Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review.

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial.

OBJECTIVES: Few studies have investigated the Multiplate platelet function analyzer in pediatrics. The authors evaluated Multiplate combined with Rotem in terms of guiding platelet transfusion after pediatric cardiac surgery with cardiopulmonary bypass (CPB). The authors further compared coagulation parameters between cyanotic and acyanotic patients. DESIGN: Subgroup analysis of a randomized clinical trial. SETTING: Tertiary hospital. PARTICIPANTS: Patients weighing between seven and 15 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rotem and Multiplate tests were performed (1) after anesthesia induction, (2) upon CPB separation, and (3) upon intensive care unit arrival. Among a total of 59 subjects, 9 patients required platelet transfusion. In multivariate linear regression, analysis EXTEM maximum clot firmness upon CPB separation was associated with the volume of transfused platelets (regression coefficient = -0.348 [95% confidence interval -1.006 to -0.028]; p = 0.039). No such association was found for the Multiplate test. Acyanotic and cyanotic heart disease were present in 32 and 27 children, respectively. There were no significant differences between these two groups in terms of platelet count and function. Postoperative blood loss was significantly higher in the cyanotic group compared with the acyanotic arm (p = 0.015; difference [95% confidence interval -2.40 {-4.20 to -0.60}]). There were no differences between groups regarding transfusion of allogeneic blood products. CONCLUSIONS: This study showed that Rotem, but not Multiplate results, were associated with platelet transfusion in pediatric cardiac surgery with no intake of platelet inhibitors. The usefulness of combining these tests in platelet transfusion decision-making needs to be evaluated in larger populations.

Fresh Frozen Plasma versus Crystalloid Priming of Cardiopulmonary Bypass Circuit in Pediatric Surgery: A Randomized Clinical Trial.

BACKGROUND: In congenital cardiac surgery, priming cardiopulmonary bypass (CPB) with fresh frozen plasma (FFP) is performed to prevent coagulation abnormalities. The hypothesis was that CPB priming with crystalloids would be different compared with FFP in terms of bleeding and/or need for blood product transfusion. METHODS: In this parallel-arm double-blinded study, patients weighing between 7 and 15 kg were randomly assigned to a CPB priming with 15 ml · kg PlasmaLyte or 15 ml · kg FFP in addition to a predefined amount of packed red blood cells used in all patients. The decision to transfuse was clinical and guided by point-of-care tests. The primary endpoints included postoperative bleeding tracked by chest tubes, number of patients transfused with any additional blood products, and the total number of additional blood products administered intra- and postoperatively. The postoperative period included the first 6 h after intensive care unit arrival. RESULTS: Respectively, 30 and 29 patients in the FFP and in the crystalloid group were analyzed in an intention-to-treat basis. Median postoperative blood loss was 7.1 ml · kg (5.1, 9.4) in the FFP group and 5.7 ml · kg (3.8, 8.5) in the crystalloid group (P = 0.219); difference (95% CI): 1.2 (-0.7 to 3.2). The proportion of patients additionally transfused was 26.7% (8 of 30) and 37.9% (11 of 29) in the FFP and the crystalloid groups, respectively (P = 0.355; odds ratio [95% CI], 1.7 [0.6 to 5.1]). The median number of any blood products transfused in addition to priming was 0 (0, 1) and 0 (0, 2) in the FFP and crystalloid groups, respectively (P = 0.254; difference [95% CI], 0 [0 to 0]). There were no study-related adverse events. CONCLUSIONS: The results demonstrate that in infants and children, priming CPB with crystalloids does not result in a different risk of postoperative bleeding and need for transfusion of allogeneic blood products.

Sevoflurane preconditioning in living liver donation is associated with better initial graft function after pediatric transplantation: a retrospective study.

INTRODUCTION: Initial allograft function determines the patient's immediate prognosis in pediatric liver transplantation. Ischemia-reperfusion injuries play a role in initial poor graft function (IPGF). In animal studies, preconditioning with inhaled anesthetic agents has demonstrated a protective effect on the liver. In humans, the few available studies are conflicting. This study assesses the association between the hypnotic agent used to maintain anesthesia during hepatectomy in living donors and the occurrence of IPGF after pediatric transplantation. METHODS: We conducted a single-center retrospective analysis of children who received a living donor liver transplant (LDLT) between 2010 and 2019. We analyzed the incidence of EAD according to the hypnotic agent used to maintain general anesthesia during donor hepatectomy. RESULTS: We included 183 pairs of patients (living donors-recipients). The anesthetics used in the donor were propofol (n = 85), sevoflurane (n = 69), or propofol with sevoflurane started 30 min before clamping (n = 29). Forty-two children (23%) developed IPGF. After multivariate logistic regression analysis, factors significantly associated with the occurrence of IPGF were the anesthesia maintenance agent used in the donor (p = 0.004), age of the donor (p = 0.03), duration of transplant surgery (p = 0.009), preoperative receiver neutrophil to lymphocyte ratio (p = 0.02), and albumin (p = 0.05). CONCLUSION: Significantly fewer children who received a graft from a donor in whom only sevoflurane was used to maintain anesthesia developed IPGF. Although additional research is needed, this preconditioning strategy may provide an option to prevent IPGF after living liver donation.

Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery.

INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

Improving Safety in Living Liver Donation: Lessons From Intraoperative Adverse Events in 438 Donors Undergoing a Left Liver Resection.

Background: Donor safety is paramount in living organ donation. Left liver resections are considered safer than right lobe hepatectomies. However, unexpected intraoperative adverse events (iAEs), defined as any deviation from the ideal intraoperative course, can also occur during left liver resections and may be life threatening or lead to postoperative complication or permanent harm to the donor and recipient. Methods: Records of 438 liver living donors (LDs) who underwent 393 left lateral sectionectomies (LLSs) and 45 left hepatectomies (LHs) between July 1993 and December 2018 in a pediatric living-donor liver transplantation center were reviewed for the appearance of iAEs that could have influenced the donor morbidity and mortality and that could have contributed to the improvement of the LD surgical protocol. Results: Clinical characteristics of LLS and LH groups were comparable. Nine iAEs were identified, an incidence of 2%, all of them occurring in the LLS group. Seven of them were related to a surgical maneuver (5 associated with vascular management and 2 with the biliary tree approach). One iAE was associated with an incomplete donor workup and the last with drug administration. Each iAE resulted in subsequent changes in the surgical protocol. Donor outcome was at risk by 5 iAEs classed as type a, recipient outcome by 2 iAEs (type b) and both by 2 iAEs (type c). Postoperative complications occurred in 87 LDs (19.9%), with no differences between the LLS and LH groups (P = 0.227). No Clavien-Dindo class IVa or b complications or donor mortality (Clavien-Dindo class V) were observed. Conclusions: iAEs debriefings induced changes in our LD protocol and may have contributed to reduced morbidity and zero mortality. iAEs analysis can be used as a quality and safety improvement tool in the context of LD procedures, which may include right liver donation, laparoscopic, and robotic living liver graft procurement.

Pain management after open liver resection: Procedure-Specific Postoperative Pain Management (PROSPECT) recommendations.

BACKGROUND AND OBJECTIVES: Effective pain control improves postoperative rehabilitation and enhances recovery. The aim of this review was to evaluate the available evidence and to develop recommendations for optimal pain management after open liver resection using Procedure-Specific Postoperative Pain Management (PROSPECT) methodology. STRATEGY AND SELECTION CRITERIA: Randomized controlled trials (RCTs) published in the English language from January 2010 to October 2019 assessing pain after liver resection using analgesic, anesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane databases. RESULTS: Of 121 eligible studies identified, 31 RCTs and 3 systematic reviews met the inclusion criteria. Preoperative and intraoperative interventions that improved postoperative pain relief were non-steroidal anti-inflammatory drugs, continuous thoracic epidural analgesia, and subcostal transversus abdominis plane (TAP) blocks. Limited procedure-specific evidence was found for intravenous dexmedetomidine, intravenous magnesium, intrathecal morphine, quadratus lumborum blocks, paravertebral nerve blocks, continuous local anesthetic wound infiltration and postoperative interpleural local anesthesia. No evidence was found for intravenous lidocaine, ketamine, dexamethasone and gabapentinoids. CONCLUSIONS: Based on the results of this review, we suggest an analgesic strategy for open liver resection, including acetaminophen and non-steroidal anti-inflammatory drugs, combined with thoracic epidural analgesia or bilateral oblique subcostal TAP blocks. Systemic opioids should be considered as rescue analgesics. Further high-quality RCTs are needed to confirm and clarify the efficacy of the recommended analgesic regimen in the context of an enhanced recovery program.

Refractory shock during the anesthetic and surgical management of an intrahepatic tumor arising from the adrenal cortex: A case report.

INTRODUCTION: Adrenocortical carcinoma is a rare type of malignant adrenal tumor with a possibility of delayed metastases. Diagnosis may be delayed with a non-secreting tumor or metastasis, and even in this case, surgical management may be complicate. PRESENTATION OF CASE: A 55-year-old man underwent elective surgery for the resection of a large intra-hepatic mass from an undetermined type according to a recent liver biopsy. He had a previous history of a non-secreting adrenal tumor that was operated ten years before. Pre-operatively, he was poorly symptomatic, with a normal arterial blood pressure. Anesthesia induction was uneventful, but at the time of tumor resection and removal, he developed extreme vasoplegia and shock with anuric renal failure, lactic acidosis, four-limb and abdominal compartment syndrome. The patient died on day 9 from delayed septic complications. According to the pathological findings, the tumor was a non-secreting adrenocortical carcinoma. DISCUSSION: Adrenocortical carcinoma (ACC) is rare condition with diverse clinical manifestations due to excessive hormonal production when the tumor is secreting and mimicking pheochromocytoma. Our patient underwent the resection a large intrahepatic non-secreting metastasis more than ten years after the initial lesion. Peri-operative and post-operative management was complicated by a refractory shock with the characteristics of a secondary systemic capillary leak syndrome. The role of endothelial lesions may be discussed. CONCLUSION: Surgery of metastatic adrenocortical carcinoma may be complicated by severe hemodynamic complications, even in the absence of hormonal secretion.