) 2016; 8 G Rena (652_CR5) 2017; 60 JP Green (652_CR16) 2012; 30 S El Messaoudi (652_CR50) 2015; 3 HB Nguyen (652_CR28) 2004; 32 WL Eppenga (652_CR54) 2014; 37 M Singer (652_CR42) 2016; 315 JR Le Gall (652_CR35) 1993; 270 AS Levey (652_CR38) 2009; 150 A Gleiss (652_CR30) 2018; 31 AI Duncan (652_CR48) 2007; 104 |
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Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher... Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate... Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have... BackgroundLactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher... BACKGROUNDLactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher... Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have... |
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SubjectTerms | Anesthesiology Antidiabetics Cohort analysis Critical Care Medicine Diabetes Diabetes mellitus Effect modification Emergency Medicine Intensive Intensive care Lactate Medical prognosis Medicine Medicine & Public Health Metabolism Metformin Mortality |
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Title | Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study |
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