Restrictive versus Decision Support Guided Fluid Therapy During Major Hepatic Resection Surgery: A Randomized Controlled Trial.

BACKGROUND: Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure (CVP), retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen™ Assisted Fluid Management system uses novel decision support software whose algorithm helps clinicians optimize fluid therapy. We tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy. METHODS: This two-arm, prospective, randomized controlled, assessor-and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1-2 ml.kg-1.h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure >65mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure). RESULTS: Ninety patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median[Q1-Q3] 2.5[1.9-3.7]mmol.L-1 vs 4.6[3.1-5.4]mmol.L-1, median difference -2.1, 95%CI(-2.7,-1.2), p<0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median[Q1-Q3] 450[300-600]ml vs 500[300-800]ml, p=0.727) although CVP was higher in the decision support group (mean (SD) of 7.7(2.0)mmHg vs 6.6(1.1)mmHg, p<0.002). CONCLUSION: Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.

Arterial Lactate Concentration at the End of Liver Transplantation is Independently Associated With One-Year Mortality.

BACKGROUND: Liver transplant patients who develop hyperlactatemia are at increased risk of postoperative morbidity and short-term mortality, but there are few data on longer-term outcomes. We therefore investigated if arterial lactate concentration obtained immediately after surgery, at the time of admission to the intensive care unit (ICU), was associated with 1-year mortality. METHODS: In this retrospective cohort study, all patients who underwent liver transplant surgery from a deceased donor between September 2013 and December 2019 were screened for inclusion. Patients who underwent combined transplantation surgery and those with a history of previous liver transplantation (ie, redo surgery) were not included. Logistic regression modeling included univariate and multivariate analyses. Receiver operating characteristic curves and areas under the curves were calculated. Lactate thresholds and association with outcome were analyzed for specificity, sensitivity, and Youden's index. RESULTS: Of 226 patients included, 18.4% died within 1 year of liver transplantation. Immediate postoperative lactate concentration was independently associated with 1-year mortality with an adjusted odds ratio of 1.35 (95% CI 1.16-1.59; P < .001) per mmol/L increase in lactate and an area under the curve of 0.80 (95% CI 0.72-0.87; P < .001). A lactate concentration of 2.25 mmol/L (cutoff determined using Youden's index) was associated with increased 1-year mortality with a sensitivity of 0.71 and a specificity of 0.72. CONCLUSIONS: Increased arterial lactate concentration on admission to the intensive care unit immediately after orthotopic liver transplantation is independently associated with increased 1-year mortality.

Intraoperative measurement of the respiratory exchange ratio predicts postoperative complications after liver transplantation.

BACKGROUND: During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), to predict postoperative complications. METHODS: This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis. RESULTS: Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25-75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96-1.12] vs 0.88[0.84-0.94]; p < 0.001). The area under the ROC curve was 0.87 (95%CI: 0.80-0.93; p < 0.001) with a RER value (Youden index) of 0.92 giving a sensitivity of 91% and a specificity of 74% for predicting the occurrence of postoperative complications. The RER outperformed all other measured variables assessing the DO2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) in predicting postoperative complications. CONCLUSION: During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications.

Incidental finding of elevated pulmonary arterial pressures during liver transplantation and postoperative pulmonary complications.

BACKGROUND: In patients with end stage liver disease (ESLD) scheduled for liver transplantation (LT), an intraoperative incidental finding of elevated mean pulmonary arterial pressure (mPAP) may be observed. Its association with patient outcome has not been evaluated. We aimed to estimate the effects of an incidental finding of a mPAP > 20 mmHg during LT on the incidence of pulmonary complications. METHODS: We examined all patients who underwent a LT at Paul-Brousse hospital between January 1,2015 and December 31,2020. Those who received: a LT due to acute liver failure, a combined transplantation, or a retransplantation were excluded, as well as patients for whom known porto-pulmonary hypertension was treated before the LT or patients who underwent a LT for other etiologies than ESLD. Using right sided pulmonary artery catheterization measurements made following anesthesia induction, the study cohort was divided into two groups using a mPAP cutoff of 20 mmHg. The primary outcome was a composite of pulmonary complications. Univariate and multivariable logistic regression analyses were performed to identify variables associated with the primary outcome. Sensitivity analyses of multivariable models were also conducted with other mPAP cutoffs (mPAP ≥ 25 mmHg and ≥ 35 mmHg) and even with mPAP as a continuous variable. RESULTS: Of 942 patients who underwent a LT, 659 met our inclusion criteria. Among them, 446 patients (67.7%) presented with an elevated mPAP (mPAP of 26.4 ± 5.9 mmHg). When adjusted for confounding factors, an elevated mPAP was not associated with a higher risk of pulmonary complications (adjusted OR: 1.16; 95%CI 0.8-1.7), nor with 90 days-mortality or any other complications. In our sensitivity analyses, we observed a lower prevalence of elevated mPAP when increasing thresholds (235 patients (35.7%) had an elevated mPAP when defined as ≥ 25 mmHg and 41 patients (6.2%) had an elevated mPAP when defined as ≥ 35 mmHg). We did not observe consistent association between a mPAP ≥ 25 mmHg or a mPAP ≥ 35 mmHg and our outcomes. CONCLUSION: Incidental finding of elevated mPAP was highly prevalent during LT, but it was not associated with a higher risk of postoperative complications.

Assessing the discriminative ability of the respiratory exchange ratio to detect hyperlactatemia during intermediate-to-high risk abdominal surgery.

BACKGROUND: A mismatch between oxygen delivery (DO2) and consumption (VO2) is associated with increased perioperative morbidity and mortality. Hyperlactatemia is often used as an early screening tool, but this non-continuous measurement requires intermittent arterial line sampling. Having a non-invasive tool to rapidly detect inadequate DO2 is of great clinical relevance. The respiratory exchange ratio (RER) can be easily measured in all intubated patients and has been shown to predict postoperative complications. We therefore aimed to assess the discriminative ability of the RER to detect an inadequate DO2 as reflected by hyperlactatemia in patients having intermediate-to-high risk abdominal surgery. METHODS: This historical cohort study included all consecutive patients who underwent intermediate-to-high risk surgery from January 1st, 2014, to April 30th, 2019 except those who did not have RER and/or arterial lactate measured. Blood lactate levels were measured routinely at the beginning and end of surgery and RER was calculated at the same moment as the blood gas sampling. The present study tested the hypothesis that RER measured at the end of surgery could detect hyperlactatemia at that time. A receiver operating characteristic (ROC) curve was constructed to assess if RER calculated at the end of the surgery could detect hyperlactatemia. The chosen RER threshold corresponded to the highest value of the sum of the specificity and the sensitivity (Youden Index). RESULTS: Among the 996 patients available in our study cohort, 941 were included and analyzed. The area under the ROC curve was 0.73 (95% CI: 0.70 to 0.76; p < 0.001), with a RER threshold of 0.75, allowing to discriminate a lactate > 1.5 mmol/L with a sensitivity of 87.5% and a specificity of 49.5%. CONCLUSION: In mechanically ventilated patients undergoing intermediate to high-risk abdominal surgery, the RER had moderate discriminative abilities to detect hyperlactatemia. Increased values should prompt clinicians to investigate for the presence of hyperlactatemia and treat any potential causes of DO2/VO2 mismatch as suggested by the subsequent presence of hyperlactatemia.

Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases.

BACKGROUND: To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs). METHODS: A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and >10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching. RESULTS: Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty. CONCLUSION: LMCRC in difficult location independently predicts surgical difficulty and severe POCs.

Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury.

BACKGROUND: The potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the "Kidney Disease: Improving Global Outcomes" (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI. METHODS: All consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a "modified" (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5-1.9 times baseline) or moderate-to-severe (stage 2-3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI. RESULTS: Among the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7-5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8-11.4]; p = 0.002). CONCLUSIONS: Mild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.

Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction.

BACKGROUND: Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient. OBJECTIVE: We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)]. METHODS: We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296). RESULTS: There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR-)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort. CONCLUSION: As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.

Management of the Open Abdomen after Liver Transplantation.

INTRODUCTION: The optimal management of the open abdomen (OA) after liver transplantation (LT) is unclear. The negative pressure wound therapy (NPWT) has been shown to be safe and can increase the chance for early fascial closure in trauma or septic patients. However, little data are available on the specific setting of LT. We aimed to report our experience of OA after LT, marked by the recent use of NPWT. METHODS: All patients with postponed wall closure after LT, from 2002 to 2014, in a single institution were included and retrospectively analyzed. Our management of OA after LT has shifted from skin-only closure (SOC) followed by abdominal wall reconstruction at a distance to the use of NPWT with early fascial closure. RESULTS: Of the 1559 LTs performed during the study period, immediate abdominal wall closure at the end of transplantation could not be achieved in 46 (2.9%) patients. Of them, SOC was performed in 22 (47.8%) patients, whereas vacuum-assisted closure (VAC) therapy was used in 24 (52.1%) patients. The comprehensive complication indexes (CCI) were similar [CCI: 66 (0-100) in the SOC group vs. 56 (0-100) in the VAC group; p = 0.55]. No evisceration or fistula occurred in both groups. One (4.2%) postoperative bleeding case was reported in the VAC group. Early fascial closure was achieved within a median of 5.5 days (1-12) for the 24 patients (100%) of the VAC group. In four of them, a biological mesh was necessary. Only nine patients (52.9%) of the survivors in the SOC group underwent abdominal reconstruction. CONCLUSION: The NPWT in patients with OA after LT enables early fascial closure with limited morbidity provided a specific attention is given to the risk of bleeding. These results support the use of NPWT as the first option in OA patients after LT.

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.

In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection.

SUMMARY BACKGROUND DATA: We compare the results of liver resection performed under in situ hypothermic perfusion versus standard total vascular exclusion (TVE) of the liver <60 minutes and > or =60 minutes in terms of liver tolerance, liver and renal functions, postoperative morbidity, and mortality. The safe duration of TVE is still debated. Promising results have been reported following TVE associated with hypothermic perfusion of the liver with durations of up to several hours. The 2 techniques have not been compared so far. METHODS: The study population includes 69 consecutive liver resections under TVE <60 minutes (group TVE<60', 33 patients), > or =60 minutes (group TVE> or =60', 16 patients), and in situ hypothermic perfusion (group TVEHYOPOTH, 20 patients). Liver tolerance (peaks of transaminases), liver and kidney function (peak of bilirubin, minimum prothrombin time, and peak of creatinine), morbidity, and in-hospital mortality were compared within the 3 groups. RESULTS: The postoperative peaks of aspartate aminotransferase (IU/L) and alanine aminotransferase (IU/L) were significantly lower (P[r] < 0.05) in group TVE HYPOTH (450 +/- 298 IU/L and 390 +/- 391 IU/L) compared with the groups TVE<60' (1000 +/- 808; 853 +/- 743) and TVE> or =60' (1519 +/- 962; 1033 +/- 861). In the group TVEHYPOTH, the peaks of bilirubin (micromol/L) (84 +/- 31), creatinine (micromol/L) (75 +/- 22), and the number of complications per patient (1.2 +/- 0.9) were comparable to those of the group TVE<60' (80 +/- 111; 109 +/- 77; and 0.8 +/- 1.1 respectively) and significantly lower to those of the group TVE> or =60' (196 +/- 173; 176 +/- 176, and 2.6 +/- 1.8). In-hospital mortality rates were 1 in 33, 2 in 16, and 0 in 20 for the groups TVE<60', TVE> or =60', and TVEHYOPOTH, respectively, and were comparable. On multivariate analysis, the size of the tumor, portal vein embolization, and a planned vascular reconstruction were significantly predictive of TVE > or =60 minutes. CONCLUSIONS: Compared with standard TVE of any duration, hypothermic perfusion of the liver is associated with a better tolerance to ischemia. In addition, compared with TVE > or =60 minutes, it is associated with better postoperative liver and renal functions and a lower morbidity. Predictive factors for TVE > or =60 minutes may help to indicate hypothermic perfusion of the liver.