Réal Lapointe

Coagulation Defects Do Not Predict Blood Product Requirements During Liver Transplantation

Background. In our experience, correction of coagulation defects with plasma transfusion does not decrease the need for intraoperative red blood cell (RBC) transfusions during liver transplantation. On the contrary, it leads to a hypervolemic state that result in increased blood loss. A previous study has shown that plasma transfusion has been associated with a decreased 1-year survival rate. The aim of this prospective study was to evaluate whether anesthesiologists could reduce RBC transfusion requirements during liver transplantation by eliminating plasma transfusion. Methods. Two hundred consecutive liver transplantations were prospectively studied over a 3-year period. Patients were divided into two groups: low starting international normalized ratio (INR) value <1.5 and high INR ≥1.5. Low central venous pressure was maintained in all patients before the anhepatic phase. Coagulation parameters were not corrected preoperatively or intraoperatively in the absence of uncontrollable bleeding. Phlebotomy and auto transfusion of blood salvaged were used following our protocol. Independent variables were analyzed in both univariate and multivariate fashion to find a link with RBC transfusions or decreased survival rate. Results. The mean number of intraoperative RBC units transfused was 0.3±0.8. Plasma, platelet, albumin, and cryoprecipitate were not transfused. In 81.5% of the patients, no blood product was used during their transplantation. The average final hemoglobin (Hb) value was 91.2±15.0 g/L. There were no differences in transfusional rate, final Hb, or bleeding between two groups (low or high INR values). The overall 1-year survival rate was 85.6%. Logistic regression showed that avoidance of plasma transfusion, phlebotomy, and starting Hb value were significantly linked to liver transplantation without RBC transfusion. The need for intraoperative RBC transfusion and Pughs score were linked to the decreased 1-year survival rate. Conclusion. The avoidance of plasma transfusion was associated with a decrease in RBC transfusions during liver transplantation. There was no link between coagulation defects and bleeding or RBC or plasma transfusions. Previous reports indicating that it is neither useful nor necessary to correct coagulation defects with plasma transfusion before liver transplantation seem further corroborated by this study. We believe that this work also supports the practice of lowering central venous pressure with phlebotomy to reduce blood loss, during liver dissection, without any deleterious effect.

Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center.

Background Orthotopic liver transplantation (OLT) has been associated with major blood loss and the need for blood product transfusions. During the last decade, improved surgical and anesthetic management has reduced intraoperative blood loss and blood product transfusions. A first report from our group published in 2005 described a mean intraoperative transfusion rate of 0.3 red blood cell (RBC) unit per patient for 61 consecutive OLTs. Of these patients, 80.3% did not receive any blood product. The interventions leading to those results were a combination of fluid restriction, phlebotomy, liberal use of vasopressor medications, and avoidance of preemptive transfusions of fresh frozen plasma. This is a follow-up observational study, covering 500 consecutive OLTs. Methods Five hundred consecutive OLTs were studied. The transfusion rate of the first 61 OLTs was compared with the last 439 OLTs. Furthermore, multivariate logistic regression was used to determine the main predictors of intraoperative blood transfusion. Results A mean (SD) of 0.5 (1.3) RBC unit was transfused per patient for the 500 OLTs, and 79.6% of them did not receive any blood product. There was no intergroup difference except for the final hemoglobin (Hb) value, which was higher for the last 439 OLTs compared with the previously reported smaller study (94 [20] vs. 87 [20] g/L). Two variables, starting Hb value and phlebotomy, correlated with OLT without transfusion. Conclusions In our center, a low intraoperative transfusion rate could be maintained throughout 500 consecutive OLTs. Bleeding did not correlate with the severity of recipient’s disease. The starting Hb value showed the strongest correlation with OLT without RBC transfusion.

MELD score and blood product requirements during liver transplantation: no link.

Background. Orthotopic liver transplantation has been traditionally associated with major blood loss and the need for allogenic blood product transfusions. In recent years, improvements in surgical and anesthetic techniques have greatly decreased the amount of blood products transfused. We have published a median of 0 for all intraoperative blood products transfused. Some authors argue that these results could be possible merely because of the relatively healthy cohort in terms of model of end-stage liver disease (MELD) score. The MELD score could be adjusted by some conditions (hepatocellular carcinoma, hemodialysis, hepatopulmonary syndrome, and amyloidosis) and was not adjusted in these series. The goal of this work was to verify the MELD score according to US standards and to find any link between the MELD score and the transfusion rate. Method. Three hundred fifty consecutive liver transplantations were studied. The MELD score was adjusted according to US standards. Patients were divided into two groups according to the median of the MELD score. Blood loss and transfusion rate were determined for these two groups. Logistic regression models were used to find any link with transfusion of red blood cell (RBC) units. Result. The MELD score before adjusting was 19±9 and 22±10 after. A mean of 0.5±1.3 RBC units/patient intraoperative were transfused with 80.6% of cases without any blood products. There was no difference for the blood loss (999±670 mL vs. 1017±885 mL) or the transfusion rate (0.4±1.2 vs. 0.5±1.4 RBC/patient) between two groups of MELD (<21 or ≥21) or any of its component (creatinine, bilirubin, and international normalized ratio). The logistic regression analysis found that only two variables were linked to RBC transfusion; starting hemoglobin value and phlebotomy. Conclusion. In this series, the MELD score was as high as US series and did not predict blood losses and blood product requirement during liver transplantation. If the MELD system has to be implemented to prioritize orthotopic liver transplantation, it should be revisited, and the starting hemoglobin value should be added to the equation.

Mechanisms of Renal Phosphate Loss in Liver Resection-Associated Hypophosphatemia

Objective:To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia. Background:Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder. Methods:Serum phosphate (PO4), ionized calcium (Ca++), HCO3−, pH and FE P, intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1, 2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed hepatic segments was also assessed. Results:Serum PO4 concentrations decreased within 24 hours, were lowest (0.66 ± 0.03 mmol/L; P < 0.001) at 48 hours, and returned to normal within 5 days of the procedure. FE P peaked at 25.07% ± 2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 ± 0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated with increased I-PTH concentrations (8.8 ± 0.9 pmol/L; P < 0.01; correlation: r = −0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = −0.56, P = 0.024). Severe hypophosphatemia and increased urinary phosphate excretion persisted for 72 hours even when I-PTH concentrations had returned to normal. I-FGF-23 decreased to its nadir of 7.8 ± 6.9 pg/mL (P < 0.001) on po day 3 and was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23, FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE P. Conclusion:Posthepatectomy hypophosphatemia is associated with increased FE P unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to excessive FE P partially on po day 1 but not thereafter. Other yet defined factors should explain post hepatectomy hypophosphatemia.

Treatment of post liver transplantation bile duct stricture with self-expandable metallic stent

OBJECTIVE The aim of this study is to report our experience using self-expandable covered metallic stents (Wallstent) to treat different types of biliary strictures after orthotopic liver transplantation (OLT). PATIENTS AND METHODS Between January 1999 and July 2004, 222 OLTs were performed with choledocho-choledochostomy (CC) bile duct reconstruction. An anastomotic biliary stricture was diagnosed and treated by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous procedures in 100 patients (45%). The group of 21 patients (mean age 57.0+/-5.6 years) that were eventually treated with a biliary Wallstent was studied retrospectively. RESULTS Significant persistent proximal or anastomotic strictures were diagnosed in 4 and 17 patients, respectively. A Wallstent was inserted by ERCP or through a percutaneous route in 18 and 3 patients, respectively. The mean interval between diagnosis and Wallstent insertion was 179.7+/-292.8 (0-1113) days. The mean total number of procedures required per patient was 7.4+/-5.5. The mean stent primary patency duration was 10.8+/-7.8 (0.9-25.1) months with a 24-month primary patency rate of 26% at a mean follow-up time of 37.8+/-17.2 months. A hepatico-jejunostomy was performed in five patients (24%). Two patients (10%) underwent retransplantation for diffuse ischemic cholangitis or chronic rejection. The overall complication rate was 4%. CONCLUSION Treatment of post-transplant biliary stenosis using a Wallstent is a valuable option for delaying or avoiding surgery in up to 70% of patients. Proximal stenosis can be treated in the same manner in selected patients with major comorbidities.

Transcatheter arterial chemoembolization of hepatocellular carcinoma as a bridge to liver transplantation: a retrospective study.

Background. Transcatheter arterial lipiodol chemoembolization (TACE) can be used in cirrhotic patients with hepatocellular carcinoma to avoid tumor progression before transplantation. Objective. To evaluate the efficacy and safety of TACE used as a bridge to liver transplantation. Methods. TACE was performed in 30 cirrhotic patients with hepatocellular carcinoma. Milan criteria were used to select patients for transplant. Patients had a good or moderately impaired liver function, no arterioportal fistulae, and a good portal perfusion. Results. 48 TACE were performed in 30 patients. Before transplantation, 4 patients were dropped off the list due to tumor extension or liver failure. Complete necrosis of the tumor was observed in 11 patients and partial necrosis in 15 patients. After transplantation, 6 patients died and tumor recurrence was observed in 5 patients with a tumor beyond Milan criteria or no response to TACE. Conclusion. TACE is useful as a bridge to liver transplantation in a selected group of cirrhotic patients with hepatocellular carcinoma. A combined therapeutic approach before surgery might improve the prognosis in these patients.

Is intra-operative ultrasound still useful for the detection of a hepatic tumour in the era of modern pre-operative imaging?

BACKGROUND The current role of intra-operative ultrasound (IOUS) is questioned because of recent progress in medical imaging. The aim of the present study was to determine the accuracy of IOUS in the detection of a hepatic tumour (HT) compared with a pre-operative multi-detector computed tomography (MDCT) scan and magnetic resonance imaging (MRI). METHODS This retrospective study included 418 patients evaluated using an 8-slice MDCT scan (SCAN8), 64-slice MDCT scan (SCAN64) and MRI alone or combined with a computed tomography (CT) scan. The pathological result was used as a gold standard. RESULTS Correlation rates for the number of detected lesions compared with pathology results were 0.627 for SCAN8, 0.785 for SCAN64, 0.657 for MRI and 0.913 for IOUS. Compared with pathology, the rate of concordance was significantly higher with IOUS (0.871) than with SCAN8 (0.736; P=0.011), SCAN64 (0.792; P<0.001) and MRI (0.742; P<0.001). IOUS was responsible for a change in operative strategy in 16.5% of patients. Surgery was extended in 12.4%, limited in 1.7% and abandoned in 2.4%. CONCLUSIONS Compared with cross-sectional pre-operative imaging, IOUS is still superior for the detection of HT and the planning of surgery. IOUS remains recommended as a routine procedure in patients having a hepatic resection in the era of modern pre-operative imaging.

Long-lasting analgesic effects of intraoperative thoracic epidural with bupivacaine for liver resection.

Objectives: Continuous epidural analgesia may be considered in liver resection but is often avoided because of possible coagulopathies and the risk of epidural hematoma in the postoperative period. On the other hand, there is no coagulation defect during the surgery. Effective prevention of postoperative pain may require continuous sensory ablation throughout the surgery event. Methods: A prospective, randomized, double-blind study was conducted to evaluate the efficacy of intraoperative epidural anesthesia on postoperative morphine consumption via patient-controlled analgesia after liver surgery in 2 groups of patients. One group (epidural) received, intraoperatively, thoracic epidural bupivacaine perfusion (0.5% at 3 mL/hr) added to preoperative intrathecal morphine (0.5 mg) and fentanyl (15 &mgr;g). The other group (placebo) was administered the same intrathecal narcotics but with a sham epidural. Forty-four patients scheduled for major liver resection (≥2 segments) were recruited. Patient-controlled analgesia morphine consumption, pain at rest and with movement, sedation, nausea, pruritus, and respiratory frequency were evaluated at 6, 9, 12, 18, 24, 36, and 48 hrs after intrathecal morphine injection. Results: Patients in the placebo group consumed twice as much morphine during each time interval than patients in the epidural group (at 48 hrs: 123 [SD, 46] vs 59 [SD, 25] mg; P < 0.0001). Pain evaluation on visual analog scale at rest and on movement was lower in the epidural group (P = 0.017 and P = 0.037). Conclusion: Intraoperative thoracic epidural infusion of bupivacaine, added to intrathecal morphine, decreased postoperative morphine consumption with better pain relief compared with the placebo.

Hypertrophy of the non-embolized liver after chemotherapy.

BACKGROUND Neoadjuvant chemotherapy (NC(+)) and portal vein embolization (PVE) enables curative resection in more patients with colorectal-liver metastases (CRLM). However, after NC(+), structural alterations have been reported with the risk of post-operative hepatic failure. We undertook to determine if NC(+) toxicity limits future remnant liver (FRL) hypertrophy after PVE. METHODS PVE was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI (5-fluorouracil + leucovorin + irinotecan) regimen (NC(+)) of 6.6 cycles. The seven remaining patients served as the control group without NC (NC(-)). RESULTS CRLM were bilateral in 69% (NC(+)) and 57% (NC(-)), and synchronous in 84% (NC(+)) and 14% (NC(-)). The FRL hypertrophy rate was 54.1% (NC(+)) and 43.7% (NC(-)) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group NC(+): one insufficient FRL hypertrophy and one severe steatosis; and group NC(-): two tumoral progressions. In both groups, the operative parameters were comparable except for pedicular clamping: 8 (NC(+)) and 36 min (NC(-)), respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were comparable. No significant pathological difference was observed between the two groups. No mortality occurred in either group. CONCLUSION In view of our limited experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not altered after FOLFIRI-based NC.

Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.

The use of neo‐adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo‐adjuvant chemotherapy on outcomes following liver resection for synchronous CLM.