Abstract
BackgroundPerioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied.MethodsThis is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18–65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 μg/kg over 10 min) followed by a continuous infusion (0.5 μg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice.DiscussionThe present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients.Trial registrationClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130
Highlights
Hepatic failure is associated with considerable morbidity and mortality
Allograft dysfunction (EAD) and primary nonfunction (PNF) Due to a widespread shortage of donor organs, there has been an increase in the acceptance of organs of marginal quality that are prone to perioperative injury and are at increased risk of early postoperative dysfunction and failure [6, 7]
This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of early allograft dysfunction (EAD) and primary graft non-function (PNF)
Summary
Hepatic failure is associated with considerable morbidity and mortality. Decompensated cirrhosis with the development of ascites has a 2-year survival rate of only around 50% [1]. Allograft dysfunction (EAD) and primary nonfunction (PNF) Due to a widespread shortage of donor organs, there has been an increase in the acceptance of organs of marginal quality that are prone to perioperative injury and are at increased risk of early postoperative dysfunction and failure [6, 7]. Initial dysfunction of the liver graft (EAD or PNF) in the immediate postoperative period is indicative of hepatocellular damage and synthetic impairment and is strongly predictive of poor graft and patient survival [8,9,10,11]. Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). The effects of dexmedetomidine application on perioperative renal function and lung function were studied
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