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Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial

BMC Medicine volume 22, Article number: 397 (2024) Cite this article

Abstract

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.

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Background

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 [1,2,3]. 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 [5,6,7,8,9,10,11]. 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
figure 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

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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
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Table 2 Donor characteristics
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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
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Fig. 2
figure 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

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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
figure 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

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Fig. 4
figure 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

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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
figure 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

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Fig. 6
figure 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

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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
figure 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

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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 [28,29,30]. 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 [32,33,34]. 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 [36,37,38]. 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.

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.

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

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Acknowledgements

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

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.

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Author notes

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

Authors and Affiliations

  1. 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

    Wei Liu, Min Du, Lin Bo & Junjun Quan

  2. Department of Hepatobiliary Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Mingman Zhang, Xiaoke Dai, Haoming Wang & Ying Le

  3. Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, China

    Wei Liu, Min Du, Mingman Zhang, Xiaoke Dai, Haoming Wang, Ying Le, Lin Bo & Junjun Quan

  4. Clinical Laboratory, Chongqing Emergency Medical Center, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China

    Shenshen Zhi

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  1. Wei Liu
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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.

Corresponding authors

Correspondence to Lin Bo or Junjun Quan.

Ethics 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.

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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.

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The authors declare no competing interests.

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Liu, W., Du, M., Zhang, M. et al. Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial. BMC Med 22, 397 (2024). https://doi.org/10.1186/s12916-024-03622-6

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BMC Medicine

ISSN: 1741-7015

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