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Liver resections with or without pedicle clamping
The American Journal of Surgery 181 (2001) 238 –246
Scientific papers
Liver resections with or without pedicle clamping Gennaro Nuzzo, M.D.a,*, Felice Giuliante, M.D.a, Ivo Giovannini, M.D.a, Maria Vellone, M.D.a, Germano De Cosmo, M.D.b, Giovanni Capelli, M.D.c a
Department of Surgery, Hepato-Biliary Surgery Unit, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy b Department of Anesthesiology, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy c Institute of Hygiene, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy Manuscript received February 22, 2000; revised manuscript September 20, 2000
Abstract Background: Decreasing operative bleeding during liver resection, and thus extent of transfusions, has become a main criterion to evaluate operative results of hepatectomies. Hepatic pedicle clamping (HPC) is widely used for this purpose. The aim of the study was to evaluate safety, efficacy, technique, and contraindications of HPC during liver resections, comparing results of resections performed with or without HPC. Methods: Data from 245 liver resections were analyzed. In all, 125 resections were performed with HPC (group A), continuous in 100 cases and intermittent in 25 cases. The average duration of ischemia in group A was 39 ⫾ 20 minutes (range 7 to 107). In 20 cases (16%) ischemia was prolonged for 60 minutes or more. A total of 120 resections were performed without HPC (group B). Major resections were 53.6% in group A (67 cases) and 38.3% in group B (46 cases). Cirrhosis was present in 36 cases, 19 in group A and 17 in group B. Results: Operative mortality was nil. Postoperative mortality was 2.9%, morbidity 22.4%. Percentage of transfused cases (34.4% versus 60.0%; P ⬍0.001) and number of blood units per transfused case (2 ⫾ 1 versus 4 ⫾ 3; P ⬍0.001) were lower in group A versus group B. Similar figures were found by considering only major resections. Postoperative blood chemistries did not show important differences between the two groups, and postoperative alterations were related more to extent and complexity of the operation than to length of HPC. Conclusions: HPC during liver resection is a safe and effective technique. This is demonstrated in a context where HPC is used continuously in most cases, intermittently in cases with impaired liver function and for more prolonged ischemia, and avoided in cases with limited bleeding, jaundice, and simultaneous bowel anastomoses. © 2001 Excerpta Medica, Inc. All rights reserved. Keywords: Liver resections; Liver ischemia; Hepatic pedicle clamping
The amount of blood transfusion during hepatectomy has a relevant impact on the morbidity and mortality of this type of surgery. In fact, independently of the risk of infection or reactions, close correlation between amount of operative transfusion and both poor postoperative outcome and late results has been reported by many articles [1– 8]. Therefore, decreasing operative bleeding during hepatic resection, and thus reducing the amount of blood transfusions during operation, is an important target. Since mortality and morbidity of liver surgery have plateaued in most hepatobiliary centers around similar figures, the capability to avoid or limit transfusions has also become a main criterion to evaluate operative results.
Hepatic pedicle clamping (HPC) is widely used during hepatectomy to reduce operative blood loss [9 –13]. However, some aspects of temporary arterial and portal occlusion remain unclear: temporal limit of warm ischemia, choice of continuous or intermittent vascular interruption, and exact contraindications. With the aim to contribute to the debate on these issues, a large, single-surgeon experience is analyzed retrospectively in this paper, by comparing the results of liver resections performed with or without pedicle clamping.
Patients and methods * Corresponding author. Tel.: 011 39 6 30154967; fax: 011 39 6 3058586. E-mail address: [email protected].
From 1984 to 1997, 245 liver resections were performed on 240 patients (128 women and 112 men), with a mean age
0002-9610/01/$ – see front matter © 2001 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 1 ) 0 0 5 5 5 - 4
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
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Table 1 Features of patients and indications for liver resection
Number of cases Mean age (⫾SD) Sex (M/F) ASA Class 1 2 3 4 Cirrhosis Previous chemotherapy Malignant tumors Hepatocellular carcinoma Metastases From colorectal cancer From noncolorectal cancer Cholangiocarcinoma Hepatoblastoma Hilar cholangiocarcinoma Gallbladder carcinoma Other Benign diseases Hemangioma Adenoma Focal nodular hyperplasia Nonparasitic cyst Hydatid cyst Intrahepatic lithiasis Congenital biliary cysts Abscess
Total
Group A (HPC)
Group B (no HPC)
245 56 ⫾ 15 (1–82) 113/132
125 (51%) 55 ⫾ 14 (2–82) 62/63
120 (49%) 55 ⫾ 16 (1–81) 51/69
137 15 91 2 36 (14.7%)* 33/245 (13.5%) 177 (72.2%) 44 101 75 26 4 4 13 9 1 68 (27.8%) 18 8 9 7 17 4 1 4
70 8 47 — 19 (15.2%) 24 (19.2%) 94 (75.2%) 20 63 46 17 3 2 3 3 — 31 (24.8%) 6 3 9 4 4 2 — 3
67 7 44 2 17 (14.2%) 9 (7.5%) 83 (69.2%) 24 38 29 9 1 2 10 6 1 37 (30.8%) 12 5 0 3 13 2 1 1
* Thirty-four hepatocellular carcinoma and 2 colorectal metastases. HPC ⫽ hepatic pedicle clamping.
of 56 ⫾ 15 years (range 1 to 82). Cirrhosis was present in 36 cases (14.7%). One hundred twenty-five (51%) liver resections were performed with HPC (group A) and 120 (49%) liver resections without HPC (group B). Groups A and B matched for age, sex, ASA class [14], indications for liver resection, status of the liver (healthy liver, cirrhosis, preoperative chemotherapy), and kind of resection. General features of patients and indications for liver resections are listed in Table 1, the type of resection performed is listed in Table 2. There were 5 re-resections. From March 1990 clamping of retrohepatic vena cava started to be associated with HPC in selected cases to obtain total vascular exclusion (TVE). Since then, TVE of the liver has been performed in 13 out of 156 patients (8.3%). These were 13 patients with a mean age of 52.3 years (range 31 to 73), 11 with primary or secondary malignancies, 1 with adenoma, and 1 with hemangioma, all in close proximity to confluences between hepatic veins and vena cava. The involved procedures were 7 right hepatectomies (2 with tangential resection of vena cava, 1 extended to segments 1 and 4, and 1 to segment 1), 5 left hepatectomies (1 extended to segments 5 and 8, and 1 to segment 1), and a resection of
segments 3 and 4 for an infiltrating retroperitoneal leiomyosarcoma. In group A, a continuous HPC was used in 100 cases (100 of 125, 80%). In 25 (25 of 125, 20%) HPC was discontinued for 5 minutes every 10 to 15 minutes of ischemia (intermittent HPC). All patients were operated on electively by the same surgeon (GN). Surgical access was obtained through bilateral subcostal laparotomy, often enlarged with a xiphoid split (Mercedes incision). During the last year, use of the Makuuchi incision [15] was started in some cases; in a patient with four previous laparotomies with a metastasis of segment 8, a transthoracic approach was needed [16]. Intraoperative liver ultrasound was used in the last 10 years to complete staging of malignant diseases and to guide resections. Parenchymal transection was performed by Kelly clamps, and hemobiliostasis was obtained by means of thin (3/0 to 4/0) transfixed sutures and reabsorbable clips. During right or left hepatectomy, section of the main portal and arterial branches was performed before parenchymal resection. In contrast, section of the main biliary duct was performed after completing parenchymal transection. Main hepatic veins were isolated extraparenchymally and, only if
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G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
Table 2 Type of resection according to Couinaud classification Major resections Right hepatectomy Right hepatectomy ⫹ segment IV Right hepatectomy ⫹ segment I Right hepatectomy ⫹ segments I–IV Right hepatectomy ⫹ atypical resection Left hepatectomy Left hepatectomy ⫹ segment I Left hepatectomy ⫹ segments V–VIII Resection of 5 segments Resection of 4 segments Resection of 3 segments Resection of segments V–VIII Minor resections Two segments One segment Atypical resection
113 (46.1%) 43 5
67 (53.6%) 20 4
46 (38.3%) 23 1
5
1
4
2
2
—
2
2
—
28 1
14 1
14 —
3
3
—
1 1 21 1
1 1 17 1
— — 4 —
58 (46.4%) 33 15 10
74 (61.7%) 35 16 23
132 (53.9%) 68 31 33
this was at risk for vein injury, the section was performed intraparenchymally. HPC was performed by means of a vascular tourniquet applied on the hepatic pedicle at a safe distance from the superior margin of the pancreas. An eventual left hepatic artery coming from the gastric artery was also clamped. To reduce total ischemia time of the liver, HPC was started after the effraction of the superficial layers of the parenchyma. HPC was not performed (group B) in cases requiring simultaneous bilioenteric or colonic anastomoses (Klatskin tumors, colorectal tumors with synchronous liver metastases) to avoid edema on the anastomosis, in those with jaundice, in those with bleeding limited by previous interruption of hilar structures, with more easy and rapid parenchymal transection, and in those operated on before the introduction of HPC. In all patients right atrial pressure (RAP) was monitored by a central venous catheter and arterial pressure by a radial catheter. During parenchymal section RAP was maintained below 5 cm H2O. In cases with indication for TVE of the liver, a SwanGanz catheter was placed for hemodynamic monitoring. The retrohepatic vena cava was completely exposed from renal confluence to diaphragm; the right adrenal vein and eventually the retrocaval venous branches were ligated. In the 20 to 30 minutes before caval clamping, 500 mL to 1,000 mL colloids and chrystalloids were infused to control the decrease in cardiac output and mean arterial pressure (MAP) associated with TVE. A 5-minute tolerance test was performed by closing in sequence the vascular tourniquet on the hepatic pedicle, a vascular clamp on the vena cava below the liver, and then a vascular clamp on the vena cava
above the liver. The maneuver was interrupted if during the tolerance test a decrease in cardiac output of more than 60% or a reduction in MAP and pulmonary wedge pressure of more than 30% were observed, or both. In 1 patient (a 73-year-old man undergoing a left hepatectomy) hemodynamic tolerance was poor and TVE was not performed (intolerance rate ⫽ 7.7%). Duration of TVE ranged from 5 to 53 minutes, with a mean of 22 ⫾ 16 minutes. Total time of ischemia in these cases ranged from 8 to 98 minutes, with a mean of 59 ⫾ 26 minutes. Neither topical refrigeration nor hypothermic liver perfusion was used. The average duration of liver ischemia in group A was 39 ⫾ 20 minutes, ranging from 7 to 107; in 20 cases (16%) ischemia was prolonged for 60 minutes or more. In the 100 cases (80%) with a continuous HPC, mean duration of ischemia was 36 minutes (range 7 to 84); in the other 25 cases (20%) with an intermittent HPC, mean duration of ischemia was 51 minutes (range 13 to 107). Choice of intermittent HPC was based on severity of preoperative liver dysfunction and expected length of HPC. Intraoperative blood transfusions were performed for hemoglobin ⬍9 g/dL and hematocrit ⬍28%, or in patients aged more than 70 years or with cardiac insufficiency, for hemoglobin ⬍10 g/dL and hematocrit ⬍30%. In order to compare the two groups, the following factors were evaluated retrospectively: perioperative mortality and morbidity rates, number of patients who required intraoperative blood transfusions, number of blood units transfused, postoperative profiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BIL), prothrombin activity (PA), and total cholesterol (CHOL). The latter has been found to be related to adequacy of postoperative recovery of liver function [17]. Results are reported as means and standard deviations (SD); comparisons were carried out using Student’s t test, the chi-square test, and Mann-Whitney-Wilcoxon rank-sum test: a P value below 0.05 was considered as statistically significant. Relationships between variables were assessed by linear, nonlinear, and logistic multiple regression analysis.
Results Operative mortality was nil. Seven patients died postoperatively after resection for primary or secondary malignancies (7 of 245 ⫽ 2.9%). Six of these patients belonged to group B, 1 to group A. The more frequent cause of death was liver failure: 4 out of 7 patients (57.1%), 1 in group A (1 of 125 ⫽ 0.8%) and 3 in group B (3 of 120 ⫽ 2.5%; P ⫽ not significant [NS]). The patient in group A had undergone a right hepatectomy with 40-minute HPC; pathology revealed liver cirrhosis, which was previously unsuspected from history and macroscopic appearance at surgery. The 3 patients in group B (2 after a major resection, and a cirrhotic patient who
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246 Table 3 Morbidity Total Overall morbidity 55 (22.4%) Major complications Biliary fistula 11 Subphrenic abscess 8 Pulmonary embolism 5 Severe liver insufficiency 4 Haemoperitoneum* 4 Gastrointestinal bleeding 3 Intestinal perforation* 3 Biliary lesion 2 ARDS 2 Deep venous thrombosis 2 Portal thrombosis 2 Intrahepatic abscess 1 Pelvic abscess 1 Intestinal occlusion* 1 Anastomotic leakage* 1 Minor complications Moderate liver insufficiency 7 Pneumonia 6 Pleural effusion (thoracentesis) 5
Group A (HPC)
Group B (no HPC)
28 (22.4%) 27 (22.5%) 5 (1 TVE) 6 5 (1 TVE) 3 3 2 4 (1 TVE) — — 4 2 1 2 (1 TVE) — 1 1 1 1 1 1 — 2 — 1 — 1 — 1 1 — 3 (1 TVE) 4 4 (2 TVE)
4 2 1
* Nine patients required a reoperation. 12 patients had more than one complication. HPC ⫽ hepatic pedicle clamping; ARDS ⫽ adult respiratory distress syndrome; TVE ⫽ total vascular exclusion.
required relaparotomy for bleeding after a wedge resection of segment III) developed also sepsis associated with liver failure. Causes of death in the other patients in group B were pulmonary embolism (after a right hepatectomy and thrombectomy of IVC), sepsis complicated further by myocardial infarction (after a right hepatectomy), and rupture of an abdominal aortic aneurism (after a left hemicolectomy with resection of segments II and III for metastases). Postoperative complications were observed in 55 cases (22.4%), including 5 with TVE, and were major complications in 17 (13.6%). Complications occurred in 28 cases (28 of 125 ⫽ 22.4%) in group A and in 27 (27 of 120 ⫽ 22.5%) in group B (Table 3). There were no specific complications related to the technique of HPC. Pleural effusion occurred in about two thirds of cases after major resections, and was not considered as a complication if thoracenthesis was not required. Reoperation was necessary in 9 cases (3.6%). In 4 of these, all in group B, postoperative bleeding from liver surface was the cause of reoperation (4 of 120 ⫽ 3.3%). The more frequent complication was transient liver insufficiency: 11 cases, 7 in group A and 4 in group B. Severe hepatic insufficiency (encephalopaty, persistent jaundice, coagulopaty, ascites) was observed in 4 patients who had undergone liver resection with HPC. More moderate liver dysfunction (total bilirubin below 3.0 mg/dL, ascites) was observed in 7 other cases, 3 in group A and 4 in group B. In cirrhotic patients, liver insufficiency occurred in 5 cases (5
241
of 19 ⫽ 26.3%) in group A and in 4 in group B (4 of 17 ⫽ 23.5%). In 113 major hepatectomies overall morbidity was 31.8% (36 cases), 29.8% in group A (20 of 67 cases) and 34.7% in group B (16 of 46 cases). A trend for a lower rate of complications in group A versus B became more evident in subgroups with increasing complexity of operation, without reaching statistical significance. In cases resected with duration of HPC longer than 60 minutes, morbidity was 40.0% (8 of 20 cases); and in those with HPC shorter than 60 minutes, morbidity was 17.1% (18 of 105 cases; P ⫽ NS). In cases resected with TVE there was no mortality; 5 cases had postoperative complications (5 of 12 ⫽ 41.6%). In cases with liver cirrhosis overall morbidity was 30% (11 of 36 cases), 26.3% (5 of 19 cases) in group A and 35.3% (6 of 17 cases) in group B (P ⫽ NS). The 3 cases with complications in group A received a continuous HPC and had transient liver insufficiency (severe in 1 case, moderate in 2). Rate of transient liver insufficiency in group B was 23.5% (4 of 17 cases). One hundred fifteen cases (115 of 245 ⫽ 46.9%) required intraoperative transfusions: 43 belonged to group A (43 of 125 ⫽ 34.4%) and 72 to group B (72 of 120 ⫽ 60%). This difference was statistically significant (P ⬍0.001; Table 4). Transfused cases in group A required 2 ⫾ 1 units of blood each (range 1 to 6), whereas those in group B required 4 ⫾ 3 units each (range 1 to 15; P ⬍0.001). Postoperative transfusions were necessary in 31 cases (31 of 245⫽12.6%): 13 in group A (10.4%) and 18 in group B (15%) (P ⫽ NS). In total, transfusions (intraoperative and postoperative) were required in 130 cases (53.1%): 53 in group A (53 of 125 ⫽ 42.4%) and 77 in group B (77 of 120 ⫽ 64.2%; P ⬍0.002). Mean requirement in transfused group A cases was 2 ⫾ 1 units (range 1 to 6), whereas in group B it was 4 ⫾ 3 units (range 1 to 16; P ⬍0.001). Concerning only major resections, 67 out of 112 cases required intraoperative transfusions (59.8%) and 19 required postoperative transfusions (17%; Table 4): intraoperative transfusions were necessary in 31 cases in group A (31 of 66 ⫽ 46.9%) and in 36 in group B (36 of 46 ⫽ 78.3%; P ⬍0.003), whereas postoperative transfusions were performed in 8 cases in group A (8 of 66 ⫽ 12.1%) and in 11 in group B (11 of 46 ⫽ 23.9%; P ⫽ NS). During operation, transfused cases in group A received 2 ⫾ 1 units (range 1 to 6); those in group B received 5 ⫾ 3 units (range 1 to 15; P ⬍0.001). Seventy-five of these major resections required intraoperative plus postoperative transfusions: 38 in group A (38 of 66 ⫽ 57.6%) and 37 in group B (37 of 46 ⫽ 80.4%). This difference was statistically significant (P ⬍0.03). Mean requirement was 2 ⫾ 1 units (range 1 to 6) in group A and 5 ⫾ 4 units (range 1 to 16) in group B. This difference was also significant (P ⬍0.001). There was a similar blood saving in continuous and intermittent HPC (Table 5). Patients who underwent TVE required intraoperative
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Table 4 Total number of transfused cases and number of blood units per transfused case in all cases and in major resections
Intraoperative transfusions Patients (n) Units of blood Postoperative transfusions Patients (n) Units of blood Total transfusions (i.o. and p.o.) Patients (n) Units of blood
Total
Group A (HPC)
Group B (no HPC)
P
Major resections
Group A (HPC)
Group B (no HPC)
P
115 (46.9%) 3⫾2 (1–15)
43 (34.4%) 2⫾1 (1–6)
72 (60%) 4⫾3 (1–15)
⬍0.001
67 (59.8%) 4⫾3 (1–15)
31 (46.9%) 2⫾1 (1–6)
36 (78.3%) 5⫾3 (1–15)
⬍0.003
31 (12.6%) 2⫾1 (1–6)
13 (10.4%) 2⫾1 (1–3)
18 (15%) 2⫾2 (1–6)
19 (17%) 2⫾1 (1–6)
8 (12.1%) 2⫾1 (1–3)
11 (23.9%) 2⫾2 (1–6)
130 (53.1%) 3⫾3 (1–16)
53 (42.4%) 2⫾1 (1–6)
77 (64.2%) 4⫾3 (1–16)
75 (67%) 4⫾3 (1–16)
38 (57.6%) 2⫾1 (1–6)
37 (80.4%) 5⫾4 (1–16)
⬍0.001
NS NS
⬍0.002 ⬍0.001
⬍0.001
NS NS
⬍0.03 ⬍0.001
Data presented as mean ⫾ SD (range). HPC ⫽ hepatic pedicle clamping; i.o. ⫽ intraoperative; p.o. ⫽ postoperative; NS ⫽ not significant.
transfusions in 7 cases (7 of 12 ⫽ 58.3%), with a mean requirement of 2.7 ⫾ 1.7 units (range 1 to 6). The analysis was carried on further by considering separately cases in group B operated on before or after introducing the use of HPC. The latter did not differ from the former in demographics, mortality, and morbidity, but included a slightly larger proportion of cirrhotic patients and showed a reduction in percent of transfused cases. This was expected, because limited bleeding was one of the criteria to avoid HPC. However, multiple logistic regression analysis, performed on all cases or only on those operated after introduction of HPC, by accounting simultaneously for magnitude and duration of the operations, reconfirmed a significant effect of HPC in reducing the risk of intraoperative blood transfusions in all cases, and also in those operated after introduction of HPC (Fig. 1). In particular, by Table 5 Features of 113 cases resected using continuous versus intermittent HPC* Continuous HPC Number of cases Mean ischemia length, minutes (range) Ischemia longer than 1 hour Length of procedure Major resections Cirrhotic patients Mortality Morbidity Intraoperatively transfused cases Intraoperatively transfused blood units
88 33 (7–84) 6 (6.8%) 282 ⫾ 106 42 (47.7%) 13 (14.7%) 1 (13%) 8 (32%) 27 (30%) 2⫾1
* Patients with total vascular exclusion were excluded. HPC ⫽ hepatic pedicle clamping.
Intermittent HPC 25 51 (13–107) 8 (32%) 294 ⫾ 276 13 (52%) 6 (24%) 0 22 (25%) 9 (36%) 2⫾1
comparing major resections, the probability of performing at least one intraoperative transfusion resulted significantly higher in those performed without HPC. Similar figures were found in minor resections. In both groups, patients resected with HPC and those without HPC, the duration of surgery also was a significant factor for a higher probability of performing intraoperative transfusion. Concerning blood chemistries, a significant increase of AST, ALT, and BIL and a significant decrease of CHOL and PA were observed on postoperative day 1. In most cases all values but ALT returned to normal ranges within 7 days. Comparisons of the variations of liver tests are reported in Table 6. Regression analysis showed that changes of ALT, AST, PA, and CHOL in patients who had undergone HPC were all correlated with duration of clamping at postoperative day 1 (r2 ⫽ 0.2 to 0.4, P ⬍0.001 for all), were more weakly correlated at postoperative day 3, and were not correlated at postoperative day 7. However, when duration of the operation was evaluated together with duration of clamping as a simultaneous independent variable, the former accounted for most of the variability of ALT, AST, PA, and CHOL, while duration of clamping became less important (partial r2 ⬍0.10). This suggested that postoperative changes of ALT, AST, PA, and CHOL were related more strictly to magnitude and complexity of the operation than to duration of HPC. An inconstant feature associated with more prolonged liver ischemia was postoperative hyperbilirubinemia. However, regression analysis showed again that peak bilirubin (without cholestasis) was more a function of the number of resected liver segments, of duration of the operation, of amount of blood transfusions, and of the presence of sepsis (multiple r2 ⫽ 0.60) rather than a function of duration of HPC (r2 ⬍0.10). Persistent jaundice was a significant de-
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
243
Fig. 1. Multiple logistic regression analysis of probability of a patient being transfused, based on duration of surgery (quantifying complexity of the procedure), magnitude of resection, and use of hepatic pedicle clamping (HPC) for patients operated on after introduction of HPC. Odds ratio (OR) and confidence interval (C.I.) are indicated.
terminant of the length of postoperative hospital stay. In general, however, this was related more to a cautious attitude toward discharge of a jaundiced patient than to a real need for hospital treatment. Median postoperative hospital stay was 12 days (range 4 to 78). It was 16 ⫾ 13 days in group A and 20 ⫾ 11 days in group B (P ⬍0.02).
Comments Good postoperative outcome of hepatic resections mainly depends upon limited operative bleeding and sufficient functional reserve of the nonresected liver. Therefore, from the beginning of this type of surgery, progression toward more difficult and extensive hepatectomies has been associated with the research for methods limiting operative bleeding. Increased knowledge of intrahepatic anatomy and introduction of operative ultrasound have allowed the development of an accurate surgical technique, thus reducing the risk of bleeding during resection. Temporary vascular occlusion of hepatic inflow (HPC) has been reported to be effective in reducing bleeding from intraparenchymal arterial and portal branches [18 –23]. Caval clamping below and above the liver associated with pedicle clamping (TVE) permits complete control of bleeding from the vena cava and from hepatic veins, which remains the most important
cause of concern during hepatic resection [24 –29]. The fear of adverse consequences associated with warm liver ischemia and with stasis in the splanchnic bed have limited the wide application of these techniques, and great experience with their application is available only in a few centers with large practices of liver surgery [10 –13,20,23,24,26,27,29 – 34]. Our retrospective analysis of data from cases resected by the same surgeon in the same institution, with or without HPC, alone or associated with caval clamping in selected cases, confirm the safety and effectiveness of HPC. As a matter of fact, the number of intraoperatively transfused cases was almost doubled in group B (without HPC) compared with group A (with HPC), by considering either all resections or major resections only, as reported in Table 4. Furthermore, 65.6% (82 of 125) of all resections performed with HPC were completed without transfusions whereas this was possible only in 40% (48 of 120) of the resections without HPC (P ⬍0.001). Also considering major resections only, in more than 50% of cases in group A (36 cases) the resection did not require any transfusion, compared with 21.7% in group B (10 cases) (P ⬍0.001). In addition, in transfused cases, the mean blood requirement per case was significantly less in group A versus group B, by considering either the whole sample or major resections only. Five cases undergoing TVE (41.7%) did not require any transfusion. With the aim of excluding the possibility that our results
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Table 6 Liver function test results before and after resection with or without hepatic pedicle clamping (HPC) Before operation
Postoperative day 1
Postoperative day 3
Postoperative day 7
HPC
HPC
HPC
HPC
no HPC
no HPC
no HPC
no HPC
Liver function test results before and after resection with or without HPC (cases with postoperative liver failure are excluded) ALT (U/L) 33.2 ⫾ 32.6 40.8 ⫾ 43.7 429.2 ⫾ 397.1 272.2 ⫾ 262.2 116.2 ⫾ 134.7 77.5 ⫾ 91.9 43.4 ⫾ 29.6 52.6 ⫾ 41.1 AST (U/L) 45.8 ⫾ 73.8 52.4 ⫾ 78.7 471.7 ⫾ 422.5 318.6 ⫾ 344.9 278.7 ⫾ 261.7 164.1 ⫾ 164.7 114.6 ⫾ 85.9 86.4 ⫾ 64.8 Total bilirubin 0.8 ⫾ 1.4 1.2 ⫾ 2.5 1.9 ⫾ 2.3 2.1 ⫾ 3.2 1.7 ⫾ 2.7 1.9 ⫾ 1.8 1.6 ⫾ 3.5 2.1 ⫾ 2.4 Total cholesterol 189.4 ⫾ 37.7 189.9 ⫾ 45.4 120.4 ⫾ 29.0 119.8 ⫾ 29.6 117.5 ⫾ 33.0 116.7 ⫾ 32.6 120.6 ⫾ 38.9 111.5 ⫾ 3.6 Prothrombin activity 94.0 ⫾ 12.4 88.2 ⫾ 14.0 63.1 ⫾ 15.9 66.4 ⫾ 15.7 78.2 ⫾ 16.1 74.0 ⫾ 18.2 81.0 ⫾ 15.2 72.4 ⫾ 18.7 Liver function test results before and after resection with or without HPC in 11 patients with postoperative liver failure ALT (U/L) 35.6 ⫾ 15.5 74.3 ⫾ 47.2 1000.9 ⫾ 789.1 775.7 ⫾ 1313.3 214.7 ⫾ 138.5 163.4 ⫾ 219.2 61.3 ⫾ 22.6 60.0 ⫾ 30.5 AST (U/L) 37.3 ⫾ 22.7 75.7 ⫾ 42.2 962.0 ⫾ 910.0 981.4 ⫾ 1764.3 463.9 ⫾ 430.0 249.7 ⫾ 359.5 159.0 ⫾ 98.7 90.0 ⫾ 63.7 Total bilirubin 0.6 ⫾ 0.2 4.3 ⫾ 4.6 3.2 ⫾ 1.6 7.0 ⫾ 5.6 4.2 ⫾ 2.2 6.0 ⫾ 6.8 5.5 ⫾ 4.0 8.7 ⫾ 9.4 Total cholesterol 155.7 ⫾ 34.9 189 ⫾ 77.1 79.7 ⫾ 22.2 85.8 ⫾ 33.5 82.8 ⫾ 25.9 101.3 ⫾ 37.5 89.0 ⫾ 20.4 83.5 ⫾ 37.6 Prothrombin activity 88.9 ⫾ 9.4 84.6 ⫾ 15.9 56.7 ⫾ 21.4 52.9 ⫾ 8.7 60.6 ⫾ 20.0 59.6 ⫾ 15.2 74.6 ⫾ 12.9 63.2 ⫾ 8.1 Liver function test results before and after major resection with or without HPC ALT (U/L) 35.8 ⫾ 36.1 50.0 ⫾ 55.9 570.6 ⫾ 492.7 312.9 ⫾ 198.3 144.8 ⫾ 146.8 84.5 ⫾ 75.8 51.8 ⫾ 32.3 47.8 ⫾ 25.5 AST (U/L) 53.1 ⫾ 89.8 67.8 ⫾ 100.6 589.1 ⫾ 489.7 370.5 ⫾ 237.8 328.9 ⫾ 263.5 174.7 ⫾ 119.8 129.3 ⫾ 92.7 86.0 ⫾ 45.6 Total bilirubin 1.0 ⫾ 1.8 1.9 ⫾ 3.5 2.6 ⫾ 2.9 3.3 ⫾ 4.5 2.4 ⫾ 3.5 2.8 ⫾ 3.1 2.4 ⫾ 4.4 3.3 ⫾ 3.5 Total cholesterol 184.3 ⫾ 39.8 198.2 ⫾ 42.0 114.0 ⫾ 31.8 115.6 ⫾ 28.3 105.1 ⫾ 30.1 99.9 ⫾ 24.9 113.3 ⫾ 30.9 98.3 ⫾ 19.7 Prothrombin activity 95.8 ⫾ 12.6 88.2 ⫾ 12.3 59.1 ⫾ 15.2 60.1 ⫾ 12.6 72.8 ⫾ 17.3 71.3 ⫾ 17.2 77.2 ⫾ 15.6 69.5 ⫾ 14.5 Liver function test results before and after resection with continuous or intermittent HPC Continuous Intermittent Continuous Intermittent Continuous Intermittent Continuous Intermittent ALT (U/L) 26.2 ⫾ 19.3 44 ⫾ 36.1 375.7 ⫾ 332.7 566.4 ⫾ 444.6 106 ⫾ 129.7 145.4 ⫾ 142.1 38.5 ⫾ 22.8 50.3 ⫾ 29.5 AST (U/L) 35 ⫾ 54 55.8 ⫾ 57.4 442.2 ⫾ 425.3 576.5 ⫾ 453.6 264.1 ⫾ 278 360.3 ⫾ 301.9 108.5 ⫾ 87.7 140.6 ⫾ 88.6 Total bilirubin 0.7 ⫾ 0.5 0.8 ⫾ 0.6 1.7 ⫾ 1.1 1.9 ⫾ 1.5 1.5 ⫾ 1.0 1.6 ⫾ 1.2 1.4 ⫾ 1.5 1.5 ⫾ 2.1 Total cholesterol 183.3 ⫾ 37.9 200.5 ⫾ 36.5 118.9 ⫾ 31.1 125.8 ⫾ 29.5 116.4 ⫾ 33.5 125.4 ⫾ 28.3 120.1 ⫾ 33.6 132.4 ⫾ 34.9 Prothrombin activity 93.9 ⫾ 11.9 92.9 ⫾ 13.2 64.2 ⫾ 16.3 60.2 ⫾ 14.2 78.4 ⫾ 16.7 74.6 ⫾ 16.1 82.0 ⫾ 16.2 80.8 ⫾ 13.1 ALT ⫽ alanine aminotransferase; AST ⫽ aspartate aminotransferase.
were caused only by increased experience of the surgeon in performing liver resections, we compared the data of patients resected before introduction of HPC in our surgical technique and patients resected after introduction of HPC. The results of multiple logistic regression analysis performed only in resections carried out after the introduction of HPC showed that the risk of at least one intraoperative transfusion, for a given duration of the operation, increases with increasing extent of resection and in the absence of HPC. For instance, Fig. 1 shows that a major resection lasting 240 minutes performed without HPC has a risk of intraoperative transfusion of 55%, significantly greater than that for a similar resection of the same duration performed with HPC (risk of intraoperative transfusion 35%). At present our attitude concerning use of HPC is neither unconditional use in all resections as a routine nor restriction to exceptional cases. We start HPC only after deepening the incision inside the liver and depending on the extent of bleeding, in order to benefit from the advantages of HPC without disregarding potential risks. The upper limit for duration of normothermic ischemia of the liver is not established exactly, but it depends mainly on functional reserve of the liver. Safety of continuous pedicle clamping exceeding 1 hour in healthy liver has been reported, and a limit of around 90 minutes is accepted [23,29,34]. In low-severity cirrhotic livers, 60minutes is considered a safe limit [11,35].
Intermittent clamping, described by Makuuchi et al [36] during hemihepatic vascular occlusion, is used with the aim to prolong duration of liver ischemia while reducing ischemic injury. By using this technique, very long durations of pedicle clamping have been reported [10,35,37]. In a controlled study on continuous versus intermittent portal triad clamping [38], better parenchymal tolerance to intermittent clamping was reported, but this was associated with a significantly higher intraoperative blood loss. In our experience intermittent clamping was used mainly for procedures requiring more prolonged ischemia. As a matter of fact mean duration of ischemia in cases with intermittent HPC was longer than that in cases with continuous HPC (51 versus 33 minutes). Also the number of cases with ischemia longer than 1 hour was greater in cases with intermittent HPC than in cases with continuous HPC (32% versus 6.8%). In these two groups no differences in number of transfused cases or transfused units per case were observed. Although limitation of length of HPC and TVE must remain a major concern for the surgeon, our results support the concept of the great tolerance to warm ischemia of the liver. Most liver resections can be performed within the already mentioned limits of duration of normothermic ischemia. Only in very selected cases, for extremely complex resections, more extensive period of vascular clamping may be needed. In such cases, hypothermic perfusion of the liver may be considered [39].
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
Use of HPC or TVE permits carrying out liver resection in a bloodless operative field and therefore with more accurate hemostasis and biliostasis. Consequently, it is reasonable to expect a reduction in related postoperative complications. Although overall morbidity in group A versus B was not significantly different, all reoperations for postoperative bleeding from liver surface occurred in group B. Besides, a trend for a lower rate of complications in group A versus B was evident for cirrhotic patients and for cases undergoing resections of increasing complexity. The occurrence of postoperative liver insufficiency is related to the functional capacity of the residual liver. Use of HPC in this study was not associated with a relevant increase of the risk. As mentioned, there was no relationship with mortality from liver failure. Also, liver failure was a cause of death in 3 patients in group B versus 1 in group A. There was a trend for a more frequent occurrence of transient liver insufficiency in group A (7 of 125 ⫽ 5.6%) versus B (4 of 120 ⫽3.3%), which did not reach significance, and there were no differences in group A versus group B cirrhotic patients. The possibility of inducing hepatocyte dysfunction by liver ischemia (by HPC or TVE) is of great concern. Patients with liver cirrhosis, cholestasis, older age, steatosis, or previous chemotherapy are at higher risk, and in these patients at present we prefer to perform intermittent clamping. Ischemia may also induce Kupffer cell dysfunction (with impaired clearance of bacteria from portal blood, thus facilitating sepsis) or dysreactivity (with abnormal inflammatory responses and Kupffer cell-hepatocyte interactions) [40]. Assessing the practical relevance of these effects awaits further studies; it is noteworthy, however, that the technique of normothermic ischemia, as applied in our cases, was not associated with relevant adverse clinical consequences. Also, postoperative evaluation of blood chemistries did not reveal important or persistent abnormalities clearly associated with HPC, while overall regression analysis showed that the duration of ischemia only accounted for a modest percentage of the postoperative variability of blood chemistries. In patients undergoing HPC longer than 60 minutes there was a higher rate of complications, which, however, did not reach statistical significance and could not be linked specifically to duration of HPC (rather than to other risk factors). An aspect that remains open to question and may have close relevance is whether effectiveness of HPC in terms of blood-saving is paralleled by similar advantages in terms of sparing intraoperative or postoperative administration of other blood products (plasma, albumin). At present our data on this aspect do not permit any specific inference. In conclusion, we support the concept that normothermic ischemia of the liver during liver surgery is an effective and safe technique. As mentioned already, it is our policy to remain cautious about the implications of prolonged liver ischemia, while taking advantage simultaneously of the use of HPC. In major resections we first prepare and interrupt
245
vascular structures at the hilum, and HPC is started only after deepening the incision in liver parenchyma to reduce duration of ischemia. The choice of intermittent HPC is based on contingent criteria (impaired liver function and need for prolonged ischemia), which reflect a realistic scenario but limit comparison with other controlled studies. Nevertheless, our data contribute to the available knowledge on the advantage of intermittent HPC in these cases. Finally, we avoid HPC when bleeding is limited, in the presence of jaundice, and to avoid edema of simultaneously performed bowel anastomoses. Within this context, the results of this study provide significant evidence of the benefits and safety of HPC.
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[18] Pringle JH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:541–9. [19] Ezaki T, Seo Y, Tomoda H, et al. Partial hepatic resection under intermittent hepatic inflow occlusion in patients with chronic liver disease. Br J Surg 1992;79:224 – 6. [20] Smadja C, Kahwaji F, Berthoux L, et al. Inte´reˆt du clampage pe´diculaire total dans les exe´re`s he´patiques pour carcinome he´pato-cellulaire chez le cirrhotique. Ann Chir 1987;41:639 – 42. [21] Delva E, Camus Y, Nordlinger B, et al. Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases. Ann Surg 1989;209:211–18. [22] Huguet C, Gavelli A, Addario Chieco P, et al. Liver ischemia for hepatic resection: where is the limit? Surgery 1992;111:251–9. [23] Huguet C, Gavelli A, Bona S. Hepatic resection with ischemia of the liver exceeding one hour. J Am Coll Surg 1994;178:454 – 8. [24] Bismuth H, Castaing D, Garden OJ. Major hepatic resection under total vascular exclusion. Ann Surg 1989;210:13–19. [25] Berney T, Mentha G, Morel P. Total vascular exclusion of the liver for the resections of lesions in contact with the vena cava or the hepatic veins. Br J Surg 1998;85:485– 8. [26] Habib N, Zorografos G, Dalla Serra G., et al. Liver resection with total vascular exclusion for malignant tumors. Br J Surg 1994;81: 1181– 4. [27] Emond JC, Wachs ME, Renz JF, et al. Total vascular exclusion for major hepatectomy in patients with abnormal liver parenchyma. Arch Surg 1995;130:824 –30. [28] Huguet C, Addario Chieco P, Gavelli A, et al. Technique of hepatic vascular exclusion for extensive liver resection. Am J Surg 1992;163: 602–5.
[29] Terblanche J, Krige JE, Bornman PC. Simplified hepatic resection with the use of prolonged vascular inflow occlusion. Arch Surg 1991;126:298 –301. [30] Malassagne B, Cherqui D, Alon R, et al. Safety of selective vascular clamping for major hepatectomies. J Am Coll Surg 1998;187:482– 6. [31] Cherqui D, Alon R, Lauzet JY, et al. Limitation of blood tranfusions during hepatectomies. Study of 150 consecutive hepatic resections on healthy and pathological livers. Gastroenterol Clin Biol 1996;20:132– 8. [32] Capussotti L, Polastri R Operative risk of major hepatic resections. Hepatograstroenterology 1998;45:184 –90. [33] Gozzetti G, Mazziotti A, Grazi GL, et al. Liver resection without blood transfusion. Br J Surg 1995;82:1105–10. [34] Hannoun L, Borie D, Delva E, et al. Liver resection with normothermic ischaemia exceeding 1 h. Br J Surg 1993;80:1161–5. [35] Wu CC, Hwang CR, Liu TJ, Peng FK. Effects and limitations of prolonged intermittent ischaemia for hepatic resection of the cirrhotic liver. Br J Surg 1996;83:121– 4. [36] Makuuchi M, Mori T, Gunven P, et al. Safety of hemihepatic vascular occlusion during resection of the liver. Surg Gynecol Obstet 1987; 164:155– 8. [37] Sakamoto Y, Makuuchi M, Takayama T, et al. Pringle’s maneuvre lasting 322 min. Hepatogastroenterology 1999;46:457– 8. [38] Belghiti J, Noun R, Malafosse R, et al. Continuous versus intermittent portal triad clamping for liver resection: a controlled study. Ann Surg 1999;229:369 –75. [39] Vaillant JC, Borie DC, Hannoun L. Hepatectomy with hypothermic perfusion of the liver. Hepatogastroenterology 1998;45:381– 8. [40] Billiar TR, Curran RD. Kupffer cell and hepatocyte interaction. A brief overview. J Parent Ent Nutr 1990;14(suppl):175S– 80S.
Scientific papers
Liver resections with or without pedicle clamping Gennaro Nuzzo, M.D.a,*, Felice Giuliante, M.D.a, Ivo Giovannini, M.D.a, Maria Vellone, M.D.a, Germano De Cosmo, M.D.b, Giovanni Capelli, M.D.c a
Department of Surgery, Hepato-Biliary Surgery Unit, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy b Department of Anesthesiology, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy c Institute of Hygiene, Catholic University of Sacred Heart, School of Medicine, L.go A Gemelli, 8, 00168 Rome, Italy Manuscript received February 22, 2000; revised manuscript September 20, 2000
Abstract Background: Decreasing operative bleeding during liver resection, and thus extent of transfusions, has become a main criterion to evaluate operative results of hepatectomies. Hepatic pedicle clamping (HPC) is widely used for this purpose. The aim of the study was to evaluate safety, efficacy, technique, and contraindications of HPC during liver resections, comparing results of resections performed with or without HPC. Methods: Data from 245 liver resections were analyzed. In all, 125 resections were performed with HPC (group A), continuous in 100 cases and intermittent in 25 cases. The average duration of ischemia in group A was 39 ⫾ 20 minutes (range 7 to 107). In 20 cases (16%) ischemia was prolonged for 60 minutes or more. A total of 120 resections were performed without HPC (group B). Major resections were 53.6% in group A (67 cases) and 38.3% in group B (46 cases). Cirrhosis was present in 36 cases, 19 in group A and 17 in group B. Results: Operative mortality was nil. Postoperative mortality was 2.9%, morbidity 22.4%. Percentage of transfused cases (34.4% versus 60.0%; P ⬍0.001) and number of blood units per transfused case (2 ⫾ 1 versus 4 ⫾ 3; P ⬍0.001) were lower in group A versus group B. Similar figures were found by considering only major resections. Postoperative blood chemistries did not show important differences between the two groups, and postoperative alterations were related more to extent and complexity of the operation than to length of HPC. Conclusions: HPC during liver resection is a safe and effective technique. This is demonstrated in a context where HPC is used continuously in most cases, intermittently in cases with impaired liver function and for more prolonged ischemia, and avoided in cases with limited bleeding, jaundice, and simultaneous bowel anastomoses. © 2001 Excerpta Medica, Inc. All rights reserved. Keywords: Liver resections; Liver ischemia; Hepatic pedicle clamping
The amount of blood transfusion during hepatectomy has a relevant impact on the morbidity and mortality of this type of surgery. In fact, independently of the risk of infection or reactions, close correlation between amount of operative transfusion and both poor postoperative outcome and late results has been reported by many articles [1– 8]. Therefore, decreasing operative bleeding during hepatic resection, and thus reducing the amount of blood transfusions during operation, is an important target. Since mortality and morbidity of liver surgery have plateaued in most hepatobiliary centers around similar figures, the capability to avoid or limit transfusions has also become a main criterion to evaluate operative results.
Hepatic pedicle clamping (HPC) is widely used during hepatectomy to reduce operative blood loss [9 –13]. However, some aspects of temporary arterial and portal occlusion remain unclear: temporal limit of warm ischemia, choice of continuous or intermittent vascular interruption, and exact contraindications. With the aim to contribute to the debate on these issues, a large, single-surgeon experience is analyzed retrospectively in this paper, by comparing the results of liver resections performed with or without pedicle clamping.
Patients and methods * Corresponding author. Tel.: 011 39 6 30154967; fax: 011 39 6 3058586. E-mail address: [email protected].
From 1984 to 1997, 245 liver resections were performed on 240 patients (128 women and 112 men), with a mean age
0002-9610/01/$ – see front matter © 2001 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 1 ) 0 0 5 5 5 - 4
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
239
Table 1 Features of patients and indications for liver resection
Number of cases Mean age (⫾SD) Sex (M/F) ASA Class 1 2 3 4 Cirrhosis Previous chemotherapy Malignant tumors Hepatocellular carcinoma Metastases From colorectal cancer From noncolorectal cancer Cholangiocarcinoma Hepatoblastoma Hilar cholangiocarcinoma Gallbladder carcinoma Other Benign diseases Hemangioma Adenoma Focal nodular hyperplasia Nonparasitic cyst Hydatid cyst Intrahepatic lithiasis Congenital biliary cysts Abscess
Total
Group A (HPC)
Group B (no HPC)
245 56 ⫾ 15 (1–82) 113/132
125 (51%) 55 ⫾ 14 (2–82) 62/63
120 (49%) 55 ⫾ 16 (1–81) 51/69
137 15 91 2 36 (14.7%)* 33/245 (13.5%) 177 (72.2%) 44 101 75 26 4 4 13 9 1 68 (27.8%) 18 8 9 7 17 4 1 4
70 8 47 — 19 (15.2%) 24 (19.2%) 94 (75.2%) 20 63 46 17 3 2 3 3 — 31 (24.8%) 6 3 9 4 4 2 — 3
67 7 44 2 17 (14.2%) 9 (7.5%) 83 (69.2%) 24 38 29 9 1 2 10 6 1 37 (30.8%) 12 5 0 3 13 2 1 1
* Thirty-four hepatocellular carcinoma and 2 colorectal metastases. HPC ⫽ hepatic pedicle clamping.
of 56 ⫾ 15 years (range 1 to 82). Cirrhosis was present in 36 cases (14.7%). One hundred twenty-five (51%) liver resections were performed with HPC (group A) and 120 (49%) liver resections without HPC (group B). Groups A and B matched for age, sex, ASA class [14], indications for liver resection, status of the liver (healthy liver, cirrhosis, preoperative chemotherapy), and kind of resection. General features of patients and indications for liver resections are listed in Table 1, the type of resection performed is listed in Table 2. There were 5 re-resections. From March 1990 clamping of retrohepatic vena cava started to be associated with HPC in selected cases to obtain total vascular exclusion (TVE). Since then, TVE of the liver has been performed in 13 out of 156 patients (8.3%). These were 13 patients with a mean age of 52.3 years (range 31 to 73), 11 with primary or secondary malignancies, 1 with adenoma, and 1 with hemangioma, all in close proximity to confluences between hepatic veins and vena cava. The involved procedures were 7 right hepatectomies (2 with tangential resection of vena cava, 1 extended to segments 1 and 4, and 1 to segment 1), 5 left hepatectomies (1 extended to segments 5 and 8, and 1 to segment 1), and a resection of
segments 3 and 4 for an infiltrating retroperitoneal leiomyosarcoma. In group A, a continuous HPC was used in 100 cases (100 of 125, 80%). In 25 (25 of 125, 20%) HPC was discontinued for 5 minutes every 10 to 15 minutes of ischemia (intermittent HPC). All patients were operated on electively by the same surgeon (GN). Surgical access was obtained through bilateral subcostal laparotomy, often enlarged with a xiphoid split (Mercedes incision). During the last year, use of the Makuuchi incision [15] was started in some cases; in a patient with four previous laparotomies with a metastasis of segment 8, a transthoracic approach was needed [16]. Intraoperative liver ultrasound was used in the last 10 years to complete staging of malignant diseases and to guide resections. Parenchymal transection was performed by Kelly clamps, and hemobiliostasis was obtained by means of thin (3/0 to 4/0) transfixed sutures and reabsorbable clips. During right or left hepatectomy, section of the main portal and arterial branches was performed before parenchymal resection. In contrast, section of the main biliary duct was performed after completing parenchymal transection. Main hepatic veins were isolated extraparenchymally and, only if
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G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246
Table 2 Type of resection according to Couinaud classification Major resections Right hepatectomy Right hepatectomy ⫹ segment IV Right hepatectomy ⫹ segment I Right hepatectomy ⫹ segments I–IV Right hepatectomy ⫹ atypical resection Left hepatectomy Left hepatectomy ⫹ segment I Left hepatectomy ⫹ segments V–VIII Resection of 5 segments Resection of 4 segments Resection of 3 segments Resection of segments V–VIII Minor resections Two segments One segment Atypical resection
113 (46.1%) 43 5
67 (53.6%) 20 4
46 (38.3%) 23 1
5
1
4
2
2
—
2
2
—
28 1
14 1
14 —
3
3
—
1 1 21 1
1 1 17 1
— — 4 —
58 (46.4%) 33 15 10
74 (61.7%) 35 16 23
132 (53.9%) 68 31 33
this was at risk for vein injury, the section was performed intraparenchymally. HPC was performed by means of a vascular tourniquet applied on the hepatic pedicle at a safe distance from the superior margin of the pancreas. An eventual left hepatic artery coming from the gastric artery was also clamped. To reduce total ischemia time of the liver, HPC was started after the effraction of the superficial layers of the parenchyma. HPC was not performed (group B) in cases requiring simultaneous bilioenteric or colonic anastomoses (Klatskin tumors, colorectal tumors with synchronous liver metastases) to avoid edema on the anastomosis, in those with jaundice, in those with bleeding limited by previous interruption of hilar structures, with more easy and rapid parenchymal transection, and in those operated on before the introduction of HPC. In all patients right atrial pressure (RAP) was monitored by a central venous catheter and arterial pressure by a radial catheter. During parenchymal section RAP was maintained below 5 cm H2O. In cases with indication for TVE of the liver, a SwanGanz catheter was placed for hemodynamic monitoring. The retrohepatic vena cava was completely exposed from renal confluence to diaphragm; the right adrenal vein and eventually the retrocaval venous branches were ligated. In the 20 to 30 minutes before caval clamping, 500 mL to 1,000 mL colloids and chrystalloids were infused to control the decrease in cardiac output and mean arterial pressure (MAP) associated with TVE. A 5-minute tolerance test was performed by closing in sequence the vascular tourniquet on the hepatic pedicle, a vascular clamp on the vena cava below the liver, and then a vascular clamp on the vena cava
above the liver. The maneuver was interrupted if during the tolerance test a decrease in cardiac output of more than 60% or a reduction in MAP and pulmonary wedge pressure of more than 30% were observed, or both. In 1 patient (a 73-year-old man undergoing a left hepatectomy) hemodynamic tolerance was poor and TVE was not performed (intolerance rate ⫽ 7.7%). Duration of TVE ranged from 5 to 53 minutes, with a mean of 22 ⫾ 16 minutes. Total time of ischemia in these cases ranged from 8 to 98 minutes, with a mean of 59 ⫾ 26 minutes. Neither topical refrigeration nor hypothermic liver perfusion was used. The average duration of liver ischemia in group A was 39 ⫾ 20 minutes, ranging from 7 to 107; in 20 cases (16%) ischemia was prolonged for 60 minutes or more. In the 100 cases (80%) with a continuous HPC, mean duration of ischemia was 36 minutes (range 7 to 84); in the other 25 cases (20%) with an intermittent HPC, mean duration of ischemia was 51 minutes (range 13 to 107). Choice of intermittent HPC was based on severity of preoperative liver dysfunction and expected length of HPC. Intraoperative blood transfusions were performed for hemoglobin ⬍9 g/dL and hematocrit ⬍28%, or in patients aged more than 70 years or with cardiac insufficiency, for hemoglobin ⬍10 g/dL and hematocrit ⬍30%. In order to compare the two groups, the following factors were evaluated retrospectively: perioperative mortality and morbidity rates, number of patients who required intraoperative blood transfusions, number of blood units transfused, postoperative profiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BIL), prothrombin activity (PA), and total cholesterol (CHOL). The latter has been found to be related to adequacy of postoperative recovery of liver function [17]. Results are reported as means and standard deviations (SD); comparisons were carried out using Student’s t test, the chi-square test, and Mann-Whitney-Wilcoxon rank-sum test: a P value below 0.05 was considered as statistically significant. Relationships between variables were assessed by linear, nonlinear, and logistic multiple regression analysis.
Results Operative mortality was nil. Seven patients died postoperatively after resection for primary or secondary malignancies (7 of 245 ⫽ 2.9%). Six of these patients belonged to group B, 1 to group A. The more frequent cause of death was liver failure: 4 out of 7 patients (57.1%), 1 in group A (1 of 125 ⫽ 0.8%) and 3 in group B (3 of 120 ⫽ 2.5%; P ⫽ not significant [NS]). The patient in group A had undergone a right hepatectomy with 40-minute HPC; pathology revealed liver cirrhosis, which was previously unsuspected from history and macroscopic appearance at surgery. The 3 patients in group B (2 after a major resection, and a cirrhotic patient who
G. Nuzzo et al. / The American Journal of Surgery 181 (2001) 238 –246 Table 3 Morbidity Total Overall morbidity 55 (22.4%) Major complications Biliary fistula 11 Subphrenic abscess 8 Pulmonary embolism 5 Severe liver insufficiency 4 Haemoperitoneum* 4 Gastrointestinal bleeding 3 Intestinal perforation* 3 Biliary lesion 2 ARDS 2 Deep venous thrombosis 2 Portal thrombosis 2 Intrahepatic abscess 1 Pelvic abscess 1 Intestinal occlusion* 1 Anastomotic leakage* 1 Minor complications Moderate liver insufficiency 7 Pneumonia 6 Pleural effusion (thoracentesis) 5
Group A (HPC)
Group B (no HPC)
28 (22.4%) 27 (22.5%) 5 (1 TVE) 6 5 (1 TVE) 3 3 2 4 (1 TVE) — — 4 2 1 2 (1 TVE) — 1 1 1 1 1 1 — 2 — 1 — 1 — 1 1 — 3 (1 TVE) 4 4 (2 TVE)
4 2 1
* Nine patients required a reoperation. 12 patients had more than one complication. HPC ⫽ hepatic pedicle clamping; ARDS ⫽ adult respiratory distress syndrome; TVE ⫽ total vascular exclusion.
required relaparotomy for bleeding after a wedge resection of segment III) developed also sepsis associated with liver failure. Causes of death in the other patients in group B were pulmonary embolism (after a right hepatectomy and thrombectomy of IVC), sepsis complicated further by myocardial infarction (after a right hepatectomy), and rupture of an abdominal aortic aneurism (after a left hemicolectomy with resection of segments II and III for metastases). Postoperative complications were observed in 55 cases (22.4%), including 5 with TVE, and were major complications in 17 (13.6%). Complications occurred in 28 cases (28 of 125 ⫽ 22.4%) in group A and in 27 (27 of 120 ⫽ 22.5%) in group B (Table 3). There were no specific complications related to the technique of HPC. Pleural effusion occurred in about two thirds of cases after major resections, and was not considered as a complication if thoracenthesis was not required. Reoperation was necessary in 9 cases (3.6%). In 4 of these, all in group B, postoperative bleeding from liver surface was the cause of reoperation (4 of 120 ⫽ 3.3%). The more frequent complication was transient liver insufficiency: 11 cases, 7 in group A and 4 in group B. Severe hepatic insufficiency (encephalopaty, persistent jaundice, coagulopaty, ascites) was observed in 4 patients who had undergone liver resection with HPC. More moderate liver dysfunction (total bilirubin below 3.0 mg/dL, ascites) was observed in 7 other cases, 3 in group A and 4 in group B. In cirrhotic patients, liver insufficiency occurred in 5 cases (5
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of 19 ⫽ 26.3%) in group A and in 4 in group B (4 of 17 ⫽ 23.5%). In 113 major hepatectomies overall morbidity was 31.8% (36 cases), 29.8% in group A (20 of 67 cases) and 34.7% in group B (16 of 46 cases). A trend for a lower rate of complications in group A versus B became more evident in subgroups with increasing complexity of operation, without reaching statistical significance. In cases resected with duration of HPC longer than 60 minutes, morbidity was 40.0% (8 of 20 cases); and in those with HPC shorter than 60 minutes, morbidity was 17.1% (18 of 105 cases; P ⫽ NS). In cases resected with TVE there was no mortality; 5 cases had postoperative complications (5 of 12 ⫽ 41.6%). In cases with liver cirrhosis overall morbidity was 30% (11 of 36 cases), 26.3% (5 of 19 cases) in group A and 35.3% (6 of 17 cases) in group B (P ⫽ NS). The 3 cases with complications in group A received a continuous HPC and had transient liver insufficiency (severe in 1 case, moderate in 2). Rate of transient liver insufficiency in group B was 23.5% (4 of 17 cases). One hundred fifteen cases (115 of 245 ⫽ 46.9%) required intraoperative transfusions: 43 belonged to group A (43 of 125 ⫽ 34.4%) and 72 to group B (72 of 120 ⫽ 60%). This difference was statistically significant (P ⬍0.001; Table 4). Transfused cases in group A required 2 ⫾ 1 units of blood each (range 1 to 6), whereas those in group B required 4 ⫾ 3 units each (range 1 to 15; P ⬍0.001). Postoperative transfusions were necessary in 31 cases (31 of 245⫽12.6%): 13 in group A (10.4%) and 18 in group B (15%) (P ⫽ NS). In total, transfusions (intraoperative and postoperative) were required in 130 cases (53.1%): 53 in group A (53 of 125 ⫽ 42.4%) and 77 in group B (77 of 120 ⫽ 64.2%; P ⬍0.002). Mean requirement in transfused group A cases was 2 ⫾ 1 units (range 1 to 6), whereas in group B it was 4 ⫾ 3 units (range 1 to 16; P ⬍0.001). Concerning only major resections, 67 out of 112 cases required intraoperative transfusions (59.8%) and 19 required postoperative transfusions (17%; Table 4): intraoperative transfusions were necessary in 31 cases in group A (31 of 66 ⫽ 46.9%) and in 36 in group B (36 of 46 ⫽ 78.3%; P ⬍0.003), whereas postoperative transfusions were performed in 8 cases in group A (8 of 66 ⫽ 12.1%) and in 11 in group B (11 of 46 ⫽ 23.9%; P ⫽ NS). During operation, transfused cases in group A received 2 ⫾ 1 units (range 1 to 6); those in group B received 5 ⫾ 3 units (range 1 to 15; P ⬍0.001). Seventy-five of these major resections required intraoperative plus postoperative transfusions: 38 in group A (38 of 66 ⫽ 57.6%) and 37 in group B (37 of 46 ⫽ 80.4%). This difference was statistically significant (P ⬍0.03). Mean requirement was 2 ⫾ 1 units (range 1 to 6) in group A and 5 ⫾ 4 units (range 1 to 16) in group B. This difference was also significant (P ⬍0.001). There was a similar blood saving in continuous and intermittent HPC (Table 5). Patients who underwent TVE required intraoperative
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Table 4 Total number of transfused cases and number of blood units per transfused case in all cases and in major resections
Intraoperative transfusions Patients (n) Units of blood Postoperative transfusions Patients (n) Units of blood Total transfusions (i.o. and p.o.) Patients (n) Units of blood
Total
Group A (HPC)
Group B (no HPC)
P
Major resections
Group A (HPC)
Group B (no HPC)
P
115 (46.9%) 3⫾2 (1–15)
43 (34.4%) 2⫾1 (1–6)
72 (60%) 4⫾3 (1–15)
⬍0.001
67 (59.8%) 4⫾3 (1–15)
31 (46.9%) 2⫾1 (1–6)
36 (78.3%) 5⫾3 (1–15)
⬍0.003
31 (12.6%) 2⫾1 (1–6)
13 (10.4%) 2⫾1 (1–3)
18 (15%) 2⫾2 (1–6)
19 (17%) 2⫾1 (1–6)
8 (12.1%) 2⫾1 (1–3)
11 (23.9%) 2⫾2 (1–6)
130 (53.1%) 3⫾3 (1–16)
53 (42.4%) 2⫾1 (1–6)
77 (64.2%) 4⫾3 (1–16)
75 (67%) 4⫾3 (1–16)
38 (57.6%) 2⫾1 (1–6)
37 (80.4%) 5⫾4 (1–16)
⬍0.001
NS NS
⬍0.002 ⬍0.001
⬍0.001
NS NS
⬍0.03 ⬍0.001
Data presented as mean ⫾ SD (range). HPC ⫽ hepatic pedicle clamping; i.o. ⫽ intraoperative; p.o. ⫽ postoperative; NS ⫽ not significant.
transfusions in 7 cases (7 of 12 ⫽ 58.3%), with a mean requirement of 2.7 ⫾ 1.7 units (range 1 to 6). The analysis was carried on further by considering separately cases in group B operated on before or after introducing the use of HPC. The latter did not differ from the former in demographics, mortality, and morbidity, but included a slightly larger proportion of cirrhotic patients and showed a reduction in percent of transfused cases. This was expected, because limited bleeding was one of the criteria to avoid HPC. However, multiple logistic regression analysis, performed on all cases or only on those operated after introduction of HPC, by accounting simultaneously for magnitude and duration of the operations, reconfirmed a significant effect of HPC in reducing the risk of intraoperative blood transfusions in all cases, and also in those operated after introduction of HPC (Fig. 1). In particular, by Table 5 Features of 113 cases resected using continuous versus intermittent HPC* Continuous HPC Number of cases Mean ischemia length, minutes (range) Ischemia longer than 1 hour Length of procedure Major resections Cirrhotic patients Mortality Morbidity Intraoperatively transfused cases Intraoperatively transfused blood units
88 33 (7–84) 6 (6.8%) 282 ⫾ 106 42 (47.7%) 13 (14.7%) 1 (13%) 8 (32%) 27 (30%) 2⫾1
* Patients with total vascular exclusion were excluded. HPC ⫽ hepatic pedicle clamping.
Intermittent HPC 25 51 (13–107) 8 (32%) 294 ⫾ 276 13 (52%) 6 (24%) 0 22 (25%) 9 (36%) 2⫾1
comparing major resections, the probability of performing at least one intraoperative transfusion resulted significantly higher in those performed without HPC. Similar figures were found in minor resections. In both groups, patients resected with HPC and those without HPC, the duration of surgery also was a significant factor for a higher probability of performing intraoperative transfusion. Concerning blood chemistries, a significant increase of AST, ALT, and BIL and a significant decrease of CHOL and PA were observed on postoperative day 1. In most cases all values but ALT returned to normal ranges within 7 days. Comparisons of the variations of liver tests are reported in Table 6. Regression analysis showed that changes of ALT, AST, PA, and CHOL in patients who had undergone HPC were all correlated with duration of clamping at postoperative day 1 (r2 ⫽ 0.2 to 0.4, P ⬍0.001 for all), were more weakly correlated at postoperative day 3, and were not correlated at postoperative day 7. However, when duration of the operation was evaluated together with duration of clamping as a simultaneous independent variable, the former accounted for most of the variability of ALT, AST, PA, and CHOL, while duration of clamping became less important (partial r2 ⬍0.10). This suggested that postoperative changes of ALT, AST, PA, and CHOL were related more strictly to magnitude and complexity of the operation than to duration of HPC. An inconstant feature associated with more prolonged liver ischemia was postoperative hyperbilirubinemia. However, regression analysis showed again that peak bilirubin (without cholestasis) was more a function of the number of resected liver segments, of duration of the operation, of amount of blood transfusions, and of the presence of sepsis (multiple r2 ⫽ 0.60) rather than a function of duration of HPC (r2 ⬍0.10). Persistent jaundice was a significant de-
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Fig. 1. Multiple logistic regression analysis of probability of a patient being transfused, based on duration of surgery (quantifying complexity of the procedure), magnitude of resection, and use of hepatic pedicle clamping (HPC) for patients operated on after introduction of HPC. Odds ratio (OR) and confidence interval (C.I.) are indicated.
terminant of the length of postoperative hospital stay. In general, however, this was related more to a cautious attitude toward discharge of a jaundiced patient than to a real need for hospital treatment. Median postoperative hospital stay was 12 days (range 4 to 78). It was 16 ⫾ 13 days in group A and 20 ⫾ 11 days in group B (P ⬍0.02).
Comments Good postoperative outcome of hepatic resections mainly depends upon limited operative bleeding and sufficient functional reserve of the nonresected liver. Therefore, from the beginning of this type of surgery, progression toward more difficult and extensive hepatectomies has been associated with the research for methods limiting operative bleeding. Increased knowledge of intrahepatic anatomy and introduction of operative ultrasound have allowed the development of an accurate surgical technique, thus reducing the risk of bleeding during resection. Temporary vascular occlusion of hepatic inflow (HPC) has been reported to be effective in reducing bleeding from intraparenchymal arterial and portal branches [18 –23]. Caval clamping below and above the liver associated with pedicle clamping (TVE) permits complete control of bleeding from the vena cava and from hepatic veins, which remains the most important
cause of concern during hepatic resection [24 –29]. The fear of adverse consequences associated with warm liver ischemia and with stasis in the splanchnic bed have limited the wide application of these techniques, and great experience with their application is available only in a few centers with large practices of liver surgery [10 –13,20,23,24,26,27,29 – 34]. Our retrospective analysis of data from cases resected by the same surgeon in the same institution, with or without HPC, alone or associated with caval clamping in selected cases, confirm the safety and effectiveness of HPC. As a matter of fact, the number of intraoperatively transfused cases was almost doubled in group B (without HPC) compared with group A (with HPC), by considering either all resections or major resections only, as reported in Table 4. Furthermore, 65.6% (82 of 125) of all resections performed with HPC were completed without transfusions whereas this was possible only in 40% (48 of 120) of the resections without HPC (P ⬍0.001). Also considering major resections only, in more than 50% of cases in group A (36 cases) the resection did not require any transfusion, compared with 21.7% in group B (10 cases) (P ⬍0.001). In addition, in transfused cases, the mean blood requirement per case was significantly less in group A versus group B, by considering either the whole sample or major resections only. Five cases undergoing TVE (41.7%) did not require any transfusion. With the aim of excluding the possibility that our results
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Table 6 Liver function test results before and after resection with or without hepatic pedicle clamping (HPC) Before operation
Postoperative day 1
Postoperative day 3
Postoperative day 7
HPC
HPC
HPC
HPC
no HPC
no HPC
no HPC
no HPC
Liver function test results before and after resection with or without HPC (cases with postoperative liver failure are excluded) ALT (U/L) 33.2 ⫾ 32.6 40.8 ⫾ 43.7 429.2 ⫾ 397.1 272.2 ⫾ 262.2 116.2 ⫾ 134.7 77.5 ⫾ 91.9 43.4 ⫾ 29.6 52.6 ⫾ 41.1 AST (U/L) 45.8 ⫾ 73.8 52.4 ⫾ 78.7 471.7 ⫾ 422.5 318.6 ⫾ 344.9 278.7 ⫾ 261.7 164.1 ⫾ 164.7 114.6 ⫾ 85.9 86.4 ⫾ 64.8 Total bilirubin 0.8 ⫾ 1.4 1.2 ⫾ 2.5 1.9 ⫾ 2.3 2.1 ⫾ 3.2 1.7 ⫾ 2.7 1.9 ⫾ 1.8 1.6 ⫾ 3.5 2.1 ⫾ 2.4 Total cholesterol 189.4 ⫾ 37.7 189.9 ⫾ 45.4 120.4 ⫾ 29.0 119.8 ⫾ 29.6 117.5 ⫾ 33.0 116.7 ⫾ 32.6 120.6 ⫾ 38.9 111.5 ⫾ 3.6 Prothrombin activity 94.0 ⫾ 12.4 88.2 ⫾ 14.0 63.1 ⫾ 15.9 66.4 ⫾ 15.7 78.2 ⫾ 16.1 74.0 ⫾ 18.2 81.0 ⫾ 15.2 72.4 ⫾ 18.7 Liver function test results before and after resection with or without HPC in 11 patients with postoperative liver failure ALT (U/L) 35.6 ⫾ 15.5 74.3 ⫾ 47.2 1000.9 ⫾ 789.1 775.7 ⫾ 1313.3 214.7 ⫾ 138.5 163.4 ⫾ 219.2 61.3 ⫾ 22.6 60.0 ⫾ 30.5 AST (U/L) 37.3 ⫾ 22.7 75.7 ⫾ 42.2 962.0 ⫾ 910.0 981.4 ⫾ 1764.3 463.9 ⫾ 430.0 249.7 ⫾ 359.5 159.0 ⫾ 98.7 90.0 ⫾ 63.7 Total bilirubin 0.6 ⫾ 0.2 4.3 ⫾ 4.6 3.2 ⫾ 1.6 7.0 ⫾ 5.6 4.2 ⫾ 2.2 6.0 ⫾ 6.8 5.5 ⫾ 4.0 8.7 ⫾ 9.4 Total cholesterol 155.7 ⫾ 34.9 189 ⫾ 77.1 79.7 ⫾ 22.2 85.8 ⫾ 33.5 82.8 ⫾ 25.9 101.3 ⫾ 37.5 89.0 ⫾ 20.4 83.5 ⫾ 37.6 Prothrombin activity 88.9 ⫾ 9.4 84.6 ⫾ 15.9 56.7 ⫾ 21.4 52.9 ⫾ 8.7 60.6 ⫾ 20.0 59.6 ⫾ 15.2 74.6 ⫾ 12.9 63.2 ⫾ 8.1 Liver function test results before and after major resection with or without HPC ALT (U/L) 35.8 ⫾ 36.1 50.0 ⫾ 55.9 570.6 ⫾ 492.7 312.9 ⫾ 198.3 144.8 ⫾ 146.8 84.5 ⫾ 75.8 51.8 ⫾ 32.3 47.8 ⫾ 25.5 AST (U/L) 53.1 ⫾ 89.8 67.8 ⫾ 100.6 589.1 ⫾ 489.7 370.5 ⫾ 237.8 328.9 ⫾ 263.5 174.7 ⫾ 119.8 129.3 ⫾ 92.7 86.0 ⫾ 45.6 Total bilirubin 1.0 ⫾ 1.8 1.9 ⫾ 3.5 2.6 ⫾ 2.9 3.3 ⫾ 4.5 2.4 ⫾ 3.5 2.8 ⫾ 3.1 2.4 ⫾ 4.4 3.3 ⫾ 3.5 Total cholesterol 184.3 ⫾ 39.8 198.2 ⫾ 42.0 114.0 ⫾ 31.8 115.6 ⫾ 28.3 105.1 ⫾ 30.1 99.9 ⫾ 24.9 113.3 ⫾ 30.9 98.3 ⫾ 19.7 Prothrombin activity 95.8 ⫾ 12.6 88.2 ⫾ 12.3 59.1 ⫾ 15.2 60.1 ⫾ 12.6 72.8 ⫾ 17.3 71.3 ⫾ 17.2 77.2 ⫾ 15.6 69.5 ⫾ 14.5 Liver function test results before and after resection with continuous or intermittent HPC Continuous Intermittent Continuous Intermittent Continuous Intermittent Continuous Intermittent ALT (U/L) 26.2 ⫾ 19.3 44 ⫾ 36.1 375.7 ⫾ 332.7 566.4 ⫾ 444.6 106 ⫾ 129.7 145.4 ⫾ 142.1 38.5 ⫾ 22.8 50.3 ⫾ 29.5 AST (U/L) 35 ⫾ 54 55.8 ⫾ 57.4 442.2 ⫾ 425.3 576.5 ⫾ 453.6 264.1 ⫾ 278 360.3 ⫾ 301.9 108.5 ⫾ 87.7 140.6 ⫾ 88.6 Total bilirubin 0.7 ⫾ 0.5 0.8 ⫾ 0.6 1.7 ⫾ 1.1 1.9 ⫾ 1.5 1.5 ⫾ 1.0 1.6 ⫾ 1.2 1.4 ⫾ 1.5 1.5 ⫾ 2.1 Total cholesterol 183.3 ⫾ 37.9 200.5 ⫾ 36.5 118.9 ⫾ 31.1 125.8 ⫾ 29.5 116.4 ⫾ 33.5 125.4 ⫾ 28.3 120.1 ⫾ 33.6 132.4 ⫾ 34.9 Prothrombin activity 93.9 ⫾ 11.9 92.9 ⫾ 13.2 64.2 ⫾ 16.3 60.2 ⫾ 14.2 78.4 ⫾ 16.7 74.6 ⫾ 16.1 82.0 ⫾ 16.2 80.8 ⫾ 13.1 ALT ⫽ alanine aminotransferase; AST ⫽ aspartate aminotransferase.
were caused only by increased experience of the surgeon in performing liver resections, we compared the data of patients resected before introduction of HPC in our surgical technique and patients resected after introduction of HPC. The results of multiple logistic regression analysis performed only in resections carried out after the introduction of HPC showed that the risk of at least one intraoperative transfusion, for a given duration of the operation, increases with increasing extent of resection and in the absence of HPC. For instance, Fig. 1 shows that a major resection lasting 240 minutes performed without HPC has a risk of intraoperative transfusion of 55%, significantly greater than that for a similar resection of the same duration performed with HPC (risk of intraoperative transfusion 35%). At present our attitude concerning use of HPC is neither unconditional use in all resections as a routine nor restriction to exceptional cases. We start HPC only after deepening the incision inside the liver and depending on the extent of bleeding, in order to benefit from the advantages of HPC without disregarding potential risks. The upper limit for duration of normothermic ischemia of the liver is not established exactly, but it depends mainly on functional reserve of the liver. Safety of continuous pedicle clamping exceeding 1 hour in healthy liver has been reported, and a limit of around 90 minutes is accepted [23,29,34]. In low-severity cirrhotic livers, 60minutes is considered a safe limit [11,35].
Intermittent clamping, described by Makuuchi et al [36] during hemihepatic vascular occlusion, is used with the aim to prolong duration of liver ischemia while reducing ischemic injury. By using this technique, very long durations of pedicle clamping have been reported [10,35,37]. In a controlled study on continuous versus intermittent portal triad clamping [38], better parenchymal tolerance to intermittent clamping was reported, but this was associated with a significantly higher intraoperative blood loss. In our experience intermittent clamping was used mainly for procedures requiring more prolonged ischemia. As a matter of fact mean duration of ischemia in cases with intermittent HPC was longer than that in cases with continuous HPC (51 versus 33 minutes). Also the number of cases with ischemia longer than 1 hour was greater in cases with intermittent HPC than in cases with continuous HPC (32% versus 6.8%). In these two groups no differences in number of transfused cases or transfused units per case were observed. Although limitation of length of HPC and TVE must remain a major concern for the surgeon, our results support the concept of the great tolerance to warm ischemia of the liver. Most liver resections can be performed within the already mentioned limits of duration of normothermic ischemia. Only in very selected cases, for extremely complex resections, more extensive period of vascular clamping may be needed. In such cases, hypothermic perfusion of the liver may be considered [39].
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Use of HPC or TVE permits carrying out liver resection in a bloodless operative field and therefore with more accurate hemostasis and biliostasis. Consequently, it is reasonable to expect a reduction in related postoperative complications. Although overall morbidity in group A versus B was not significantly different, all reoperations for postoperative bleeding from liver surface occurred in group B. Besides, a trend for a lower rate of complications in group A versus B was evident for cirrhotic patients and for cases undergoing resections of increasing complexity. The occurrence of postoperative liver insufficiency is related to the functional capacity of the residual liver. Use of HPC in this study was not associated with a relevant increase of the risk. As mentioned, there was no relationship with mortality from liver failure. Also, liver failure was a cause of death in 3 patients in group B versus 1 in group A. There was a trend for a more frequent occurrence of transient liver insufficiency in group A (7 of 125 ⫽ 5.6%) versus B (4 of 120 ⫽3.3%), which did not reach significance, and there were no differences in group A versus group B cirrhotic patients. The possibility of inducing hepatocyte dysfunction by liver ischemia (by HPC or TVE) is of great concern. Patients with liver cirrhosis, cholestasis, older age, steatosis, or previous chemotherapy are at higher risk, and in these patients at present we prefer to perform intermittent clamping. Ischemia may also induce Kupffer cell dysfunction (with impaired clearance of bacteria from portal blood, thus facilitating sepsis) or dysreactivity (with abnormal inflammatory responses and Kupffer cell-hepatocyte interactions) [40]. Assessing the practical relevance of these effects awaits further studies; it is noteworthy, however, that the technique of normothermic ischemia, as applied in our cases, was not associated with relevant adverse clinical consequences. Also, postoperative evaluation of blood chemistries did not reveal important or persistent abnormalities clearly associated with HPC, while overall regression analysis showed that the duration of ischemia only accounted for a modest percentage of the postoperative variability of blood chemistries. In patients undergoing HPC longer than 60 minutes there was a higher rate of complications, which, however, did not reach statistical significance and could not be linked specifically to duration of HPC (rather than to other risk factors). An aspect that remains open to question and may have close relevance is whether effectiveness of HPC in terms of blood-saving is paralleled by similar advantages in terms of sparing intraoperative or postoperative administration of other blood products (plasma, albumin). At present our data on this aspect do not permit any specific inference. In conclusion, we support the concept that normothermic ischemia of the liver during liver surgery is an effective and safe technique. As mentioned already, it is our policy to remain cautious about the implications of prolonged liver ischemia, while taking advantage simultaneously of the use of HPC. In major resections we first prepare and interrupt
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vascular structures at the hilum, and HPC is started only after deepening the incision in liver parenchyma to reduce duration of ischemia. The choice of intermittent HPC is based on contingent criteria (impaired liver function and need for prolonged ischemia), which reflect a realistic scenario but limit comparison with other controlled studies. Nevertheless, our data contribute to the available knowledge on the advantage of intermittent HPC in these cases. Finally, we avoid HPC when bleeding is limited, in the presence of jaundice, and to avoid edema of simultaneously performed bowel anastomoses. Within this context, the results of this study provide significant evidence of the benefits and safety of HPC.
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