Background Cardiac surgery induces metabolic and haemodynamic changes, often resulting in hyperlactatemia. Hyperlactatemia is a marker of adverse postoperative outcomes including organ dysfunction, prolonged mechanical ventilation, and increased mortality (1). The time-course of lactate concentration after cardiac surgery remains poorly understood, limiting the use of lactate as a prognostic biomarker or therapeutic target. The objective of this study was to quantify the time-course of lactate concentrations in postoperative adult cardiac surgical patients. Specifically, we aimed to assess the influence of organ dysfunction, surgery type and inotropic support on lactate kinetics.
Methods Data were obtained from the Medical Information Mart for Intensive Care III and IV databases (2, 3). Arterial lactate concentrations and sampling times, patient demographics, surgery type, comorbidities (hepatic and renal dysfunction) and inotropic support were extracted. Lactate kinetics were described using a turnover model with first-order elimination. Production rate (56 mmol/h/70 kg) and volume of distribution (23.4 L/70 kg) were fixed a priori based on literature values (4). A hypothetical stimulus compartment was used to stimulate lactate production following surgery. This had a nominal input of 1 at the time of intensive care admission and first-order elimination parameterised as a stimulatory half-time. This was applied to the lactate production rate using a linear link. Modelling was in NONMEM (v 7.5.1, ICON Development Solutions).
Results Lactate concentrations (n=22,811) were extracted from 2,375 adults (median age 69 [21–91] years; weight 85.6 [34.4–181] kg). Surgeries were predominantly coronary artery bypass grafts (71%), followed by valvular (23%), with the remainder uncategorised. A 1-compartment model was adequate to describe lactate disposition. Parameter estimates and their population parameter variability were clearance 47.9 (0.30) L/h/70 kg and surgical stimulatory half-time 4.4 (0.38) h. The slope of the stimulatory effect was 1.64 (0.85). Epinephrine increased lactate production rate 1.28-fold. There was no detectable effect of organ dysfunction or surgery type on lactate production or elimination.
Conclusion This study characterises postoperative lactate kinetics in a broad population of adult cardiac surgery patients and quantifies the stimulatory effect of epinephrine on lactate production. This model offers guidance for anticipating lactate trajectories in the intensive care environment and the expected time to return to baseline concentrations. Ongoing work will integrate this model into a time-to-event framework to investigate the relationship between lactate concentration and clinical outcomes, including intensive care length of stay and 90-day mortality.
References
- Andersen LW. Lactate Elevation During and After Major Cardiac Surgery in Adults: A Review of Etiology, Prognostic Value, and Management. Anesth Analg. 2017;125(3):743-52.
- Johnson A, Bulgarelli, L., Pollard, T., Horng, S., Celi, L. A., & Mark, R. MIMIC-IV (version 0.4): Physionet; 2020.
- Johnson AE, Pollard TJ, Shen L, Lehman LW, Feng M, Ghassemi M, et al. MIMIC-III, a freely accessible critical care database. Sci Data. 2016;3:160035.
- Phypers B, Pierce JT. Lactate physiology in health and disease. Continuing Education in Anaesthesia Critical Care & Pain. 2006;6(3):128-32.