We enrolled 60 patients in our study, aged between 6 and 24 months. All of them had received the same anesthetic protocol under similar conditions and undergone elective total surgical repair using CPB.
After the approval of the Ethical Committee of Ain Shams University with FMASU MD 64/2020, this interventional, randomized, and prospective clinical study was conducted at Ain Shams University Hospitals from February 2020 to February 2021. Written informed consent was obtained from the patients’ legal guardians after explaining the procedure and its potential complications.
We enrolled 60 patients, aged from 6 months to 2 years of both sexes, diagnosed with non-cyanotic congenital heart diseases underwent total repair under cardiopulmonary bypass (CPB), and scheduled for elective operations.
Patients who were scheduled for palliative surgeries, reoperation, underwent emergency surgeries, patients with reduced left ventricular function as determined by left ventricular ejection fraction less than 40%, patients with renal or liver impairment as determined by elevated creatinine levels or liver enzymes more than normal values for age, or patients with any neurological dysfunction as epilepsy and cerebral palsy were excluded.
Patients for both groups were admitted to the hospital the night before the procedure. In the morning, the patients were shifted to the operating room, and the peripheral intravascular access was inserted. After applying the standard monitoring devices with pulse oximetry, 5 leads electrocardiogram, capnography (end-tidal CO2), and non-invasive blood pressure, all operations were performed using a standard general anesthesia protocol with using intravenous induction with ketamine (1–2 mg/kg) and atropine (0.01–0.02 mg/kg) after the intravenous blood access was obtained, then injection of midazolam (0.05–0.1 mg/kg), fentanyl (10–20 mcg/kg), and cisatracurium (0.15 mg/kg) were followed.
After induction, the endotracheal tube was inserted; its position was confirmed with chest auscultation and capnography tracing. An intraarterial catheter using a femoral puncture was inserted. The central venous catheter was inserted using a transjugular (or femoral) approach with ultrasound guidance. The maintenance of anesthesia was done with sevoflurane inhalational (1–2%), infusion of morphine (20 mcg/kg/h), and cisatracurium (2 mcg/kg/min).
A median sternotomy approach and CPB with mild systemic hypothermia (32–28 °C) were used. Topical cooling with ice was used in both groups.
Conventional ultrafiltration was performed by the end of CPB in all patients, to increase hematocrit to 40%, and was started earlier in the group of patients who received HTK solution.
Patients were randomly allocated by computer-generated randomization and using opaque-sealed envelopes into two groups according to the type of the cardioplegic solution used.
Patients who were allocated to the HTK group received the cold HTK solution (4–8 °C), administered as a single dose for up to 3 h of ischemia, antegrade in the aortic root, for 6–8 min, with an infusion of 30 mL/kg.
Patients who were allocated to the HHB group received the HHB solution; the crystalloid solution was obtained by adding 15 ml of 15% KCL (30 mEq), 25 ml of 8.4% NaHCO3 (25 mEq), and 5ml of 2% lidocaine (100 mg) to a 1L Ringer’s lactate. A blood cardioplegia circuit was added to the CPB machine. The perfusionist added 60 mEq KCL to the crystalloid solution via using the cardioplegia delivery system. The HHB cardioplegia was given by the perfusionist on CPB with a heat exchanger as the temperature was regulated to 4 °C and a pressure control (up to 200 mmHg prior to the heat exchanger). The dilution ratio was a 4:1 (4 parts autologous blood to 1 part crystalloid) mixture. The cardioplegia was delivered at a dose of 30 ml/kg initially, administered into the aortic root for 4–5 min, followed by repeated doses of (15 ml/kg) at 20–25 min intervals using the same pattern.
We compared HTK cardioplegia with HHB cardioplegia regarding their effectiveness in pediatric myocardial preservation. The parameters which were evaluated in this study are age (months), weight (kilogram), gender, duration of surgery, CPB, aortic clamping time (minutes), left ventricular function (EF%), level of cardiac troponin, maximum vasoactive inotropic score, ICU length of stay (LOS) (days), hospital LOS, and the incidence of prolonged postoperative mechanical ventilation more than 24 h.
The primary outcome was cardiac troponin level which was measured preoperatively (basal) once then at the end of the procedure (0 h post-CPB) and at 4, 8, 12, 18, 24, and 48 h postoperatively.
The secondary outcomes were the left ventricular ejection fraction (EF%) and the fractional shortening (FS) percentage, the maximum vasoactive inotropic score, ICU-LOS (days), the incidence of prolonged postoperative mechanical ventilation (>24 h), and the hospital LOS (days).
The left ventricular systolic function was estimated by using transesophageal echocardiography pre- and post-CPB. And by using transthoracic echocardiography after 24 and 48 h postoperatively, M Mode modality was applied to measure the left ventricular ejection fraction (EF) and fractional shortening (FS).
The inotropic support for each patient was estimated according to the maximum vasoactive inotropic score (VIS). Maximum VIS for both the first 24 h and the next 24 h were calculated. It was calculated according to Gaies et al.’s study as follows: VIS= dopamine dose (mcg/kg/min) + dobutamine dose (mcg/kg/min) + 100 × epinephrine dose (mcg/kg/min) + 10 × milrinone dose (mcg/kg/min) + 10,000 × vasopressin dose (U/kg/min) + 100 × norepinephrine dose (mcg/kg/min) (Gaies et al. 2010).
Inotropes and vasopressors were added after CPB if the systolic blood pressure is less than 90 mmHg in adequately preloaded patients.
The collected data was revised, coded, tabulated, and introduced to a PC using the Statistical package for Social Science (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp). Data was presented and suitable analysis was done according to the type of data obtained for each parameter. Shapiro Wilk’s test was used to evaluate the normal distribution of continuous data (Ghasemi and Zahediasl 2012). The mean, standard deviation (± SD), and range were used for parametric numerical data, while the median and interquartile range (IQR) was used for non-parametric numerical data. Student’s T test was used to assess the statistical significance of the difference between the two study group means. Mann-Whitney test (U test) was used to assess the statistical significance of the difference of a non-parametric variable between two study groups. Regarding the level of significance, P value < 0.05 was considered significant, P value < 0.001 was considered highly significant, and P value > 0.05 was considered insignificant.
The sample size was calculated using the G*power program, setting the type-1 error (α) at 0.05 and the power (1-β) at 0.8. Results from the previous study (Caputo et al., 2002) showed that the mean (95% confidence interval (CI)) of Troponin I in the cold blood cardioplegia group (CBC) was 2.4(0.7), while for cold crystalloid cardioplegia (CCC) group, it was 4.3 (1.8). The CI was transformed to standard deviation through the formula: SQRT (n)* CI/ (t alpha, df *2) to be ±1.14 and±2.82 for CBC and CCC, respectively. Calculation according to these values produced a sample size of 30 cases per group taking into consideration a 20% dropout rate.