This retrospective study enrolled 192 consecutive newborns, infants and small children who underwent cardiac surgery using CPB and who required RBC transfusion to prime the CPB circuit. A second group of 47 patients being transfused after CPB was separately analyzed. All patients underwent surgery at our institution between January 2006 and December 2008. The duration of RBC storage of the transfused blood was not available before January 2006 in our database. During the study period, 948 patients were operated on for congenital heart disease at our Institution. Two hundred forty-five were adult (>16 years) congenital patients, and 123 were excluded because they were operated on without CPB; the remaining 580 did not receive RBC transfusions to prime the CPB circuit: 98 of these patients received RBC transfusions after CPB, and the remaining were not transfused. It is our policy not to use blood prime in patients weighing more than 10 kg, unless they are severely anemic.
For patients needing a blood prime, it is our policy to ask the blood bank to provide us with RBCs stored for less than seven days; however, this is not mandatory, and depending on availability patients may receive RBCs stored for a longer period of time.
The study design was approved by the local Ethics Committee and the need for parental consent was waived given the retrospective nature of the study. The primary endpoint of the study was to determine patients' morbidity based on the duration of storage of the blood that patients received and to compare major morbidity rates in patients receiving newer vs. older blood. The secondary endpoint was to examine the metabolic profile of patients during CPB based on RBC storage time.
Pediatric patients undergoing a cardiac operation using CPB during the study period in whom RBCs were used in the priming solution of the CPB circuit were included in the blood-prime group. The use of RBCs in the priming solution is a current practice at our institution in cases when the use of a crystalloid or colloid priming solution would result in a severe hemodilution. Patients receiving RBCs both in the priming solution and after CPB were included in this group. Patients receiving RBC transfusions only after CPB were separately analyzed (post-CPB transfusion group).
Anesthesia, cardiopulmonary bypass, and cardiac surgery technique
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. 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 or femoral central venous 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, USA).
In the blood-prime group the CPB circuit was primed with a solution containing 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. Only one bag of stored RBCs was used to prime the circuit.
Patients in the post-CPB transfusion group 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 of surgical procedure being performed and personal preferences. All procedures were performed 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 using antegrade intermittent blood cardioplegia.
After completion of the CPB and removal of the cannulas, heparin was reversed using protamine sulfate at a 1:1 ratio.
During and after CPB, additional RBCs were administered as needed in order to maintain a hematocrit value within our standard range. These additional RBCs either came from the first blood bag or from a second blood bag. No patient received RBCs from more than two blood bags during the operation. No leukodepleted blood was used for intraoperative transfusions.
Pre- and intraoperative data were derived from our institutional database. Data collected included age (months), weight (kilograms), hematocrit (%), serum creatinine level (mg/dL), serum bilirubin level (mg/dL), platelet count (cells/μL), prothrombin activity (%), activated partial thromboplastin time (seconds), antithrombin activity (%), redo operations, type of operation, the Aristotle severity score of the operation , CPB duration (minutes), priming volume (mL), lowest temperature (°C) reached while on CPB, and lowest hematocrit (%) reached while on CPB.
The duration of storage time of the RBCs used during and after CPB was obtained from our computerized blood bank files. Records of metabolic data during CPB were collected from perfusionists' files.
After 10 minutes on CPB, the following data were collected: arterial pH, arterial pCO2 (mmHg), and arterial base excess as well as potassium (mEq/L), calcium (mEq/l), lactate (mmol/L), and glucose (mg/dL) blood concentrations. The peak values of potassium, lactate and glucose obtained during CPB were also collected.
Outcome variables were derived from our institutional database. The following variables were collected: mechanical ventilation time (hours), intensive care unit (ICU) stay (hours), blood loss (mL/12 hours), peak postoperative creatinine level (mg/dL), and peak postoperative bilirubin level (mg/dL) as well as the need for postoperative allogeneic RBC, fresh frozen plasma, or platelet transfusions. Postoperative morbidity and mortality data were also collected. Parameters collected included data regarding low cardiac output (defined as the need for inotropic support for more than 48 hours postoperatively), acute renal failure (ARF) (defined as the need for renal replacement therapy), pulmonary complications (defined as respiratory distress syndrome or pneumonia), neurological complications (defined as stroke, coma, or neurologic defects still present at hospital discharge), gastroenterological complications (defined as bleeding, necrotizing enterocolitis, or liver failure), sepsis, and in-hospital mortality.
Major morbidity was defined as the presence of one or more of the following: ARF, sepsis, or pulmonary, neurological, or gastroenterological complications.
The patients were divided into two groups: patients receiving newer blood and patients receiving older blood. The storage time of the RBCs used was analyzed using the following steps:
1. For patients receiving more than one unit of RBCs, the oldest unit of RBCs received was used for group allocation.
2. The median value of blood storage time was assessed, and patients were attributed to the newer blood group if they received only blood that had been stored for a period of time (days) equal to or shorter than the median value. Patients were attributed to the older blood group if they received any amount of RBC stored for a period of time longer than the median value.
3. For analysis of the metabolic data during CPB, the same procedure was followed, but only the unit of blood used for priming the circuit was taken into consideration when allocating patients to groups based on the duration of RBC storage.
4. The group of patients receiving only postoperative transfusions was selected based on an age range similar to the blood-prime group.
Continuous variables are presented as median values and interquartile ranges, and categorical variables are presented as numbers and/or percentages in the tables and the text. To compare data between groups, we used two-sided tests. The Wilcoxon rank-sum test was used to compare continuous variables and Pearson's chi-square test was used to compare categorical variables. Yates correction was applied when appropriate.
In order to better elucidate the relationship between RBC storage time and the primary endpoint variable (major morbidity), we performed a logistic regression analysis based on the oldest RBCs each patient received. To adjust for potential confounders, other pre- and intraoperative factors thought to be associated with conditions included in the definition of major morbidity were explored. A forward stepwise multivariable logistic regression analysis was performed to detect whether or not RBC storage time was an independent risk factor for major morbidity. The same analysis was applied to relevant single morbidity events.