Manuel Muñoz, MD, PhD
University of Málaga
Patient blood management (PBM) in hepatic surgery, especially orthotopic liver transplantation (OLT), still presents a formidable challenge although such procedures are performed by experienced surgical and anesthetic teams. Nonetheless, major liver surgery can be performed safely in most patients, including Jehovah’s Witness patients, by implementing a comprehensive, multidisciplinary PBM program that includes preoperative, intraoperative and postoperative interventions .
In the preoperative period, the patient’s status should be optimized to reduce the risk of allogeneic transfusion. This should include: 1) evaluation and optimization of hemostasis (platelet count and clotting studies, revision of anticoagulant and antiplatelet drugs, administration of vitamin K, etc.) to reduce the risk of intraoperative hemorrhage; 2) optimization of nutritional status with the use of supplemental enteral feeding or total parenteral nutrition, if necessary; 3) optimization of hemoglobin levels by the use of drugs to enhance red blood cell production (e.g. iron, folate, vitamin B12 and erythropoiesis-stimulating agents [ESA]). After regulatory changes because of safety concerns regarding their long-term administration (thromboembolic events, mortality, tumor progression, etc.), the use of ESAs in cancer patients has decreased considerably. However, this might not be the case for patients undergoing OLT for hepatocarcinoma, as they will receive ESA therapy only for a short period and their liver will be removed. Intravenous (IV) iron has no major influence on the regulation of erythropoiesis and, therefore, there is no risk of increasing hemoglobin levels beyond recommended ranges. In addition, IV iron administration may allow significant reduction of ESA dosage.
Preoperative autologous blood donation (PABD) was once promoted to decrease allogeneic transfusion requirements, but nowadays is only recommended in selected cases. Recently, in a series of 193 patients undergoing hepatectomy for hepatocellular carcinoma, Kato et al. found that PABD (1–3 units, with ESA administered before surgery in patients donating ≥ 2 units) was feasible, significantly decreased the requirements for allogeneic blood transfusion and had no impact on survival .
In the intraoperative period, measures should be aimed at decreasing surgical blood loss. General anesthesia is the standard of care and anesthesiologists should monitor central venous pressure (CVP), cardiac output (generally by a non-invasive method), and acid–base balance for volume management during OLT. Maintenance of a low CVP (5–10 cm H2O) seems to be critical during the anesthesia management of OLT, and this is one of the reasons for implementing a relatively restrictive volume management, using blood products and albumin to increase colloid osmotic pressure, while limiting the infusion of normal saline . In addition, avoidance of hypothermia, of high intrathoracic pressures, of hypercapnia and restricting blood sampling may help minimize blood loss. However, a recent systematic review concluded that maintaining a low CVP, hemodilution, hemodilution with controlled hypotension, and hypoventilation do not appear to decrease perioperative morbidity or offer any long-term survival benefit. Nonetheless, hemodilution shows promise in reducing blood transfusion requirements in liver resection surgery .
There may be multiple causative factors for excessive bleeding during major liver surgery like fibrinolysis, thrombocytopenia, dilutional coagulopathy, hypothermia, or technical difficulty. A meticulous surgical technique, assisted by new surgical devices (water jet dissectors [Hydrojet], ultrasonic dissectors [CUSA], radiofrequency dissectors [Cool-tip RF], argon beam coagulation, etc.), is the cornerstone of intraoperative blood conservation. Devices using radiofrequency energy take advantage of its unique combination of radiofrequency current and internal electrode cooling to perform sealing of the small vessels and biliary ducts. Its use is indicated mostly in cirrhotic patients with challenging hepatectomies (segment VIII, central resections) . However, the available evidence suggests these techniques may not be superior to the clamp-crushing methods using small forceps. Therefore, newer devices should be used within the limits of each instrument, as well as the surgical skills of the surgeon .
Local agents, including collagen and cellulose pads, and fibrin glues and sealants, have also been developed as adjunctive measures to promote hemostasis. Topical or systemic antifibrinolytic agents may also be used. Three meta-analyses of randomized trials concluded that aprotinin and tranexamic acid may potentially reduce blood loss and transfusion requirements in liver transplantation and liver resections, without increasing postoperative morbidity (thromboembolic events) or mortality. However, the authors stated that all the trials were at high risk of bias, thus hampering the confidence in this conclusion [7-9]. Nowadays, the prophylactic use of antifibrinolytics in OLT is controversial. Similarly, prophylaxis with recombinant activated factor VII does not appear to prevent mortality and bleeding resulting from liver resection and OLT .
Common blood products available for correction of intra- or postoperative coagulopathy include fresh frozen plasma, platelets, and cryoprecipitate. Additionally, 4-factor prothrombin complex concentrate (PCC; 1200–3000 U) can significantly improve coagulation in a very short period of time and with a much lower volume expansion than fresh frozen plasma. Similarly, fibrinogen concentrate should be preferred to cryoprecipitate as it allows fibrinogen repletion in a more precise, rapid manner, and with less volume exposure (up to 6 g can be given in less than 3 minutes).The main adverse effects of PCC and fibrinogen are thromboembolic events and allergic reactions . The use of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for coagulation management constitutes the more recent trend in point-of-care coagulation monitoring. TEG/ROTEM assesses the kinetics of clot formation as well as the strength and stability of the formed clot, and recognizes coagulation problems faster, more specifically, and sometimes in situations when the coagulation profile is still normal. TEG/ROTEM allows goal-directed therapy with the required coagulation factors to improve hemostasis and reduce transfusion requirements, thus adjusting the dosage and reducing adverse events . It can be expected that the use of TEG/ROTEM will become standard of care in major liver surgery in the near future.
A final option for decreasing blood loss is the reutilization of the patient’s own blood. Intraoperative cell salvage (ICS) has proven highly efficient for saving blood and reducing complications during surgical procedures such as OLT . However, ICS is usually thought of as contraindicated in OLT or liver resection involving hepatocarcinomas, due to the risk of dissemination of tumor cells. However, the results of a recent meta-analysis of observational studies do not support the theoretical concern of increased cancer recurrence or development of metastases with the use of ICS during cancer surgery . These results suggest that the use of additional safety measures such as leukoreduction filters (which have been proven to remove a variety of malignant cells) or irradiation of salvaged blood (which kills tumor cells or abolishes their proliferative capacity) is not needed when using ICS in cancer surgery; however, this issue remains debated .
In the postoperative period, vigilant monitoring and management of postoperative bleeding, rapid rewarming, minimization of iatrogenic blood loss, optimization of ventilation and oxygenation and minimization of oxygen consumption, adequate management of nutrition, antibiotic therapy and immunosuppression and anemia treatment should be implemented. Regarding the latter, it must be stressed that restrictive evidence-based transfusion strategies should be used over the entire perioperative period .
A multidisciplinary PBM program aimed to increase preoperative red cell mass, decrease surgical blood loss, and optimize tolerance to postoperative anemia may result in a substantial reduction of transfusion requirements in liver resections and OLT. The need for blood products in major liver surgery has progressively decreased over time, but there is still room for improvement.
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