Postreperfusion Syndrome Research Articles

Effect of Prereperfusion Ephedrine on Postreperfusion Syndrome and Graft Function in Living Donor Liver Transplantation

A characteristic pattern of hemodynamic changes that may occur after reperfusion during liver transplantation (LT) is known as postreperfusion syndrome (PRS). We investigated the effect of prophylactic ephedrine administration on PRS and postoperative laboratory results in living donor LT. The medical records of adult recipients who underwent living donor LT were reviewed. A total of 308 recipients were divided into the prophylaxis group and the nonprophylaxis group. Graft factors, preoperative and intraoperative recipient factors, and postoperative laboratory results were compared between the 2 groups. Graft factors and preoperative and intraoperative recipient factors did not differ between the 2 groups, except the prevalence of diabetes mellitus and etiology of liver disease. After reperfusion, PRS occurred more frequently (43.2% vs 25.0%; P = .006), and mean arterial pressure was more reduced compared with prereperfusion values (33.7 ± 15.8% vs 22.3 ± 23.5%; P < .001) in the nonprophylaxis group than the prophylaxis group. Postoperative laboratory results did not differ between the 2 groups. In conclusion, prereperfusion administration of ephedrine reduced the incidence and severity of PRS. Further prospective studies on the relationship between prophylactic medication and posttransplantation outcomes are needed.

An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation.

Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.

Short-term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial.

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine-tryptophan-ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patient's portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n=40) or into systemic circulation (circulatory rinse group, CRg, n=40). The primary outcome objective was the lowest mean arterial blood pressure within 5min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early graft's and patient's outcomes. Within 5min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three-month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.

The photoplethysmographic amplitude to pulse pressure ratio can track sudden changes in vascular compliance and resistance during liver graft reperfusion: A beat-to-beat analysis.

During liver transplantation, the thermodilution cardiac output (CO) technique cannot respond to sudden hemodynamic changes associated with postreperfusion syndrome. Photoplethysmography (PPG) can reflect changes in intravascular volume and thus can be used to assess vasomotor tone and arterial stiffness on the pressure–volume relation. We investigated whether a beat-to-beat analysis of the arterial pressure–PPG relationship can estimate dynamic changes in vascular characteristics immediately after liver graft reperfusion.In 10 recipients, arterial blood pressure and PPG waveforms recorded simultaneously were analyzed from the beginning of fall to nadir in systolic blood pressure immediately after reperfusion. On a beat-to-beat basis, we compared the ratio of the amplitude of PPG to arterial pulse pressure (PPGamp/PP, as relative vascular compliance) to total peripheral resistance (TPR) and Windkessel compliance (Cwk) obtained from the Modelflow CO algorithm.Following graft reperfusion, PPGamp/PP and Cwk increased (median 41.5%; P = .005 and 42.0%; P < .001, respectively), whereas TPR decreased (median −46.4%; P < .001). Beat-to-beat PPGamp/PP was negatively correlated with TPR (median r = –0.80 [95% CI –0.85 to –0.76] on linear regression and r2 = 0.84 [95% CI 0.73–0.92] on curvilinear regression), and was positively correlated with Cwk (median r = 0.86 [95% CI 0.81–0.91] on linear regression and r2 = 0.88 [95% CI 0.75–0.96] on curvilinear regression).Our results suggest that relative compliance, obtained from beat-to-beat analysis of PPG and arterial pressure waveforms, can track abrupt changes in vascular characteristics associated with postreperfusion syndrome. This simple index would contribute to differential diagnoses of sudden hypotension.

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality?

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality? PurposePost-reperfusion syndrome (PRS) is a serious complication of liver transplantation, at present two main definitions are in use, and they differ both clinically and temporally. The primary objective of this study was to evaluate these two definitions as risk factors for post-transplantation mortality and primary graft non-function. Materials and methodsWe conducted a retrospective observational study on 794 patients undergoing orthotopic liver transplantation at our university hospital. The presence of PRS was evaluated according to both definitions and correlated with the end points: three months mortality, primary graft non-function (PGNF) and the combined outcome of the two. ResultsBoth definitions proved to be independent risk factors for three months mortality and the combined outcome. The definition according to Aggarwal et al. was also an independent risk factor for PGNF when adjusted for the propensity score.The Hilmi definition, despite being more comprehensive, did not improve the predictivity of the Aggarwal definition for the evaluated outcomes. ConclusionsPRS proved to be an independent risk factor for post-transplantation mortality and occurrence of PGNF. The pathophysiological mechanisms of this entity are still not fully understood and preventive strategies could help in reducing patients and graft losses.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study

During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia-Important Lessons From the First 12 Cases.

BackgroundA program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia.MethodsDeclined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate.ResultsTwelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP.ConclusionsNormothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.

Liberation From Renal Replacement Therapy After Cadaveric Liver Transplantation.

BackgroundRenal failure requiring renal replacement therapy (RRT) is common in patients with end-stage liver disease (ESLD) and is associated with worse outcomes following liver transplantation (LT). We investigated the factors associated with liberation from posttransplant RRT and studied the impact of RRT on patient and graft outcomes.MethodsA 5-year retrospective study of ESLD patients who received pretransplant RRT was conducted. Variables associated with liberation from RRT at 30 days and at 1-year posttransplant were analyzed. We used propensity matching to compare patient and graft outcomes in the study cohort to those of a control group who underwent LT but not pretransplant RRT.ResultsSixty-four patients were included in the study. Twenty-four (38%) were liberated from RRT at 30 days posttransplant. Duration of pretransplant RRT (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.98) and severe postreperfusion syndrome (OR, 0.26; 95% CI, 0.08-0.87) were significantly associated with continued RRT at 1-month posttransplant. At one year, 34 (53%) patients were liberated from RRT. Age was significantly associated with lack of liberation from RRT (OR, 0.933; 95% CI, 0.875-0.995). Compared with propensity matched controls, patients who received RRT pretransplant had worse graft and patient survival at 1 year (52% vs 82%; P = 0.01, and 53% vs 83%; P = 0.003, respectively).ConclusionsIn ESLD patients who received pretransplant RRT, one third were liberated from RRT at 1 month, and half at 1 year. Longer duration of pretransplant RRT, postreperfusion syndrome, and older age were associated with lower likelihood of liberation from RRT. Patients who required pretransplant RRT had worse graft and patient survivals compared to matched patients who did not require RRT. Patients who were liberated from RRT post-LT had similar outcomes to patients who never required pre-LT RRT.

Liver Transplantation Results by Donor Age

ObjectiveThe objective of this study was to compare liver transplantation outcomes as a function of donor age. Material and MethodsWe performed 212 liver transplantations between 2008 and 2014. We described a prospective cohort study and grouped the patients by liver donor age. We compared quantitative and categorical variables using statistical analysis. ResultsNo statistically significant differences were found among any graft age groups in gender (always more males), time on waiting list, age, height, Child Pugh Turcotte (CHILD) score, Model for End-stage Liver Disease (MELD) score, need for intraoperative blood products, or intensive care unit stay. The most frequent etiology of liver failure was alcohol. A brain-dead donor was the most frequent type in all groups. The whole graft was used except in 4 cases. No statistically significant differences were found among groups in the surgical technique, postreperfusion syndrome, arterial complications, biliary complications, venous complications, acute rejection, and retransplantation. The 3-year patient survival rate was 64% in the <60-year graft age group, 48% in the 60- to 69-year group, 64% in the 70- to 79-year group, and 40% in the ≥80-year group (P = .264). The 3-year graft survival rate was 62% in the <60-year graft age group, 47% in the 60- to 69-year group, 65% in the 70- to 79-year group, and 40% in the ≥80-year group (P = .295). ConclusionsGiven the need to increase the pool of liver donors, older donors should be considered as a source for liver transplantation, although careful selection is required.

Postreperfusion hyperkalemia in liver transplantation using donation after cardiac death grafts with pathological changes

With the increasing use of donation after cardiac death (DCD), especially of the graft liver with steatosis or other pathological changes, the frequency of postreperfusion hyperkalemia in liver transplantation has increased significantly. The present study aimed to determine the factors associated with developing postreperfusion hyperkalemia in liver transplantation from DCD. One hundred thirty-one consecutive adult patients who underwent orthotopic liver transplantation from DCD were retrospectively studied. Based on serum potassium within 5 minutes after reperfusion, recipients were divided into two groups: hyperkalemia and normokalemia. According to preoperative biopsy results, the DCD graft livers were classified into five categories. Univariate analysis was performed using Chi-square test to identify variables that were significantly different between two groups. Multivariate logistic regression was used to confirm the risk factors of developing hyperkalemia and postreperfusion syndrome. Correlation analysis was used to identify the relationship between the serum concentration of potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion. Twenty-two of 131 liver recipients had hyperkalemia episodes within 5 minutes after reperfusion. The rate of hyperkalemia was significantly higher in recipients of macrosteatotic DCD graft liver (78.6%, P<0.001) than that in recipients of non-macrosteatotic DCD graft liver. The odds ratio of developing postreperfusion hyperkalemia in recipients of macrosteatotic DCD graft liver was 51.3 (P<0.001). Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia within 5 minutes after reperfusion. The highest rate of postreperfusion syndrome also occurred in the recipients with macrosteatotic DCD graft liver (71.4%, P<0.001). A strong relationship existed between the serum potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion in macrosteatotic DCD graft liver recipients. Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia and postreperfusion syndrome in the recipients.

Normothermic Machine Perfusion of Deceased Donor Liver Grafts Is Associated With Improved Postreperfusion Hemodynamics.

BackgroundGraft reperfusion poses a critical challenge during liver transplantation and can be associated with hemodynamic instability/postreperfusion syndrome. This is sequel to ischemia-reperfusion injury and normothermic machine preservation (NMP) may affect hemodynamic changes. Herein, we characterize postreperfusion hemodynamics in liver grafts after NMP and traditional cold preservation.Materials and methodsIntraoperative records of patients receiving grafts after NMP (n = 6; NMP group) and cold storage (CS) (n = 12; CS group) were compared. The mean arterial pressure (MAP) was defined as the average pressure in the radial artery during 1 cardiac cycle by invasive monitoring. Postreperfusion syndrome was defined as MAP drop greater than 30% of baseline, lasting for 1 minute or longer within the first 5 minutes from graft reperfusion.ResultsDonor, recipient, demographics, and surgical parameters were evenly matched. Normothermic machine preservation grafts were perfused for 525 minutes (395-605 minutes) after initial cold ischemic time of 91 minutes (73-117 minutes), whereas in CS group cold ischemic time was 456 minutes (347-685 minutes) (P = 0.001). None developed postreperfusion syndrome in the NMP group against n = 2 (16.7%) in CS group (P = 0.529). Normothermic machine preservation group had better intraoperative MAP at 90 minutes postreperfusion (P = 0.029), achieved with a significantly less vasopressor requirement (P = <0.05) and less transfusion of blood products (P = 0.030) compared with CS group.ConclusionsNormothermic machine perfusion is associated with a stable intraoperative hemodynamic profile postreperfusion, requiring significantly less vasopressor infusions and blood product transfusion after graft reperfusion and may have benefit to alleviate ischemia-reperfusion injury in liver transplantation.

Influence of Obesity on Liver Transplantation Outcomes.

The aim of this work was to determine the impact of obesity on the morbidity and mortality of liver transplantation (LT) recipients. A single-center, observational-cohort, retrospective study was conducted in patients undergoing LT from January 2008 to December 2014 to compare complications and survival between those with body mass index (BMI)<35 kg/m2 and those with BMI≥35 kg/m2. The study included 170 patients: 162 (95.3%) with BMI<35 kg/m2 and 8 (4.7%) with BMI≥35 kg/m2. The groups significantly differed in overall mortality and graft survival: The risk of death was 3.54-fold higher (95% confidence interval, 1.39-9.03) and the mean graft survival was shorter (61 vs 21 mo; P= .001) in the group with BMI≥35 kg/m2. The groups did not significantly differ in rates of biliary complications, arterial and portal vein thrombosis, retransplantation or reintervention, intraoperative requirement for blood products, length of intensive care unit stay, or post-reperfusion syndrome or rejection rates. Although no significant differences were found between these groups in post-transplantation complications, BMI≥35 kg/m2 emerged as a mortality risk factor in these patients.

The impact of donor liver graft quality on postoperative outcome in liver transplant recipients. A single centre experience.

The Donor Risk Index (DRI) has become a universal score for organ allocation in liver transplantation (LT) worldwide. The aim of this study was to evaluate the impact of liver graft quality measured by DRI, CIT, WIT and donor age on intraoperative hemodynamics (reperfusion syndrome) and early postoperative outcome, defined as initial graft poor function (within 3 days of LT), of deceased donor liver transplant (DDLT) recipients. Secondary end-points were the assessment of the impact of graft quality on the intraoperative and postoperative day 1 hemostasis (evaluated using ROTEM assay). We retrospectively analyzed 135 patients who underwent deceased-donor LT between January 2013 and December 2014. Patient demographic data (age, sex, cause of End-Stage Liver Disease), preoperative paraclinical data (total bilirubin, creatinine, serum sodium), severity of liver disease scores (Model for End-Stage Liver Disease - MELD and MELD-sodium), intraoperative blood loss and blood products transfusion, incidence of post reperfusion syndrome, postoperative biochemical data (including total bilirubin, hepatic transaminases, lactate levels) and outcome (initial graft poor function diagnosis) were noted. Donor characteristics including DRI, CIT, WIT and donor age were noted. Coagulation was assessed by rotational thromboelastometry (ROTEM) after reperfusion of the graft and on postoperative day 1 in order to determine the effects of liver graft quality on hemostasis. Donor age has significantly correlated with decreased derived ROTEM parameters time to the maximum velocity of clot formation - MaxVt (p = 0.000), area under the curve (AUC) (p = 0.008) and maximum clot elasticity (MCE) (p = 0.018) although no difference in transfusion requirements has been observed. A longer CIT was associated with an increase in AST and ALT observed during the early postoperative period: day 1 ALT (p = 0.032) and AST (p = 0.008), day 2 ALT (p = 0.001) and AST (p = 0.001) and day 3 AST (p = 0.010) and ALT (p = 0.001). Higher DRI correlated with higher bilirubin levels measured on postoperative day 1 (p = 0.027) and 2 (p = 0.001). Patients who developed initial graft poor function received liver grafts from older donors (p = 0.05) with a higher DRI (p = 0.002). Our results suggest a significant impact of donor age and DRI on perioperative coagulation kinetics that may be a result of initial graft poor function. Although CIT and DRI correlated with a more severe cholestasis and hepatocitolysis during the early postoperative period these seems to be short-lived.

The early stage of cirrhotic cardiomyopathy is a risk factor for postreperfusion syndrome during liver transplantation? A retrospective observational study

Objectives: Despite normal or high cardiac output at rest, cirrhotic patients often exhibit abnormal cardiac function when subjected to stress. During the pretransplant cardiac workup, the diagnosis of cirrhotic cardiomyopathy would be easily missed without the aid of some supportive criteria because most patients have normal rest echocardiography. The period of highest hemodynamic instability during liver transplantation occurs after revascularization of the liver graft and is called postreperfusion syndrome. The aim of this study was to investigate if patients at risk for cirrhotic cardiomyopathy have a higher risk for postreperfusion syndrome during liver transplantation. The secondary purpose of the study was to assess if the supportive criteria used for cirrhotic cardiomyopathy evaluation correlate with the severity of the liver disease. Material and Methods: The study group included 52 patients undergoing orthotopic liver transplantation for cirrhosis. The variables recorded were: demographic data, MELD and MELD Na scores, the length of the QT interval corrected for heart rate, plasma levels of brain natriuretic peptide (BNP), cold and warm ischemia times, vasopressor use, transfusional requirements and the occurrence of postreperfusion syndrome during transplantation. Results: The patients were divided into 2 subgroups based on the occurrence of the postreperfusion syndrome. There was no statistically significant difference in BNP levels, length of QTc interval, MELD or MELD Na scores between the subgroups. BNP levels were correlated with QTc interval length (p=0.005), MELD and MELD Na scores (p=0.025 and p=0.001). The correlation between QTc interval length and the severity scores was not statistically significant. Conclusions: Our study showed that postreperfusion syndrome was not correlated with the severity of the liver disease or with the presence of risk factors indicating cirrhotic cardiomyopathy. From the supportive criteria studied, only BNP levels correlate with the severity of the liver disease.

Acute kidney injury and post-reperfusion syndrome in liver transplantation.

In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRS-induced AKI, avoiding confounding factors, we have limited our study to “acute kidney injury AND DCD AND liver transplantation”. Accordingly, three out of five studies were selected for our purpose.

Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, "Reperfusion" AND "liver transplantation" were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

Vasoplegic endothelial dysfunction in orthotopic liver transplantation.

The mechanism of hemodynamic instability during organ transplantation is undoubtedly multifactorial. Although risk factors may be associated with the characteristics of organ receptors, such as reduced levels of vasopressin or diastolic dysfunction of the left ventricle, or related to ischemia time or the surgical technique, it is reasonable to assume that dysregulation of nitric oxide (NO) production leads to increased guanosine 3′5′-cyclic monophosphate (cGMP) synthesis and an organic vasodilation stage probably contributes to vasoplegic syndrome. Classically, the post-reperfusion syndrome is characterized by hypotension and low vascular resistance after blood flow restoration, when cGMP and NO are increased by positive regulation induced by nitric oxide synthase (NOS). The increase in the level of cytokines and endotoxins, resulting in a systemic inflammatory response, is the mediator of the positive NOS regulation. The production of large NO amounts causes vasodilation and oxidative stress. The mechanism of action of methylene blue (MB) is based on the direct inhibition of soluble guanylate cyclase (sGC) by oxidation of the ferrous iron bound to the enzyme. MB also interacts with sGC by binding to the iron heme complex. Consequently, it avoids the increase in cGMP and vascular relaxation mediated by NO, a fact closely linked to the pathophysiology of shock. Another effect of MB is its action as a selective inducible isoform of nitric oxide synthase (iNOS) inhibitor, reducing the overall NO production and preventing the increase in radical peroxynitrite and peroxynitrous acid. In addition to its effect on sGC and iNOS, MB inhibits the production of reactive oxygen species, acting as an alternative electron receptor for xanthine oxidase, competing with molecular oxygen for electron transfer.

Intestinal transplantation: The anesthesia perspective.

Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis, drug interactions between anesthetic and immunosuppressive agents and venous access are some of the anesthetic considerations for this group.

Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years

We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts.