Impact of metformin use on the prognostic value of lactate in sepsis

Green, Jeffrey P.; Berger, Tony; Garg, Nidhi; Suarez, A.E.; Hagar, Yolanda; Radeos, Michael S.; Panacek, Edward A.

doi:10.1016/j.ajem.2012.01.014

Cited by 18 publications

(30 citation statements)

References 29 publications

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“…For the study cohort, providers identified adult patients with suspected acute infections in real time; data were then retrospectively extracted into standardized data collection forms by review of the electronic medical record (EMR), as previously described. 13 For this analysis, eligible patients were 21 years of age or older (patients less than this age were triaged to a separate pediatric ED), had two or more systemic inflammatory response syndrome (SIRS) criteria on triage or initial ED vital signs and laboratory studies, had both serum lactate and glucose level measurements in the ED, and were hospitalized, with admitting diagnoses of infection. International Classification of Disease, 9th Revision, (ICD-9), ED admitting codes were used to define infection, as previously described in adult patients with sepsis.…”

Section: Methodsmentioning

confidence: 99%

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

Green

Berger

Garg

et al. 2012

Academic Emergency Medicine

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Background Admission hyperglycemia has been reported as a mortality risk factor for septic nondiabetic patients; however, hyperglycemia’s known association with hyperlactatemia was not addressed in these analyses. Objectives The objective was to determine whether the association of hyperglycemia with mortality remains significant when adjusted for concurrent hyperlactatemia. Methods This was a post hoc, nested analysis of a retrospective cohort study performed at a single center. Providers had identified study subjects during their ED encounters; all data were collected from the electronic medical record (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous lactate and glucose testing in the ED were enrolled. The setting was the ED of an urban teaching hospital from 2007 to 2009. To evaluate the association of hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate ≥ 4.0 mmol/L), a logistic regression model was created. The outcome was a diagnosis of hyperlactatemia, and the primary variable of interest was hyperglycemia. A second model was created to determine if coexisting hyperlactatemia affects hyperglycemia’s association with mortality; the main outcome was 28-day mortality, and the primary risk variable was hyperglycemia with an interaction term for simultaneous hyperlactatemia. Both models were adjusted for demographics; comorbidities; presenting infectious source; and objective evidence of renal, respiratory, hematologic, or cardiovascular dysfunction. Results A total of 1,236 ED patients were included, and the median age was 77 years (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days of their initial ED visits. After adjustment, hyperglycemia was significantly associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95% confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia was not (OR = 0.78, 95% CI = 0.39 to 1.57). Conclusions In this cohort of septic adult nondiabetic patients, mortality risk did not increase with hyperglycemia unless associated with simultaneous hyperlactatemia. The previously reported association of hyperglycemia with mortality in nondiabetic sepsis may be due to the association of hyperglycemia with hyperlactatemia.

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Section: Methodsmentioning

confidence: 99%

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

Green

Berger

Garg

et al. 2012

Academic Emergency Medicine

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“…The link between metformin and lactic acidosis is especially important in relation to sepsis and septic shock, where elevated serum lactate is associated with increased morbidity and mortality . The cause and effect association of metformin with mortality in sepsis patients with lactic acidosis has repeatedly been doubted with multiple studies showed the mortality rate to be lower or unchanged among metformin users with sepsis and high lactic acid . Metformin levels have not been found to be linked to mortality in cases of lactic acidosis, even in patients with sepsis .…”

Section: Sepsismentioning

confidence: 99%

“…25 The cause and effect association of metformin with mortality in sepsis patients with lactic acidosis has repeatedly been doubted with multiple studies showed the mortality rate to be lower or unchanged among metformin users with sepsis and high lactic acid. 26,27 Metformin levels have not been found to be linked to mortality in cases of lactic acidosis, [27][28][29][30] even in patients with sepsis. 27 In fact, some studies show a lower mortality risk in sepsis patients on chronic metformin therapy compared to those not on the therapy.…”

Section: Sepsis Metformin and Lactatementioning

confidence: 99%

“…26,27 Metformin levels have not been found to be linked to mortality in cases of lactic acidosis, [27][28][29][30] even in patients with sepsis. 27 In fact, some studies show a lower mortality risk in sepsis patients on chronic metformin therapy compared to those not on the therapy. 26 Other studies show no differences in the clearance and normalization (over 24 h) of serum lactate between sepsis patients on chronic metformin therapy and those who have not taken metformin.…”

Section: Sepsis Metformin and Lactatementioning

confidence: 99%

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Is metformin poised for a second career as an antimicrobial?

Malik

Mehdi

Ali

et al. 2018

Diabetes Metabolism Res

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Metformin, a widely used antihyperglycaemic, has a good safety profile, reasonably manageable side-effects, is inexpensive, and causes a desirable amount of weight loss. In 4 studies of patients with tuberculosis (1 prospective and 3 retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of proinflammatory cytokines and improved survival. Laboratory studies showed effectiveness of the drug on multiple pathogens, including Trichinella spiralis, Staphylococcus aureus, Pseudomonas aeruginosa, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Metformin administration in humans and mice produced major changes in the composition of the gut microbiota. These recently discovered microbe-modulating properties of the drug have led investigators to predict wide therapeutic utility for metformin. The recent easing in United States Food and Drug Administration (FDA) guidelines regarding administration of metformin to patients with kidney disease, and reduced anxiety about patient safety in terms of lactic acidosis, increase the probability of broadening of metformin's usage as a treatment of infectious agents. In this text we review articles pertinent to metformin's effects on microorganisms, both pathogens and commensals. We highlight the possible role of metformin in a wide range of infectious diseases and a possible expansion of its therapeutic profile in this field. A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens. Metformin was found to have efficacy as an antimicrobial agent in patients with tuberculosis. Mice infected with Trypanosomiasis cruzi had higher survival when also treated with metformin. The drug in vitro was active against T. spiralis, S. aureus, P. aeruginosa, and hepatitis B virus. In addition there is emerging literature on its role in sepsis. We conclude that metformin may have a potential role in the therapy for multiple infectious diseases. Metformin, in addition to its traditional effects on glucose metabolism, provides anti-microbial benefits in patients with tuberculosis and in a very wide range of other infections encounters in vitro and in vivo.

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“…However, lactate metabolism is far more complex, and plasma lactate concentrations may be altered by e.g. metabolic stress through β-stimulation [11][12][13] or pharmacological substances [14,15]. Lactate can also serve as an energy substrate in various organs, such as the heart and the brain, and is a precursor for gluconeogenesis in the liver and kidney [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate

Grip¹,

Falkenström

Promsin³

et al. 2020

Crit Care

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Background: Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied. Aim: To establish and validate a feasible method to study lactate kinetics in critically ill patients. Methods: Healthy volunteers (n = 6) received a bolus dose of 13 C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using noncompartmental modeling calculating rates of appearance (R a) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10). Results: R a for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques. Conclusion: This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients.

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Impact of metformin use on the prognostic value of lactate in sepsis

Cited by 18 publications

References 29 publications

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

Is metformin poised for a second career as an antimicrobial?

Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate

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