Thrombocytopenia in Liver Transplant

Thrombocytopenia is a common complication of both chronic liver disease and liver transplantation (LT). The mechanism of thrombocytopenia is multifactorial implicating not only sequestration in the spleen, or in the graft, reduction in the mean platelet survival but also decreased platelet production due to low synthesis of thrombopoietin (TPO) or direct toxicity to the bone marrow. Platelets play a dualistic role in liver transplant, both beneficial and detrimental. The beneficial role of platelets is due to platelet-derived serotonin that is involved in liver regeneration. During surgery for liver transplant, in addition to the preoperative causes for thrombocytopenia, we have other mechanisms that will contribute to further deterioration of the platelets count and function: hemodilution, immunological reactions, and sequestration in the newly transplanted graft. This might result in a life-threatening level of thrombocytes. The concern is when we should treat thrombocytopenia because despite life-saving benefits, transfusion has also been related to complications and platelet transfusion has been identified as an independent risk factor for postoperative complications. Risks related to platelet concentrate administration are allergic reactions, alloimmunization, bacterial sepsis, and transfusion-related acute lung injury (TRALI). Administration of platelets is not indicated if there is no bleeding or immediate bleeding risk. New emerging therapies like thrombopoietin-receptor agonist will furthermore limit the administration of blood products

Anesthesia for Liver Transplantation

Liver transplantation is a high-risk surgery performed on a high-risk patient and is the only treatment for end-stage liver disease. Ever since the first successful liver transplant performed, patient survival increased due to improvement of surgical technique and anaesthetic management as well as the emergence of new generations of immunosuppressants. The pre-anaesthetic evaluation is mandatory and plays an important role in patient inclusion on the transplant list. Liver transplantation is performed under general anaesthesia, and the anaesthetic monitoring is very important for a successful liver transplantation as it can expose problems before irreversible damage occurs. Haemodynamic instability is common during surgery, requiring complex invasive haemodynamic monitoring. Continuous assessment of the patient’s volemic status and the amount of perfused fluids represent the key to a successful liver transplantation. Inadequate fluid therapy can lead to pulmonary oedema, abnormal gas exchange, congestion, decrease in perfusion and oedema of the graft. Liver reperfusion takes place in the neohepatic phase and is the most unstable period during liver transplantation, representing a real challenge for the anaesthetist. It can have severe consequences due to a decrease in cardiovascular function with haemodynamic instability, abnormal acid base balance and metabolic abnormalities

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Perioperative Care in Patients with Chronic Liver Disease: What Can We Do More?

Chronic liver diseases represent a prevalent pathology that exerts considerable pressure on healthcare providers and various healthcare systems worldwide [...

Anaesthesia for Liver Transplantation: An Update

Liver transplantation (LT) is a challenging surgery performed on patients with complex physiology profiles, complicated by multi-system dysfunction. It represents the treatment of choice for end-stage liver disease. The procedure is performed under general anaesthesia, and a successful procedure requires an excellent understanding of the patho-physiology of liver failure and its implications. Despite advances in knowledge and technical skills and innovations in immunosuppression, the anaesthetic management for LT can be complicated and represent a real challenge. Monitoring devices offer crucial information for the successful management of patients. Hemodynamic instability is typical during surgery, requiring sophisticated invasive monitoring. Arterial pulse contour analysis and thermo-dilution techniques (PiCCO), rotational thromboelastometry (RO-TEM), transcranial doppler (TCD), trans-oesophageal echocardiography (TEE) and bispectral index (BIS) have been proven to be reliable monitoring techniques playing a significant role in decision making. Anaesthetic management is specific according to the three critical phases of surgery: pre-anhepatic, anhepatic and neo-hepatic phase. Surgical techniques such as total or partial clamping of the inferior vena cava (IVC), use of venovenous bypass (VVBP) or portocaval shunts have a significant impact on cardiovascular stability. Post reperfusion syndrome (PRS) is a significant event and can lead to arrhythmias and even cardiac arrest

Opioid-Sparing Analgesia Impacts the Perioperative Anesthetic Management in Major Abdominal Surgery

Background and Objectives: The management of acute postoperative pain (APP) following major abdominal surgery implies various analgetic strategies. Opioids lie at the core of every analgesia protocol, despite their side effect profile. To limit patients’ exposure to opioids, considerable effort has been made to define new opioid-sparing anesthesia techniques relying on multimodal analgesia. Our study aims to investigate the role of adjuvant multimodal analgesic agents, such as ketamine, lidocaine, and epidural analgesia in perioperative pain control, the incidence of postoperative cognitive dysfunction (POCD), and the incidence of postoperative nausea and vomiting (PONV) after major abdominal surgery. Materials and Methods: This is a clinical, observational, randomized, monocentric study, in which 80 patients were enrolled and divided into three groups: Standard group, C (n = 32), where patients received perioperative opioids combined with a fixed regimen of metamizole/acetaminophen for pain control; co-analgetic group, Co-A (n = 26), where, in addition to standard therapy, patients received perioperative systemic ketamine and lidocaine; and the epidural group, EA (n = 22), which included patients that received standard perioperative analgetic therapy combined with epidural analgesia. We considered the primary outcome, the postoperative pain intensity, assessed by the visual analogue scale (VAS) at 1 h, 6 h, and 12 h postoperatively. The secondary outcomes were the total intraoperative fentanyl dose, total postoperative morphine dose, maximal intraoperative sevoflurane concentration, confusion assessment method for intensive care units score (CAM-ICU) at 1 h, 6 h, and 12 h postoperatively, and the postoperative dose of ondansetron as a marker for postoperative nausea and vomiting (PONV) severity. Results: We observed a significant decrease in VAS score, as the primary outcome, for both multimodal analgesic regimens, as compared to the control. Moreover, the intraoperative fentanyl and postoperative morphine doses were, consequently, reduced. The maximal sevoflurane concentration and POCD were reduced by EA. No differences were observed between groups concerning PONV severity. Conclusions: Multimodal analgesia concepts should be individualized based on the patient’s needs and consent. Efforts should be made to develop strategies that can aid in the reduction of opioid use in a perioperative setting and improve the standard of care

What Is Different in Acute Hematologic Malignancy-Associated ARDS? An Overview of the Literature

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy

VCAM-1 Targeted Lipopolyplexes as Vehicles for Efficient Delivery of shRNA-Runx2 to Osteoblast-Differentiated Valvular Interstitial Cells; Implications in Calcific Valve Disease Treatment

Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface of oVIC was used as a target, and a peptide with high affinity for VCAM-1 was coupled to the surface of lipopolyplexes encapsulating C60-PEI/shRunx2 (V-LPP/shRunx2). We report here that V-LPP/shRunx2 lipopolyplexes are cyto- and hemo-compatible and specifically taken up by oVIC. These lipopolyplexes are functional as they downregulate the Runx2 gene and protein expression, and their uptake leads to a significant decrease in the expression of osteogenic molecules (OSP, BSP, BMP-2). These results identify V-LPP/shRunx2 as a new, appropriately directed vehicle that could be instrumental in developing novel strategies for blocking the progression of CAVD using a targeted nanomedicine approach

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

Background: General anesthesia (GA) in pediatric patients represents a clinical routine. Factors such as increased birth age and maternal chronic conditions cause more infants to experience hypoxic-ischemic encephalopathy, an additional risk for anesthesia. Aim: This study evaluates the effect of one sevoflurane-induced GA episode on the immature brain previously exposed to perinatal asphyxia (PA). Methods: Postnatal day 6 (PND6) Wistar rats were exposed to a 90-min episode of normoxia/PA and at PND15 to a 120-min episode of normoxia/GA. Four groups were analyzed: Control (C), PA, GA, and PA-GA. Post-exposures, fifteen pups/group were sacrificed and the hippocampi were isolated to assess S-100B and IL-1B protein levels, using ELISA. At maturity, the behavior was assessed by: forced swimming test (FST), and novel object recognition test. Results: Hippocampal S-100B level was increased in PA, GA, and PA-GA groups, while IL-1B was increased in PA, but decreased in PA-GA. The immobility time was increased in PA and PA-GA, in FST. Conclusions: Both PA and GA contribute to glial activation, however with no cumulative effect. Moreover, PA reduces the rats’ mobility, irrespective of GA exposure, while memory evaluated by the novel object recognition test was not influenced