Impact of Dexmedetomidine on Acute Kidney Injury Following Living Donor Liver Transplantation: A Randomized Controlled Study
Phase: PHASE4
Conditions: Acute Kidney Injury, Liver Diseases
Sponsor: Asan Medical Center

 
Official Title of the study: Impact of Dexmedetomidine on Acute Kidney Injury Following 
Living Donor Liver Transplantation: a randomized clinical trial 
 
 
 
NCT number: NCT03522688 
IRB approval date: 2th December 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Introduction 
Acute kidney injury (AKI) is a major complication of liver transplantation (LT) and the 
incidence of post-operative AKI ranges between 12% and 80%, depending on the definition 
adopted. There is increasing evidence that post-operative AKI following LT is independently 
associated with increased costs, recipient and graft outcomes. Although various strategies have 
been suggested to protect against postoperative AKI after LT, AKI still has a strong impact on 
the prognosis of LT. The underlying mechanism of postoperative AKI appears to be 
multifactorial, with numerous preoperative, intraoperative and postoperative factors involved. 
Among all, hepatic ischemia-reperfusion injury (IRI) and subsequent inflammatory response 
has been considered as one of main causes of AKI in LT.  
Dexmedetomidine (DEX) is a selective α2-agonist and a sedative with anti-inflammatory, 
analgesic and antioxidant effects. The kidney protective effect of DEX has been highlighted by 
preventing IRI with decreased systemic inflammatory response and reduced reactive oxygen 
species. Currently, the effects of DEX on kidney functions has been intensively researched in 
both animal and human studies. However, the majority of randomized clinical trials with DEX 
for AKI have been studied in heart surgery and only a limited number of prospective studies 
have been conducted in that regard in recipients undergoing living donor liver transplantation 
(LDLT).  
In this study, therefore, we evaluated the impact of intraoperative DEX infusion on the 
incidence of AKI in recipients undergoing LDLT. We also investigated that intraoperative 
lactate, incidence of delirium, early allograft dysfunction (EAD), duration of mechanical 
ventilation (MV), intensive care unit (ICU) length of stay (LOS) and hospital LOS. 
 
 
 

Study Protocol 
Study design and ethical approval 
The single-center, double-blinded, randomized controlled study was approved by the 
institutional review board of the Asan Medical Center (2017-0409) and registered with 
ClinicalTrials.gov (NCT03522688). The trial was conducted at Asan Medical Center in Seoul, 
Korea between July 2017 and October 2019. Written consent was obtained from all patients. 
We collected and analyzed the data in accordance with the ethical standards set in the 1964 
Declaration of Helsinki and its amendments. 
 
Participants 
Adult recipients scheduled for elective LDLT from July 2017 to October 2019 at Asan 
Medical Center in Seoul, Korea, were screened for eligibility. Recipients were excluded if they 
met at least one of the following criteria: recipients with serum creatinine >1.4 mg/dL, any 
history of chronic kidney disease, dual living donor LT, intraoperative use of veno-veno bypass, 
left main coronary artery occlusion >50%, hemodynamically significant arrhythmia, left 
ventricular ejection fraction <50%, use of an α2 agonist to treat hypertension, or a history of 
severe allergy to drugs. In total, 134 participants were assessed for eligibility and randomly 
assigned to either the DEX group (n = 67) or control group (n = 67). Four recipients who used 
veno-venous bypass during the surgery were removed from the study. Finally, 130 participants 
[DEX (n = 65) and control (n = 65) groups] were analyzed. For randomization, random 
computer-generated numbers were stored in sealed envelopes that were opened following the 
induction of anesthesia by an anesthesia nurse who was unaware of the study. 
 
 
 

Intervention 
DEX (Precedex®, dexmedetomidine hydrochloride, Hospira, Inc., Lake Forest, IL, USA) 
was continuously infused at a rate of 0.4 μg/kg/h and omission of bolus administration. Infusion 
of DEX was starting after anesthetic induction and discontinued 2 hours after graft reperfusion. 
The control group received a same volume of 0.9% saline for the same duration. All 
interventions were achieved by the anesthetic nurses not responsible for the research. 
 
Primary Outcomes  
The primary outcome was incidence of AKI and for that reason the serial assessments of 
creatinine levels were recorded within the first postoperative week. Postoperative AKI is 
defined according to the Kidney Disease: Improving Global Outcomes guideline (KDIGO) 
which described AKI as a change in the serum creatinine from baseline on postoperative days 
1–7. The baseline serum creatinine was the concentration measured just before surgery. AKI is 
defined as an increase in serum creatinine above baseline of ≥0.3 mg/dL within 2 days or 
≥50%–99% within 7 days. Once AKI is established, a staging system then divides its severity 
according to KDIGO criteria. Subgroup analysis was also performed to assess the incidence of 
AKI by ABO compatibility.  
 
Secondary Outcomes 
Serial levels of lactate were collected during the surgical procedure just before the initiation 
of induction (T0), 1 hour after skin incision (T1), 30min after the removal of the liver (T2), just 
after reperfusion of the graft (T3), 1 hour after reperfusion (T4) and at end of surgery (T5). 
Additionally, the maximum level of lactate (Tmax) was evaluated during the postoperative 3 
days following LDLT. Incidence of delirium, EAD, and graft failure after 12 months post-LT 
were also monitored. Finally, duration of MV, ICU LOS and hospital LOS were recorded. The 

incidence of delirium between ICU arrival and postoperative day 7 was assessed using the 
Confusion Assessment Method for the ICU with postoperatively at 12-h intervals or as needed 
according to the patient’s condition. EAD was defined based on postoperative day 7 laboratory 
values of serum bilirubin higher than 10 mg/dL or INR higher than 1.6. Graft failure was 
defined as patient death or retransplantation within 1 year. Patients who were alive with a 
functioning graft 1 year after LT were censored.  
 
Statistical analysis 
Data are presented as the mean ± standard deviation, median (interquartile range), or 
frequency (percentages) unless otherwise stated. Continuous variables were compared using 
the Student t test or Mann–Whitney U test; categorical variables were compared using the 
Pearson chi-square test or Fisher exact test, as appropriate. Longitudinally measured outcomes 
were modeled as a function of time, group and their two-way interaction, using a linear mixed 
model. The Sidak correction was used to adjust for multiple comparisons. For all analyses, 
p<0.05 was considered statistically significant. SPSS 23 (IBM Corp, Armonk, NY) software 
was used for all statistical analyses.