Predictors of Increased Lactate in Neonatal Cardiac Surgery: The Impact of Cardiopulmonary Bypass.
Nasr VG, Staffa SJ, Boyle S, Regan W, Brown M, Smith-Parrish M, Kaza A, DiNardo JA.J Cardiothorac Vasc Anesth. 2021 Jan;35(1):148-153. doi: 10.1053/j.jvca.2020.06.009. Epub 2020 Jun 10.PMID: 32620493
Take Home Points
- High lactate levels are known to correlate with hypoperfusion and tissue hypoxia.
- Rate of increase of lactate during cardiac surgery has been previously identified as a risk factor for morbidity and mortality in cardiac surgery in children.
- In this study, three additional predictors were found to be associated with changes in lactate concentration during cardiopulmonary bypass in neonates:
- Circulatory arrest time
- Time of mean arterial pressure < 25 mmHg.
- Time of mean arterial pressure 35 – 39 mmHg.
The first two variables were positive predictors, while the third was negatively correlated with change in lactate.
Commentary by Lori Q. Riegger MD, Associate Professor of Anesthesiology, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan: Lactate levels are used as an important biomarker for oxygen delivery, with high lactate levels classically corresponding to decreased systemic perfusion and tissue hypoxia.1 Several studies have demonstrated associations between hyperlactatemia and postoperative morbidity and mortality after pediatric cardiac surgery. Peak lactate levels were higher in nonsurvivors of congenital heart surgery,2 and the “lactime,” or the time in which the lactate level is > 2 mmol/L, has been demonstrated to correlate with mortality as well as postoperative ventilator days and hospital days.3 Over the first 24 hours after cardiac surgery, an increased rate of lactate by 0.6 mmol/L/h has been shown to increase the risk of death, need for extracorporeal support (ECMO), and dialysis.4 While a change > 2 mmol/L from the last lactate on cardiopulmonary bypass (CPB) to the first lactate in the cardiac intensive care unit has been identified as a risk factor for morbidity after cardiac surgery in children.5 This current study aimed to examine factors which predict hyperlactatemia during CPB in neonates.
This retrospective study examined 376 neonates from July 2015 to December 2018 who underwent cardiac surgery with cardiopulmonary bypass (CPB). Lactate measurements were collected at several time points during the surgery (pre-bypass, initiation of CPB, at the end of CPB, at the end of the operating room time and first in the cardiac intensive care), and changes were examined using nonparametric Wilcoxon signed rank for paired data. The changes in lactate from one point to the next were computed for analysis.
The cohort was 60% male, and the median age was 5 days with a range of 1-30 days. Fifty-nine percent had two ventricles while the remaining had single ventricle physiology, and 68% of the study group were a STAT category 4 or 5. One quarter of the patients were premature, 27% had preoperative endotracheal tubes, 4% required postoperative ECMO within 48 hours, and 3% did not survive postoperatively. Significant increases in lactate were noted both in the time from pre-CPB to end of CPB (p < 0.001) and from the beginning to the end of CPB (p < 0.001). Median time before CPB was 162 minutes (IQR 142 – 181), median CPB time was 150 minutes (IQR 112 – 190), and the median time after CPB was 112 minutes (IQR 95 – 138). The median CPB temperature target was 24°C (IQR 18-28). Mean inotrope score was 2.23 (IQR 0 – 5.18) pre-CPB and 4.79 (IQR 2.98 – 8.03) post-CPB.
Univariate median regression analysis of predictor variables and lactate change from CPB start to end was performed. Variables with p < 0.1 were added to the multivariate model stepwise and this revealed several independent predictors of change in lactate from CPB start to end, including circulatory arrest time per 30 min (coefficient 1.216; 95% CI 0.754-1.678; p < 0.001), duration of MAP < 25 mmHg per 30 min (coefficient 0.423; 95% CI 0.196-0.651; p < 0.001), and duration of MAP 35-39 mmHg per 30 min (coefficient -0.246; 95% CI -0.397—o.095; p=0.001).
The authors note that circulatory arrest as well as hypotension on CPB are times when oxygen delivery to the tissues is limited even in the setting of adequate oxygen carrying capacity. Hence, the predictors found were not unexpected. Interestingly, they found that higher MAP (35-39 mmHg) was a negative predictor for increases in lactate. It may be that a MAP between 25-35 mmHg is pivotal for optimum oxygen delivery while on CPB. Future studies would be needed to determine this, potentially again using lactate as a surrogate. They also note that neither the use of regional antegrade cerebral perfusion nor the target temp of 24°C were found to be associated with high lactate levels. Additionally, they did not find that the age of the blood transfused influenced lactate levels, although they postulate that this may be due to their institutional practice of only using blood < 7 days old for neonates. In this study, the authors note that every 30 minutes of circulatory arrest led to an increase of 1.216 mmol/L of lactate and every 30 minutes of MAP < 25 mm Hg led to an increase of 0.423 mmol/L lactate, emphasizing the need to minimize circulatory arrest and hypotension in order to decrease hyperlactatemia and the potential adverse events associated with it.
What does this mean for us?
Multiple studies involving children requiring cardiac surgery with CPB have demonstrated the relationship between high lactate levels (including peak level, change in lactate over time, length of time above a certain level) and increases in morbidity including ECMO, need for dialysis, cardiac arrest as well as mortality. This, in turn, has led to an emphasis on goal directed therapy to improve tissue perfusion to vital organs, including heart, brain and kidneys using a variety of monitoring and therapeutic modifications.
In particular, using near infrared spectroscopy monitoring to assess the regional oxygenation saturation (rSO2) during CPB may allow optimization of oxygen delivery and perfusion by focusing attention on ideal hemoglobin, MAP, pump blood and gas flow, temperature management, and pH strategies. There is evidence that a low somatic-cerebral rSO2 gradient is associated with increases in lactate concentrations and hence, the use of infra-red spectroscopy technology may become another useful monitoring tool for the adequacy of oxygen delivery during CPB. 6
Although any laboratory number needs correlation with the clinical scenario, the identification of these three risk factors for high lactate during neonatal CPB should lead to an increased awareness of the length of time of circulatory arrest as well as the necessity of circulatory arrest when antegrade cerebral perfusion is an option. This study also supports increased vigilance regarding adequate MAP during CPB to ensure sufficient tissue perfusion.
Serial lactate assessments are easily measured and may demonstrate a clinical trajectory associated with deleterious outcomes. Predictors for hyperlactatemia in children undergoing CPB identified in the current study, may allow an earlier treatment response and a change in overall strategy to decrease this biomarker and its undesirable associations.
Future studies, ideally ones involving multiple centers, are warranted to confirm similar findings at other institutions, determine if there are other risk factors, and assess whether modification of these risk factors can improve clinical outcomes in this vulnerable patient population.
- Stephens EH, Epting CL, Backer CL, et al. Hyperlactatemia: An update on postoperative lactate. World J Pediatr Congenit Heart Surg. 2020;11(3):316-24
- Cheung PY, Chui N, Joffe AR, et al. Postoperative lactate concentrations predict the outcome of infants aged 6 weeks or less after intracardiac surgery: A cohort follow-up to 18 months. J Thorac Cardiovasc Surg. 2005;130(3):837-43
- Kalyanaraman M, DeCampli WM, Campbell AI, Bhalala U, et al. Serial blood lactate levels as a predictor of mortality in children after cardiopulmonary bypass surgery. Pediatr Crit Care Med. 2008;9(3):285-9
- Schumacher KR, Reichel RA, Vlasic JR, et al. Rate of increase in serum lactate level risk-stratifies infants after surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2014; 148: 589-95
- Kanazawa T, Egi M, Shimizu K, et al, Intraoperative change of lactate level is associated with postoperative outcomes in pediatric cardiac surgery patients: Retrospective observational study. BMC Anesthesiol. 2015;15:29
- Bojan M, Bonavelio E, Dolcino A, et al. Somatic and cerebral near infra-red spectroscopy for the monitoring of perfusion during neonatal cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2019;29:955-9.
Congenital Heart Anesthesia and Intensive Care Section Editors
Rania Abbasi – Indianapolis, IN
Nischal Gautam – Houston, TX