Effects of acute normovolemic hemodilution on perioperative coagulation and fibrinolysis in elderly patients undergoing hepatic carcinectomy. Effect of infra-hepatic inferior vena cava clamping on bleeding during hepatic dissection: a prospective, randomized, controlled study. Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections. Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution before liver resection. Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial. Intraoperative blood salvage during liver resection: a randomized controlled trial. [Acute normovolemic hemodilution combined with controlled hypotension in patients undergoing liver tumorectomy]. A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection. Low central venous pressure reduces blood loss in hepatectomy.
To observe the effects of acute normovolemic hemodilution (ANH) on coagulation function and fibrinolysis in elderly patients undergoing hepatic carcinectomy.
                Thirty elderly patients (aged 60-70 years) with liver cancer (American Society of Anesthesiologists physical status I-II) scheduled for hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n = 15) and control group (n = 15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (HES) (130/0.4), and basic liquid containing 6% HES and routine Ringer's solution, respectively. In all the studied patients, blood samples were drawn at five different time points: before anesthesia induction (T1), 30 minutes after ANH (T2), 1 hour after start of operation (T3), immediately after operation (T4), and 24 hours after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (activated GPIIb/GPIIIa and P-selectin) were measured.
                The perioperative blood loss was not significantly different between the two groups (P > 0.05). The volume of allogeneic blood transfusion in ANH group was significantly smaller than that in control group (350.5 +/- 70.7 mL vs. 457.8 +/- 181.3 mL, P < 0.01). Compared with the data of T1, prothrombin time (PT) and activated partial thromboplastin time in both groups prolonged significantly after T3 (P < 0.05), but still within normal range. There were no significant changes in thrombin time and D-dimer between the two groups and between different time points in each group (all P > 0.05). SFMC and F1 + 2 increased in both groups, but without statistical significance. P-selectin expression on the platelet surface of ANH group was significantly lowered at T2 and T3 compared with the level at T1 (P < 0.05). Compared with control group, P-selectin was significantly lower in ANH group at T2-T5 (all P < 0.05).
                In elderly patients undergoing resection of liver cancer, ANH may not hamper fibrinolysis and coagulation function. It could therefore be safe to largely reduce allogeneic blood transfusion. The success of hepatectomy can be associated with intraoperative blood loss because massive blood loss causes a poor prognosis. This study was designed to evaluate the effect of infrahepatic inferior vena cava (IVC) clamping on the bleeding amount during hepatectomy.
                Eighty-five patients scheduled to undergo hepatic resection were randomly assigned to the IVC clamping or an IVC nonclamping group according to age, indocyanine green retention rate at 15 minutes, operative procedure, and number of tumors by prospective, randomized method. All analyses were compared by Mann-Whitney U test.
                Forty-three patients were assigned to the IVC clamping group and 42 to the nonclamping group (IVC clamping group vs. non-clamping): total blood loss (499 vs. 584 ml; p = 0.567), amount of bleeding during hepatectomy (233 vs. 285 ml; p = 0.474), amount of bleeding during hepatectomy/area of dissection (4.9 vs. 6.6 ml/cm(2); p = 0.63), CVP difference (-3 cmH(2)O vs. -1 cmH(2)O; p < 0.01), and diameter of the right hepatic vein (-2.2 cm vs. 0; p < 0.01).
                Although we had speculated that infrahepatic IVC clamping would reduce blood loss during hepatectomy, we failed to demonstrate any beneficial effects in this clinical setting with low CVP. Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH).
                The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population.
                During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups.
                Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood. We have studied the use of ultrapurified polymerized bovine haemoglobin (HBOC-201) in patients undergoing preoperative haemodilution before liver resection. After autologous blood donation of 1 litre, 12 patients (six males, six females, mean age 59 (35-69) yr) received Ringer's lactate solution 2 litre and, in a random design, 6% hydroxyethyl starch 70,000/0.5 (HES) 3 ml kg-1 or HBOC-201 0.4 g kg-1 within 30 min. Blood samples were obtained for blood chemistry, co-oximetry, haematology, coagulation profiles and immunology examinations before operation, on the day of surgery, on days 2-4 and 7 after operation, on the discharge day and 3 months after operation. There were no differences in patient characteristics, blood loss, amount of solutions infused, transfused allogeneic blood or duration of hospital stay. There were no local or systemic allergic reactions with infusion of HES or HBOC-201. Patients receiving HBOC-201 developed more pronounced leucocytosis and reticulocytosis during the early postoperative days compared with HES-treated patients. The mean maximum plasma haemoglobin concentration was 1.0 (SD 0.2) g dl-1 at the end of infusion of HBOC-201 was 8.5 h. Patients in both groups experienced temporary changes in liver enzymes and coagulation variables which returned to normal before discharge. Urinalysis revealed no difference between groups and no free haemoglobin was detected in urine. Patients receiving HBOC-201 showed no IgE and only a slight increase in IgG titres to HBOC-201 on the day of discharge; these were not detectable at 3 months. Single-dose administration of HBOC-201 was well tolerated by patients undergoing elective liver resection surgery and appears to be safe as a substitute during preoperative haemodilution. Blood loss in hepatic resection is an important determinant of operative outcome.
                To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection.
                Randomized controlled trial.
                University hospital.
                Eighty patients scheduled to undergo hepatic resection were randomly assigned to receive liver transection under normoventilation (n = 40) or hypoventilation (n = 40).
                During liver transection, in the normoventilation group, the tidal volume was 10 mL/kg and the respiratory rate was 10/min; in the hypoventilation group, the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min. Liver transection was performed under total or selective inflow occlusion.
                Blood loss.
                Between the normoventilation and hypoventilation groups, no significant difference was found in total blood loss (median [range]: 630 mL [72-3600 mL] vs 630 mL [120-3520 mL]; P =.44) or blood loss per transection area (median [range]: 7.3 mL/cm(2) [1.2-55.4 mL/cm(2)] vs 9.8 mL/cm(2) [0.9-79.9 mL/cm(2)]; P =.55). During liver transection, the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group (median [range]: -0.7 cm H(2)O [-3.0 to 1.8 cm H(2)O] vs -0.2 cm H(2)O [-4.0 to 2.0 cm H(2)O]; P =.007). The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group (maximum [range]: 50 mm Hg [28-66 mm Hg] vs 37 mm Hg [27-60 mm Hg]; P<.001). Transection time, postoperative liver function, hospitalization length, morbidity, and mortality were similar in the 2 groups.
                This randomized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection. A randomized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss.
                Although reduction of central venous pressure (CVP) is thought to decrease blood loss during liver resection, no consistently effective and safe method for obtaining the desired reduction of CVP has been established.
                Living liver donors scheduled to undergo liver graft procurement were randomly assigned to a blood salvage group, in which a blood volume equal to approximately 0.7% of the patient's body weight was collected before the liver transection, or a control group. The surgeons were blinded to the randomization results. The primary outcome measure was blood loss during liver parenchymal division. A multivariate analysis was also performed.
                Seventy-nine donors were allocated intraoperatively to the blood salvage group (n = 40) or the control group (n = 39). The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P = 0.005). The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025).
                Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection. To evaluate the effects of acute normovolemic hemodilution (ANH) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy.
                Thirty patients undergoing elective liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group (group A), ANH combined with controlled hypotension group (group B) and control group (group C). All the patients were anesthetized via endotracheal intubation. Before the operation, ANH was performed in groups A and B after anesthesia induction, and controlled hypotension was initiated in group B during tumorectomy. Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation, after ANH, and immediately, 1 day and 7 days after the operation. The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed.
                In group A, heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml. In group C, every patient received heterogeneous blood transfusion (664.8-/+248.1 ml), but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant (P<0.01). Hemodynamics was basically stable during operation in the 3 groups.
                ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy. Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection.
                One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay.
                From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025).
                For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit. To investigate the effect of low central venous pressure (LCVP) on blood loss during hepatectomy for hepatocellular carcinoma (HCC).
                By the method of sealed envelope, 50 HCC patients were randomized into LCVP group (n=25) and control group (n=25). In LCVP group, CVP was maintained at 2-4 mmHg and systolic blood pressure (SBP) above 90 mmHg by manipulation of the patient's posture and administration of drugs during hepatectomy, while in control group hepatectomy was performed routinely without lowering CVP. The patients' preoperative conditions, volume of blood loss during hepatectomy, volume of blood transfusion, length of hospital stay, changes in hepatic and renal functions were compared between the two groups.
                There were no significant differences in patients' preoperative conditions, maximal tumor dimension, pattern of hepatectomy, duration of vascular occlusion, operation time, weight of resected liver tissues, incidence of post-operative complications, hepatic and renal functions between the two groups. LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group, being 903.9+/-180.8 mL vs 2 329.4+/-2 538.4 (W=495.5, P<0.01) and 672.4+/-429.9 mL vs 1 662.6+/-1 932.1 (W=543.5, P<0.01). There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups. The length of hospital stay was significantly shortened in LCVP group as compared with the control group, being 16.3+/-6.8 d vs 21.5+/-8.6 d (W=532.5, P<0.05).
                LCVP is easily achievable in technique. Maintenance of CVP<or= 4 mmHg can help reduce blood loss during hepatectomy, shorten the length of hospital stay, and has no detrimental effects on hepatic or renal function.
None of the interventions seemed to decrease peri-operative morbidity or offer any long-term survival benefit. Haemodilution shows promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias in the trials. Further randomised clinical trials with low risk of bias and random errors that assess clinically important outcomes such as peri-operative mortality are necessary to assess any cardiopulmonary interventions aimed at decreasing blood loss and blood transfusion requirements in patients undergoing liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.