Effect of pharmacological preconditioning with sevoflurane during hepatectomy with intermittent portal triad clamping.

BACKGROUND: During hepatectomy, intermittent portal triad clamping (IPC) reduces ischemia-reperfusion injuries. Pharmacological preconditioning with sevoflurane revealed similar properties. The aim of the study was to evaluate the combination of a sevoflurane preconditioning regimen with IPC on ischemia-reperfusion injuries. METHODS: Three regimens of anesthesia were applied: group SEV with continuous application of sevoflurane, group PRO with continuous propofol infusion and group PC where continuous propofol was substituted by sevoflurane (adjusted to reach MAC∗1.5) for 15 min before IPC. Endpoints were the values of AST and ALT, factor V, prothrombin time, bilirubinemia over the 5-postoperative days (POD), morbidity and mortality at POD30 and POD90. RESULTS: The ALT values at POD5 were lower in the PC group (n = 27) 74 (48 -98) IU/L compared to PRO (n = 26) and SEV (n = 67) respectively 110 (75 -152) and 100 (64 -168) IU/L (p = 0.038). The variation of factor V compared to preoperative values was less important in the PC and SEV groups respectively -14% and -16% vs -30% (PRO) (p = 0.047). CONCLUSION: Our study suggests that sevoflurane attenuates ischemia-reperfusion injuries on liver function, compared to propofol, without benefit for a specific regimen of pharmacological preconditioning when IPC is applied.

Arterial Lactate Concentration at the End of an Elective Hepatectomy Is an Early Predictor of the Postoperative Course and a Potential Surrogate of Intraoperative Events.

OBJECTIVES: To test the prognostic impact of arterial lactate concentration at the end-of-surgery (LCT-EOS) on postoperative outcome after elective liver-resections and to identify the predictors of an increase in LCT-EOS. BACKGROUND DATA: A recent systematic-review of risk-prediction-models for liver resections has evidenced their poor accuracy and a deficit in the evaluation of intraoperative events. LCT-EOS is a marker of impaired tissue oxygenation. METHODS: This prospectively-designed study was based on a training-cohort of 519 patients and a validation-cohort of 466 patients. For each of the endpoints (high comprehensive complication index (CCI) scores, 90-day-mortality and severe-morbidity), prognostic-models were built by logistic-regression using the training-cohort. These models were thereafter tested in the validation-cohort and their performance (discrimination, accuracy, calibration) assessed. Independent predictors of LCT-EOS were also identified. RESULTS: In the training-cohort, LCT-EOS cutoff best discriminating high-CCI, 90-day-mortality and severe-morbidity were 3, 3 and 2.8 mmol/L (and the corresponding AUROC 0.86, 0.87 and 0.76). LCT-EOS was an independent predictor of endpoints and adding LCT-EOS to the other predictors increased by 16.4%, 34.5% and 17.7% the accuracy of the models for high-CCI, 90-day-mortality and severe-morbidity, respectively. The models had high calibration and accuracy. Diabetes, repeat-hepatectomy, major-hepatectomy, synchronous-major-procedure, inflow-occlusion and blood-transfusion were independent predictors of LCT-EOS >3 mmol/L. CONCLUSIONS: LCT-EOS >3 mmol/L is an early predictor of postoperative-outcome and should be used as a tool to determine patients requiring critical-care and as an endpoint in studies measuring the impact of perioperative interventions.

Central venous-to-arterial carbon dioxide difference as a prognostic tool in high-risk surgical patients.

INTRODUCTION: The purpose of this study was to evaluate the clinical relevance of high values of central venous-to-arterial carbon dioxide difference (PCO2 gap) in high-risk surgical patients admitted to a postoperative ICU. We hypothesized that PCO2 gap could serve as a useful tool to identify patients still requiring hemodynamic optimization at ICU admission. METHODS: One hundred and fifteen patients were included in this prospective single-center observational study during a 1-year period. High-risk surgical inclusion criteria were adapted from Schoemaker and colleagues. Demographic and biological data, PCO2 gap, central venous oxygen saturation, lactate level and postoperative complications were recorded for all patients at ICU admission, and 6 hours and 12 hours after admission. RESULTS: A total of 78 (68%) patients developed postoperative complications, of whom 54 (47%) developed organ failure. From admission to 12 hours after admission, there was a significant difference in mean PCO2 gap (8.7 ± 2.8 mmHg versus 5.1 ± 2.6 mmHg; P = 0.001) and median lactate values (1.54 (1.1-3.2) mmol/l versus 1.06 (0.8-1.8) mmol/l; P = 0.003) between patients who developed postoperative complications and those who did not. These differences were maximal at admission to the ICU. At ICU admission, the area under the receiver operating characteristic curve for occurrence of postoperative complications was 0.86 for the PCO2 gap compared to Sequential Organ Failure Assessment score (0.82), Simplified Acute Physiology Score II score (0.67), and lactate level (0.67). The threshold value for PCO2 gap was 5.8 mmHg. Multivariate analysis showed that only a high PCO2 gap and a high Sequential Organ Failure Assessment score were independently associated with the occurrence of postoperative complications. A high PCO2 gap (≥6 mmHg) was associated with more organ failure, an increase in duration of mechanical ventilation and length of hospital stay. CONCLUSION: A high PCO2 gap at admission in the postoperative ICU was significantly associated with increased postoperative complications in high-risk surgical patients. If the increase in PCO2 gap is secondary to tissue hypoperfusion then the PCO2 gap might be a useful tool complementary to central venous oxygen saturation as a therapeutic target.

Detection and follow-up, after partial liver resection, of the urinary paracetamol metabolites by proton NMR spectroscopy.

BACKGROUND: Combination drug therapy is often used to achieve optimal analgesia in surgery. Paracetamol can be used as one component of an analgesic regime following hepatic resection. OBJECTIVE: This study was designed to investigate paracetamol and its metabolites by proton NMR spectroscopy in patient urine and to assess whether N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite) formation is increased after liver resection. METHOD: We studied the excretion of acetaminophen and its metabolites by 5 patients who were operated on for partial liver resection by proton NMR spectroscopy. As an intravenous infusion 1 g of paracetamol was given over 15 min every 6 h during 48 h. The first injection was given in the operating theatre after liver resection was completed. Urine samples were collected before injection (T1) and 24 and 48 h after the first injection (T2 and T3); the samples were frozen and kept at -20°C up to the analysis by NMR spectroscopy. RESULTS: Metabolites of the paracetamol were detected for all patients. Among the discerned metabolites, 4 were identified as metabolites of paracetamol: paracetamol glucuronide, paracetamol sulfate, N-acetyl-L-cysteinyl paracetamol (metabolite of NAPQI) and paracetamol. Their ratios, respectively, were: 46-82.9, 12.6-30.0, 0.5-5.5 and 1.43-3.54%. CONCLUSION: This study showed that there was no increase in the formation of toxic metabolite (NAPQI) after treatment with paracetamol in these few cases of liver resections. A larger study is necessary to confirm these results.