Ivo Giovannini

Pedicle clamping with ischemic preconditioning in liver resection

Hepatic pedicle clamping (HPC) is widely used to control intraoperative bleeding during hepatectomy; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion. Recently, it has been shown that ischemic preconditioning (IP) reduces the ischemia‐reperfusion damage for up to 30 minutes of continuous clamping in healthy liver. We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver submitted to hepatectomy. IP was used in 21 patients (group A); mean ± SD of liver ischemia was 54 ± 19 minutes (range, 27‐110; in 7 cases >60 minutes). In the other 21 patients, continuous clamping alone was used (Group B); liver ischemia lasted 36 ± 14minutes (range, 13‐70; in 2 cases >60 minutes). Two patients in Group A (9.5%) and 3 in Group B (14.2%) received blood transfusions. In spite of the longer duration of ischemia (P = .001), patients with IP had lower aspartate aminotransferase (AST; P = .03) and alanine aminotransferase (ALT; P = not significant) at postoperative day 1, with a similar trend at postoperative day 3. This was reconfirmed by multiple regression analysis, which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups, the increases were significantly smaller (P < .001) with the use of preconditioning. In conclusion, the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia. This technique should be preferred to continuous clamping alone in healthy liver. Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping. (Liver Transpl 2004;10:S53–S57.)

Respiratory quotient and patterns of substrate utilization in human sepsis and trauma.

Three hundred measurements of indirect calorimetric and hemodynamic variables were performed in 99 critically ill septic and nonseptic surgical patients. Septics manifested, with respect to nonseptics, higher O2 consumption, metabolic rate and cardiac index, and lower respiratory quotient in the presence of higher glucose infusion rates and glucose infusion rate/metabolic rate ratios. Among septics there was a group of more severely ill patients with signs of multiple organ failure who manifested a dissociated pattern characterized by a tendency to decreased O2 consumption in the presence of increasing cardiac index and central venous O2 partial pressure: they had higher respiratory quotients, with respect to the other septics, for a given glucose infusion rate/metabolic rate ratio. The lower mean respiratory quotient of septics indicates that they depend generally more than nonseptic trauma patients on fat as an energy substrate and confirms a previously obtained evidence of limited hepatic lipogenesis in sepsis. At the same time, however, it is suggested that fat utilization becomes impaired (and hepatic lipogenesis becomes prominent) in sepsis at a stage in which signs of impaired oxidative metabolism and major metabolic abnormalities also develop.

Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients.

Objective: To assess correlates of hypocholesterolemia in moderate to critical surgical illness. Design: Prospective analysis of laboratory and clinical data. Setting: Department of surgery in a university hospital. Patients: 135 patients undergoing uncomplicated abdominal surgery or with sepsis, liver failure, hemorrhage, severe cholestasis, or multiple organ dysfunction syndrome (MODS). Interventions: Surgical and/or medical therapy according to clinical status. Measurements and main results: Determinations of total cholesterol, additional variables, and clinical data. Cholesterol decreased after surgery, in sepsis, liver failure, acute hemorrhage, and MODS and increased in cholestasis. Hypocholesterolemia correlated with decreases in plasma proteins and indices of hepatic protein synthetic adequacy, with hemodilution from blood loss, and was moderated or prevented by cholestasis. Conclusions: These results help to explain the dynamics of the development, clinical relevance, and negative prognostic value of hypocholesterolemia in critical illness.

Liver dysfunction and sepsis determine operative mortality after liver resection

Liver failure is the principal cause of death after hepatectomy. Its progression towards death and its relationship with sepsis are unclear. This study analysed predictors of mortality in patients with liver dysfunction and the role of sepsis in the death of these patients.

Liver resections with or without pedicle clamping

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.

Advantages of multidisciplinary management of bile duct injuries occurring during cholecystectomy

BACKGROUND The aim of the present study was to highlight the advantages of treatment of bile duct injury (BDI) occurring during cholecystectomy on the basis of a multidisciplinary cooperation of expert surgeons, radiologists, and endoscopists. METHODS Sixty-six patients had major BDIs or short- or long-term failures of repair. BDI was diagnosed intraoperatively in 27 patients (40.9%) and postoperatively in 39 (59.1%) patients. Among referred patients, 30 had complications from bile leak, 15 from obstructive jaundice, and 20 from recurrent cholangitis. Two patients died from sepsis after delayed referral before repair was attempted. Eleven additional patients had minor BDIs with bile leak both with and without choleperitoneum. RESULTS Of patients with major BDI, surgical repair was performed in 41 (64.1%). Postsurgical morbidity rate was 15.8%, and there was no mortality. The rate of excellent or good results after surgical repair was 78.0% (32 of 41 patients), and this increased to 87.8% (36 of 41 patients) by continuing treatment with stenting in postsurgical strictures. Biliary stenting alone was performed in 23 patients (35.9%), with excellent or good results in 17 (73.9%). More than 200 endoscopic and percutaneous procedures were performed for initial assessment, treatment of sepsis, nonsurgical repair, contribution to repair, and follow-up. Patients with minor BDIs underwent various combinations of surgical and endoscopic or percutaneous treatments, always with good results. CONCLUSIONS A multidisciplinary approach was of paramount importance in many phases of treatment of BDI: initial assessment, treatment of secondary complications, resolution of sepsis, percutaneous stenting before surgical repair, dilatation of strictures after repair, final treatment in patients not repaired surgically, and follow-up.

Plasma arginine correlations in trauma and sepsis

Summary.Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis.Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine.ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r2 = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r2 = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances.These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

Role of the surgeon as a variable in long-term survival after liver resection for colorectal metastases

Survival analyses after hepatectomy for colorectal liver metastases (CRLM) mostly address tumor‐related factors; this study has simultaneously evaluated interventional factors which may be influenced by the surgeon.

Does hepatic pedicle clamping affect disease-free survival following liver resection for colorectal metastases?

Objective: To evaluate the impact of liver ischemia from hepatic pedicle clamping (HPC) on long-term outcome after hepatectomy for colorectal liver metastases (CRLM). Background: Liver resection offers the only chance of cure for patients with CRLM. Several clinical and pathologic factors have been reported as determinants of poor outcome after hepatectomy for CRLM. A controversial issue is that hepatic ischemia/reperfusion injury from HPC may adversely affect long-term outcome by accelerating the outgrowth of residual hepatic micrometastases. Methods: Patients undergoing liver resection for CRLM in 2 tertiary referral centers, between 1992 and 2008, were included. Disease-free survival and specific liver-free survival were analyzed according to the use, type, and duration of HPC. Results: Five hundred forty-three patients had primary hepatectomy for CRLM. Hepatic pedicle clamping was performed in 355 patients (65.4%), and intermittently applied in 254 patients (71.5%). Postoperative mortality and morbidity rates were 1.3% and 18.5%, respectively. Hepatic pedicle clamping had a highly significant impact in reducing the risk of blood transfusions and was not correlated with significantly higher postoperative morbidity. Liver recurrence rate was not significantly different according to the use, type, and duration of HPC, in patients resected after preoperative chemotherapy as well. On univariate analysis, HPC did not significantly affect overall and disease-free survival. These results were confirmed on the multivariate analysis where blood transfusions, primary tumor nodal involvement, and the size of CRLM of more than 5 cm prevailed as determinants of poor outcome. Conclusions: This study confirms the safety and effectiveness of HPC and demonstrates that in the human situation, there is no evidence that HPC may adversely affect long-term outcome after hepatectomy for CRLM.

Plasma Carnitine Levels and Urinary Carnitine Excretion during Sepsis

Carnitine is an indispensable factor for the beta-oxidation of medium- and long-chain fatty acids, and it plays a possible role in the oxidation of branched-chain amino acids. Plasma and urinary levels of free carnitine and short-chain acyl-carnitines were studied in 67 surgical patients, after non-septic surgical procedures or during sepsis. The septic state was associated with increased urinary excretion of free carnitine (p less than 0.001), as well as with lower plasma levels of short-chain acyl-carnitines (p less than 0.001); the latter feature correlated with the level of hypermetabolism, as evaluated by the metabolic rate and by the arterial-mixed venous O2 difference. In 26 patients during total parenteral nutrition D, L-acetyl-carnitine was administered (100 mg/kg/24 hrs, in continuous iv infusion) and was associated, in septic patients only, with a significant decrease in the respiratory quotient, suggesting enhanced oxidation of low respiratory quotient substrates (fatty acids and/or branched-chain amino acids). Carnitine supplementation during total parenteral nutrition might be of theoretical benefit in some clinical conditions, such as sepsis, in which the following conditions coexist enhanced utilization of substrates whose oxidation is partially or totally carnitine dependent; prolonged absence of exogenous intake of carnitine (as in long-term total parenteral nutrition); eventual impairment of carnitine synthesis due to hepatic dysfunction; increased, massive urinary loss of carnitine.