Assessment of Individualized Mean Perfusion Pressure Targets for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury-The PrevHemAKI Randomized Controlled Trial.

BACKGROUND: Retrospective studies support that mean perfusion pressure (MPP) deficit in cardiac surgery patients is associated with a higher incidence of acute kidney injury (CS-AKI). The aim of our study was to apply an algorithm based on MPP in the postoperative period to determine whether management with an individualized target reduces the incidence of CS-AKI. METHODS: Randomized controlled trial of patients undergoing cardiac surgery with extracorporeal circulation. Adult patients submitted to valve replacement and/or bypass surgery with a high risk of CS-AKI evaluated by a Leicester score >30 were randomized to follow a target MPP of >75% of the calculated baseline or a standard hemodynamic management during the first postoperative 24 h. RESULTS: Ninety-eight patients with an eGFR of 54 mL/min were included. There were no differences in MAP and MPP in the first 24 h between the randomized groups, although a higher use of noradrenaline was found in the intervention arm (38.78 vs. 63.27, p = 0.026). The percentage of time with MPP < 75% of measured baseline was similar in both groups (10 vs. 12.7%, p = 0.811). MAP during surgery was higher in the intervention group (73 vs. 77 mmHg, p = 0.008). The global incidence of CS-AKI was 36.7%, being 38.6% in the intervention group and 34.6% in the control group (p = 0.40). There were no differences in extrarenal complications between groups as well. CONCLUSION: An individualized hemodynamic management based on MPP compared to standard treatment in cardiac surgery patients was safe but did not reduce the incidence of CS-AKI in our study.

Portal hypertension has no role in perioperative bleeding during liver transplantation with systematic porto-caval shunt.

BACKGROUND: More than a half of patients undergoing liver transplantation (LT) receive intraoperative transfusion. Portal hypertension (PHT) may contribute to perioperative blood loss. We study the relationship between preoperative hepatic venous pressure gradient (HVPG) values and intraoperative transfusion requirements in adult patients undergoing LT. METHODS: 160 cirrhotic patients undergoing first elective LT (2009-2019) with an HVPG measurement within the previous 6 months were included. Surgical technique was piggyback with portocaval shunt (PCS). The association of HVPG and other variables with transfusion requirements and blood loss were studied. RESULTS: Blood loss (ml/kg) was positively correlated with HVPG, among other variables, but at multivariable analysis it only remained associated with MELD-Na and HCC indication. Regarding RBC transfusion, MELD-Na and hemoglobin were independently associated with the need and magnitude of RBC transfusion. Subanalysis by surgical stage (hepatectomy, anhepatic, neohepatic) and by serial HVPG cut-offs found no clear associations with either bleeding or transfusion. DISCUSSION: The severity of PHT plays a minor role on bleeding and transfusion during LT in a contemporary cohort with systematic PCS. Main determinants of transfusion are liver function and baseline hemoglobin, which would seem the suitable goal to optimize transfusion in LT.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome.

BACKGROUND: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS: Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.

Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection.

OBJECTIVES: Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients. DESIGN: Single center case series. SETTING: Local study. SUBJECTS: Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions. INTERVENTIONS: Plasma exchange. Two to six sessions (1.2 plasma volumes). Human albumin (5%) was used as the main replacement fluid. Fresh frozen plasma and immunoglobulins were administered after each session to avoid coagulopathy and hypogammaglobulinemia. MEASUREMENTS AND MAIN RESULTS: Serum markers of inflammation and macrophage activation. All patients showed a dramatic reduction in inflammatory markers, including the main cytokines, and improved severity scores after plasma exchange. All survived to ICU admission. CONCLUSIONS: Plasma exchange mitigates cytokine storm, reverses organ failure, and could improve survival in critically ill patients with coronavirus disease 2019 infection.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.

BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Impact of hepatic encephalopathy on liver transplant waiting list mortality in regions with different transplantation rates.

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.

A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.

BACKGROUND & AIMS: Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality rates (15%-20%). Previously described models are seldom used to determine prognoses of these patients, partially because they have not been validated externally and because they include subjective variables, such as bleeding during endoscopy and Child-Pugh score, which are evaluated inconsistently. We aimed to improve determination of risk for patients with AVB. METHODS: We analyzed data collected from 178 patients with cirrhosis (Child-Pugh scores of A, B, and C: 15%, 57%, and 28%, respectively) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict the mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n = 240) and Spain (n = 221). RESULTS: Among study subjects, the 6-week mortality rate was 16%. MELD was the best model in terms of discrimination; it was recalibrated to predict the 6-week mortality rate with logistic regression (logit, -5.312 + 0.207 • MELD; bootstrapped R(2), 0.3295). MELD values of 19 or greater predicted 20% or greater mortality, whereas MELD scores less than 11 predicted less than 5% mortality. The model performed well for patients from Canada at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. CONCLUSIONS: We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.

Assessing portal hypertension in liver diseases.

Portal hypertension is a common complication of chronic liver diseases and is responsible for most clinical consequences of cirrhosis, which represent the more frequent causes of death and liver transplantation in these patients. This review is aimed at clarifying the state-of-the art assessment of portal hypertension and at discussing recent developments in this field. Particular attention is paid to new noninvasive techniques that will be soon available for potential routine use.

Assessment of portal hypertension by transient elastography in patients with compensated cirrhosis and potentially resectable liver tumors.

BACKGROUND & AIMS: Patients with cirrhosis and small hepatocellular carcinoma with normal bilirubin and hepatic venous pressure gradient (HVPG) <10 mm Hg have >70% 5-year survival after hepatic resection. On the contrary, patients with HVPG ≥10 mm Hg (clinically significant portal hypertension, CSPH) frequently develop decompensation following surgery, with around 50% 5-year survival. Liver stiffness (LS) evaluation by transient elastography might non-invasively identify CSPH. We investigated the usefulness of LS predicting CSPH in patients with compensated cirrhosis and potentially resectable liver tumors. METHODS: Ninety-seven consecutive Child-Pugh A patients with potentially resectable liver tumors referred for HVPG measurement were prospectively evaluated. In fasting conditions LS was measured before the hemodynamic study. RESULTS: HVPG could be measured in all patients, whereas LS could not be measured in 18 (18.5%) obese patients. In the 79 patients with valid LS, 32 (40.5%) had CSPH; mean HVPG was 8.8±4.7 mm Hg. Mean LS was 18.4±12.3 kPa. LS showed a moderate correlation with HVPG (r=0.552; p<0.001). LS<13.6 kPa had high sensitivity (91%) but low specificity (57%) excluding CSPH. Conversely, LS>21 kPa had low sensitivity (53%) and high specificity (91%) predicting CSPH. 35% of patients had LS between 13.6 and 21 kPa ("grey zone"). CONCLUSIONS: These data suggest that in real-life scenarios half of patients with potentially resectable liver nodules can be non-invasively classified as having or not CSPH by LS. However, in the remaining half, LS is either not applicable or inaccurate. In this last population HVPG is still a non replaceable method to detect CSPH.