Central venous oxygen saturation and blood lactate levels during cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery

Continuous ScVO₂ monitoring for pediatric patients was introduced in our Department in 2007. Therefore, all the pediatric (younger than 18 years) patients undergoing a cardiac operation in the period from January 2007 through October 2009 were considered for being included in this study. This group comprised 732 patients. One hundred thirty-four patients were excluded because they were operated on without CPB. Continuous ScVO₂ monitoring is usually applied in operations of medium to high complexity; therefore, 254 patients were excluded because of the simple nature of the operation. The remaining 344 patients were analyzed, and a group of 68 patients was excluded because they did not receive continuous SCVO₂ monitoring.

From the remaining group of 266 patients, 10 patients were excluded because they demonstrated a pre-CPB lactate value higher than 3.0 mmol/L. A final group of 256 nonconsecutive patients was therefore retrieved, and constituted the patient group for this study.

The following data were collected from the Institutional Database or direct analysis of the perfusion files: demographics: age (months), weight (kg), gender; type of surgical operation with Aristotle complexity score [16]; preoperative laboratory data: hematocrit (percentage), platelet count (cells/microliter), prothrombin time (seconds), activated partial thromboplastin time (seconds), antithrombin (percentage), serum creatinine value (milligrams per deciliter); CPB data: CPB duration (minutes), lowest temperature on CPB (degrees Centigrade), use of blood prime, ScVO₂ values (percentage), and lactate values (mmol/L). Lactate values were obtained from standard arterial blood gas analysis (Nova Biomedical, Waltham, MA).

ScVO₂ values are routinely recorded in the perfusion files at an interval of 10 minutes, whereas lactate values are recorded in correspondence with the arterial blood gas analysis, at intervals of 20 to 30 minutes. In our daily practice, the perfusionist is instructed not to record low values of ScVO₂ maintained for a short period of time (< 5 minutes) because of surgical maneuvers and the need for decreasing pump flow according to the surgeon's instructions. Therefore, the ScVO₂ values recorded are usually maintained for a time of at least 10 minutes, until the subsequent recording.

For each patient, we detected the nadir ScVO ₂ value (lowest SCVO₂ on CPB) and the peak lactate value (highest lactate value on CPB).

ScVO₂ was measured by using a double-lumen CVC inserted through the right internal jugular vein into the superior vena cava, in a position proximal to the insertion of the venous cannulation for CPB. The CVC catheter incorporates fiberoptic technology for oxygen saturation and was released a few years ago for use in neonates and pediatric patients (Pediasat; Edwards Lifesciences, Irvine, CA). Details of the positioning were previously published by our group, as well as validation data [17]. In particular, our protocol avoids entering the right atrium in all the procedures requiring the opening of this chamber, to obtain hemoglobin saturation data even during CPB. ScVO₂ data are obtained by connecting the Pediasat CVC to a dedicated monitor (Vigileo; Edwards Lifesciences, Irvine, CA).

Anesthesia was carried out according to our institutional practice. Induction of anesthesia was achieved with intravenous midazolam. A high-dose opioid anesthetic (fentanyl, 50 μg/kg) was used for maintenance of anesthesia and supplemented with midazolam and sevoflurane as tolerated. Neuromuscular blockade was achieved with vecuronium or atracurium. All patients underwent endotracheal intubation and were mechanically ventilated. Standard monitoring was used, which included a radial or femoral artery catheter for measurement of systemic arterial blood pressure and intermittent blood sampling, a double-lumen right internal jugular catheter, and esophageal and rectal temperature probes.

Cardiac cannulation was performed after intravenous administration of 300 IU/kg of unfractionated heparin and only after an activated clotting time of longer than 450 seconds was achieved. Additional heparin boluses were used to maintain an activated clotting time in this range before and during CPB. Double venous cannulation of the superior and inferior vena cava was generally performed. The arterial cannula was placed into the ascending aorta. The CPB circuit included a hollow fiber oxygenator (Dideco D901 or D902; Sorin Group, Mirandola, Italy) with an arterial line filter and a centrifugal pump (Bio-Medicus; Medtronic, Minneapolis, MN). In the blood-primed patients, the CPB circuit was primed with a solution containing red blood cells (RBCs) and a 4% albumin solution. The solution was titrated to reach a hematocrit value of 30% once the patient was connected to the circuit and CPB was initiated. The total priming volume varied between 350 mL and 450 mL. Therefore, the amount of RBCs used in the priming solution varied according to the patient's baseline hematocrit, weight, and the priming volume used. In all patients, less than a 250-mL volume of RBCs and only one bag of stored RBCs were used for priming the circuit. Non-blood-primed patients received a 4% albumin solution for priming the CPB circuit. CPB flow was targeted at 150 mL/kg and subsequently adjusted according to the patient's temperature.

The target patient temperature was chosen by the surgeon based on the type or surgical procedure being performed and personal preferences. All procedures were performed by using a regimen of mild (32°C to 34°C), moderate (26°C to 31°C), or deep (20°C to 25°C) hypothermia. Patients were treated with an alpha-stat strategy if mild hypothermia was used and with a pH-stat strategy if moderate or deep hypothermia was used.

Cardiac arrest was obtained and maintained by using antegrade intermittent blood cardioplegia. After completion of the CPB and removal of the cannulas, heparin was reversed by using protamine sulfate at a 1:1 ratio.

The following outcome data were recorded: mechanical ventilation time (hours); ICU stay (days); neurologic complications (stroke, choreoathetosis, seizures); acute renal failure (need for renal-replacement therapy); pulmonary complications (respiratory distress syndrome; poor gas exchange resulting in a delayed weaning from mechanical ventilation; pneumonia); gastroenteric complications (necrotizing enterocholitis, mesenteric ischemia, gastric bleeding); need for extracorporeal membrane oxygenation or ventricular-assist device; or sepsis (with positive blood cultures). Major morbidity was defined as the presence of at least one of these complications, with or without hospital mortality. Hospital mortality was defined as mortality occurring during the hospital stay.

Continuous variables were explored for normality of distribution by using a Kolmogorov-Smirnov test, and in case of nonnormal distribution were presented as median and interquartile range and analyzed with nonparametric tests. Categoric data are presented as number and percentage. The Kruskal-Wallis test was applied for comparing between-group differences. Correlation between continuous variables was assessed by using a linear or polynomial regression analysis, producing an r² correlation coefficient.

Association of independent variables with the two outcome measurements (major morbidity and mortality) was explored by using a logistic regression analysis. To control for other covariates, multivariate logistic regression analysis was used, producing odds ratios with a 95% confidence interval.

The predictive accuracy of nadir ScVO₂ and peak lactate for major morbidity and mortality was explored by using the receiver operating characteristic (ROC) curve and the relative area under the curve (AUC). For each parameter, different cut-off points were tested for sensitivity, specificity, and positive and negative predictive power.