Intraoperative hypotension during liver transplantation and postoperative outcomes: Retrospective cohort study.

STUDY OBJECTIVES: Evaluation of the association between intraoperative hypotension (IOH) and important postoperative outcomes after liver transplant such as incidence and severity of acute kidney injury (AKI), MACE and early allograft dysfunction (EAD). DESIGN: Retrospective, single institution study. SETTINGS: Operating room. PATIENTS: 1576 patients who underwent liver transplant in our institution between January 2005 and February 2022. MEASUREMENTS: IOH was measured as the time, area under the threshold (AUT), or time-weighted average (TWA) of mean arterial pressure (MAP) less than certain thresholds (55,60 and 65 mmHg). Associations between IOH exposures and AKI severity were assessed via proportional odds models. The odds ratio from the proportional odds model estimated the relative odds of having higher stage of AKI for higher exposure to IOH. Associations between exposures and MACE and EAD were assessed through logistic regression models. Potential confounding variables including patient baseline and surgical characteristics were adjusted for all models. MAIN RESULTS: The primary analysis included 1576 surgeries that met the inclusion and exclusion criteria. Of those, 1160 patients (74%) experienced AKI after liver transplant surgery, with 780 (49%), 248(16%), and 132 (8.4%) experiencing mild, moderate, and severe injury, respectively. No significant association between hypotension exposure and postoperative AKI (yes or no) nor severity of AKI was observed. The odds ratios (95% CI) of having more severe AKI were 1.02 (0.997, 1.04) for a 50-mmHg·min increase in AUT of MAP <55 mmHg (P = 0.092); 1.03 (0.98, 1.07) for a 15-min increase in time spent under MAP <55 mmHg (P = 0.27); and 1.24 (0.98, 1.57) for a 1 mmHg increase in TWA of MAP <55 mmHg (P = 0.068). The associations between IOH and the incidence of MACE or EAD were not significant. CONCLUSION: Our results did not show the association between IOH and investigated outcomes.

Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery.

BACKGROUND: The Hypotension Prediction Index is a commercially available algorithm, based on arterial waveform features, that predicts hypotension defined as mean arterial pressure less than 65 mmHg for at least 1 min. We therefore tested the primary hypothesis that index guidance reduces the duration and severity of hypotension during noncardiac surgery. METHODS: We enrolled adults having moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring. Participating patients were randomized to hemodynamic management with or without index guidance. Clinicians caring for patients assigned to guidance were alerted when the index exceeded 85 (range, 0 to 100) and a treatment algorithm based on advanced hemodynamic parameters suggested vasopressor administration, fluid administration, inotrope administration, or observation. Primary outcome was the amount of hypotension, defined as time-weighted average mean arterial pressure less than 65 mmHg. Secondary outcomes were time-weighted mean pressures less than 60 and 55 mmHg. RESULTS: Among 214 enrolled patients, guidance was provided for 105 (49%) patients randomly assigned to the index guidance group. The median (first quartile, third quartile) time-weighted average mean arterial pressure less than 65 mmHg was 0.14 (0.03, 0.37) in guided patients versus 0.14 (0.03, 0.39) mmHg in unguided patients: median difference (95% CI) of 0 (-0.03 to 0.04), P = 0.757. Index guidance therefore did not reduce amount of hypotension less than 65 mmHg, nor did it reduce hypotension less than 60 or 55 mmHg. Post hoc, guidance was associated with less hypotension when analysis was restricted to episodes during which clinicians intervened. CONCLUSIONS: In this pilot trial, index guidance did not reduce the amount of intraoperative hypotension. Half of the alerts were not followed by treatment, presumably due to short warning time, complex treatment algorithm, or clinicians ignoring the alert. In the future we plan to use a lower index alert threshold and a simpler treatment algorithm that emphasizes prompt treatment.

Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction: A Retrospective Cohort Study.

BACKGROUND: Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury. METHODS: This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury. RESULTS: Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors. CONCLUSIONS: In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome.

Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma.

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation.

Life-Threatening Complications of Atrial Fibrillation Ablation: 16-Year Experience in a Large Prospective Tertiary Care Cohort.

OBJECTIVES: This study sought to assess the incidence and outcomes of life-threatening complications from atrial fibrillation ablations in a high volume center. BACKGROUND: With increasing rates of atrial fibrillation ablation procedures, an increase in life-threatening procedure-related complications has been reported despite improvements in technology and ablation strategies. METHODS: Between 2000 and 2015, 10,378 patients underwent atrial fibrillation ablation at our institution and were enrolled in a prospectively maintained data registry. We identified all patients who had life-threatening cardiac, neurological, respiratory, or vascular complications to the ablation resulting in death or requiring emergent intervention. RESULTS: Major life-threatening complications occurred in 100 patients (0.9%). The most common was pericardial effusion requiring pericardiocentesis (0.5%), with 7 (0.07%) requiring emergent surgical repair for cardiac perforation. Stroke occurred in 27 patients (0.3%) with a vast majority having an ischemic stroke (93%) followed by hemorrhagic (3.5%) and ischemic stroke with hemorrhagic conversion (3.5%). The yearly incidence of stroke decreased from an average of 1.1% per year in the first tertile (2000 to 2004) to 0.2% per year in the last 2 tertiles (2005 to 2015). Permanent neurological deficits occurred in 23 patients. Vascular complications causing hemorrhagic shock occurred in 7 patients (0.06%), 5 of whom required urgent surgical intervention. Acute coronary syndrome requiring urgent percutaneous coronary revascularization occurred in 2 patients whereas 1 developed a right coronary artery air embolus. No procedural death or atrio-esophageal fistulae occurred. CONCLUSIONS: In a large quaternary care center, the incidence of life-threatening complications is low. Experienced operators, high volume, continuous quality improvement initiatives, and efficient back-up support have allowed exemplary safety profiles and 0 procedure-related deaths over 16 years.

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death.

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.

The intraoperative glycemic response to intravenous insulin during noncardiac surgery: a subanalysis of the DeLiT randomized trial.

Patient characteristics may affect patients' response to insulin. We examined the impact of body weight and presence of diabetes on the response to insulin during noncardiac surgery. We studied 202 patients who were enrolled in the DeLiT Trial and received intraoperative intravenous insulin. Univariable and multivariable analyses (Bonferroni corrected) assessed the relationship between patient's response to the initial intraoperative I.V. bolus of regular insulin and the factors of interest. Blood glucose concentrations decreased 8.3 ± 10mg/dL (0.46 ± 0.56mmol/L) per unit of I.V. insulin in 30minutes. The response to insulin was similar in patients with or without diabetes (adjusted mean difference [97.5% confidence interval], 0.2 [-3.9, 4.2] mg/dL, 0.01 [-0.22, 0.24] mmol/L; P = .93). No relationship was found between insulin response and body weight (P=0.38). Our results suggest that adjustment for body weight and the presence of diabetes may not improve intraoperative insulin treatment algorithms.

Postoperative adverse effects after recent or remote lithium therapy.

Patients receiving preoperative lithium therapy for bipolar disorder may present unique challenges in the perioperative period and during critical illness. Two cases of critically ill patients who developed lithium-induced adverse reactions in the perioperative period due to the low therapeutic index are reported.

Oxygen consumption predicts outcome in porcine partial liver grafts.

BACKGROUND: High oxygen consumption (OC) in recipients of cadaveric whole liver grafts is associated with a poor prognosis. The aim of this study is to investigate the relationship between intraoperative hepatic OC and graft function and survival in a porcine partial liver graft model. MATERIAL AND METHODS: Experiments followed the Guiding Principles in the Care and Use of Laboratory Animals. Fourteen female pigs, 46-69 kg, received liver allografts of 17%-39% liver volume and were followed for 14 d. We measured donor and recipient body weights, percentage graft weight and expressed it as a percentage of standard liver volume, cold ischemia time, hepatic artery flow (HAF), portal vein flow (PVF), graft volume at sacrifice, serum lactate, prothrombin time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, albumin, total protein, alkaline phosphatase, total bilirubin, and recipient survival. OC was calculated as follows: OC (mL/100 g/min) = ([Hemoglobin {Hb} × 1.34 × SaO2 + 0.003 × PaO2] × HAF + [Hb × 1.34 × SpO2 + 0.003 × PpO2] × PVF - [Hb × 1.34 × SvO2 + 0.003 × PvO2] × [HAF + PVF])/graft weight (100 g), and animals were divided into two groups: low OC group (OC < 2.0 mL/100 g/min) and high OC group (OC ≥ 2.0 mL/100 g/min). RESULTS: In survival analysis, four of seven low OC recipients (57% [n = 7]) survived until the end of the study period compared with one of seven high OC recipients (14% [n = 7]). The low OC group had a significantly higher survival rate than that of the high OC group (P = 0.041). Low OC was associated with higher HAF (mL/100 g/min) after reperfusion compared with that of the high OC group, 29.0 ± 13.8 versus 16.0 ± 11.1 mean ± standard deviation; P = 0.073. Serum alkaline phosphatase and total bilirubin in the low OC group were significantly better than those of the high OC group. Serum lactate was comparable in both groups. Graft weight at the time of sacrifice in the low OC group tended to be higher than that in the high OC group, but not significantly (P = 0.097). CONCLUSIONS: High intraoperative OC is associated with lower HAF, decreased graft function, and decreased survival in the porcine partial liver graft model.

Deceased donor hyperglycemia and liver graft dysfunction.

CONTEXT: Hyperglycemia is common in deceased donors, and provokes numerous adverse events in hepatocytic mitochondria. OBJECTIVE: To determine whether hyperglycemia in deceased donors is associated with graft dysfunction after orthotopic liver transplant. METHODS: Charts on 572 liver transplants performed at the Cleveland Clinic between January 2005 and October 2010 were reviewed. The primary measure was time-weighted averages of donors' glucose measurements. Liver graft dysfunction was defined as (1) primary nonfunction as indicated by death or retransplant or (2) liver graft dysfunction as indicated by an aspartate amino transferase level greater than 2000 U/L or prothrombin time greater than 16 seconds during the first postoperative week. The relationship of interest was estimated by using a multivariable logistic regression. RESULTS: The incidence of graft dysfunction was 25%. No significant relationship was found between the range of donor glucose measurements and liver graft dysfunction after donor characteristics were adjusted for (P= .14, Wald test, adjusted odds ratio [95% CI] for liver graft dysfunction corresponding to a relative doubling in time-weighted average for donor glucose of 1.43 [0.89-2.30]). The results thus do not suggest that strict glucose control in donors is likely to improve graft quality.

Transfusion of older red blood cells is associated with decreased graft survival after orthotopic liver transplantation.

Investigations have demonstrated conflicting results regarding the influence of the red blood cell (RBC) storage duration on outcomes. We evaluated whether graft failure or mortality after orthotopic liver transplantation (OLT) increased when recipients were transfused with older RBCs. This study included 637 patients who underwent OLT between January 2001 and June 2011. Baseline and perioperative data were obtained from our blood bank, the Unified Transplant Center database, and the United Network for Organ Sharing database. Recipients whose transfused RBCs were all stored for ≤ 15 days were grouped in a younger group, and recipients who were transfused with RBCs stored for >15 days were placed in an older group. The relationship between graft survival/mortality and the age of intraoperatively transfused RBCs was studied by Kaplan-Meier estimation with a log-rank test and multivariate Cox proportional hazards regression. Three hundred thirty-four patients and 303 patients were grouped in the younger and the older RBC groups, respectively, on the basis of the ages of intraoperatively transfused RBCs. Kaplan-Meier estimates of graft survival/mortality as a function of the posttransplant time were significantly different: the older group experienced the outcome sooner than the younger group [P = 0.02 (log-rank test)]. After covariate adjustments, the risk of graft failure/mortality was significantly different at any given time after transplantation between patients receiving intraoperative transfusions of older RBC units and patients receiving intraoperative transfusions of younger RBC units (hazard ratio = 1.65, 95% confidence interval = 1.18-2.31). In conclusion, patients who received intraoperative transfusions of RBCs with longer storage times had an increased risk of adverse outcomes.

The role of the A2a receptor agonist, regadenoson, in modulating hepatic artery flow in the porcine small-for-size liver graft.

BACKGROUND: Hepatic artery vasoconstriction plays a major role in the pathophysiology of the small-for-size (SFS) liver graft injury and is reversed by adenosine. The A2a adenosine receptor (AR) has been suggested to be one of the key receptors that modulate hepatic hemodynamic changes. The aim of the study is to define the effects of the A2a AR agonist, regadenoson, in modulating hepatic artery flow (HAF) in SFS liver grafts of a porcine model. METHODS: Seven female recipient pigs (66-70 kg) receiving 20% liver grafts were treated with regadenoson, 0.1 ug/kg/min starting on POD1 (n = 7). Results were compared with those with untreated 20% liver grafts (n= 8). The recipients were observed for 14 d. Hepatic artery flow (HAF) and portal vein flow (PVF) were recorded. Liver biopsies and serum samples were also taken at the designed time points through postoperative day (POD)14. RESULTS: Dose-response curves of regadenoson established 0.1 ug/kg/min as the most effective dose of regadenoson for maintaining an increase in HAF. No adverse effects were seen with regadenoson infusion. HAF immediately increased by up to 2.2-fold after regadenoson infusion. The levels of daily average of HAF and percentage of HAF in total liver blood flow were 34.5% and 41.8%, respectively, higher in the regadenoson group than in the untreated group. Histologic scores of hepatic artery spasm and bile duct necrosis were significantly lower in the regadenoson group than in the untreated group (P = 0.01 and 0.04, respectively). The complication rates of hepatic artery thrombosis and gastrointestinal bleeding were lower in the regadenoson group than in the untreated group (0/7, 0% versus 2/8, 25% and 0/7, 0% versus 2/8 and 25%, respectively). The 14-d survival rates were 4/7 (57.1 %) in regadenoson group compared with 2/8 (25%) in the untreated group. CONCLUSION: Adenosine A2a AR agonist, regadenoson, increases HAF in the recipients of SFS grafts with modest improvements in outcome.

Elevated catecholamines and hepatic artery vasospasm in porcine small-for-size liver graft.

BACKGROUND: Elevated levels of norepinephrine (NE) have been reported in recipients of small-for-size liver (SFS) grafts in the perioperative period. The aim of the study is to test the hypothesis that although circulating catecholamines are elevated in recipients of SFS grafts, they are not the primary agents responsible for the hepatic artery (HA) vasospasm. METHODS: Female porcine recipients receiving a 20% (n = 10) partial liver graft were compared with a control group, using 60% partial liver transplanted grafts (n = 9). Hepatic blood flow (PVF, HAF) and levels of plasma catecholamines (epinephrine and NE) were measured at designated time points through postoperative day (POD) 7. Phentolamine (PA), an α-adrenergic blocker, was administered at doses of 1 to 112.5 ug/kg/min through an indwelling HA to the recipients of 20% group on POD1 (n = 5). RESULTS: In the 20% group following reperfusion, HA vasospasm was found at 10, 60, and 90 min, and persisted on POD 3 and POD 7. Plasma NE levels increased after reperfusion in 20% and 60% groups and peaked at 6 h with 10- to 13-fold increased levels compared with baseline. In the 20% group, NE levels remained elevated up to POD 7. PA infusion at low (1-10 ug/kg/min) and high (12.5-112.5 ug/kg/min) doses did not reverse the reduced HAF observed in 20% group recipients. CONCLUSION: Elevated serum NE does not appear to be the primary factor mediating HA vasospasm in the porcine SFS graft.

Hepatic blood flow plays an important role in ischemia-reperfusion injury.

Severe ischemia/reperfusion (IR) injury is associated with poor hepatic microperfusion. The aim of this study was to investigate the role of hepatic artery flow (HAF) and portal vein flow (PVF) in IR injury. From January 2004 to June 2008, 566 patients underwent orthotopic liver transplantation (OLT). The data were retrospectively reviewed via the transplant database. Patients with hepatic artery (HA) or portal vein (PV) thrombosis and retransplant patients were excluded. Intraoperative PVF and HAF values and graft weights were measured routinely, and the central venous pressure, mean arterial pressure, cardiac output, and cardiac index were recorded with hepatic blood flow measurements. Complete data were available for 312 primary OLT recipients (215 males and 97 females; mean age = 54 ± 10 years). The patients' follow-up ranged from 215 to 1746 days (705 ± 408 days). IR injury was defined by the aspartate aminotransferase (AST) level on postoperative day (POD) 2, and the patients were divided into 3 groups: (1) mild IR injury [AST < 500 U/L; n = 160 (51%)], (2) moderate IR injury [AST = 500-1000 U/L; n = 85 (27%)], and (3) severe IR injury [AST > 1000 U/L; n = 67 (21%)]. The demographics and pre-OLT variables (the Model for End-Stage Liver Disease score (MELD), platelet counts, PV thrombosis, transjugular intrahepatic portosystemic shunts, and shunts on computed tomography scans) were similar in all groups. The graft survival rate was 99% in group 1, 95.2% in group 2 (P = 0.02), and 92.3% in group 3 (P = 0.016). The patient survival rates were similar in the 3 groups. The cold ischemia time (CIT) was significantly higher in group 3 versus group 1 (P < 0.007). In the statistical analysis, low HAF, PVF, total liver blood flow (TLBF), and augmented HAF values were associated with a greater likelihood of elevated AST levels on POD 2. The strongest univariate predictors of AST were reduced augmented HAF (mL/minute/100 g) values (P < 0.001) and reduced TLBF (mL/minute/100 g) values (P < 0.001). In a covariate analysis with adjustments for CIT and donor variables, the blood flow parameters remained important predictors of graft function. In conclusion, this report demonstrates for the first time that reduced hepatic blood flow is a significant finding in patients with severe hepatic IR injury.

Glucose balance of porcine liver allograft is an important predictor of outcome.

BACKGROUND: The role of glucose metabolism in predicting postoperative liver graft function after transplantation is unclear. We investigated the relation between intraoperative glucose balance of the liver allograft and the postoperative graft function and survival in a porcine partial liver transplant model. MATERIALS AND METHODS: Experiments follow Guiding Principles in the Care and Use of Animals. Fourteen female pigs received liver allografts of 17%-39% recipient liver volume. Recipients were classified into two groups based on positive glucose balance: the mean intraoperative blood glucose of the graft outflow was greater than the blood glucose of inflow, negative glucose balance: the mean blood glucose of graft outflow was less than blood glucose of inflow. Perioperative data and survival were studied. RESULTS: In the positive group (n=9) intraoperative hepatic artery flow was significantly higher (P=0.028), and oxygen consumption was lower (P=0.018) than the negative group (n=5). Postoperatively, maximal serum aspartate aminotransferase (AST) (P=0.028), alanine aminotransferase (ALT) (P=0.028), and total bilirubin (P=0.027) of the positive group were significantly lower than the negative group. In survival analysis, the positive group had significantly better survival rate than the negative group (P=0.034). Using Periodic acid-Schiff staining, glycogen content of the allograft in the positive group at 10 min post-reperfusion was significantly decreased in comparison with the baseline value in the normal liver (P=0.005), however not statistically different in the negative group (P=0.175). CONCLUSION: Intraoperative glucose balance can be used as an early predictor of the graft function following transplantation of partial liver allografts.

Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome.

The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100 g/min) were 29 +/- 12 (mean +/- SD) and 74 +/- 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7-14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 +/- 8 ml/100 g/min at 90 min and remained low out to POD 7-14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome.

Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation.

Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (-0.02, 0.07) with P = 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (>12 ng/mL), P = 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT.