The association of pre-operative anaemia with survival after orthotopic liver transplantation.

Anaemia is common in patients with end-stage liver disease. Pre-operative anaemia is associated with greater mortality after major surgery. We analysed the association of pre-operative anaemia (World Health Organization classification) with survival and complications after orthotopic liver transplantation using Cox and logistic regression models. We included patients undergoing their first orthotopic liver transplantation between 2004 and 2016. Out of 599 included patients, 455 (76%) were anaemic before transplantation. Pre-operative anaemia was not associated with the survival of 485/599 (81%) patients to 1 year after liver transplantation, OR (95%CI) 1.04 (0.64-1.68), p = 0.88. Pre-operative anaemia was associated with higher rates of intra-operative blood transfusions and acute postoperative kidney injury on multivariable analysis, OR (95%CI) 1.70 (0.82-2.59) and 1.72 (1.11-2.67), respectively, p < 0.001 for both. Postoperative renal replacement therapy was associated with pre-operative anaemia on univariate analysis, OR (95%CI) 1.87 (1.11-3.15), p = 0.018.

Lipocalin-2 serum levels are increased in acute hepatic failure.

Lipocalin-2 (LCN-2), which is expressed in immunocytes as well as hepatocytes, is upregulated in cells under stress from infection or inflammation with increase in serum levels. We sought to investigate the relevance of LCN-2 in the setting of acute hepatic failure, particularly when addressed with the molecular adsorbent recirculating system (MARS). We measured serum LCN-2 concentrations with enzyme-linked immunosorbent assay (ELISA) in 8 patients with acute-on-chronic-liver failure (ACLF) and acute liver failure (ALF) who were treated with MARS. The controls were 14 patients with stable chronic hepatic failure (CHF). LCN-2 was determined immediately before and after the first MARS session. Baseline LCN-2 serum concentrations were significantly increased among ACLF and ALF patients as compared with CHF (P = .004 and P = .0086, respectively). There was no significant difference between the ALF and ACLF group. Moreover, serum LCN-2 levels did not change significantly during the MARS treatment. Serum LCN-2 levels, therefore, may be useful to discern acute from chronic hepatic failure and to monitor the course as well as the severity of the disease.

On the ropivacaine-reducing effect of low-dose sufentanil in intrathecal labor analgesia.

BACKGROUND: Combining ropivacaine with sufentanil for intrathecal (i.t.) analgesia in labor is well recognized, but information on dosing is limited. This study aimed to determine the ED 50 of i.t. ropivacaine and to assess the effect of adding defined low doses of sufentanil. METHODS: This was a two-phase, double-blind, randomized and prospective study. One hundred and fifteen parturients receiving combined spinal epidural analgesia were allocated to one of four groups to receive ropivacaine or sufentanil alone or in combination. In phase one, sufentanil dose-response was calculated using logistic regression. In phase two, ED 50 of ropivacaine and of the combination with a fixed dosage of sufentanil at ED 20 and ED 40 was evaluated using the technique of up-down sequential allocation. Analgesic effectiveness was assessed 15 min after injection using a 100 mm visual analog scale, with <10 mm lasting for 45 min defined as effective. Furthermore, side effects and duration were recorded. RESULTS: The ED 50 of i.t. ropivacaine was 4.6 mg [95% confidence intervals (95% CI) 4.28, 5.31]. Adding sufentanil at ED 20 significantly decreased the ED 50 of i.t. ropivacaine to 2.1 mg (95%CI 1.75, 2.5) (P<0.005); at ED 40, the reduction was similar (P<0.005). Combining sufentanil with ropivacaine resulted in a dose-independent prolongation of analgesia. Besides pruritus, which was well tolerated, there were no differences in side effects. CONCLUSION: Adding sufentanil at ED 20 results in a more than 50% dose-sparing effect of ropivacaine and considerably prolongs analgesia. Increasing dosage implicates no clinical benefit.

Nucleosome serum levels in acute hepatic failure and MARS treatment.

Serum nucleosomes have been suggested to be markers for cell death and apoptosis. Increased hepatocyte apoptosis can be demonstrated in acute liver failure (ALF) as well as acute-on-chronic liver failure (ACLF). We investigated the relevance of nucleosomes in the setting of acute hepatic failure. Further, we studied the effects of the molecular adsorbent recirculating system (MARS) on this marker of cell death. We measured serum nucleosome concentrations with ELISA in 12 patients with ACLF and 7 patients suffering from ALF, with 14 patients experiencing stable chronic hepatic failure (CHF) as controls. In a subset of 8 ACLF and ALF patients treated with MARS, nucleosomes were determined immediately before and after the first MARS session. Baseline nucleosome serum concentrations were significantly increased in ACLF and ALF patients as compared with CHF patients (P = .0161 and P = .0037, respectively). There was no significant difference between the ALF and ACLF groups. Moreover, serum nucleosome levels did not change significantly during MARS treatment in ALF and ACLF patients. Serum nucleosome levels therefore may be useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease. Our results, however, warrant further larger clinical studies regarding the clearance of nucleosome in artificial liver-assist devices and to assess their role in acute hepatic failure.

Pro-inflammatory interleukin-18 and Caspase-1 serum levels in liver failure are unaffected by MARS treatment.

BACKGROUND: The pro-inflammatory cytokine IL-18 and its activator Caspase-1 are involved in acute liver failure and acute-on-chronic-liver-failure. In acute liver failure and acute-on-chronic-liver-failure, the MARS system has been used to support liver function. Enhancement of IL-18, as seen in other extracorporeal-support systems like hemodialysis might thus have mitigated beneficial effects of the MARS system in acute hepatic failure. PATIENTS AND METHODS: We measured serum concentrations of IL-18 and Caspase-1 in 10 patients with acute liver failure and 10 patients suffering from acute-on-chronic-liver-failure, who were all treated with MARS. Thirteen patients suffering from chronic hepatic failure and 15 healthy individuals served as controls. Data are given as mean with 95% CI. RESULTS: Baseline IL-18 serum concentrations were significantly increased in acute liver failure and acute-on-chronic-liver-failure patients as compared to chronic hepatic failure (P=0.0039 and P=0.0011, respectively) and controls (P=0.0028 and P=0.0014, respectively). Caspase-1 serum concentrations were as well significantly elevated in the acute liver failure and acute-on-chronic-liver-failure groups as compared to chronic hepatic failure patients (P=0.0039 and P=0.0232, respectively) and controls P<0.0001 and P<0.0007, respectively). IL-18 and Caspase-1 did not change significantly during MARS treatment in acute liver failure and acute-on-chronic-liver-failure patients. CONCLUSIONS: MARS had no effect on IL-18 and Caspase-1 serum concentrations in acute liver failure and acute-on-chronic-liver-failure, providing no evidence of harmful effects by the increase of these potentially hepatocidal cytokines.

Plasma disappearance rate of indocyanine green in liver dysfunction.

The presence of hepatic dysfunction significantly affects the length of hospital stay and the outcome in critically ill patients. Considering the important partial hepatic functions of metabolism, synthesis, detoxification, and excretion, the worse clinical course of patients suffering from hepatic dysfunction is not surprising. The most often used indicator of hepatic dysfunction is bilirubin. However, bilirubin and other commonly used static laboratory tests provide only indirect measures of hepatic function. In contrast to these static tests, dynamic liver tests, such as indocyanine green (ICG) disappearance rate should provide better direct measures of the actual functional state of the liver at the time of assessment. The ICG is a water-soluble inert compound that is injected intravenously. It mainly binds to albumin in the plasma. ICG is then selectively taken up by hepatocytes, independent of adenosine triphosphate (ATP), and later excreted unchanged into the bile via an ATP-dependent transport system. The ICG is not metabolized; it does not undergo enterohepatic recirculation. Thus, ICG excretion rate in bile reflects the hepatic excretory function and hepatic energy status. Because of these features, ICG has been found to be useful to assess liver function in liver donors and transplant recipients, in patients with chronic liver failure, and as a prognostic factor in critically ill patients. Further trials concerning liver dysfunction have applied the noninvasive bedside assessment of ICG among other clinical variables to monitor the progress and/or the reversal of liver dysfunction.

Perioperative kinetics of heat shock protein 60 in serum during orthotopic liver transplantation.

INTRODUCTION: Heat shock proteins (HSP) play essential roles in the synthesis, transport, and folding of proteins. During ischemia/reperfusion (I/R) injury to orthotopic liver transplants (OLT), disassembly of oligomeric complexes and unfolding of proteins are likely to occur, producing a major burden on HSP to prevent and/or reverse these events. To date, all studies have evaluated HSP expression in tissues after an I/R injury. No data are available on HSP serum levels during I/R injury in liver graft recipients. PATIENTS AND METHODS: We evaluated the intraoperative and perioperative kinetics of HSP60 in the serum of 25 liver graft recipients. RESULTS: We observed a significant increase in serum levels of HSP60 at 4 hours compared with 30 minutes after reperfusion of the graft (P = .028). The perioperative HSP60 kinetics in serum neither correlated with the cold ischemia time nor the indocyanin green clearance. The type of preservation solution had no effect on serum HSP60 levels. CONCLUSION: This first study provides evidence for increased serum levels of HSP60 after reperfusion in OLT. The perioperative kinetics of HSP60 in serum may result from suppressed protein synthesis caused by a reduced energy charge of hepatocytes during early reperfusion, impaired transcription, and/or corticosteroid treatment. Further studies are needed to clarify the role of HSP60 under clinical conditions including immunosuppressive medications in human OLT.

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass.

UNLABELLED: Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.