Table 2 Secondary endpoints of the IVC CLAMP Trial.

Blood transfusions:

Administration of PRBC transfusion is documented for the intraoperative and postoperative period until 48 hours postoperatively. Documentation includes number of patients receiving PRBC transfusions as well as amount of transfused packed red blood cells [ml]. Transfusion triggers are given in table 4 to standardize administration of PRBC.

Operation time [min]:

Time from skin incision to placement of last skin staple/suture.

Transection time [min]:

Time from beginning to end of liver transection.

Transection area [cm²]:

Surface area of the specimen.

Duration of postoperative hospital stay [days]:

Time from day of operation to day of discharge.

Duration of ICU stay [days]:

Time on the Intensive Care Unit (ICU). Patients' stay in the recovery room and Intermediate Care (IMC) unit exceeding 24 hours is considered as ICU stay.

Morbidaity:

Besides SAEs the following predefined complications are documented as AEs within IVC CLAMP:

Posthepatectomy haemorrhage: Drop of haemoglobin >3 g/dl (after 6 hours after the end of surgery) or any postoperative transfusion of PRBCs for a falling haemoglobin and/or the need for reintervention (i.e. embolisation or re-laparotomy)

Postoperative biliary leakage: Presence of bile fluid (bilirubin level > twice the serum level) in the abdominal cavity or drains > 48 hours beyond the end of surgery or the need for reintervention (i.e. interventional drainage or relaparotomy due to bile fluid collections or biliary peritonitis).

Further biliary complications: Biliary complications such as postoperative biliary stricture detected via ERCP or MRCP

Intraabdominal fluid collection/abscess: Intraabdominal fluid collection detected on any imaging modality (e.g. ultrasound, CT scan) associated with abdominal discomfort/pain or elevation of infectious parameters.

Posthepatectomy liver failure: Postoperative deterioration of the liver's synthetic, excretory, and detoxifying functions ≥ day 5:

   • Increased INR or need of coagulation products (FFP, coagulation factors) to normalize the INR

   • Serum bilirubin ≥ twice upper limit of normal

   • Encephalopathy

- Pneumonia: Pulmonary infection with evidence of increased infection parameters (CRP > 2 mg/dl and/or leukocytes > 10 000/ml) which are unlikely to be caused by a different pathologic process and evidence of pulmonary infiltrates on chest x-ray, requiring antibiotic therapy.

In-hospital mortality:

Death due to any reason within the patient's initial hospital stay.

Liver function:

ALT, AST, GGT, Quick's time/INR, bilirubin, and albumin preoperatively, intraoperatively and on postoperative days 1, 3 and 7.

Kidney function:

Serum creatinine and BUN preoperatively, intraoperatively and on postoperative days 1, 3 and 7.

Need for portal triad clamping:

Need for additional vascular control during actual parenchymal transection.

Haemodynamics and haemodynamic intolerance:

Heart rate, blood pressure and CVP are documented during liver transection. If fluid administration plus additional PRBCs prove insufficient in maintaining mean arterial pressure of at least 65 mmHg as does the use of up to 0.2 μg/kg body weight Noradrenaline every minute in infusion injection (i.e. 40 ml/h of Noradrenaline 1 mg/50 ml in a 70 kg body weight standard patient), executing anaesthetist may use up to two times 100 μg of Noradrenaline in bolus injections. If the executing anaesthetist uses Noradrenaline in bolus injections the patient is not considered haemodynamically stable any more. If the executing anaesthetist uses more than two times 100 μg of Noradrenaline in bolus injections the patient is considered in a life-threatening condition and treatment according to protocol is terminated. In this case the patient is analysed according to intention-to-treat.

Re-laparotomy:

Laparotomy within 30 days after the index operation.