Yang SC, Huang CJ, Chen CL, Wang CH, Wu SC, Shih TH, Juang SE, Lee YE, Jawan B, Cheng YF, Cheng KW. Living donor liver transplantation with body-weight more or less than 10 kilograms. World J Gastroenterol 2015; 21(23): 7248-7253 [PMID: 26109812 DOI: 10.3748/wjg.v21.i23.7248]
Corresponding Author of This Article
Kwok-Wai Cheng, MD, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123 Ta-Pei Road, Niao Song, Kaohsiung 83301, Taiwan. kwcheng@ms2.hinet.net
Research Domain of This Article
Transplantation
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Sheng-Chun Yang, Chia-Jung Huang, Chih-Hsien Wang, Shao-Chun Wu, Tsung-Hsiao Shih, Sin-Ei Juang, Ying-En Lee, Bruno Jawan, Kwok-Wai Cheng, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
Chao-Long Chen, Department of Surgery and Liver Transplant Program, Kaohsiung Chang Gung Memorial and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
Yu-Feng Cheng, Department of Radiology, Kaohsiung Chang Gung Memorial and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
ORCID number: $[AuthorORCIDs]
Author contributions: Yang SC, Huang CJ contributed equally to this work as first author, designed, collected, analyzed the data and interpretation, wrote the report; Cheng KW designed, collected, analyzed the data and interpretation, wrote the report; Chen CL, Wang CH, Wu SC, Shih TH, Juang SE, Lee YE, Jawan B and Cheng YF participated in data collection, analysis and data interpretation.
Ethics approval: The study was reviewed and approved by the Institutional Review Board for Human Studies of Chang Gung Memorial Hospital (101-1945B).
Conflict-of-interest: All authors declare no conflict of interest and funding in this work.
Data sharing: Informed consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kwok-Wai Cheng, MD, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123 Ta-Pei Road, Niao Song, Kaohsiung 83301, Taiwan. kwcheng@ms2.hinet.net
Telephone: +886-77317123 Fax: +886-77318762
Received: January 12, 2015 Peer-review started: January 13, 2015 First decision: March 10, 2015 Revised: March 27, 2015 Accepted: May 4, 2015 Article in press: May 4, 2015 Published online: June 21, 2015 Processing time: 159 Days and 6.7 Hours
Abstract
AIM: To compare the outcomes of pediatric patients weighing less than or more than 10 kg who underwent liver transplantation.
METHODS: Data for 196 pediatric patients who underwent living donor liver transplantation between June 1994 and February 2011 were reviewed retrospectively. The information for each patient was anonymized and de-identified before analysis. The data included information regarding the pre-transplant conditions, intraoperative fluid replacement and outcomes for each patient. The 196 patients were divided into two groups: those with body weights of less than 10 kg were included in group 1 (G1; n = 101), while those with body weights of more than 10 kg were included in group 2 (G2; n = 95). For each group, the patients’ ages, body weights, heights, pediatric end stage liver disease scores, anesthesia times, and warm and cold ischemic times were analyzed. In addition, between-group comparisons were also made. Mann-Whitney U tests were used to compare all the variables except for complications and survival rates, which were analyzed using χ2 tests and Kaplan-Meier tests, respectively.
RESULTS: The general medical conditions of the G1 patients were worse than those of the G2 patients, as shown by the higher pediatric end stage liver disease scores and poorer Z-scores. In addition, the pre-operative Hb and serum albumin levels were all lower for the G1 patients than for the G2 patients. The G1 patients also had significantly more intraoperative blood loss than the G2 patients. In addition, the intraoperative fluid requirements for the G1 patients, including leukocyte poor red blood cell transfusions, 5% albumin infusions and crystalloid infusions, were significantly higher than those for the G2 patients. The risk of intraoperative portal vein thrombosis was higher for the patients in G1 than for those in G2. However, the one-year survival rates (95.9% and 96.8% for G1 and G2, respectively) and three-year survival rates (94.9% and 94.6% for G1 and G2, respectively) for both groups were similar.
CONCLUSION: Patients weighing less than 10 kg typically have poorer conditions, but their survival rates are comparable to those of children weighing more than 10 kg.
Core tip: Although pediatric patients weighing less than 10 kg who underwent living donor liver transplantation usually had worse pre-transplant conditions, more intraoperative bleeding and more portal vein complications, their three-year survival rate was 94%, a rate comparable to that achieved by children weighing more than 10 kg. A prerequisite for achieving these excellent results is good and effective teamwork. Cooperation between surgeons, plastic surgeons, and anesthesiologists in the operating theater is fundamental, but the contributions of radiologists are also critical. Radiologists should be available in the operating room to perform Doppler ultrasounds or place vascular stents, as required.
Citation: Yang SC, Huang CJ, Chen CL, Wang CH, Wu SC, Shih TH, Juang SE, Lee YE, Jawan B, Cheng YF, Cheng KW. Living donor liver transplantation with body-weight more or less than 10 kilograms. World J Gastroenterol 2015; 21(23): 7248-7253
Performing living donor liver transplantation (LDLT) for pediatric patients, especially those with body weights of less than 10 kg, poses a challenge for all the participants in the liver transplant team, including anesthesiologists[1,2]. The outcomes of such transplants for pediatric patients weighing less than 10 kg differ from those for pediatric patients weighing more than 10 kg[1-4]. We have previously reported that the average change in core temperature during an LDLT for pediatric patients weighing less than 10 kg is significantly different from that in heavier children[5]. Furthermore, a lower survival rate for lower weight children was reported by Arnon et al[3], and according to other studies, this poorer survival results from higher risks of perioperative vascular complications, bile duct complications and infections[4,6,7]. In pediatric kidney transplantation, the ideal body weight for a recipient has also been found to be greater than 10 kg[8]. Most of the previous reports regarding pediatric organ transplantation have primarily evaluated the outcomes in terms of the morbidity and mortality of the procedure in question[1-4]. However, little information can be found in the literature concerning the anesthetic fluid requirements for pediatric patients with different body weights undergoing LDLT. Thus, the aim of the current study was to evaluate, analyze, and compare data retrospectively regarding the anesthetic fluid requirements for pediatric patients weighing less and more than 10 kg who underwent LDLT, while at the same time also comparing and analyzing the complications and survival rates for such patients.
MATERIALS AND METHODS
Ethics approval
This retrospective study was approved by the Institutional Review Board for Human Studies of Chang Gung Memorial Hospital (101-1945B).
Patient selection and data collection
We collected and analyzed the data from the anesthesia records of pediatric patients who underwent LDLT between June 1994 and February 2011. The information for each patient was anonymized and de-identified before analysis. The general anesthesia, intraoperative monitoring and blood transfusion protocols used[9], as well as their documentation[10], were similar to those described in previously published reports[5,9,11-13]. Estimated blood losses were made through visual estimations of a small (250 mL) suction bottle (Receptal® Accurate Measurement Device, Hospira, Inc. Lake Forest, Il 60045, United States) and the weight of laparotomy sponges. The pediatric patients were divided into two groups: those with body weights of less than 10 kg were included in group 1 (G1), while those with weights of more than 10 kg were included in group 2 (G2). For each group, the patients’ ages, body weights, heights, pediatric end stage liver disease scores (PELDS), anesthesia times, and warm and cold ischemic times were analyzed. In addition, between-group comparisons were made. The gender and age specific Z-scores of the height and weight measurements were also calculated[14]. Likewise, intraoperative blood loss, ascitic loss and fluid replacement amounts were recorded and compared. Laboratory data, including hemoglobin (Hb) levels, serum albumin levels, platelet counts, activated partial thromboplastine times (APTT), international normal ratios (INRs), serum creatinine levels, total bilirubin levels and pH levels were also collected, analyzed, and compared between groups. All data related to body weight were converted to a per-kg basis for comparison. The frequency of perioperative morbidity and one- and three-year survival rates were also compared between the groups.
Statistical analysis
Mann Whitney U tests were used to compare data for all the variables, except for the morbidity and one- and three-year survival rates. The incidences of morbidity were compared by χ2, while the one- and three-year survival rates were compared by Kaplan-Meier tests. A P value < 0.05 was regarded as statistically significant. Data are presented as mean ± SD.
The statistical methods used in this study were reviewed by Dr. Shao-Chun Wu of Chang Gung University, Taiwan.
RESULTS
The patient etiologies (for G1 and G2, respectively) were as follows: biliary atresia (92 patients and 70 patients), neonatal hepatitis (7 and 4), glycogen storage disease (0 and 12), Alagille syndrome (1 and 5), urea cycle disease (1 and 0), fulminant hepatitis (0 and 1), cryptogenic (0 and 1), Wilson’s disease (0 and 1) and hepatitis C virus (0 and 1). Table 1 shows the gender- and age-specific Z-scores for the height and weight measurements in both groups. The Z-score in G1 was < -3, which indicated that the patients had suffered from moderate to severe malnutrition[14]. Table 2 shows the characteristics of the patients in G1 and G2. The PELD scores were significantly higher for the G1 patients, while the pre-operative Hb and serum albumin levels were all lower for the G1 patients. The coagulation test results indicated that APTT and INR were both significantly prolonged in G1 patients and that the G1 patients had higher total bilirubin levels and platelet counts before the operation. Table 3 shows that the average anesthesia time for G1 was longer than the average time for G2, but also that the warm and cold ischemic times were similar between the groups. The extubation times were significantly longer among the G1 patients compared with the times for the G2 patients (Table 4). The absolute amount of blood loss for the two groups was similar. When body weight was taken into consideration and the data were converted to a per-kg basis, it was revealed that the G1 patients had significantly more ascites and greater blood loss per kilogram. Therefore, the G1 patients received significantly more crystalloids, 5% albumin and red blood cells to replace their losses (Table 3). Table 4 shows that the G1 patients also required more sodium bicarbonate to maintain acceptable pH levels and also received more supplemental calcium. Table 5 shows the outcomes of the patients: the perioperative morbidities, except for portal vein complications, were similar between the groups; the one- and three-year survival rates were also similar between the groups (Figure 1). G1 had significantly more perioperative portal vein thrombosis compared with G2, with an odds ratio of 14.143 and a 1.783-112.174 95% confidence interval. Although G1 had more incidences of perioperative portal vein thrombosis, those cases were detected quickly and treated immediately[4], and thus did not seem to affect the survival rates. Overall, the survival rates for both groups were similar, with 95.9% and 96.8% one-year survival rates and 94.9% and 94.6% three-year survival rates for G1 and G2, respectively (Figure 1 and Table 5).
Table 1 The gender and age specific Z-scores of the measurements in height and weight in both groups.
Table 3 Anesthesia time, intraoperative blood loss and fluids replacement.
G1 (n = 101)
G2 (n = 95)
P value
Anesthesia time (h)
13.5 ± 9.3
13.3 ± 2.2
0.035
Blood loss (mL)
215.3 ± 238.8
284.8 ± 447.8
0.573
Blood loss (mL/kg)
28.6 ± 36.7
15.0 ± 21.2
< 0.001
Ascites (mL/kg)
234 ± 379
161.3 ± 383
< 0.001
Crystalloid (mL/kg/h)
16.8 ± 5.5
12.1 ± 5.5
< 0.001
Red blood cells (mL/kg)
29.0 ± 29.0
10.0 ± 17.3
< 0.001
Fresh frozen plasma (mL/kg)
1.5 ± 7.6
5.1 ± 11.0
0.571
5% Albumin (mL/kg)
8.8 ± 6.8
2.3 ± 2.0
< 0.001
Sodium bicarbonate (mEq/kg)
3.4 ± 1.9
2.3 ± 1.9
< 0.001
Calcium chloride (mg/kg)
0.7 ± 0.5
0.34 ± 0.3
< 0.001
Lasix administration (mg/kg)
0.5 ± 1.9
1.0 ± 2.9
0.884
Cold ischemic time (min)
58.6 ± 20.5
65.5 ± 29.1
0.243
Warm ischemic time (min)
49.5 ± 13.9
47.6 ± 14.9
0.226
Table 4 Intra- and postoperative laboratory data between groups.
G1 (n = 101)
G2 (n = 95)
P value
pH - after anesthesia
7.34 ± 0.07
7.36 ± 0.07
0.060
pH - dissection
7.27 ± 0.06
7.30 ± 0.07
0.003
pH - anhepatic
7.26 ± 0.06
7.29 ± 0.10
0.013
pH - reperfusion
7.23 ± 0.06
7.27 ±.09
0.006
pH - end of surgery
7.28 ± 0.07
7.29 ± 0.08
0.215
INR post-operation
2.1 ± 1.0
1.9 ± 0.6
0.900
APTT post-operation (second)
77.2 ± 25.5
55.2 ± 20.9
< 0.001
Platelet post-operation (1000/μL)
109.5 ± 62.9
128.3 ± 74.6
0.070
Postoperative hemoglobin (g/dL)
7.6 ± 1.3
8.5 ± 1.5
0.001
Hemoglobin at extubation (g/dL)
8.2 ± 1.5
8.8 ± 1.5
0.072
Extubation time (h)
61.1 ± 243.5
23.6 ± 36.0
0.047
Table 5 Comparison of the morbidity and mortality between groups.
G1 (n = 101)
G2 (n = 95)
P value
Bile duct complication
5
7
0.528
Hepatic artery complication
9
3
0.092
Hepatic vein complication
2
6
0.274
Portal vein complication
12
1
0.001
Reopen
19
13
0.324
One-year survival rate (%)
95.9
96.8
0.515
Three-year survival rate (%)
94.9
94.6
0.515
DISCUSSION
Our results showed that the G1 patients had significantly different preoperative conditions compared with the G2 patients (Tables 1 and 2). Although the current study included only living donor liver transplantation, organ allocation has nothing to do with PELDS[15]. However, when PELDS were applied to the patients in this study, the G1 patients were indeed found to have higher average PELDS values, with mean values of 15.9 ± 10.9 and 6.8 ± 8.9 for G1 and G2, respectively. PELDS provide a useful model consisting of five objective parameters: total serum bilirubin, INR, albumin, growth failure and age. PELDS can predict death or deterioration in the condition of the patient that may require transfer to the intensive care unit while the patient awaits liver transplantation[16]. The PELDS and the Z-score, an anthropometric parameter for malnutrition[17], indicated that the medical conditions of the G1 patients were indeed worse and that their indications for liver transplantation were relatively urgent compared with those for the G2 patients. Furthermore, more challenging complications and difficulties are to be expected in LT for pediatric patients weighing less than 10 kg[1-4]. Table 3 further revealed that the total anesthesia time for G1 patients was significantly longer than that for G2 patients, most likely because of more difficult placement of arterial lines and the central venous catheter. In addition, more surgical time was needed for G1 patients to solve the intraoperative vascular complications, such as portal vein thrombosis[4,18]. Significant differences in ascites and blood loss were also noted when body weight was taken into consideration. High blood loss index is a risk factor that contributes to poor outcomes of the graft in pediatric LT[19]. The mean blood loss values for G1 and G2 were 28.6 ± 36.7 and 15.0 ± 21.2 mL/kg, respectively. Higher blood loss in infants weighing less than 10 kg has also been reported in open heart surgery[20]. Indeed, blood loss and transfusion requirements were correlated inversely with age and body weight[20]. More blood loss may cause more labile hemodynamic changes, the development of metabolic acidosis and higher incidences of ionized hypocalcemia[12]. Table 3 shows that the G1 patients received significantly more crystalloids (16.8 ± 5.5 vs 12.1 ± 5.5), more RBC (29.0 ± 29.0 vs 10.0 ± 17.3 ) and more 5% albumin (8.8 ± 6.8 vs 2.3 ± 2.0) to meet their losses and that they also received more sodium bicarbonate and supplemental calcium chloride to correct for metabolic acidosis and ionized hypocalcemia[21,22].
Fluid homeostasis differs between infants and children, with the body’s water content decreasing gradually from neonate to infant and from child to adult[23]. G1 patients received more crystalloids, based not only on more blood and ascitic fluid loss, but also on the recommended fluid requirements reported by Holiday and Segar[24] and the massive intraoperative fluid shift in liver transplantation setting (Table 3).
Table 5 shows that the postoperative complications, except for portal vein thrombosis, and the one- and three-year survival rates, were similar between the groups. Portal vein thrombosis is a serious complication of LT, which is associated with high morbidity and mortality in pediatric liver transplantation[19,25,26]. In this study, we experienced 13 cases (12 in G1 and 1 in G2) of perioperative portal vein thrombosis, detected by routine perioperative Doppler ultrasound[4]. Early detection and surgical intervention are crucial in treating portal vein complications. Seven patients with portal vein complications were detected intraoperatively by Doppler ultrasound[4,18]; immediate surgical interventions, such as graft reposition, collateral shunt ligation, thrombectomy and reconstruction of the portal vein, local infusion of heparin through inferior mesenteric vein catheter and endovascular stenting rescued 5/7 patients’ grafts, as well as ensuring the patient’s survival[18]. Multivariate analysis showed that body weight less than 10 kg and age less than one year old were important risk factors of portal vein thrombosis[4]. Although the exact mechanism of portal vein thrombosis is not clear, it is probable that both mechanical factors and hypercoagulopathy contribute to these thrombotic events[26], despite the patients having profound coagulation defects[27]. The hemostasis system of chronic or end-stage liver disease is complex: the pro- and anti-hemostatic pathways can change concomitantly in liver disease, but the change of the anti-hemostatic pathways is usually not well reflected in the routine coagulation tests, because in the latter measures, only the quantity of the procoagulant factors of the complex hemostatic system[27,28]. End-stage liver disease patients may be in hemostatic balance or a rebalanced condition, providing good hemostatic function, but on the other hand, both bleeding and thrombotic complications in the same patient can be encountered[27,28], as seen in our G1 patients (Table 5). The concern for the high incidence of intraoperative portal vein thrombosis in patients weighing less than 10 kg[4] resulted in the administration of significantly less FFP in G1 compared with G2, despite having more bleeding (Table 3).
We have reported that 8.4% of our pediatric LDLT had acquired hyponatremia at the end of the operation. The cause is not related to the body weight, but the only risk factor was administration of more than 3.5 ml/kg per hour of hypotonic solution[29].
In conclusion, the G1 patients had worse preoperative conditions, as shown by their lower Z-scores and higher PELDS compared with the G2 patients. The G1 patients also had more ascites and more blood loss intraoperatively, and required more intensive fluid resuscitation. G1 patients also had more incidences of perioperative portal vein thrombosis, indicating that infants with body weights of less than 10 kg have more surgical and anesthesia risks compared with infants weighing more than 10 kg. When a life-saving procedure can achieve a three-year survival rate of over 94%, it is worthwhile to perform it, no matter how difficult and complicated the procedure may be, even with known high potential lethal complications, such as portal vein thrombosis. A prerequisite for achieving these excellent results is good and effective teamwork. Cooperation between surgeons, plastic surgeons, and anesthesiologists in the operating theater is fundamental; however, the contributions of radiologists are also critical. Radiologists should be available in the OR to perform Doppler ultrasounds before closing the abdomen at the end of the LT procedure to assure sufficient flow in the portal and hepatic arteries[30], and they should also be able to insert a portal vein stent at the operating table if necessary. When a patient has indications requiring an LT, a low body weight of less 10 kg should not be viewed as a reason to delay performing the procedure.
COMMENTS
Background
In the pediatric surgical setting, patients with body weight less than 10 kg are reported to have higher surgical risk in cardiac surgery, and in kidney and liver transplantation in terms of morbidity and mortality.
Research frontiers
This study showed that pediatric weight less than 10 kg had a worse pre-transplant condition, intraoperative bleeding and had higher portal vein complications; however, their 3 year survival was 94%, which was almost as good as that achieved in children of more than 10 kg.
Innovations and breakthroughs
Good cooperation between surgeons, plastic surgeons and anesthesiologists are fundamental in the operating theater; however, the contribution of radiologists is also mandatory. They should be available in the OR to perform Doppler ultrasound before closing the abdomen at the end of a liver transplantation (LT) procedure to assure sufficient flow in the portal, hepatic and hepatic artery, and they should also be able to insert portal vein stent at the operating table if needed.
Applications
This study showed that when there is an indication for liver transplantation, small body weight (less than 10 kg) should not be a reason to delay or hesitate in performing the liver transplantation.
Terminology
Small pediatric patient less than 10 kg is not a contraindication for living donor liver transplantation.
Peer-review
A good and informative paper.
Footnotes
P- Reviewer: Karnsakul W S- Editor: Yu J L- Editor: Stewart G E- Editor: Liu XM
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