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BMC Med
BMC Med
BMC Medicine
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BioMed Central London

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10.1186/s12916-024-03622-6
Research
Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial
Liu Wei 13
Du Min 13
Zhang Mingman 23
Dai Xiaoke 23
Wang Haoming 23
Le Ying 23
Zhi Shenshen 4
Bo Lin 1455973437@qq.com

13
Quan Junjun junjunquan1002@163.com

13
1 https://ror.org/05pz4ws32 grid.488412.3 Department of Anesthesiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014 P.R. China
2 https://ror.org/05pz4ws32 grid.488412.3 Department of Hepatobiliary Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China
3 Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, China
4 grid.190737.b 0000 0001 0154 0904 Clinical Laboratory, Chongqing Emergency Medical Center, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
16 9 2024
16 9 2024
2024
22 3974 6 2024
9 9 2024
© The Author(s) 2024
2024
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Background

The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI).

Methods

Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI.

Results

There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038).

Conclusions

Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12916-024-03622-6.

Keywords

Propofol
Desflurane
Living-related liver transplantation
Infant
Hepatic function
Renal function
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pmcBackground

Liver transplantation (LT) provides an effective treatment for end-stage liver diseases in pediatric patients. In recent years, with advances in surgical techniques, treatment strategies, and intensive care, the survival rate of pediatric LT has been significantly improved [1–3]. Hepatic ischemia–reperfusion (HIR) is one of the most common pathophysiological processes during LT procedure [4, 5], which not only causes damage to the liver itself but also leads to injuries in remote organs, including the brain, lung, kidney, and heart. The multi-organ injuries caused by HIR have complex properties, including a systemic inflammatory response, intracellular calcium overload, oxidative stress response, vascular endothelial injury, and autophagy activation [5–11]. In China, a substantial proportion of pediatric LT involves living-related LT (LRLT) [12].

Infants constitute the majority of recipients of LRLT and possess underdeveloped organs with limited reserves and regulatory functions. The long operation time and intricate nature of LT procedure, reflected by significant hemodynamic fluctuations and severe internal environment disruptions, render LRLT recipients particularly susceptible to organ injuries [13]. Propofol, a general anesthetic agent, has been shown to own the potential to protect against ischemia–reperfusion injury (IRI) in multiple organs [14]. Desflurane, characterized by rapid induction and swift recovery due to its low blood/gas solubility ratio, is an inhalation anesthetic. Emerging evidence indicates that desflurane may have a protective effect against IRI, exhibiting anti-inflammatory effects in animal models and clinical investigations [15]. However, the specific protective effects of these anesthetics on liver and renal functions in pediatric LT, as well as their potential association with graft ischemia–reperfusion, remain unclear. Although some studies have focused on comparing the effects of propofol intravenous anesthesia and desflurane on liver and kidney function after living donor LT, no consistent conclusions have been drawn [16, 17]. Meanwhile, there are no relevant data for the pediatric population, especially infants. Therefore, the objective of this study was to compare postoperative hepatic and renal functions between the infants undergoing LRLT who received either propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalational anesthesia. The elevation of liver transaminase levels was used as an indicator of the degree of hepatic ischemia–reperfusion injury (HIRI). The primary outcome was the alterations of liver transaminase and serum creatinine (Scr) levels during the initial 7 days post-surgery in the two groups, with renal injury, incidence of acute kidney injury (AKI), serious complications, and length of hospital stay as secondary outcomes.

Methods

Study design

This study, a single-center, randomized clinical trial was designed to compare the efficacy of desflurane (Suprane, Baxter, Puerto Rico) and propofol (Diprivan, AstraZeneca, UK) in LRLT. The randomization process was overseen by senior consultants in-charge. All enrolled patients were grouped according to information contained in a randomly numbered sealed envelope, a process performed by a senior consultant who did not participate in follow-up trials. This study was conducted in accordance with the Declarations of Helsinki and Istanbul and approved by the Ethics Committee of our medical center. Written informed consent was acquired from eligible guardians. This trial has been duly registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) and the registration number was ChiCTR2100041620. This work has been reported in line with Consolidated Standards of Reporting Trials (CONSORT) Guidelines [18].

Study population and anesthesia

Infants who were diagnosed with congenital biliary atresia were scheduled to undergo LRLT at our medical center between March 2021 and May 2023. These infants were randomly divided into two groups: the propofol group (group P) and the desflurane group (group D). Exclusion criteria included (1) hypersensitivity to propofol, (2) pre-existing renal impairment necessitating hemodialysis prior to surgery, (3) preoperative presence of multiple organ dysfunction, (4) autoimmune disorders, (5) combined liver and kidney transplantation, and (6) secondary LT.

General anesthesia was initiated using a combination of 0.1 mg/kg midazolam, 3 mg/kg propofol, 1 µg/kg sufentanil, and 0.1 mg/kg cisatracurium. The anesthetic regimens for group P involved propofol infusion at 4 to 12 mg/kg/h, along with remifentanil infusion within the range of 0.1-0.2 µg/kg/min. For group D, the anesthesia induction protocol was the same as that for group P. However, anesthesia was maintained using a concentration of 5–10% desflurane, mixed with 30% oxygen during the intraoperative stage, along with remifentanil. After anesthesia induction, the internal jugular vein and radial artery were rapidly catheterized using Liu’s technique [19], which facilitated the prompt establishment of invasive arterial pressure and central venous pressure monitoring. To maintain hemodynamic stability, continuous infusion of norepinephrine, dopamine, or epinephrine was the treatment for achieving the target mean arterial pressure. To improve the safety of the procedure, all infant recipients were equipped with autologous blood recovery devices. The electrolyte balance, acid–base balance, and transfusion composition were precisely adjusted based on the findings of arterial blood gas analysis.

Importantly, all living donors were the infant’s own father or mother, ensuring a familial origin for the liver grafts. In this study, the general condition, liver anatomy, and functional status of all donors were consistent. All donors underwent left lateral liver lobectomy. The median incision of the abdomen was made to fully expose the left lateral lobe of the liver. The second and then the first portal veins of the liver were dissected successively, and the hepatic parenchyma was incised with an ultrasonic suction knife. The bile duct, hepatic artery, portal vein, and hepatic vein were cut successively, and the left lateral lobe of the liver was removed. The isolated liver was injected with 0–4℃ lactated Ringer’s solution and UW solution through the portal vein immediately after resection. Tracheal catheters were removed from all donors in the postanesthesia care unit (PACU) after surgery and returned to the ward safely. There were no adverse events related to anesthesia during the entire perioperative period.

All infants underwent orthotopic resection of diseased liver and piggyback LT. The hepatic portal vessels and biliary tract were dissected, and the portal vein was blocked to remove the diseased liver. The hepatic veins were reshaped and anastomosed, followed by the anastomosis of the portal vein. Then, the hepatic veins and portal vein were opened sequentially to restore blood flow in the liver. After the hepatic artery anastomosis was performed, the left lateral lobe hepatic duct of the donor liver was anastomosed to the recipient's jejunum using a Roux-Y anastomosis. Once all anastomoses were completed and hemostasis was achieved, the surgical incision was closed. After LRLT, all patients were systematically moved to the intensive care unit (ICU) with intubation. Vital signs, mechanical ventilation parameters, urine volume, biochemical parameters, and vital organ functions (e.g., liver and kidney) were closely monitored after the operation. All patients received a consistent treatment regimen, including the management of immune rejection after transplantation. The anesthesia teams and surgeons involved in the current trial are fixed.

Data collection and time points

Comprehensive data collection was performed prior to surgery, including patient demographics such as age, sex, weight, pediatric model of end-stage liver disease (PELD) score, as well as baseline laboratory test variables and utilization of blood products. Throughout the intraoperative phase, clinically relevant information was also recorded, comprising operation duration, warm and cold ischemia duration, duration of the anhepatic period, graft–recipient weight ratio, blood loss, transfusion of blood products and fluids, urine output, and instances of reperfusion syndrome. Essential vital signs, including heart rate, mean arterial pressure, central venous pressure, and body temperature were meticulously documented at six time points: baseline (before the operation), preanhepatic (before portal vein occlusion), anhepatic (before reperfusion), 5 min post-portal vein reopening (reperfusion), 2 h post-reperfusion of the new liver (neohepatic stage), and the end of the surgery (termination). Reperfusion syndrome, characterized by a sudden decrease in mean arterial pressure by more than 30% or exceeding 30 mmHg within 5 min post-reperfusion, sustained for more over 1 min. The anesthesia, operation stages, and time points were shown in Fig. 1. To provide a comprehensive postoperative profile, length of stay in ICU, duration of mechanical ventilation, total length of stay, and incidence of mild and severe complications were also recorded. Additionally, the method of anesthesia and anesthetic drugs were concealed in all anesthesia records admitted to ICU. Generally, mild complications were more common after surgery, accompanied by easy treatments and quick recovery, and they did not affect the main prognosis outcome for the patient. Mild complications included non-life-threatening occurrences such as pneumonia, atelectasis, pleural effusion, abdominal effusion, chylous fistula, and infections. Severe complications refer to those with serious consequences and difficult treatment, which might seriously affect the prognosis of children or significantly increase their medical burden. These serious complications included abdominal compartment syndrome, intravascular thrombosis, hemadostenosis, biliary stricture, respiratory failure, septicemia, organ dysfunction, anastomotic fistula, acute rejection, and hemorrhage. The data collectors did not know how patients were grouped.Fig. 1 The anesthesia, operation stages, and time points of this study. ALP alkaline phosphatase, ALT alanine aminotransferase, AST aspartate aminotransferase, BUN blood urea nitrogen, GGT gamma-glutamyl transferase, ICU intensive care unit, LDH lactate dehydrogenase, KDIGO Kidney Disease: Improving Global Outcomes, POD postoperative days, Scr serum creatinine, TB total bilirubin, TIVA total intravenous anesthesia

Liver and kidney function tests

The key indicators of liver function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH), were measured. Additionally, indicators of renal function, namely Scr and urea nitrogen (BUN), were also assessed. This comprehensive evaluation occurred at eight time points, including the ICU arrival and daily assessments over the initial seven postoperative days. Postoperative acute kidney injury (AKI) was determined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria [20]. This criterion categorizes patients into AKI stages 1, 2, and 3, with stages 2 and 3 indicating severe AKI. The short-term prognosis after LRLT was recorded and analyzed.

Statistical analysis

The sample size for this study was calculated using the PASS software (version 15.0), as described in previous studies [17, 21]. A total of 74 subjects (37 patients in each group) were found to be sufficient for achieving statistical significance in the mean level of ALT on the first day after surgery, with a two-sided type I error of 0.05 and a power of 0.80. Continuous measures were presented as mean ± standard deviation or median (interquartile range (IQR)) and were analyzed using Student’s t-test or the Wilcoxon rank-sum test. Categorical and counting data were presented as number (%) and analyzed using the Chi-square test or Fisher’s exact test. Repeated-measures analysis of variance (ANOVA) was utilized to analyze continuous variables at different time points. Generalized estimating equations and multiple comparisons were used to compare hemodynamic data during reperfusion and laboratory tests, which were subsequently adjusted using the Sidak correction. The outcomes were expressed as odds ratios (ORs) accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using SPSS (version 23.0; IBM Corporation, Armonk, NY, USA). P-value less than 0.05 was considered statistically significant.

Results

Patients and peri-operative characteristics

A total of 88 recipients who underwent LRLT were screened for eligibility. Out of these, 12 recipients were excluded for various reasons. These exclusions included 2 patients who declined enrolment, 2 patients with pre-existing renal function impairment prior to surgery, 4 patients with preoperative multiple organ dysfunction, and 4 patients who did not strictly follow the drug regimen during surgery (combined intravenous and inhalation anesthesia was used). Consequently, the final analysis was conducted on 76 patients (CONSORT Flowchart). The median ages were 4.5 and 5.0 months old in group P and group D, respectively. There were 18 females and 20 males in group P, along with 19 female and 19 male patients in group D (Table 1). No significant differences were observed in terms of preoperative demographic data, blood routine parameters, coagulation function, liver function, and renal function between the two groups, as shown in Table 1. All donors were either the father or mother of the child, and there were no significant differences in gender, age, liver function, or time of operation between the two groups, as shown in Table 2. Table 1 Preoperative recipient demographics and laboratory tests

	Variable	Group P (n = 38)	Group D (n = 38)	P value	
Demographics	Age (Mon)	4.5 (4.0, 6.0)	5.0 (4.1, 5.9)	0.386	
	Sex, male [n (%)]	20 (61.0)	19 (48.7)	0.299	
	Weight (kg)	6.48 ± 0.85	6.33 ± 1.08	0.490	
	PELD score	9.15 ± 6.28	10.41 ± 5.49	0.355	
	GRBW	0.04 (0.03,0.05)	0.04 (0.03,0.05)	0.843	
Liver function	
	TB (μmol/L)	256.37 ± 87.1	287.2 ± 83.4	0.115	
	TP (g/L)	65.4 ± 7.9	65.7 ± 7.5	0.865	
	ALB (g/L)	40.04 ± 5.56	39.64 ± 4.36	0.725	
	GLOB (g/L)	24.2 (19.3, 31.2)	25.7 (19.1, 29.8)	0.648	
	ALT (U/L)	226 (169.3, 330.1)	235 (132, 373.5)	0.983	
	AST (U/L)	356.5 (247.5, 553.9)	400.5 (232.8, 623.0)	0.344	
	AST/ALT	1.61(1.06, 2.03)	1.80 (1.49, 2.29)	0.131	
	ALP (U/L)	649 (478, 904)	596 (497, 804)	0.526	
	GGT (U/L)	447 (250, 735)	529 (172, 812)	0.674	
	LDH (U/L)	320 (281, 375)	313 (282, 364)	0.803	
	CHE (U/L)	4595 ± 2109	4004 ± 1446	0.159	
Renal function	
	BUN (mmol/L)	2.45 (2.00, 3.33)	2.70 (2.35, 3.27)	0.196	
	Scr (μmol/L)	16.1 ± 3.7	17.3 ± 4.1	0.181	
	UA (μmol/L)	137.5 (104.5, 161.8)	142.5 (97.3, 173.8)	0.536	
Electrolytes	
	K+ (mmol/L)	5.05 (4.67, 5.18)	4.89 (4.53, 5.30)	0.614	
	Na+ (mmol/L)	137 (135, 138)	136 (135, 138)	0.240	
	Cl+ (mmol/L)	104.7 (101.9, 106.6)	104.2 (101.2, 107.0)	0.975	
Values are presented as the mean ± standard deviation, median (IQR) or number (%)

ALB Albumin, ALP Alkaline phosphatase, ALT Alanine transaminase, AST Aspartate aminotransferase, BUN Blood urea nitrogen, CHE Cholinesterase, GGT Gamma-glutamyl transpeptidase, GLOB Globulin, LDH Lactate dehydrogenase, TB Total bilirubin, TP Total protein, Scr Serum creatinine, UA Uric acid

Table 2 Donor characteristics

Variables	Group P (n = 38)	Group D (n = 38)	P value	
Baseline	
 Age (year)	31.74 ± 5.22	31.81 ± 6.56	0.961	
 Sex, male (n (%))	16 (42.11)	15 (39.47)	0.815	
 BMI (kg.m−2)	23.78 ± 3.05	23.95 ± 2.53	0.797	
 HR (bmp)	83.32 ± 7.45	81.92 ± 9.56	0.480	
 SBP (mmHg)	111.92 ± 10.02	115.21 ± 11.09	0.179	
 DBP (mmHg)	74.45 ± 9.37	73.71 ± 7.60	0.708	
 Hepatitis B surface antigen	0	0	1	
 Diabetes mellitus	0	0	1	
 Hypertension	0	0	1	
Liver function	
 ALT (U/L)	26.97 ± 22.12	21.52 ± 13.29	0.197	
 AST (U/L)	24.41 ± 18.80	22.17 ± 9.40	0.513	
 ALB (g/L)	47.53 ± 3.00	47.83 ± 2.89	0.661	
 TB (μmol/L)	10.36 ± 5.17	8.87 ± 4.28	0.176	
Coagulation function	
 PT (s)	11.17 ± 0.77	10.94 ± 0.67	0.160	
 APTT (s)	28.11 ± 1.72	28.18 ± 2.52	0.886	
Intra-operative	
 Cold ischemia time (min)	82 (72, 93)	79 (74, 88)	0.480	
 Warm ischemia time (min)	2 (1, 2)	2 (1, 2)	0.591	
 Blood loss (ml)	200.92 ± 120.72	170.39 ± 69.77	0.181	
 Urine volume (ml)	600 (400, 975)	525(350, 1075)	0.798	
 Operating time (min)	254.82 ± 34.19	257.71 ± 31.80	0.703	
 Anesthesia duration (min)	343.58 ± 36.62	348.32 ± 37.07	0.577	
 Donor liver weight (g)	247.37 ± 44.70	250.26 ± 54.89	0.802	
 Fatty liver (n (%))	2 (5.26)	0 (0.00)	0.474	
Values are presented as the mean ± standard deviation, median (IQR) or number (%)

ALB Albumin, ALT Alanine transaminase, APTT Activated partial thromboplastin time, AST Aspartate aminotransferase, BMI Body mass index, DBP Diastolic blood pressure, SBP Systolic blood pressure, TB Total bilirubin, PT Prothrombin time

Intraoperative indicators and vital signs

The surgical and anesthetic data were summarized in Table 3. Compared with group D, heart rate in group P was significantly increased at reperfusion. There was no significant difference in other vital signs and the other assessed parameters at each time point between the groups (Table 3 and Fig. 2). A total of 12 patients in group D and 16 patients in group P experienced post-reperfusion syndrome (P = 0.452). These patients did not suffer severe cardiovascular collapse and arrhythmia. Table 3 Intraoperative factors

Variable	Group P (n = 38)	Group D (n = 38)	P value	
Operation time (min)	430 (385, 467)	435 (403, 483)	0.363	
Cold ischemia time (min)	82 (72, 93)	79 (74, 88)	0.480	
Warm ischemia time (min)	2 (1, 2)	2 (1, 2)	0.591	
Anhepatic phase(min)	44 (40, 51)	45 (42, 51)	0.767	
Blood loss (ml/kg)	51.7 (31.9, 72.8)	41.9 (33.6, 66.7)	0.212	
Total fluid intake (ml)	715 (611,781)	690 (580, 794)	0.344	
RBC transfusion (u)	1.5 (1.0, 1.5)	1.5 (1.0, 1.5)	0.652	
FFP transfusion (n (%))	16 (42.1%)	19 (50.0%)	0.490	
20% Albumin (g)	30.0 (25.0, 35.0)	30.0 (20.0, 30.0)	0.302	
Cryoprecipitate (n (%))	4 (5.2%)	2 (10.5%)	0.395	
Urine volume(ml)	199.9 ± 85.6	189.1 ± 95.4	0.603	
Values are presented as the mean ± standard deviation, median (IQR), or the number of users (%)

FFP Fresh frozen plasma, RBC Red cell suspension

Fig. 2 Vital signs at six time points. A Heart rate (HR). B Mean arterial pressure (MAP). C Central venous pressure (CVP). D Temperature (Temp). Values are presented as median (IQR); *P < 0.01

Liver and kidney functions

After reperfusion, the peaks of AST and ALT values in group P were significantly lower than those in group D within the initial 72 h after surgery (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006 (95% CI: 58–366), respectively), expressed in terms of median (IQR) (Fig. 3). Compared to group D, the ALT values in group P exhibited significantly lower levels upon arrival at the ICU (P = 0.005), on the first day (P = 0.047), second day (P = 0.024), third day (P = 0.007), fourth day (P = 0.001), fifth day (P = 0.011), and sixth day (P = 0.016) post-surgery. Similarly, the AST values demonstrated significant reductions in group P upon the ICU arrival (P = 0.001), on the first day (P = 0.035), second day (P = 0.009), third day (P = 0.002), and fourth day (P = 0.001) post-surgery. TB values demonstrated significant reductions in group P upon ICU arrival (P = 0.011), as well as on the first day (P = 0.029) and second day (P = 0.010) after surgery. GGT values also significantly decreased in group P upon arrival at the ICU (P = 0.030), on the third day (P = 0.008), and fourth day (P = 0.048) post-surgery, while LDH values revealed a notable decrease on the second day post-surgery (P = 0.007) after a significant reduction upon arrival at the ICU (P = 0.024). However, there was no significant difference in ALP values at all time points between the two groups (Fig. 4).Fig. 3 Aminotransferase peak of liver transplantation recipients within 7 days of surgery. A ALT peak. B AST peak. ALT alanine aminotransferase, AST aspartate aminotransferase; **P < 0.01

Fig. 4 Liver and kidney function tests of liver transplantation recipients. A Alanine transaminase (ALT). B Aspartate aminotransferase (AST). C Total bilirubin (TB). D alkaline phosphatase (ALP). E Gamma-glutamyl transpeptidase (GGT). F Lactate dehydrogenase (LDH). POD postoperative days. Values are presented as median (IQR); *P < 0.05, **P < 0.01

The Scr levels in group P were found to be significantly lower than those in group D upon arrival at the ICU and on the first day (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively), as shown in Fig. 5. There was no significant difference in urea nitrogen levels between the two groups. The prevalence of postoperative AKI, as defined by the KDIGO criteria, was observed to be 52.6% in group P (36.8% in stage 1, 13.2% in stage 2, and 2.6% in stage 3). In contrast, in Group D, it amounted to 65.7% (26.2% in stage 1, 31.6% in stage 2, and 7.9% in stage 3). Although there was no notable difference in the overall incidence of AKI between the two groups after surgery, a significant reduction in the occurrence of severe AKI was evident in group P (15.8% vs. 39.5%, P = 0.038). Here, stage 1 was defined as mild AKI, while stages 2 and 3 were defined as severe AKI, as illustrated in Fig. 6.Fig. 5 Kidney function tests of liver transplantation recipients. A Serum creatinine (Scr). B Blood urea nitrogen (BUN). POD postoperative days. Values are presented as median (IQR); *P < 0.05, ***P < 0.001

Fig. 6 The prevalence of postoperative AKI according to KDIGO criteria. A The prevalence of postoperative AKI within 7 days of surgery. B Distribution of different stages of AKI. C Occurrence of mild to severe AKI. AKI acute kidney injury. KDIGO Kidney Disease: Improving Global Outcomes; *P < 0.05

Complications and outcomes

No significant difference was observed in the incidence of mild complications (61.0% vs. 48.7%, P = 0.299) and serious complications (37.3% vs. 18.0%, P = 0.085) between the two groups. Similarly, there were no notable differences in the duration of postoperative mechanical ventilation (96 (45, 136) vs. 90 (55, 142) hours, P = 0.715), hospital stay (27 (25, 35) vs. 26 (23, 32) days, P = 0.246), and length of ICU stay (11 (9, 13) vs. 12 (10, 19) days, P = 0.138) between the two groups, as depicted in Fig. 7.Fig. 7 Complications and Outcomes of the two groups. A Duration of mechanical ventilation. B Length of ICU stay. C Length of hospital stay. ICU intensive care unit

Discussion

HIR not only causes liver injury but also significantly contributes to injury in distant organs during LT [22]. AKI is one of common complications in the early stages after LT and a predictor of poor prognosis for patients, significantly impacting the survival rate post-transplantation [23]. Given these factors, our primary focus was to investigate the early postoperative alterations in liver and kidney functions. In the field of perioperative management of LT, reducing HIRI in LT has become a prominent academic and clinical topic. This reduction is a crucial strategy for protecting organ vitality and minimizing detrimental effects. Propofol and desflurane are commonly used as intraoperative maintenance anesthetics and well known for their ability to reduce mitigate cardiac and cerebral damages caused by ischemia–reperfusion events through diverse mechanisms [24, 25]. Although there have been similar studies in the past, their methods and anesthesia procedures differed from ours. The previous conclusions were inconsistent or even opposite, and the target populations and subjects were not the same [17, 26, 27]. In our study, the age, primary disease, disease duration, and surgical type of the study subjects were uniform, and the confounding factors were well controlled. In China, infants undergoing LRLT account for a large proportion, and this study may provide important evidence and guidance for this group of people in choosing anesthesia drugs. Meanwhile, this study may contribute to clarifying the effects of different anesthesia drugs on postoperative organ function in infant LT, as well as their correlation with graft ischemia–reperfusion, and offering a direction for future exploration of the mechanism of organ protection by anesthetic drugs.

The 72-h peak transaminase levels had been selected as indicators to assess the degree of HIRI. They are not only important clinical indicators for routine postoperative monitoring but also highly correlated with LT surgery. In contrast, some new biomarkers such as matrix metalloproteinase (MMP) are involved in multiple biological processes, including tissue remodeling and growth, wound repair, tissue defense mechanisms, immune responses, as well as inflammatory reactions and autoimmune diseases. Therefore, their specificity and sensitivity are relatively poor. Consistent with previous approaches, our study used peak transaminase levels within 72 h of LT as an indicator for evaluating HIRI [28–30]. The results showed that the peaks of ALT and AST in TIVA group were significantly lower than those in desflurane inhalation group, suggesting propofol administration might confer early hepatoprotection against HIRI. Our study also included the assessment of liver and kidney function parameters at different time points 7 days after LT. Notably, liver dysfunction markers including aminotransferase, TB, GGT and LDH were significantly lower after new organ transplantation in group P compared to those in group D. These findings supported the potential of propofol-based TIVA in efficiently reducing early liver function impairment and further facilitating the recovery of liver metabolism and synthesis function in infant recipients. Numerous studies have emphasized the antioxidative properties of propofol, indicating that it is closely related to mitochondrial function [31]. Propofol could reduce AST and LDH levels in ischemia–reperfusion livers by inhibiting NF-κB activation and modulating the release of inflammatory cytokines [32–34]. Previous study has reported that propofol exerted definite hepatoprotective effects against ischemia–reperfusion injury via Sirt1 regulation, which may be related to its anti-inflammatory and antioxidant capacity [35]. Moreover, the prophylactic use of propofol was found to mitigate oxidative stress in the ischemia–reperfusion liver by reducing tissue or cellular reactive oxygen species. This effect of reducing HIRI might be due to the upregulation of Nrf-2, heme oxygenase 1, and quinone oxidoreductase 1 by propofol, which was consistent with clinical and experimental studies [36–38]. Intriguingly, other studies have shown that desflurane also has the potential to reduce IRI due to its strong regulatory effects on immune and cytokine activity [39, 40]. A previous study reported that propofol had a protective effect on ischemia–reperfusion organs, could suppress the activity of neutrophils, and might therefore produce its beneficial effects by reducing free radicals, Ca2+ influx, and neutrophil activity [41]. And one randomized controlled trial highlighted improvements of liver and kidney functions after desflurane anesthesia in liver transplant donors, possibly due to its greater stability and minimal metabolic effects [21]. In contrast, a separate study of 62 adult living donor liver transplant recipients anesthetized with desflurane or other anesthesia methods showed no significant differences in intraoperative inflammatory factors and postoperative recovery [17].

The divergent conclusions from various studies could be attributed to multiple factors. We analyzed and speculated on the reasons for the difference between our results and those of others. Firstly, our study focused on infants with biliary atresia, neither adults over the age of 18 nor children older than 1 year old. Due to the limitations of primary disease and age of patients in this study, all subjects had similar pathophysiological characteristics and ischemia–reperfusion process, which was more consistent and comparable. Secondly, the size of infant liver donors relative to their weight was larger than that of adult patients, which could cause inflammatory agents and anaerobic metabolites to overload into the recipient system, thereby resulting in more pronounced damage. In addition, previous studies involving propofol used desflurane intermittently during anesthesia maintenance, which differed from our protocol. Therefore, this study could not be directly compared with previous studies because changes in preoperative conditions, age, liver cirrhosis course, and recipient weight may also have contributed to different outcomes.

Acute renal failure is a prevalent and serious complication after LT, with reported incidences ranging from 17 to 95% [42]. Several studies have demonstrated HIRI plays a decisive role in postoperative AKI in liver transplant recipients [43]. In our analysis of 76 infant LRLT recipients, the incidence of postoperative AKI in groups P and D was 52.6% and 65.7%, respectively, and the incidence of severe AKI was significantly lower in group P. Our findings revealed that Scr levels were markedly elevated in group D, indicating a lesser extent of damage associated with propofol compared to desflurane. Elevated LDH levels in kidney tissue are commonly associated with post-transplantation HIRI. The transportation of oxygen free radicals and enteric endotoxins subsequent to HIR may result in necrosis of renal tubule and glomerular endothelial cells, further damaging renal tubule epithelial cells. Therefore, by-products of oxygen free radical degradation, such as malondialdehyde, could disrupt cell membrane structure and lead to elevated serum LDH levels [37]. Simultaneously, the inflammatory response after HIRI might cause leukocyte infiltration, edema, and diminished microvascular blood flow, thereby exacerbating renal injury [44]. A potential association has been found between sevoflurane anesthesia and a slightly lower incidence of AKI in pediatric LT compared to propofol [32]. Meanwhile, studies have demonstrated that desflurane may make the kidney function of liver transplant donors after anesthesia better than TIVA [16]. Nevertheless, our study showed that while propofol did not reduce the AKI incidence of infant recipients, it did alleviate the extent of renal damage, suggesting a protective effect of propofol on kidney function. This protection may be due to the fact that propofol could reduce oxidative stress in kidney tissue and regulate inflammatory cell chemokines [45, 46].

LT often leads to significant hemodynamic fluctuations, accompanied by intraoperative hypotension, which independently correlates with subsequent postoperative organ injury [47]. A retrospective study by Chueng found that compared with desflurane inhalation anesthesia, liver transplant recipients under intravenous anesthesia with propofol alone showed better hemodynamic stability and improved circulatory perfusion [48]. In our current study, there were no notable differences in hemodynamic parameters and the incidence of reperfusion syndrome between the two groups at different time points. We speculate that the choice of anesthetic may not be the primary determinant of intraoperative hemodynamic stability and may depend more on careful supervision by the intraoperative management and anesthesia team.

However, our study also had limitations. It was a single-center, randomized controlled study with a relatively small sample size, and larger clinical trials and multi-center studies are necessary to generate stronger evidences. The clinical observation period of this study was limited to the length of hospital stay, and the examination results were evaluated only 7 days after surgery, which limited the assessment of long-term organ functions. In the further study, a longer follow-up period is necessary to determine the long-term effects of the two drugs on organ function in pediatric recipients. In terms of selecting markers for reperfusion injury, the indicators used in this study were relatively limited. In recent years, the correlation between the levels of novel biomarkers such as neutrophil extracellular traps (NETs) and HIRI after LT has garnered considerable attention. In future study, it is imperative to incorporate new and specific biomarkers to comprehensively validate the conclusions. Meanwhile, a more diverse range of evaluation metrics should be included to comprehensively assess the impact of medications on the long-term prognosis. Based on the traits and characteristics of the drugs, the two anesthetic agents were administered in different ways, and it was difficult to blind the anesthesia provider. In addition, laboratory indicators used in the study as an alternative method to assess IRI and impairment of organ function might have limitations and more sensitive and specific markers should be incorporated in further studies. A mixture of inhalation and intravenous anesthesia is common in real-world clinical anesthesia maintenance, but our study did not include a composite group for comparison, which would increase the risk of confounding factors.

Conclusions

HIRI and abnormal liver and kidney functions are the most common pathophysiological characteristics of LRLT. In the present study, propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations and further studies are also needed to clarify the underlying mechanisms.

Supplementary Information

Supplementary Material 1.

Abbreviations

AKI Acute kidney injury

ALP Alkaline phosphatase

ALT Alanine aminotransferase

ANOVA Analysis of variance

AST Aspartate aminotransferase

BUN Urea nitrogen

CIs Confidence intervals

GGT Gamma-glutamyl transferase

HIRI Hepatic ischemia–reperfusion injury

HIR Hepatic ischemia–reperfusion

ICU Intensive care unit

IQR Interquartile range

IRI Ischemia–reperfusion injury

KDIGO Kidney Disease: Improving Global Outcomes

LDH Transglutaminase

LT Liver transplantation

LRLT Living-related liver transplantation

ORs Odds ratios

PACU Postanesthesia care unit

PMELD Pediatric model of end-stage liver disease

Scr Serum creatinine

TB Total bilirubin

TIVA Total intravenous anesthesia

Acknowledgements

The authors thank all the anesthesia teams and surgeons involved in the current trial.

Authors’ contributions

W.L. and M.D.: conceptualization, data collection, data analysis and interpretation, writing – original draft. L.B. and J.J.Q.: conceptualization, investigation, data curation, methodology, formal analysis, project administration, visualization, and writing – original draft. M.M.Z. and X.K.D.: conceptualization and writing – review and editing. H.M.W., Y.L. and S.S.Z.: conceptualization, data interpretation, writing – review and editing. All authors read and approved the final manuscript.

Funding

This study was supported by the Chongqing Medical Youth Top Talent Project and the Miao Talent Project of the Children’s Hospital of Chongqing Medical University.

Availability of data and materials

All relevant data and materials are stored at the Children’s Hospital of Chongqing Medical University and can be obtained from the first author and corresponding author.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Children’s Hospital of Chongqing Medical University, China (Approval Notice 285/2020) and written informed consent was provided prior to participation.

Consent for publication

We confirm that the manuscript has been read and approved by all named authors. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We take full responsibility for the work being reported. It is the original study and has been neither published elsewhere nor submitted for publication.

Competing interests

The authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Wei Liu and Min Du contributed equally to this work.
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References

1. Ebel NH Lai JC Bucuvalas JC Wadhwani SI A review of racial, socioeconomic, and geographic disparities in pediatric liver transplantation Liver Transpl 2022 28 9 1520 1528 10.1002/lt.26437 35188708
Ebel NH, Lai JC, Bucuvalas JC, Wadhwani SI. A review of racial, socioeconomic, and geographic disparities in pediatric liver transplantation. Liver Transpl. 2022;28(9):1520–8.35188708
2. Rawal N Yazigi N Pediatric liver transplantation Pediatr Clin North Am 2017 64 3 677 684 10.1016/j.pcl.2017.02.003 28502445
Rawal N, Yazigi N. Pediatric liver transplantation. Pediatr Clin North Am. 2017;64(3):677–84.28502445
3. Pham YH Miloh T Liver Transplantation in children Clin Liver Dis 2018 22 4 807 821 10.1016/j.cld.2018.06.004 30266163
Pham YH, Miloh T. Liver Transplantation in children. Clin Liver Dis. 2018;22(4):807–21.30266163
4. Nemeth N Peto K Magyar Z Klarik Z Varga G Oltean M Mantas A Czigany Z Tolba RH Hemorheological and microcirculatory factors in liver ischemia-reperfusion injury-an update on pathophysiology, molecular mechanisms and protective strategies Int J Mol Sci 2021 22 4 1864 10.3390/ijms22041864 33668478
Nemeth N, Peto K, Magyar Z, Klarik Z, Varga G, Oltean M, Mantas A, Czigany Z, Tolba RH. Hemorheological and microcirculatory factors in liver ischemia-reperfusion injury-an update on pathophysiology, molecular mechanisms and protective strategies. Int J Mol Sci. 2021;22(4):1864.33668478
5. Zhang R Zhang L Manaenko A Ye Z Liu W Sun X Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway J Hepatol 2014 61 5 1048 1055 10.1016/j.jhep.2014.06.020 24972044
Zhang R, Zhang L, Manaenko A, Ye Z, Liu W, Sun X. Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway. J Hepatol. 2014;61(5):1048–55.24972044
6. Zhang Y Yuan D Yao W Zhu Q Liu Y Huang F Feng J Chen X Huang Y Chi X Hyperglycemia aggravates hepatic ischemia reperfusion injury by inducing chronic oxidative stress and inflammation Oxid Med Cell Longev 2016 2016 3919627 10.1155/2016/3919627 27656261
Zhang Y, Yuan D, Yao W, Zhu Q, Liu Y, Huang F, Feng J, Chen X, Huang Y, Chi X, et al. Hyperglycemia aggravates hepatic ischemia reperfusion injury by inducing chronic oxidative stress and inflammation. Oxid Med Cell Longev. 2016;2016: 3919627.27656261
7. Li X Li X Chi X Luo G Yuan D Sun G Hei Z Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans Exp Ther Med 2015 9 2 411 416 10.3892/etm.2014.2088 25574207
Li X, Li X, Chi X, Luo G, Yuan D, Sun G, Hei Z. Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans. Exp Ther Med. 2015;9(2):411–6.25574207
8. Luo C Yuan D Li X Yao W Luo G Chi X Li H Irwin MG Xia Z Hei Z Propofol attenuated acute kidney injury after orthotopic liver transplantation via inhibiting gap junction composed of connexin 32 Anesthesiology 2015 122 1 72 86 10.1097/ALN.0000000000000448 25254904
Luo C, Yuan D, Li X, Yao W, Luo G, Chi X, Li H, Irwin MG, Xia Z, Hei Z. Propofol attenuated acute kidney injury after orthotopic liver transplantation via inhibiting gap junction composed of connexin 32. Anesthesiology. 2015;122(1):72–86.25254904
9. Luo GJ Yao WF He Y Luo CF Li XY Hei ZQ Ulinastatin prevents acute lung injury led by liver transplantation J Surg Res 2015 193 2 841 848 10.1016/j.jss.2014.08.051 25277357
Luo GJ, Yao WF, He Y, Luo CF, Li XY, Hei ZQ. Ulinastatin prevents acute lung injury led by liver transplantation. J Surg Res. 2015;193(2):841–8.25277357
10. Zhang A Chi X Luo G Hei Z Xia H Luo C Wang Y Mao X Xia Z Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation PLoS One 2013 8 10 e75262 10.1371/journal.pone.0075262 24116032
Zhang A, Chi X, Luo G, Hei Z, Xia H, Luo C, Wang Y, Mao X, Xia Z. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation. PLoS One. 2013;8(10): e75262.24116032
11. Ge M Chen C Yao W Zhou S Huang F Cai J Hei Z Overexpression of Brg1 alleviates hepatic ischemia/reperfusion-induced acute lung injury through antioxidative stress effects Oxid Med Cell Longev 2017 2017 8787392 10.1155/2017/8787392 28798861
Ge M, Chen C, Yao W, Zhou S, Huang F, Cai J, Hei Z. Overexpression of Brg1 alleviates hepatic ischemia/reperfusion-induced acute lung injury through antioxidative stress effects. Oxid Med Cell Longev. 2017;2017:8787392.28798861
12. Pu S Jin S Xiang B Yang J Li K Xie X Huang B Lai W Yan L Zhang M The current status and outcomes of pediatric liver transplantation in western China: a multi-center retrospective study Pediatr Transplant 2020 24 8 e13810 10.1111/petr.13810 32845541
Pu S, Jin S, Xiang B, Yang J, Li K, Xie X, Huang B, Lai W, Yan L, Zhang M, et al. The current status and outcomes of pediatric liver transplantation in western China: a multi-center retrospective study. Pediatr Transplant. 2020;24(8): e13810.32845541
13. Yeh YT Liu C Tsai HL Chen CY Lin NC Chang JW Tsao PC Lee YS Hsia CY Loong CC Living donor liver transplantation for small infants aged less than 6 months: the experience of a single institute J Pediatr Surg 2021 56 7 1157 1161 10.1016/j.jpedsurg.2021.03.022 33840505
Yeh YT, Liu C, Tsai HL, Chen CY, Lin NC, Chang JW, Tsao PC, Lee YS, Hsia CY, Loong CC. Living donor liver transplantation for small infants aged less than 6 months: the experience of a single institute. J Pediatr Surg. 2021;56(7):1157–61.33840505
14. Wu J Yu C Zeng X Xu Y Sun C Protection of propofol on liver ischemia reperfusion injury by regulating Cyp2b10/ Cyp3a25 pathway Tissue Cell 2022 78 101891 10.1016/j.tice.2022.101891 35985247
Wu J, Yu C, Zeng X, Xu Y, Sun C. Protection of propofol on liver ischemia reperfusion injury by regulating Cyp2b10/ Cyp3a25 pathway. Tissue Cell. 2022;78: 101891.35985247
15. Tao KM Yang LQ Liu YT Tao Y Song JC Wu FX Yu WF Volatile anesthetics might be more beneficial than propofol for postoperative liver function in cirrhotic patients receiving hepatectomy Med Hypotheses 2010 75 6 555 557 10.1016/j.mehy.2010.07.028 20709457
Tao KM, Yang LQ, Liu YT, Tao Y, Song JC, Wu FX, Yu WF. Volatile anesthetics might be more beneficial than propofol for postoperative liver function in cirrhotic patients receiving hepatectomy. Med Hypotheses. 2010;75(6):555–7.20709457
16. Ko JS Gwak MS Choi SJ Kim GS Kim JA Yang M Lee SM Cho HS Chung IS Kim MH The effects of desflurane and propofol-remifentanil on postoperative hepatic and renal functions after right hepatectomy in liver donors Liver Transpl 2008 14 8 1150 1158 10.1002/lt.21490 18668648
Ko JS, Gwak MS, Choi SJ, Kim GS, Kim JA, Yang M, Lee SM, Cho HS, Chung IS, Kim MH. The effects of desflurane and propofol-remifentanil on postoperative hepatic and renal functions after right hepatectomy in liver donors. Liver Transpl. 2008;14(8):1150–8.18668648
17. Shin S Joo DJ Kim MS Bae MI Heo E Lee JS Kim DW Yoo YC Propofol intravenous anaesthesia with desflurane compared with desflurane alone on postoperative liver function after living-donor liver transplantation: a randomised controlled trial Eur J Anaesthesiol 2019 36 9 656 666 10.1097/EJA.0000000000001018 31083000
Shin S, Joo DJ, Kim MS, Bae MI, Heo E, Lee JS, Kim DW, Yoo YC. Propofol intravenous anaesthesia with desflurane compared with desflurane alone on postoperative liver function after living-donor liver transplantation: a randomised controlled trial. Eur J Anaesthesiol. 2019;36(9):656–66.31083000
18. Bennett JA The Consolidated Standards of Reporting Trials (CONSORT): guidelines for reporting randomized trials Nurs Res 2005 54 2 128 132 10.1097/00006199-200503000-00007 15778654
Bennett JA. The Consolidated Standards of Reporting Trials (CONSORT): guidelines for reporting randomized trials. Nurs Res. 2005;54(2):128–32.15778654
19. Liu W Tu Z Liu L Tan Y Combined short- and long-axis method for internal jugular vein catheterization in premature newborns: a randomized controlled trial Acta Anaesthesiol Scand 2021 65 3 420 427 10.1111/aas.13728 33147353
Liu W, Tu Z, Liu L, Tan Y. Combined short- and long-axis method for internal jugular vein catheterization in premature newborns: a randomized controlled trial. Acta Anaesthesiol Scand. 2021;65(3):420–7.33147353
20. Ostermann M Bellomo R Burdmann EA Doi K Endre ZH Goldstein SL Kane-Gill SL Liu KD Prowle JR Shaw AD Controversies in acute kidney injury: conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Conference Kidney Int. 2020 98 2 294 309 10.1016/j.kint.2020.04.020 32709292
Ostermann M, Bellomo R, Burdmann EA, Doi K, Endre ZH, Goldstein SL, Kane-Gill SL, Liu KD, Prowle JR, Shaw AD, et al. Controversies in acute kidney injury: conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020;98(2):294–309.32709292
21. Ko JS Gwak MS Choi SJ Yang M Kim MJ Lee JY Kim GS Kwon CH Joh JW The effects of desflurane and sevoflurane on hepatic and renal functions after right hepatectomy in living donors* Transpl Int 2010 23 7 736 744 10.1111/j.1432-2277.2009.01050.x 20102552
Ko JS, Gwak MS, Choi SJ, Yang M, Kim MJ, Lee JY, Kim GS, Kwon CH, Joh JW. The effects of desflurane and sevoflurane on hepatic and renal functions after right hepatectomy in living donors*. Transpl Int. 2010;23(7):736–44.20102552
22. Zhai Y Petrowsky H Hong JC Busuttil RW Kupiec-Weglinski JW Ischaemia-reperfusion injury in liver transplantation–from bench to bedside Nat Rev Gastroenterol Hepatol 2013 10 2 79 89 10.1038/nrgastro.2012.225 23229329
Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW. Ischaemia-reperfusion injury in liver transplantation–from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013;10(2):79–89.23229329
23. Umbro I Tinti F Scalera I Evison F Gunson B Sharif A Ferguson J Muiesan P Mitterhofer AP Acute kidney injury and post-reperfusion syndrome in liver transplantation World J Gastroenterol 2016 22 42 9314 9323 10.3748/wjg.v22.i42.9314 27895419
Umbro I, Tinti F, Scalera I, Evison F, Gunson B, Sharif A, Ferguson J, Muiesan P, Mitterhofer AP. Acute kidney injury and post-reperfusion syndrome in liver transplantation. World J Gastroenterol. 2016;22(42):9314–23.27895419
24. Yu W Gao D Jin W Liu S Qi S Propofol prevents oxidative stress by decreasing the ischemic accumulation of succinate in focal cerebral ischemia-reperfusion injury Neurochem Res 2018 43 2 420 429 10.1007/s11064-017-2437-z 29168092
Yu W, Gao D, Jin W, Liu S, Qi S. Propofol prevents oxidative stress by decreasing the ischemic accumulation of succinate in focal cerebral ischemia-reperfusion injury. Neurochem Res. 2018;43(2):420–9.29168092
25. Heiberg J Royse CF Royse AG Andrews DT Propofol attenuates the myocardial protection properties of desflurane by modulating mitochondrial permeability transition Anesth Analg 2018 127 2 387 397 10.1213/ANE.0000000000003450 29933271
Heiberg J, Royse CF, Royse AG, Andrews DT. Propofol attenuates the myocardial protection properties of desflurane by modulating mitochondrial permeability transition. Anesth Analg. 2018;127(2):387–97.29933271
26. Wu ZF Lin WL Lee MS Hung NK Huang YS Chen TW Lu CH Propofol vs desflurane on the cytokine, matrix metalloproteinase-9, and heme oxygenase-1 response during living donor liver transplantation: A pilot study Medicine (Baltimore) 2019 98 48 e18244 10.1097/MD.0000000000018244 31770287
Wu ZF, Lin WL, Lee MS, Hung NK, Huang YS, Chen TW, Lu CH. Propofol vs desflurane on the cytokine, matrix metalloproteinase-9, and heme oxygenase-1 response during living donor liver transplantation: A pilot study. Medicine (Baltimore). 2019;98(48): e18244.31770287
27. Cho HY Lee HJ Kim WH Lee HC Jung CW Hong SK Yang SM Influence of anesthesia type on post-reperfusion syndrome during liver transplantation: a single-center retrospective study Anesth Pain Med (Seoul) 2022 17 3 304 311 10.17085/apm.21104 35918864
Cho HY, Lee HJ, Kim WH, Lee HC, Jung CW, Hong SK, Yang SM. Influence of anesthesia type on post-reperfusion syndrome during liver transplantation: a single-center retrospective study. Anesth Pain Med (Seoul). 2022;17(3):304–11.35918864
28. Levitsky J Asrani SK Abecassis M Ruiz R Jennings LW Klintmalm G External validation of a pretransplant biomarker model (REVERSE) predictive of renal recovery after liver transplantation Hepatology 2019 70 4 1349 1359 10.1002/hep.30667 31002431
Levitsky J, Asrani SK, Abecassis M, Ruiz R, Jennings LW, Klintmalm G. External validation of a pretransplant biomarker model (REVERSE) predictive of renal recovery after liver transplantation. Hepatology. 2019;70(4):1349–59.31002431
29. Dewitte A Defaye M Dahmi A Ouattara A Joannes-Boyau O Chermak F Chiche L Laurent C Battelier M Sigaut S Prognostic impact of early recovering acute kidney injury following liver transplantation: a multicenter retrospective study Transplantation 2022 106 4 781 791 10.1097/TP.0000000000003865 34172644
Dewitte A, Defaye M, Dahmi A, Ouattara A, Joannes-Boyau O, Chermak F, Chiche L, Laurent C, Battelier M, Sigaut S, et al. Prognostic impact of early recovering acute kidney injury following liver transplantation: a multicenter retrospective study. Transplantation. 2022;106(4):781–91.34172644
30. Lai Q Melandro F Manzia TM Spoletini G Crovetto A Gallo G Hassan R Mennini G Angelico R Avolio AW The role of donor gamma-glutamyl transferase as a risk factor for early graft function after liver transplantation J Clin Med. 2023 12 14 4744 10.3390/jcm12144744 37510859
Lai Q, Melandro F, Manzia TM, Spoletini G, Crovetto A, Gallo G, Hassan R, Mennini G, Angelico R, Avolio AW, et al. The role of donor gamma-glutamyl transferase as a risk factor for early graft function after liver transplantation. J Clin Med. 2023;12(14):4744.37510859
31. Li Volti G Avola R Tibullo D Editorial - propofol as an intraoperative strategy for organ protection Eur Rev Med Pharmacol Sci 2017 21 17 3980 3981 28975962
Li Volti G, Avola R, Tibullo D. Editorial - propofol as an intraoperative strategy for organ protection. Eur Rev Med Pharmacol Sci. 2017;21(17):3980–1.28975962
32. Li H Weng Y Yuan S Liu W Yu H Yu W Effect of sevoflurane and propofol on acute kidney injury in pediatric living donor liver transplantation Ann Transl Med 2019 7 14 340 10.21037/atm.2019.06.76 31475210
Li H, Weng Y, Yuan S, Liu W, Yu H, Yu W. Effect of sevoflurane and propofol on acute kidney injury in pediatric living donor liver transplantation. Ann Transl Med. 2019;7(14):340.31475210
33. Xu Z Yu J Wu J Qi F Wang H Wang Z Wang Z The effects of two anesthetics, propofol and sevoflurane, on liver ischemia/reperfusion injury Cell Physiol Biochem 2016 38 4 1631 1642 10.1159/000443103 27119513
Xu Z, Yu J, Wu J, Qi F, Wang H, Wang Z, Wang Z. The effects of two anesthetics, propofol and sevoflurane, on liver ischemia/reperfusion injury. Cell Physiol Biochem. 2016;38(4):1631–42.27119513
34. Bellanti F Mirabella L Mitarotonda D Blonda M Tamborra R Cinnella G Fersini A Ambrosi A Dambrosio M Vendemiale G Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1α activation in hepatic ischemia/reperfusion injury Free Radic Biol Med 2016 96 323 333 10.1016/j.freeradbiomed.2016.05.002 27154980
Bellanti F, Mirabella L, Mitarotonda D, Blonda M, Tamborra R, Cinnella G, Fersini A, Ambrosi A, Dambrosio M, Vendemiale G, et al. Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1α activation in hepatic ischemia/reperfusion injury. Free Radic Biol Med. 2016;96:323–33.27154980
35. Liu Y Du X Zhang S Liu X Xu G Propofol alleviates hepatic ischemia/reperfusion injury via the activation of the Sirt1 pathway Int J Clin Exp Pathol 2017 10 11 10959 10968 31966440
Liu Y, Du X, Zhang S, Liu X, Xu G. Propofol alleviates hepatic ischemia/reperfusion injury via the activation of the Sirt1 pathway. Int J Clin Exp Pathol. 2017;10(11):10959–68.31966440
36. Hovaguimian F Schläpfer M Beck-Schimmer B Organ protection in allograft recipients: anesthetic strategies to reduce postoperative morbidity and mortality Curr Opin Organ Transplant 2014 19 2 121 130 10.1097/MOT.0000000000000062 24553502
Hovaguimian F, Schläpfer M, Beck-Schimmer B. Organ protection in allograft recipients: anesthetic strategies to reduce postoperative morbidity and mortality. Curr Opin Organ Transplant. 2014;19(2):121–30.24553502
37. Ge M Chen H Zhu Q Cai J Chen C Yuan D Jin Y Yao W Hei Z Propofol post-conditioning alleviates hepatic ischaemia reperfusion injury via BRG1-mediated Nrf2/HO-1 transcriptional activation in human and mice J Cell Mol Med 2017 21 12 3693 3704 10.1111/jcmm.13279 28749008
Ge M, Chen H, Zhu Q, Cai J, Chen C, Yuan D, Jin Y, Yao W, Hei Z. Propofol post-conditioning alleviates hepatic ischaemia reperfusion injury via BRG1-mediated Nrf2/HO-1 transcriptional activation in human and mice. J Cell Mol Med. 2017;21(12):3693–704.28749008
38. Zhang Z Yan B Li Y Yang S Li J Propofol inhibits oxidative stress injury through the glycogen synthase kinase 3 beta/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway Bioengineered 2022 13 1 1612 1625 10.1080/21655979.2021.2021062 35030972
Zhang Z, Yan B, Li Y, Yang S, Li J. Propofol inhibits oxidative stress injury through the glycogen synthase kinase 3 beta/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Bioengineered. 2022;13(1):1612–25.35030972
39. Zheng Y Lu H Huang H Desflurane preconditioning protects against renal ischemia-reperfusion injury and inhibits inflammation and oxidative stress in rats through regulating the Nrf2-Keap1-ARE signaling pathway Drug Des Devel Ther 2020 14 1351 1362 10.2147/DDDT.S223742 32308368
Zheng Y, Lu H, Huang H. Desflurane preconditioning protects against renal ischemia-reperfusion injury and inhibits inflammation and oxidative stress in rats through regulating the Nrf2-Keap1-ARE signaling pathway. Drug Des Devel Ther. 2020;14:1351–62.32308368
40. Zhong M Che L Du M Liu K Wang D Desflurane protects against liver ischemia/reperfusion injury via regulating miR-135b-5p J Chin Med Assoc 2021 84 1 38 45 10.1097/JCMA.0000000000000427 32898087
Zhong M, Che L, Du M, Liu K, Wang D. Desflurane protects against liver ischemia/reperfusion injury via regulating miR-135b-5p. J Chin Med Assoc. 2021;84(1):38–45.32898087
41. Yao W Han X Zhang Y Guan J Ge M Chen C Wu S Chen J Luo G Huang P Intravenous anesthetic protects hepatocyte from reactive oxygen species-induced cellular apoptosis during liver transplantation in vivo Oxid Med Cell Longev 2018 2018 4780615 10.1155/2018/4780615 30510620
Yao W, Han X, Zhang Y, Guan J, Ge M, Chen C, Wu S, Chen J, Luo G, Huang P, et al. Intravenous anesthetic protects hepatocyte from reactive oxygen species-induced cellular apoptosis during liver transplantation in vivo. Oxid Med Cell Longev. 2018;2018:4780615.30510620
42. Dong V Nadim MK Karvellas CJ Post-liver transplant acute kidney injury Liver Transpl 2021 27 11 1653 1664 10.1002/lt.26094 33963666
Dong V, Nadim MK, Karvellas CJ. Post-liver transplant acute kidney injury. Liver Transpl. 2021;27(11):1653–64.33963666
43. Kalisvaart M de Haan JE Hesselink DA Polak WG Hansen BE IJzermans J Gommers D Metselaar HJ de Jonge J The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation Transpl Int 2017 30 7 660 9 10.1111/tri.12891 27864895
Kalisvaart M, de Haan JE, Hesselink DA, Polak WG, Hansen BE, IJzermans J, Gommers D, Metselaar HJ, de Jonge J. The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation. Transpl Int. 2017;30(7):660–9.27864895
44. Jagarlamudi N Wong F Acute kidney injury: prediction, prognostication and optimisation for liver transplant Hepatol Int 2020 14 2 167 179 10.1007/s12072-020-10018-0 32128705
Jagarlamudi N, Wong F. Acute kidney injury: prediction, prognostication and optimisation for liver transplant. Hepatol Int. 2020;14(2):167–79.32128705
45. Hsing CH Chou W Wang JJ Chen HW Yeh CH Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury Nephrol Dial Transplant 2011 26 4 1162 1172 10.1093/ndt/gfq572 20864551
Hsing CH, Chou W, Wang JJ, Chen HW, Yeh CH. Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury. Nephrol Dial Transplant. 2011;26(4):1162–72.20864551
46. Zhang Z Tian L Jiang K Propofol attenuates inflammatory response and apoptosis to protect d-galactosamine/lipopolysaccharide induced acute liver injury via regulating TLR4/NF-κB/NLRP3 pathway Int Immunopharmacol 2019 77 105974 10.1016/j.intimp.2019.105974 31735662
Zhang Z, Tian L, Jiang K. Propofol attenuates inflammatory response and apoptosis to protect d-galactosamine/lipopolysaccharide induced acute liver injury via regulating TLR4/NF-κB/NLRP3 pathway. Int Immunopharmacol. 2019;77: 105974.31735662
47. Joosten A Lucidi V Ickx B Van Obbergh L Germanova D Berna A Alexander B Desebbe O Carrier FM Cherqui D Intraoperative hypotension during liver transplant surgery is associated with postoperative acute kidney injury: a historical cohort study BMC Anesthesiol 2021 21 1 12 10.1186/s12871-020-01228-y 33430770
Joosten A, Lucidi V, Ickx B, Van Obbergh L, Germanova D, Berna A, Alexander B, Desebbe O, Carrier FM, Cherqui D, et al. Intraoperative hypotension during liver transplant surgery is associated with postoperative acute kidney injury: a historical cohort study. BMC Anesthesiol. 2021;21(1):12.33430770
48. Lu CH Yeh CC Huang YS Lee MS Hsieh CB Cherng CH Wu ZF Hemodynamic and biochemical changes in liver transplantation: a retrospective comparison of desflurane and total intravenous anesthesia by target-controlled infusion under auditory evoked potential guide Acta Anaesthesiol Taiwan 2014 52 1 6 12 10.1016/j.aat.2014.05.004 24999212
Lu CH, Yeh CC, Huang YS, Lee MS, Hsieh CB, Cherng CH, Wu ZF. Hemodynamic and biochemical changes in liver transplantation: a retrospective comparison of desflurane and total intravenous anesthesia by target-controlled infusion under auditory evoked potential guide. Acta Anaesthesiol Taiwan. 2014;52(1):6–12.24999212
