The effect of systemic corticosteroid therapy and hyperglycaemia on the clinical utility of lactate measurement: a prospective observational study

BL Mulchandani, AK Shah, SA Akunuri, AW Hitchings, EH Baker. St George\\'s University of London, London, UK

Introduction: Lactate is a product of anaerobic metabolism which is normally detectable in blood at concentrations <1.5 mmol/L. An elevated blood lactate concentration may indicate impaired tissue oxygen supply or utilisation. The lactate concentration is clinically useful in a number of settings, including in the diagnosis of severe sepsis; as a general marker of tissue oxygenation and illness severity; and in the diagnosis of drug-induced mitochondrial dysfunction. To interpret the lactate concentration correctly in these settings, it is important to understand the other factors that may confound its assessment.

Aim: To elucidate the effects of potential confounding variables on venous lactate concentration, with particular reference to drug therapy, dietary intake, and blood glucose concentration, in a cohort of patients admitted to hospital with respiratory disease.

Methods: A prospective observational study was performed in 15 patients with acute exacerbations of chronic respiratory disease. Ethical approval was obtained and all participants gave written informed consent. Participants were recruited via a convenience (opportunity) sampling method. Patients with hepatic failure were excluded. A cannula was sited in a forearm vein and venous blood samples for lactate and glucose concentration measurement were obtained on 7 occasions over a 24 hour period, before and after mealtimes as well as before bed. Data were also collected on clinical diagnosis, co-morbidities, anthropometric measurements, respiratory function, renal and hepatic profiles, and acute illness severity.

Results: The mean (± standard deviation) daily lactate concentration was 1.7±0.9 mmol/L. There was no association between mean venous lactate concentration and respiratory function, renal or hepatic function, or markers of acute illness severity. Venous lactate concentration was positively correlated with venous glucose concentration (r2=0.483, p<0.001). Mean daily venous lactate concentrations were higher in patients on systemic corticosteroid therapy (2.3± 0.8 mmol/L) than in those not taking corticosteroids (1.2±0.5 mmol/L), p= 0.008. There was a stronger association between venous lactate and glucose concentrations among patients on corticosteroids (r2 =0.610), compared to those who were not (r2 =0.280). This is depicted in the figure (Figure 1). Two patients in the sample had diabetes mellitus (both were taking metformin), and they had a significantly higher mean lactate concentration than those without diabetes mellitus (p=0.002).

Conclusion: Hyperglycaemia appears to be associated with an increased venous lactate concentration, particularly among patients taking systemic corticosteroids. There are several possible explanations for this, including the effects of hyperglycaemia on lactate metabolism (causality); the effect of hyperlactatemia on glucose homeostasis (reverse causality); and shared mechanisms such as induced insulin resistance (confounding). In view of small numbers further validation is needed. Elevated lactate appears not be related to tissue oxygenation. In clinical practice, the lactate concentration is often taken as a surrogate marker of tissue oxygenation and illness severity. Our findings indicate that its utility for this purpose may be impaired in the context of co-existing hyperglycaemia or corticosteroid therapy.