Intraoperative Low-Dose Dexmedetomidine Administration Associated with Reduced Hepatic Ischemia-Reperfusion Injury in Pediatric Deceased Liver Transplantation: A Retrospective Cohort Study

Abstract

Background Dexmedetomidine (DEX) attenuates hepatic ischemia-reperfusion injury (HIRI) in adult liver transplantation (LT), but its effects on postoperative liver graft function in pediatric LT remain unclear. We sought to investigate whether intraoperative DEX administration was associated with improved liver graft function in pediatric LT recipients. It was hypothesized that DEX administration was associated with reduced HIRI and improved liver graft function. Material/Methods From November 2015 to May 2020, 54 deceased pediatric LT recipients were categorized into a control group and a DEX group. Intraoperatively, the DEX group received an additional infusion of DEX at 0.4 μg/kg/h from incision to the end of the operation in comparison with the control group. Preoperative, intraoperative, and postoperative data were reviewed. Postoperative liver enzyme levels and HIRI severity were assessed and compared. Independent risk factors for HIRI were determined by multivariate logistic regression analysis using a stepwise forward conditional method. Results We enrolled 28 and 26 patients in the DEX and control groups, respectively. Patients in the DEX group exhibited a reduced incidence of moderate-to-severe HIRI (88.5% vs 60.7%, P =0.020) and decreased level of serum alanine aminotransferase (median [interquartile range]: 407 [230–826] vs 714 [527–1492] IU/L, P =0.048) compared with the controls. Binary logistic analysis revealed that longer cold ischemia time (odds ratio [OR]=1.006; 95% confidence interval [CI]=1.000–1.013; P =0.044) and intraoperative DEX use (OR=0.198; 95% CI=0.045–0.878; P =0.033) were independent predictors for moderate-to-severe HIRI. Conclusions Intraoperative low-dose DEX administration was associated with a lower incidence of moderate-to-severe HIRI in pediatric deceased LT. However, further studies are needed to confirm our results and elucidate the underlying mechanisms.

Effect of dexmedetomidine on liver transplantation: a meta-analysis

“…No new clinical trial was found after searching the clinical trial registration platform ClinicalTrial.gov and WHO ICTRP. Finally, nine studies were included in the meta-analysis, with a total of 648 participants ( Choi et al, 2016 ; Fayed et al, 2016 ; Sayed and Yassen, 2016 ; Xu et al, 2016 ; Lee et al, 2020 ; Lee et al, 2021 ; Ustun et al, 2021 ; Zhang et al, 2021 ; Zhang et al, 2022 ). See Figure 1 for the combined search results.…”

Effect of intraoperative dexmedetomidine on hepatic ischemia-reperfusion injury in pediatric living-related liver transplantation: A propensity score matching analysis

“…In accordance with the present results, Fayed and colleagues demonstrated that an intraoperative infusion of DEX at 0.8 µg/kg/h could exert hepatoprotective effects against HIRI in adult living-related LT recipients, as shown by an improved liver graft function, better histopathological scores, and decreased ICAM-1 levels ( 6 ). A recent retrospective study showed that intraoperative low-dose DEX was associated with reduced HIRI in pediatric deceased LT ( 10 ). Another ongoing randomized controlled trial (NCT03770130) is currently investigating the effects of intraoperative DEX compared to placebo on EAD and PNF in adult deceased LT ( 31 ).…”

“…Subsequently, researchers from the Tianjin First Center Hospital have demonstrated that intraoperative DEX administration protected against myocardial, kidney, and brain injuries in pediatric living-related LT ( 7 – 9 ). More recently, Zhang and colleagues ( 10 ) observed that intraoperative low-dose DEX administration was associated with reduced HIRI in pediatric deceased LT. However, mixed results have been reported in the literature ( 11 – 13 ), and some researchers ( 11 ) failed to detect a benefit of perioperative DEX infusion on postoperative cognitive dysfunction in adult living-related LT.…”

Dexmedetomidine ameliorates liver injury and maintains liver function in patients with hepatocellular carcinoma after hepatectomy: a retrospective cohort study with propensity score matching

“…As a highly selective a 2 -receptor agonist, dexmedetomidine (DEX) is widely used in clinical anesthesia for satisfactory sedation and analgesia without causing respiratory depression and hemodynamic instability (7). Moreover, animal and human studies have reported that DEX is effective in preventing postoperative delirium, promoting liver regeneration, inhibiting sepsis-induced systemic inflammatory response and injury, and improving the functions of important organs such as the kidney, lung, intestinal tract, and heart postoperatively or in the intensive care unit (ICU) (8)(9)(10)(11). Several fundamental experiments have proved the protective effects of DEX on liver function after surgery by demonstrating that perioperative DEX use significantly reduced inflammatory response and oxidative stress injury in hepatectomy or liver transplantation surgeries (12)(13)(14).…”