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Volume: 19 Issue: 10 October 2021


Correlation of Deceased Donor Factors to Postreperfusion Severe Hyperglycemia in Adult Patients Undergoing Liver Transplant


Objectives: In this study, our objective was to identify perioperative factors associated with postreperfusion severe hyperglycemia, with a particular focus on deceased donor factors.
Materials and Methods: Perioperative data from 100 patients without diabetes who were undergoing liver transplant from deceased donors were reviewed. Mean blood glucose levels were calculated at each liver transplant surgical phase, with a cutoff level of 12.7 mmol/L (230 mg/dL) during the neo-hepatic phase defined as postreperfusion severe hyperglycemia. Patients were divided into those with and without postreperfusion severe hyperglycemia. Selected perioperative variables were compared between the 2 groups.
Results: Of 100 patients, 55 developed postreperfusion severe hyperglycemia. Among donor variables, a statistically significant difference between groups was only shown for graft-to-recipient liver weight ratio (P < .001). With regard to preoperative recipient variables, the 2 groups showed a significant difference in mean age (P = .001). Patients in the postreperfusion severe hyperglycemia group required significantly more packed red blood cell transfusions (P = .002), sodium bicarbonate (P = .054), and vasopressors (P = .002) during the operation. Moreover, in terms of laboratory findings, although the last arterial pH was acceptable in both groups, a last lower arterial pH was observed in patients with postreperfusion severe hyperglycemia (P = .011). Higher mean blood glucose levels were detected in the postre­perfusion hyperglycemia group during the pre-anhepatic and anhepatic phases (P = .024, P = .001, respectively).
Conclusions: In patients undergoing liver transplant, incidence of postreperfusion severe hyperglycemia was influenced by graft-to-recipient liver weight ratio. Furthermore, postreperfusion severe hyperglycemia was associated with intraoperative clinical and laboratory disturbances in liver transplant recipients.

Key words : Blood glucose, End-stage liver disease, Graft-to-recipient liver weight ratio, Reperfusion


Glucose homeostasis is frequently impaired in patients with end-stage liver disease, which is caused by multiple mechanisms such as peripheral resis­tance to insulin and hyperinsulinemia.1 In addition, liver transplantation (LT) is associated with various metabolic disturbances. During LT, blood glucose status often worsens in recipients, and progressive hyperglycemia may occur; indeed, blood glucose levels often peak after liver graft reperfusion.2 Hyperglycemia during LT can be caused by a variety of exogenous factors, including surgical stress, steroids, blood transfusions, and catecholamine vasopressors.3 According to results from experimental studies, hyperglycemia increases the inflammatory response, which can exacerbate ischemia-reperfusion injury.4,5 High blood glucose variability, but not hyperglycemia, during the intraoperative period and the early period after LT may also be associated with the development of certain complications, such as acute kidney injury.6 Hence, the most logical approach is to manage variabilities in blood glucose during LT.

There are few clinical studies on postreperfusion severe hyperglycemia (PRSH) in LT, and many of these studies have mainly emphasized the effects of PRSH on post-LT outcomes, such as infection, renal failure, and graft function.7

It is important to identify factors associated with PRSH to ensure appropriate management strategies. However, the relationship between donor factors and PRSH is not yet clear. In one study, Chung and colleagues8 reported the contribution of donor factors to PRSH in patients undergoing living donor LT. However, to our knowledge, the relationship between perioperative factors of deceased donor LT (DDLT) and PRSH has not been reported. In the present study, our goal was to identify perioperative factors associated with PRSH and with regard to deceased donor factors.

Materials and Methods

Our retrospective study included 100 adult patients without diabetes pretransplant (age ≥18 years) who had undergone DDLT at the Organ Transplant Center of Mashhad University between August 2013 and December 2019. The University Ethics Committee approved this retrospective study (approval number: IR.MUMS.MEDICAL.REC. 1397.174) and waived the need for written informed consent.

Exclusion criteria included recipients who had received dextrose (20%, 50%) during LT for cor­rection of hypoglycemia or hyperkalemia, liver retransplant, and multiorgan transplant.

The classic technique without venovenous bypass or the piggyback technique was used for LT. Donated liver grafts were prepared using University of Wisconsin solution.

All patients received standard induction anesthesia with fentanyl (1-2 μg/kg), propofol (0.5-2 mg/kg), and muscle relaxants with either succinylcholine and/or cisatracurium. Anesthesia was maintained with isoflurane in low to moderate concentrations (0.5-1.0 minimum alveolar concentration) and bolus cisatracurium. A remifentanil infusion (0.05-0.3 μg/kg/min) and bolus fentanyl were administered throughout LT based on the patient’s hemodynamic responses. Mechanical ventilation was delivered at a tidal volume of 8 to 10 mL/kg using a mixture of medical air and oxygen at a fresh gas flow rate of 2 L/min, and respiratory rate was adjusted as needed to maintain normocapnia. After induction of anesthesia, a central venous pressure catheter and a radial arterial line were placed to allow continuous hemodynamic monitoring and blood sampling. The intravenous fluid included 1% to 2% albumin in normal saline, and the rate of infusion was regulated according to central venous pressure, urine output, and volume of blood loss. Excessive metabolic acidosis (base excess less than -6.0) was treated with sodium bicarbonate. Body core temperature was maintained using a whole body-sized warm blanket.

The use of inotropes and vasopressors was at the discretion of the anesthesiologist and in response to the patient’s hemodynamic status. Transfusion of packed red blood cells (PRBCs) was used to target hematocrit level of 25% to 30%. Coagulation components were replaced under thromboelastography guidance to correct intraoperative coagulopathies.

Intraoperative blood glucose management
Glucose-containing solutions were not routinely used during LT. Blood glucose levels were assessed by arterial blood sampling at least every 1 hour until the end of LT. Mean blood glucose levels ≥12.7 mmol/L (230 mg/dL) during the neo-hepatic phase was defined as PRSH.

During LT, whenever the blood glucose level exceeded 11 mmol/L (200 mg/dL) after a bolus dose of 2 units of regular insulin, continuous infusion of insulin (2 U/h) was started. The target glucose level was 7.7 to 9.9 mmol/L (140-180 mg/dL). Blood glucose was monitored every 0.5 hour after starting the regular insulin infusion; for patients with uncontrolledblood glucose levels, the infusion rate was doubled. Hypoglycemia, blood glucose level <3.9 mmol/L (70 mg/dL), was corrected using 20% or 50% dextrose solution.

Patients were divided into 2 groups (PRSH and non-PRSH) using a mean blood glucose cutoff level of 12.7 mmol/L (230 mg/dL) during the neo-hepatic phase. Donor variables collected for analyses included age, sex, total ischemia time of liver graft, and fatty changes in the graft. In addition, prepared donor livers and recipient livers were weighed after hepatectomy, and the graft-to-recipient liver weight ratio was calculated.

Preoperative recipient variables collected for analyses included age, sex, body mass index, indication for LT, Model for End-Stage Liver Disease (MELD) score, Child-Pugh-Turcotte score, history of ascites, hepatorenal syndrome, hepatic encephalopathy, gastrointestinal bleeding, concurrent diseases, and echocardiographic and laboratory findings. All preoperative variables were based on the latest data before LT. Intraoperative variables included surgical time, amount of crystalloid or colloid infusion, blood and blood product transfusion, hourly urine output (mL/kg/h), amount of ascites, postre­perfusion syndrome (PRS), administered drugs (vasopressors, calcium gluconate, sodium bicarbonate, and regular insulin), and mean blood glucose (mg/dL) at the pre-anhepatic phase, anhepatic phase, and neo-hepatic phase of LT, as well as last arterial pH level.

Statistical analyses
Results are expressed as number (%) for categorical variables and mean ± SD or median (range) for continuous variables. The chi-square test or the Fisher exact test was used for qualitative variables, and the Mann-Whitney test was used for continuous variables. P < .05 was considered statistically significant. All statistical analyses were performed with the use of SPSS version 16 software.


This retrospective observational study included 100 patients who underwent DDLT. Of these, 55 patients were classified into the PRSH group.

The mean age of donors was 39 ± 16 years, and most were men (69%). The proportions of graft-to-recipient liver weight ratio <1.09% and >1.1% were 47% and 53%, respectively. The mean total ischemic time of the graft was 204 minutes. On graft biopsy, 46% showed fatty changes <5%, 38% showed fatty changes of 5% to 10%, and 16% had fatty changes of 10% to 30%. The relationship between donor factors and PRSH is shown in Table 1.

Pretransplant recipient variables for both patient groups are shown in Table 2. Mean age of recipients was 45 years, and most were men (75%). Dominant causes for LT in our study group were cryptogenic cirrhosis (28%) and hepatitis B virus cirrhosis (21%). Among recipients, 53% of patients had Child-Pugh-Turcotte class B. The overall MELD score was 19.7 ± 5.12 points. All recipients had endotracheal tube extubation in the operating room.

During DDLT, patients with PRSH required significantly more PRBC transfusions (P = .002), more sodium bicarbonate (P = .054), and more vasopressors (P = .002) than patients without PRSH. With regard to laboratory findings, patients with PRSH had lower last arterial pH (P = .011). However, arterial pH was acceptable in both study groups.

Throughout DDLT, blood glucose levels progres­sively increased (Figure 1). Significantly higher mean blood glucose levels were observed in the PRSH group during the pre-anhepatic and anhepatic phases (P = .024 and P = .001, respectively). Table 3 shows the comparison of intraoperative variables between the PRSH and non-PRSH groups.


Our observational study indicated that, during DDLT, processes leading to PRSH were influenced by donor-related factors, particularly graft-to-recipient liver weight.

To our knowledge, only 1 study evaluated the relationship between PRSH and liver donor factors. This retrospective study, by Chung and colleagues,8 identified that liver graft size, extent of fatty change, and PRS were independent donor-associated predictors of PRSH during living donor LT.

Graft size plays an important role in determining outcomes after partial graft LT. Indeed, graft-to-recipient weight ratio is an important criterion during selection of donors for living donor LT.9 In our study, we investigated whole graft LT from deceased donors. Various definitions of estimated standard liver weight have been proposed in the literature.10 Therefore, we considered the graft-to-recipient liver weight ratio in our study.

Graft size affects glucose influx into the recipient’s circulation. The sudden increase of blood glucose in the early neo-hepatic phase can occur as a result of glucose influx from the grafted liver, secondary to ischemic injury.11,12 Restoration of the transplanted graft function after LT is associated with suppression of PRSH.13

Postreperfusion syndrome has been defined as at least a 30% decrease in mean arterial pressure occurring during the first 5 minutes after liver graft reperfusion and lasting longer than 1 minute.14 The underlying pathophysiological mechanisms of PRS associated with hyperglycemia are not well known. However, production of inflammatory mediators may contribute to PRS, which can eventually lead to activation of hepatic gluconeogenesis and peripheral insulin resistance.15 Interestingly, hyperglycemia exacerbates ischemia-reperfusion injury by inducing inflammation.16

In our study, we found that incidence of PRS was not significantly different between the 2 study groups; thus PRS may have a negative effect on intraoperative glucose homeostasis independent of PRSH. Moreover, patients with PRSH needed more PRBC transfusions and higher doses of vasopressor and sodium bicarbonate during surgery. Hence, PRSH is a complex and unclear issue.

An accepted criteria for liver donation at our center is graft fatty change of ≤30%. In the present study, our 2 study groups showed no significant differences in the extent of graft fatty changes, which is contrary to the results from Chung and colleagues.8 In light of these contradictions, further studies are recommended to explain the differences in findings between DDLT versus living donor LT. The main limitation of our study was that glucose-related cytokine levels were not assayed.


Incidence of PRSH in DDLT recipients was strongly influenced by donor-related factors. The graft-to-recipient liver weight ratio was identified as an independent predictor of PRSH. Because PRSH is a complex process and might be an indicator of graft outcome, further studies on this topic are recommended.


  1. Garcia-Compean D, Jaquez-Quintana JO, Maldonado-Garza H. Hepatogenous diabetes. Current views of an ancient problem. Ann Hepatol. 2009;8(1):13-20.
    CrossRef - PubMed
  2. Park CS. Predictive roles of intraoperative blood glucose for post-transplant outcomes in liver transplantation. World J Gastroenterol. 2015;21(22):6835-6841. doi:10.3748/wjg.v21.i22.6835
    CrossRef - PubMed
  3. Liu LL, Niemann CU. Intraoperative management of liver transplant patients. Transplant Rev (Orlando). 2011;25(3):124-129. doi:10.1016/j.trre.2010.10.006
    CrossRef - PubMed
  4. Di Filippo C, Cuzzocrea S, Rossi F, Marfella R, D'Amico M. Oxidative stress as the leading cause of acute myocardial infarction in diabetics. Cardiovasc Drug Rev. 2006;24(2):77-87. doi:10.1111/j.1527-3466.2006.00077.x
    CrossRef - PubMed
  5. Bemeur C, Ste-Marie L, Montgomery J. Increased oxidative stress during hyperglycemic cerebral ischemia. Neurochem Int. 2007;50(7-8):890-904. doi:10.1016/j.neuint.2007.03.002
    CrossRef - PubMed
  6. Yoo S, Lee HJ, Lee H, Ryu HG. Association between perioperative hyperglycemia or glucose variability and postoperative acute kidney injury after liver transplantation: a retrospective observational study. Anesth Analg. 2017;124(1):35-41. doi:10.1213/ANE.0000000000001632
    CrossRef - PubMed
  7. Ammori JB, Sigakis M, Englesbe MJ, O'Reilly M, Pelletier SJ. Effect of intraoperative hyperglycemia during liver transplantation. J Surg Res. 2007;140(2):227-233. doi:10.1016/j.jss.2007.02.019
    CrossRef - PubMed
  8. Chung HS, Kim ES, Rho MC, Park CS. Contribution of donor factors to post-reperfusion severe hyperglycemia in patients undergoing living donor liver transplantation. Ann Transplant. 2015;20:303-311. doi:10.12659/AOT.893648
    CrossRef - PubMed
  9. Alim A, Erdogan Y, Yuzer Y, Tokat Y, Oezcelik A. Graft-to-recipient weight ratio threshold adjusted to the model for end-stage liver disease score for living donor liver transplantation. Liver Transpl. 2016;22(12):1643-1648. doi:10.1002/lt.24523
    CrossRef - PubMed
  10. Chan SC, Liu CL, Lo CM, et al. Estimating liver weight of adults by body weight and gender. World J Gastroenterol. 2006;12(14):2217-2222. doi:10.3748/wjg.v12.i4.2217
    CrossRef - PubMed
  11. Kang R, Han S, Lee KW, et al. Portland Intensive Insulin Therapy During Living Donor Liver Transplantation: association with postreperfusion hyperglycemia and clinical outcomes. Sci Rep. 2018;8(1):16306. doi:10.1038/s41598-018-34655-6
    CrossRef - PubMed
  12. Okada T, Kawahito S, Mita N, et al. Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation. J Med Invest. 2013;60(3-4):205-212. doi:10.2152/jmi.60.205
    CrossRef - PubMed
  13. Chung HS, Lee S, Kwon SJ, Park CS. Perioperative predictors for refractory hyperglycemia during the neohepatic phase of liver transplantation. Transplant Proc. 2014;46(10):3474-3480. doi:10.1016/j.transproceed.2014.06.078
    CrossRef - PubMed
  14. Paugam-Burtz C, Kavafyan J, Merckx P, et al. Postreperfusion syndrome during liver transplantation for cirrhosis: outcome and predictors. Liver Transpl. 2009;15(5):522-529. doi:10.1002/lt.21730
    CrossRef - PubMed
  15. Yan Y, Li S, Liu Y, et al. Temporal relationship between inflammation and insulin resistance and their joint effect on hyperglycemia: the Bogalusa Heart Study. Cardiovasc Diabetol. 2019;18(1):109. doi:10.1186/s12933-019-0913-2
    CrossRef - PubMed
  16. Zhang Y, Yuan D, Yao W, et al. Hyperglycemia aggravates hepatic ischemia reperfusion injury by inducing chronic oxidative stress and inflammation. Oxid Med Cell Longev. 2016;2016:3919627. doi:10.1155/2016/3919627
    CrossRef - PubMed

Volume : 19
Issue : 10
Pages : 1058 - 1062
DOI : 10.6002/ect.2021.0140

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From the 1Department of Anesthesia and Intensive Care, Faculty of Medicine, Mashhad University of Medical Sciences, and the 2Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
Acknowledgements: We thank Razia Toloue at the organ transplant center of Mashhad University of Medical Sciences for her assistance in data collection. The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Soheila Milani, Department of Anesthesia and Intensive Care, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 9137913316
Phone: +98 513 854 3031
E-mail: and