Study design and patients
This was a prospective study of infants with congenital biliary atresia who had to undergo selective liver transplantation from January to December 2017 at Tianjin First Central Hospital. This study was approved by the Medical Ethics Committee of the hospital (#2016N0039KY) and written informed consent was obtained from the infants’ guardians. The privacy rights of human subjects always be observed. This study was registered at ClinicalTrials.gov (#NCT03024840).
The inclusion criteria were: 1) 4-12 months of age; 2) American Society of Anesthesiologists (ASA) physical status III or IV); and 3) scheduled to undergo elective pediatric living related donor liver transplantation. The exclusion criteria were: 1) known or suspected allergy to propofol, soy, or egg; 2) congenital heart disease, or impairment of renal or pulmonary function before liver transplantation; or 3) compound other site operation. All living donors were family members (father or mother). Every case of transplantation has passed ethical review and approval from Tianjin First Center Hospital.
Anesthesia and intraoperative management
All infants underwent combined intravenous and inhalation anesthesia. Preoperatively, routine fasting was performed (formula and milk were banned for 6 h before surgery; breast milk was not allowed for 4 h before surgery, and drinking was banned for 2 h before surgery). Atropine (0.01 mg/kg) was intramuscularly injected 30 min before anesthesia. After being transferred to the operating room, routine monitoring of pulse oxygen saturation (SpO2) and electrocardiogram (ECG) was conducted. Peripheral venous access was opened. Rapid induction of anesthesia was performed using: methylprednisolone at 1 mg/kg, midazolam at 0.05 mg/kg, etomidate at 0.2 mg/kg, fentanyl at 2 µg/kg, and vecuronium bromide at 0.08 mg/kg. Auscultation of both lungs was performed after oral tracheal intubation to ensure clear breath sounds of both lungs. The ventilator was connected to mechanical ventilation to observe the normal waveform of the end-tidal carbon dioxide (PETCO2). Fraction of inspiration oxygen was 50%-60% (100% at the anhepatic phase), tidal volume was 8-10 ml/kg, respiratory rate was 20-26 breaths/min, and the inspiration and expiration ratio was 1.0:1.5-2.0. PETCO2 partial pressure of 30-35 mmHg and airway pressure of 18-25 cmH2O (1 cm H2O=0.098 kPa) were maintained. After anesthesia induction was stable, the bispectral index (BIS) values were monitored. B-mode ultrasound-guided radial artery catheterization for invasive blood pressure monitoring and placement of triple-lumen central venous catheter through the right internal jugular vein for monitoring of central venous pressure (CVP) and intraoperative infusion were performed. Anesthesia maintenance was done using: continuous intravenous infusion of 1% propofol at 9-15 mg/kg/h, remifentanil at 0.1-0.2 µg/kg/min, and cisatracurium besylate at 0.12 mg/kg/h. Fentanyl at 1-3 µg/kg was added intermittently to maintain the depth of anesthesia. The intraoperative fluid infusion was warmed. Sodium lactate and glucose injection and albumin solution were intravenously infused. Body temperature was maintained at 36.0-37.5°C. According to the results of intraoperative blood gas analysis and coagulation function monitoring, the appropriate amount of concentrated red blood cells and fresh frozen plasma were infused. By adjusting the transfusion speed and continuous intravenous infusion of small doses of dopamine, mean arterial pressure (MAP) of 40-65 mmHg (1 mmHg=0.133 kPa), CVP of 6-8 mmHg, heart rate (HR) of 110-170 beats/min, SpO2 of 95-100%, body temperature of 35.5-37.5°C, BIS of 40-60, PETCO2 of 35-45 mmHg, hemoglobin (Hb) >80 g/L, and urine volume >1 ml/kg/h were maintained. According to the results of arterial blood gas analysis, the breathing parameters were adjusted in time. A heating blanket and infusion heating device were used to maintain the body temperature constant.
Data collection and examination methods
Central venous blood (1 mL) was collected into coagulation tubes at the beginning of skin incision after anesthesia (T1), 30 min after anhepatic phase (T2), 1 h after neohepatic phase (T3), and 24 h after neohepatic phase (T4). The samples were placed at room temperature for 10 min, centrifuged at 6000 rpm for 10 min, and stored at -80°C.
NSE and S-100β were detected with the use of enzyme-linked immunosorbent assay (ELISA) (Shanghai Biovol Technologies). HR, MAP, CVP, and BIS were recorded at each time point.
Two doctors independently conducted evaluations 1 day before surgery and 3 months after surgery. The Bayley Scales of Infant Development (BSID) is a standardized technique and measurement tool for evaluating the psychomotor behaviors of children aged from 2 months to 3 years . BSID revised by the Hunan Medical University in 1990 was used to assess the psychomotor and behavior development conditions of all infants investigated . According to the raw score, the corresponding mental development index (MDI) and psychomotor development index (PDI) were calculated to analyze the effect of liver transplantation on the neurocognitive behaviors of infants. All examinations were carried out in a quiet environment. The MDI and PDI are standard scores obtained from conversion table based on the corresponding raw score of age and other values. The average number is 100, and the standard deviation is 16; >90 points indicate normal level, and < 90 indicate poor development. The postoperative delirium of infants was independently evaluated by two physicians at 30 min, 2 h, and 4 h after extubation using the pediatric anesthesia emergence delirium (PAED) scale .
Statistical analyses were performed using SPSS 20.0 (IBM, Armonk, NY, USA). Continuous data were tested with the Kolmogorov-Smirnov test and are presented as means ± standard deviation or medians (first and third quartiles), as appropriate; they were analyzed using repeated-measures ANOVA with the post hoc test across different time points. Categorical data are presented as numbers (percentage) and compared with the chi-square test. Pearson correlation was used to analyze the correlations among the NSE and S-100β at T3, PAED score at 30 min, MDI and PDI at 1 month after surgery. P values <0.05 were considered statistically significant.