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

Jonathan Grip, Tobias Falkenström, Panuwat Promsin, Jan Wernerman, Åke Norberg, Olav Rooyackers, Jonathan Grip, Tobias Falkenström, Panuwat Promsin, Jan Wernerman, Åke Norberg, Olav Rooyackers

Abstract

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 13C-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 non-compartmental modeling calculating rates of appearance (Ra) 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: Ra 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.

Trial registration: ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true.

Keywords: ICU; Labeled lactate; Lactate; Lactate kinetics; Method validation; Stable isotope.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Plasma enrichment of labeled lactate over time in all subjects. Decay curves of plasma lactate enrichments after a bolus dose of 13C-labeled lactate in healthy volunteers (filled black lines, n = 6) and ICU patients (red dotted lines n = 10). The left panel includes all values, 43 samples per subject, and the right panel shows a reduced number, 14 samples per subject
Fig. 2
Fig. 2
Relationship between plasma concentration and rate of appearance and clearance of lactate. Relation between plasma lactate concentrations and rate of appearance of lactate (upper panel) and metabolic clearance of lactate (bottom panel) as calculated from a bolus dose of 13C-labeled lactate in healthy volunteers (blue circles, n = 6) and ICU patients (red circles, n = 10). The lines of regression and associated statistics apply to the group of ICU patients only

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