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Ann Thorac Surg 1997;64:735-738
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Serum Lactates Correlate With Mortality After Operations for Complex Congenital Heart Disease

Departments of Pediatrics, Anesthesiology, and Surgery, Duke Children's Hospital, Duke University Medical Center, Durham, North Carolina

Accepted for publication March 21, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The objective of this study was to determine whether serum lactate levels predict mortality in children less than 1 year of age who have undergone cardiopulmonary bypass and operations for complex congenital heart disease.

Methods. The initial lactate, maximum lactate, and lactate levels at 4 to 6 hours after operation were analyzed for each of 48 children less than 12 months of age who underwent cardiopulmonary bypass.

Results. Data were analyzed for the 6 patients who died and the 42 patients who survived. For the patients who died, the initial postoperative serum lactate, maximum lactate, and 4- to 6-hour lactate levels were significantly higher than those in the patients who survived. All patients with an initial lactate less than 7 mmol/L, a maximum lactate less than 9 mmol/L, or a 4- to 6-hour lactate level less than 4 mmol/L survived to hospital discharge.

Conclusions. Serum lactate levels may be a useful predictor of mortality in children less than 1 year of age who have undergone cardiopulmonary bypass. An elevation in serum lactate level after a complex operation for congenital heart disease should be taken as a serious indicator of potential mortality.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Monitoring of oxygen delivery and consumption is limited in infants after repair of congenital heart disease because of difficulties in measuring cardiac output and the unreliability of mixed venous saturation monitoring in patients with residual intracardiac communications. Inadequate tissue oxygen delivery is reflected by lactic acidosis resulting from anaerobic metabolism [1–4]. Lactic acidosis is frequently encountered among critically ill patients, including children, in the period after cardiothoracic operations. An elevation in serum lactate levels results from systemic hypoperfusion and tissue hypoxia. When multisystem organ dysfunction ensues, the risk of death may increase [1].

Several studies have shown a strong correlation between high blood lactate levels and an increased risk of morbidity and mortality [2, 3, 5–8]. These studies have investigated the role of serum lactates in clinical entities such as shock, extracorporeal life support, myocardial infarction, and trauma. However, the role of serum lactates in the postoperative management of patients with congenital heart disease remains incompletely defined.

Surgery for congenital heart disease has undergone several advances in recent years. With improved myocardial and cerebral protection, surgical technique, and perioperative care, early primary repair is being performed for an increasing number of patients. Additionally, certain lesions that were previously considered inoperable, including hypoplastic left heart syndrome, are now being approached aggressively in infancy, with good results. Therefore, an increasing number of newborns and infants with congenital heart disease are being considered for early operative intervention. Although the perioperative care of these patients is continually improving, a substantial incidence of morbidity and mortality still exists. Identification of predictors of morbidity and mortality in the postoperative period and early intervention might improve outcome; however, such predictors are currently lacking.

The development of predictors of death involves evaluating multiple different cardiorespiratory physiologic indices. This approach is often difficult in infants with congenital heart disease because of their small size, which limits invasive monitoring capabilities and reliable diagnostic options. Additionally, physiologic abnormalities, such as atrial level shunting, may preclude the accurate measurement of cardiac output, mixed venous oxygen content, and, thus, oxygen delivery and consumption. Despite these obstacles, the search for predictors to help direct aggressive interventions in this patient population remains an important goal.

The purpose of this study was to determine whether serum lactate levels are predictive of mortality after operations for complex congenital heart disease in infants. We hypothesized that the development of elevated serum lactate levels would correlate with an increased risk of death. We conducted a retrospective cohort study of lactate levels over a 6-month period in 48 infants who required operations for "high-risk" congenital heart disease.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Over a 6-month period, we measured serial serum lactate levels in 48 consecutive high-risk infants who were admitted to the pediatric intensive care unit of a tertiary care hospital after cardiac operations. These lactate measurements were obtained as part of routine postoperative management. High-risk patients were defined as infants less than 1 year of age who underwent cardiac operations with cardiopulmonary bypass after the diagnosis of a complex congenital heart lesion. These lesions were defined before data collection and included transposition of the great vessels, hypoplastic left heart syndrome, left ventricular outflow tract obstruction, tetralogy of Fallot, atrioventricular septal defects, total anomalous pulmonary venous return, pulmonary atresia, and double outlet right ventricle. Data were obtained retrospectively. The diagnosis of each child, the duration of cardiopulmonary bypass, the duration of deep hypothermic circulatory arrest, if any, and the outcome were recorded. Survival was defined as discharge home.

Measured serum lactate values (millimoles per liter) included the initial lactate level upon admission to the pediatric intensive care unit, the maximum lactate level, and the lactate level at 4 to 6 hours after admission. Samples for serum lactate measurement were obtained from arterial blood, placed on ice, and delivered immediately to the laboratory for analysis (Kodak Ektachem 700XR Analyzer C Series). Data were compared between the infants who died and the infants who survived using the Mann-Whitney U test. All data are presented as mean ± standard error of the mean.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The study population consisted of 48 high-risk infants with congenital heart disease. Six patients died in the postoperative period and 42 infants survived. The overall hospital mortality rate for patients undergoing operations for congenital heart disease during this period was 5.8%. The group who died averaged 0.5 ± 0.3 months of age; the group of infants who lived averaged 3.7 ± 0.6 months (p = 0.01). The mean time on cardiopulmonary bypass for the group who died was 134.3 ± 41.3 minutes, as compared with 95.2 ± 6.3 minutes for the survival group (p = not significant). The percentage of patients who required deep hypothermic circulatory arrest was 67% in the group who did not survive and 60% in the group who did survive (p = not significant). The mean time of deep hypothermic circulatory arrest was 29.5 ± 11.4 minutes for the infants who died and 17.8 ± 2.8 minutes for the infants who lived (p = not significant).

The normal serum lactate value for an unstressed patient is less than 2.0 ± 0.5 mmol/L in our clinical laboratory. Preoperative serum lactate levels did not differ between the groups of infants. Additionally, no correlation was seen between preoperative and postoperative levels. The initial postoperative lactate level was significantly increased in the patients who died as compared with those who survived (13.7 ± 2.4 versus 4.5 ± 0.4 mmol/L; p = 0.0001). The maximum lactate was 16.1 ± 4.1 mmol/L for the group of infants who died, compared with 4.5 ± 0.4 mmol/L for the group who survived (p = 0.0001). The 4- to 6-hour lactate value was also significantly elevated for the infants who did not survive (12.3 ± 4.3 versus 2.4 ± 0.4 mmol/L; p = 0.005). These data are summarized in Table 1. All patients with an initial lactate level less than 7 mmol/L, a maximum lactate less than 9 mmol/L, or a 4- to 6-hour lactate less than 4 mmol/L survived (sensitivity 100%). Fifty-five percent (6/11) of the patients with an initial lactate greater than 7 mmol/L, 86% (6/7) of the patients with a maximum lactate greater than 9 mmol/L, and 55% (6/11) of the patients with a 4- to 6-hour lactate level of greater than 4 mmol/L died. The diagnoses and serial lactate values for the patients who died are listed in Table 2.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

Lactate is a marker of anaerobic metabolism and tissue oxygen deficit. Increases in tissue lactate concentration and acidosis correlate with depletion of high-energy phosphate compounds and with cellular dysfunction [4, 9–11]. Because lactic acid is a product of anaerobic metabolism, we speculated that in infants who are in the immediate postoperative period from congenital heart disease procedures, elevated lactate levels represent inadequate tissue oxygen delivery. This decrease in oxygen delivery represents a combination of tissue hypoperfusion and hypoxemia and should prompt a systematic diagnostic evaluation [1]. Proper cellular function throughout the body requires a continuous supply of energy to maintain cellular integrity [12]. Lactic acidosis is an imbalance between the metabolic needs of the tissues and their oxygen supply [13]. Thus, elevated serum lactate levels have been correlated with increased mortality rates [3, 6, 8].

Our study shows that serial serum lactate levels, which are easily obtained, may predict individual patients with an increased risk of mortality. Our data demonstrate that serum lactate levels are significantly elevated in patients who die after operations for congenital heart disease as compared with those who survive. The initial postoperative lactate, the maximum value, and the 4- to 6-hour value correctly identified these patients. A 4- to 6-hour value was chosen because the patient should be stabilized in the intensive care unit within this time frame. Improvements in cardiac output and tissue oxygen delivery should be occurring within 6 hours of operation and, therefore, lactates should have reached their maximum and should be starting to decline.

For lactate measurements to be useful, specific lactate levels should be defined that prompt either (1) further evaluation or intervention in a patient who is deteriorating or (2) a reduction in monitoring and therapy in a patient who is improving. When we examined our data to determine predictors, we found that an initial lactate less than 7 mmol/L, a maximum lactate less than 9 mmol/L, or a 4- to 6-hour lactate level less than 4 mmol/L predicted survival with a positive predictive value of 100% and a negative predictive value of 55%, 86%, and 55%, respectively. These numbers may be useful as guidelines in patients after operations for congenital heart disease. If the lactate levels fall below those outlined, the patient has a low risk of death. In contrast, if the levels are greater than those listed, the patient has an increased risk for death, and the clinician should consider therapeutic interventions as discussed later. By performing serial lactate measurements as opposed to using a single predictor in high-risk patients, clinicians can obtain supportive evidence for abnormal convalescence earlier in the postoperative course. When the lactate level falls to values that predict a low risk for death, the frequency of investigations may be reduced. Additionally, when lactate levels are nearly normal, vasoactive agents may be reduced. These reductions in the intensity of medical care may ultimately decrease the cost of care and, potentially, the length of the intensive care unit admission while not affecting overall outcome.

The 6 patients who died were all less than 1 month of age. All of these 6 patients had critical congenital heart disease requiring early operative intervention, including critical aortic stenosis (with endocardial fibroelastosis), total anomalous pulmonary venous return with obstruction, hypoplastic left heart syndrome, double outlet right ventricle, and pulmonary atresia with intact ventricular septum (see Table 2). Although a younger age at operation was an important factor, taken alone this was not a useful predictor. However, in a patient less than 1 month of age with increased serum lactate values, the patient care team may need to consider earlier and more aggressive interventions because younger patients may have the most complex varieties of heart disease and may represent the group at greatest risk for death. The duration of deep hypothermic circulatory arrest and of cardiopulmonary bypass, although potentially correlated with a younger patient age, did not correlate significantly with mortality. However, this study had limited power to detect the influence of these factors on mortality.

This role of serum lactates in the postoperative management of patients with congenital heart disease has been incompletely studied. Anand and Hickey [14] compared different anesthetic techniques in neonatal cardiac operations and showed a peak lactate value at the end of the procedure. However, the first follow-up lactate value was not obtained for 6 hours. This timing of data collection would miss the possibility of an increase in serum lactate in the immediate postoperative period before decreasing at 6 hours after operation [14, 15]. Anand and Hickey did hypothesize that persistent metabolic acidosis may contribute to poor outcome in critically ill infants after repair of congenital heart disease using cardiopulmonary bypass. Other studies have shown that this association may be exaggerated in the young infant [16, 17].

The data from our study agree with prior investigations that analyzed the correlation between lactic acidosis and outcome in disease entities other than operative correction of congenital heart disease. Grayck and colleagues [8] showed lactate values to be a useful marker for the development of intracranial hemorrhage in infants on extracorporeal life support. Vincent and associates [3] showed in adults with circulatory shock that changes in lactate concentration can provide an early and objective evaluation of a patient's response to therapy. Cowan and associates [6] demonstrated in another study of adult shock that serial lactate measurements were a better prognostic indicator than single values.

The systematic evaluation of a patient with an increase in serum lactate requires an examination of all potential conditions that may disrupt the oxygen supply/demand ratio and lead to inadequate oxygen delivery. Three general categories of abnormalities should be considered in patients after operations for congenital heart disease: (1) the adaptation of the cardiorespiratory system to the changes in loading conditions that occur after operation, (2) the effects of cardiopulmonary bypass on organ system function, and (3) the presence of residual anatomic disease. Evaluation for these potential abnormalities must be individualized. Once the cause for the abnormality in oxygen supply versus demand is determined, therapy can be directed at the specific pathophysiologic or anatomic problem.

Aggressive early interventions should be designed to increase global oxygen delivery by a combination of increasing cardiac output and arterial oxygen content. Cardiac output may be increased by optimizing heart rate, increasing preload, increasing ventricular contractility, and decreasing afterload. Arterial oxygen content may be maximized by increasing hemoglobin concentration and increasing oxygen saturation (increase inspired oxygen fraction and optimize ventilatory settings). Improved oxygen delivery may lead to improved survival for this patient population.

The use of serum lactate levels to identify infants who have a high risk of death after cardiac operations does have limitations. The lactate levels measured were from arterial samples. Thus, the values reflected systemic perfusion more than true end-organ perfusion. Additionally, lactic acid is a relatively late marker of hypoperfusion. A more specific and earlier marker for hypoperfusion of end organs may be mixed venous saturation. However, mixed venous saturation may not be determined accurately in patients with residual atrial mixing lesions. Further prospective clinical studies analyzing the prognostic value of both serum lactate and mixed venous saturation in this patient population are warranted. We also note that this was a univariate analysis in a complex group of patients in which many factors may be important in determining the outcome of surgical procedures.

Our study reveals that the initial postoperative lactate level, the maximum lactate, and the lactate at 4 to 6 hours after operation are useful prognostic indicators. On the basis of our data, a beneficial approach to infants who have undergone cardiopulmonary bypass for operations on congenital heart lesions would be to follow up serum lactate concentrations routinely every 4 hours until the infant is clinically stable. Subsequently, the frequency of lactate determinations can be decreased. If repeat lactate values are less than 3 mmol/L, further serial measurements of lactate are probably unnecessary. However, any subsequent periods of clinical instability should prompt a determination of serum lactate concentration and consideration of an increase in the frequency of lactate observations. When lactate levels are consistently normal, the medical care team should consider decreasing the frequency of lactate determinations as well as the overall level of cardiorespiratory support.

In summary, this study investigated the predictive value of serum lactate concentrations in infants less than 1 year of age who underwent cardiopulmonary bypass for complex congenital heart operations. We conclude that serum lactate levels provide an excellent predictor of mortality in this patient population. Elevation of the serum lactate level or a trend toward elevation after these operations should be taken as a serious indicator of potential death and justifies aggressive diagnostic and therapeutic interventions. Such early interventions may lead to even further decreases in morbidity and mortality after operations for congenital heart disease.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Presented in part at the Twenty-fifth Annual Society of Critical Care Medicine Symposium in New Orleans, LA, Feb 6, 1996.

Address reprint requests to Dr Cheifetz, Division of Pediatric Critical Care Medicine, Duke University Medical Center, Box 3046, Durham, NC 27710 (e-mail: cheif002{at}mc.duke.edu).

	References

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Ira M. Cheifetz Ross M. Ungerleider Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheifetz, I. M. Articles by Meliones, J. N. Search for Related Content PubMed PubMed Citation Articles by Cheifetz, I. M. Articles by Meliones, J. N.