Management of Intra- and Postoperative Bleeding in Elective Liver Surgery
Liver resections are associated with a significant risk of bleeding, as the liver, although comprising only 2-3% of an adult's body weight, receives about 25% of the cardiac output.
The main indications for elective liver surgery include the resection of malignant and benign masses, with a mortality rate of < 4%, which is significantly lower than urgent liver interventions following abdominal trauma (mortality rate over 50%) [1, 30]. Although intraoperative blood loss in elective liver procedures is low compared to liver trauma, it is one of the main predictors of postoperative mortality and morbidity, along with other factors such as operation duration, transfusion requirements, and extent of resection [6].
The causes of bleeding problems in elective liver surgery are multifactorial. Pre-existing liver parenchyma damage leads to a disturbance in the synthesis of coagulation factors and inhibitors [12], which is intensified postoperatively by the additional loss of liver tissue due to surgery. Preoperative chemotherapy can also lead to relevant liver dysfunctions. Examples include steatohepatitis after irinotecan therapy [7] and sinusoidal obstruction after oxaliplatin therapy [31].
Preoperative evaluation of individual surgical risk is often challenging. Laboratory parameters such as INR, bilirubin, and albumin allow an assessment of the liver's synthetic capacity but are not very informative for evaluating functional reserve. Imaging evaluations of liver parenchyma texture (ultrasound, CT, MRI) do not provide a reliable assessment of preoperative liver function. Liver function tests such as LiMAx ("maximal liver function capacity") can be helpful for estimating liver functional reserve [33]. The LiMAx test is a dynamic, liver-specific C13 breath test based on the metabolism of 13C-methacetin by the liver-specific cytochrome P450-1A2 system, reflecting the current liver performance at the time of measurement.
Besides parenchyma quality, the extent of resection and the type of resection technique play a crucial role in intraoperative blood loss in liver surgery. Electrosurgical instruments with simultaneous tissue sealing allow nearly bloodless transection of liver parenchyma, significantly reducing severe intraoperative bleeding to a very low percentage.
Anesthetic management also significantly influences intraoperative bleeding complications. High central venous pressure (CVP) or elevated pulmonary arterial pressure (PAP) can significantly increase bleeding tendency and have negative consequences for postoperative liver regeneration, making preoperative evaluation of cardiovascular and pulmonary diseases important for preventing bleeding complications.
Surgical Techniques
The "Sharp-Transsection", i.e., cutting the liver tissue with scissors, is one of the oldest methods [32]. In 1958, Tien-Yu Lin described the manual "Finger-Fracture" technique (digitoclasia) as an alternative [35]. In this technique, the liver parenchyma is initially broken between two fingers until only bile duct and vascular structures remain, which are then managed with clips, ligatures, and diathermy. Retrospective studies from the 1980s showed that the "Finger-Fracture" technique was significantly superior to the "Sharp-Transsection" in terms of intraoperative blood loss, but it is no longer used today [21]. An advancement of the "Finger-Fracture" technique is the "Clamp-Crush" method, where a clamp is used for parenchyma dissection [15].
Dissection of liver tissue using mechanical stapling devices (Vascular Stapler) is much faster and associated with less blood loss. Similar to the "Clamp-Crush" technique, the tissue is transected, and the vascular structures are simultaneously closed with a multi-row staple line. Retrospective studies have shown that this technique can reduce intraoperative blood loss by nearly 50% compared to the "Clamp-Crush" technique [27]. However, a recent randomized study found no significant difference in blood loss [25].
A study investigating the sealing and dissection device ("LigaSure®") based on bipolar current flow found no significant advantages in terms of blood loss and postoperative morbidity compared to the "Clamp-Crush" technique, but it did show a significantly lower consumption of suture material and significantly shorter operation times [4, 14]. A comparison of the Harmonic Scalpel®, which is based on ultrasonic dissection and coagulation, showed no advantages in terms of intraoperative blood loss compared to "Clamp-Crush" dissection in a Japanese study [34].
Studies demonstrate that the Cavitron Ultrasonic Surgical Aspirator (CUSA) significantly reduces intraoperative blood loss and transfusion requirements during liver resections [9]. CUSA's function is based on the selective fragmentation of liver parenchyma by ultrasound-generated energy with irrigation, which cools the device and suspends the fragmented tissue before aspiration.
The water jet dissector (water jet) uses high-pressure fluid for liver cell fragmentation, freeing vessels and bile duct structures from the parenchyma and selectively managing them. Two studies showed that the water jet method significantly reduces intraoperative blood loss, operation time, and liver ischemia time [18, 26]. In a prospective randomized study, parenchyma resection using water jet, CUSA, or Harmonic Scalpel® showed no advantages over the "Finger-Fracture" technique [16]. A 2009 meta-analysis reached similar conclusions [23].
With adequate technique, liver resections with low blood loss are achievable with any of the listed dissection techniques. Regardless of the method chosen, which is left to personal preferences and experience, an experienced and particularly well-coordinated surgical team is required to reduce blood loss and operation time. A retrospective study demonstrated that the "two-surgeon method" of parenchyma dissection is highly significantly correlated with reduced transfusion requirements: one surgeon dissects, the other coagulates [22].
Hemostatic Agents
Hemostatic agents are topically effective drugs of synthetic or biological origin used intraoperatively for vessel sealing. Three substance classes are primarily used clinically: collagens, fibrins, and cyanoacrylates.
Collagen
- Duracol
- Biocol
- Gelfoam
- Lyostipt
- Antema
Fibrin
- Tissucol
- Tachosil
- Floseal
- Beriplast
Cyanoacrylate
- Histoacryl
- Tisuacryl
- Dermabond
- Glustitch
In liver surgery, cyanoacrylates are not widely used because they can cause necrosis at resection surfaces and induce systemic inflammation mediators [20].
Collagens are used in both solid (collagen fleece) and liquid forms. In solid form, the products are manufactured with a special coating containing coagulation factors (e.g., thrombin) or other antithrombolytic substances (protein C and S). Various studies have shown that collagens have the advantage of a faster hemostatic effect compared to conventional hemostasis using bipolar forceps or "argon beam" [3, 10]. However, the data is contradictory, as other studies refute the advantages of collagens [37].
Fibrins are almost exclusively applied in liquid form. They consist of two components (fibrinogen and calcium chloride) that must be mixed immediately before use. Studies have shown no significant advantages in blood loss and transfusion requirements during liver resections [5, 8].
HaemoCer™ PLUS
A representative of a new generation of hemostatic agents is HaemoCer™ PLUS, used in the film. It is a plant-based hydrophilic polysaccharide that is not only biocompatible but also completely degrades in the body within 48 hours. Upon contact with blood, HaemoCer™ PLUS initiates a dehydration process, extracting liquid blood components and binding them within seconds in a gel matrix. This leads to an accumulation of fibrin, thrombin, erythrocytes, and platelets at the bleeding site, ultimately forming a natural clot and stopping the bleeding. The mechanism of action of HaemoCer™ PLUS is based on accelerating the physiological coagulation cascade without chemical or pharmaceutical influence.
Pringle and Hemi-Pringle Maneuvers
In the Pringle maneuver, the portal vein and common hepatic artery are clamped intraoperatively within the hepatoduodenal ligament [24]. The maneuver can be performed continuously or intermittently. The liver tolerates ischemia induced by the maneuver for up to 60 minutes, provided there are no significant parenchymal damages [13]. The total ischemia time can be divided into several intervals. Studies have shown no difference in blood loss and transfusion requirements between continuous and intermittent Pringle maneuvers [2].
In the Hemi-Pringle maneuver, the branches of the hepatic artery and portal vein of a liver lobe carrying the segments to be resected are clamped. This limits ischemic damage to the liver, but the maneuver has no significant impact on intraoperative blood loss [11, 17].
Open and Minimally Invasive Liver Resections
The first minimally invasive liver resections were performed 20 years ago, initially limited to benign, peripherally located findings [28]. Nowadays, more complex resections are also feasible laparoscopically. A recent meta-analysis of 610 patients who underwent laparoscopic resection of colorectal liver metastases showed significantly lower blood loss and transfusion requirements compared to patients who underwent open resection [29].
Non-Surgical Measures
The intraoperative maintenance of a low central venous pressure (CVP) during the resection phase is standard in modern liver surgery. CVP can be reduced both pharmacologically and through restrictive volume management [19]. A reduction of CVP to below 5 mm Hg has shown significantly lower blood loss and transfusion requirements, as well as a positive impact on mortality and morbidity in various studies [19, 36].