EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital.

Material and Methods: We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge.

Results: Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic liver transplant (7.3% vs 0%, P = .09) were similar between the groups.

Conclusions: During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

Key words : Anesthetic management, Pediatric, Orthotopic liver transplant, Fulminant hepatic failure, End-stage liver disease

Orthotopic liver transplant (OLT) is the standard of care for children with fulminant hepatic failure (FHF) and end-stage liver disease (ESLD).^1-3 The first pediatric liver transplant performed by Thomas E. Starzl, MD, in 1963. The success rate in OLT gradually depends on perioperative management.

Fulminant hepatic failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency owing to impairment of liver function caused by massive or submassive liver necrosis. Acute liver failure is almost synonymous with FHF.1 End-stage liver disease may be associated with several abnormalities including the development of complications of cirrhosis, including ascites, spontaneous bacterial peritonitis, esophageal variceal hemorrhage, hyperdynamic circulation, portopulmonary hypertension, and portorenal syndrome.

This article sought to evaluate anesthetic management and short-term morbidity and mortality in a series of pediatrics patients who underwent an OLT for FHF according to the Kings College Criteria for ESLD.

Materials and Methods

After obtaining approval from the Institutional Review Board (KA12/249), between May 2002 to May 2012, 41 patients underwent OLT for FHF or ESLD. The patients were younger than 16 years and categorized into 2 groups according to the reason for OLT: group FHF (n=22) and group ESLD (n=19).

The patients in group FHF had been diagnosed with acute liver failure, which was defined as severe impairment of liver function plus encephalopathy that developed within 8 weeks of the first signs of illness in the absence of underlying chronic hepatic disease.⁴ Plasmapheresis was performed in group FHF until a donor liver was available.

The same anesthetic and surgical techniques were used in all patients. They were admitted to the intensive care unit at the end of the surgery. The same surgical and anesthesia team performed all OLTs. After the operation, patients were routinely maintained on mechanical ventilation until spontaneous breathing effort was evident and hemodynamic stability had been achieved.

The information gathered from the subjects’ records included demographic features of sex, age, weight, body surface area; cause of ESLD or FHF; preoperative and postoperative values for serum creatinine, total and direct bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, hemoglobin, platelet count, prothrombin time, and activated partial thromboplastin time; use and volume of crystalloid, colloid, packed red cell blood cells, fresh frozen plasma, platelets, cell saver; anhepatic phase duration; diuretics; vasopressors; anesthesia duration; and urine output. We also noted the length of stay in the intensive care unit and the hospital, time to extubation, mortality rates at 1 year, and the need for plasmapheresis and dialysis.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 14.0, IBM Corporation, Armonk, NY, USA). The 2 groups were compared using the chi-square and the Mann-Whitney U tests when appropriate. Data are expressed as mean values ± standard deviations (mean ± SD). P < .05 was considered significant.

During the 10-year period, we assessed 41 patients who were younger than 16 years old who underwent an OLT. The major indications for OLT were viral hepatitis in group FHF (63.6%) and Wilson disease in group ESLD (21.1%). The mean age and weight for groups FHF and ESLD were 8.6 ± 2.7 years versus 10.8 ± 3.8 years (P = .03) and 29.2 ± 11.9 kg versus 33.7 ± 16.9 kg (P = .46). The source of the donor liver was a deceased donor in 4.5% of patients in group FHF and 21.1% in group ESLD (P = .10). Length of stay in intensive care unit preoperatively for groups FHF and ESLD was 3.14 ± 4.00 vs 1.47 ± 3.83 days (P = .003). When compared with the patients in group FHF, those in group ESLD more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Patient characteristics, primary diagnoses, and preoperative laboratory values for 2 groups are detailed in Table 1.

There were no differences between the 2 groups regarding the length of anhepatic phase (65 ± 21 min vs 73 ± 18 min; P = .13) and operative time (9.1 ± 1.6 h vs 9.5 ± 1.8 h; P = .23). Colloid solution (20% human albumin) (13.33 ± 10.77 mL/kg vs 10.41 ± 7.00 mL/kg; P = .63), packed red blood cells (26.39 ± 20.85 mL/kg vs 18.21 ± 14.73 mL/kg; P = .11), fresh frozen plasma (23.47 ± 12.62 vs 18.43 ± 11.02 mL/kg; P = .11) were similar intra-operatively for both groups. Patients in group FHF received more crystalloid solution intraoperatively than those in group ESLD (66 ± 40 mL/kg vs 105 ± 52 mL/kg; P = .01). Intraoperative urine output was similar for the FHF and ESLD groups, 2.33 ± 1.48 mL/kg/h vs 3.2 ± 2.15 mL/kg/h (P = .10). The intraoperative vasopressor requirements were similar in both groups (P > .05). As well, intraoperative cell saver use (3.81 ± 6.73 mL/kg vs 10.73 ± 24.20 mL/kg, P = .80) was similar in both groups (P > .05). Compared with those patients in group FHF, those in group ESLD were more frequently extubated in the operating room (31.8% vs 89.5% P < .001). Table 2 shows intraoperative parameters for 2 groups.

Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d; P = .05), postoperative length of stay in the hospital (23.91 ± 13.14 d vs 41.68 ± 55.45 d; P = .15), and mortality rates at 1 year after the OLT (7.3% vs 0%; P = .09) were similar between the groups. Postoperative laboratory values at 1 and 7 day after OLT and other data for the groups are detailed in Table 3.

We analyzed anesthetic management with short-term outcome in pediatric patients who underwent an OLT for FHF or ESLD. Our results suggest that those children with FHF require more perioperative intensive care than those with ESLD. According to the literature, no studies systematically investigated the anesthetic management along with short-term outcome in pediatrics patients who underwent an OLT for FHF or ESLD. The survival rate in hepatic failure is low without a liver transplant, despite improvements in intensive care management. Many factors may play a role in morbidity and mortality duration of OLT.^5,6 On the other hand, a pediatric liver transplant is expensive for a medical center, owing to the cost of the intensive care.⁷

Patients with FHF have a survival rate between 60% and 76%⁶; our patients with FHF had a survival rate of 81.8% 1 year after OLT. Also, the mortality rates 1 year after OLT (7.3% vs 0%; P = .09) were similar between the groups. Outcomes after the OLT have significantly improved because of perioperative care. A short wait list time for OLT is an important factor in the success of pediatric patients with FHF.

In the present study, plasmapheresis with fresh frozen plasma was usually performed in group FHF until a donor liver was available. We used more fresh frozen plasma in group FHF preoperatively (152.00 ± 104.63 mL/kg vs 18.86 ± 28.99 mL/kg, P = .0).

Our study also found that the Glasgow Coma score system does not represent a potential pretransplant method to predict posttransplant outcome. No correlation with 1-year patient survival was seen. This study expands earlier studies that corroborate the predictive value of Glasgow Coma score on postpediatric liver transplants. Conversely, deterioration of mental status results in patients requiring mechanical ventilation and intensive support during hospitalization.8 In our study, the length of stay in the intensive care unit pre-operatively for groups FHF and ESLD were 3.14 ± 4.00 vs 1.47 ± 3.83 day (P = .003). Compared with patients in group FHF, those in group ESLD were more frequently extubated in the operating room (31.8% vs 89.5% P < .001).

Several investigators have reported high incidence rates of respiratory complications after an OLT. In this study, no differences were observed in postoperative hemodynamics, respiratory, and renal systems between the groups.

There were some limitations to our study. Primarily, all patients were under 16 years old, but there was a difference between the groups regarding age (P = .03). Also, there were no differences between the groups regarding weight and body surface area. Another limitation of this study, which was limited clinical data, was retrospective—we analyzed registry data, missing data were common and misclassification of important exposures was possible.

In summary, this study represents a single-center analysis of short-term outcomes after pediatric OLT for FHF or ESLD at a university hospital. In the present study, pretransplant intensive care unit acuity and mechanical ventilation requirement do not predict patient survival. Fulminant hepatic failure requires intensive care unit and perioperative mechanical ventilation support.

Volume: 12 Issue: 1 March 2014 - Supplement - 1

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