Hyponatremia and Liver Transplantation: A Narrative Review.

Hyponatremia is a common electrolyte disorder in patients with end-stage liver disease (ESLD) and is associated with increased mortality on the liver transplantation (LT) waiting list. The impact of hyponatremia on outcomes after LT is unclear. Ninety-day and one-year mortality may be increased, but the data are conflicting. Hyponatremic patients have an increased rate of complications and longer hospital stays after transplant. Although rare, osmotic demyelination syndrome (ODS) is a feared complication after LT in the hyponatremic patient. The condition may occur when the serum sodium (sNa) concentration increases excessively during or after LT. This increase in sNa concentration correlates with the degree of preoperative hyponatremia, the amount of intraoperative blood loss, and the volume of intravenous fluid administration. The risk of developing ODS after LT can be mitigated by avoiding large perioperative increases in sNa concentration . This can be achieved through measures such as carefully increasing the sNa pretransplant, and by limiting the intravenous intra- and postoperative amounts of sodium infused. SNa concentrations should be monitored regularly throughout the entire perioperative period.

Nociceptin is present in synovial fluid of patients undergoing total knee arthroplasty.

BACKGROUND: Osteoarthritis is a mechanical abnormality characterized by chronic joint pain associated with degeneration of the articular cartilage, synovitis, and local inflammation, leading to loss of function and pain. A connection exists between the peripheral nervous system and inflammatory joint degeneration. The process by which inflammation is influenced by the nervous system is known as neuroinflammation. One of the neuropeptides involved in peripheral neuroinflammation is nociceptin, a peptide related to the opioid class of substances. Nociceptin has both pro- and anti-inflammatory effects. Some studies show that nociceptin can be measured in synovial fluid, while other studies have not been able to detect it. The presence of nociceptin in synovial fluid could imply a molecular role for the neuropeptide in the joint, both physiologically as well as pathophysiologically. The goal of this pilot study was to determine whether nociceptin was present in the synovial fluid of osteoarthritic knees. METHODS: Patients undergoing primary total knee arthroplasty were enrolled after Institutional Review Board approval was obtained. Synovial fluid was aspirated from patients' operative knee joints and blood samples were obtained. A commercially available enzyme Immunoassay kit was used to test for nociceptin. A linear mixed-effects model was developed to account for the repeated measurements and baseline covariates. Least squares (adjusted) means were derived from the model to compare the sample types and to compare subgroups. RESULTS: Twenty patients were included in this study. Nociceptin was detected in the synovial fluid and plasma of all patients. The mean concentration (± standard deviation) of nociceptin in synovial fluid was 28.7 ± 18.2 pg/ml. The mean concentration of nociceptin in plasma was 45.2 ± 24.3 pg/ml pre-procedure, and 40.1 ± 20.6 pg/ml post-tourniquet deflation. The nociceptin concentration in synovial fluid was significantly lower than the nociceptin concentration in plasma, both pre-procedure and post-tourniquet deflation (p = 0.002 and p = 0.016 respectively). The nociceptin concentration in both plasma and synovial fluid was significantly lower in females versus males (p = 0.012). CONCLUSION: We demonstrated that nociceptin is present in synovial fluid and plasma of patients undergoing total knee arthroplasty. This implies a potential role for nociceptin in modulating inflammation in osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02528916 . Retrospectively registered on August 19, 2015.

Osmotic demyelination syndrome: are patients with end-stage liver disease a special risk group?

The osmotic demyelination syndrome (ODS) is a serious neurological complication associated with the rapid correction of chronic hyponatremia and is associated with high morbidity and mortality. The incidence of ODS after liver transplantation (LT) is 0.8% to 1.4% and is higher than in the general population. Patients with end stage liver disease (ESLD) are very susceptible to ODS primarily because chronic hyponatremia is the most common electrolyte disorder in these patients. Impaired liver function also leads to disruption of astrocyte metabolism resulting in abnormalities of blood-brain barrier function and a decreased ability to generate new intracellular osmotically active compounds (osmolytes) in response to osmotic changes. LT is the only definitive treatment for hyponatremia in ESLD. Massive fluid shifts that occur intraoperatively can change serum sodium concentration (sNa) significantly. The severity of preoperative chronic hyponatremia is an important risk factor for ODS after LT. ODS after LT is most likely due to unintentional sodium administration intraoperatively. Measures to prevent ODS should cover the entire perioperative period. Chronic symptomatic hyponatremia should be carefully treated if LT is imminent. An intraoperative management strategy to minimize increases in sNa is vital and includes limiting fresh frozen plasma and cryoprecipitate administration by using concentrated clotting factors, administering hypotonic intravenous fluids and sodium-free buffering solutions, as well as using low-sodium continuous renal replacement therapy. sNa levels and urine output should be monitored frequently intraoperatively as well as postoperatively. Neurological symptoms are common after LT, and a high index of suspicion must be maintained to diagnose ODS.

Hypercoagulability in End-stage Liver Disease: Review of Epidemiology, Etiology, and Management.

In this review, we analyze the epidemiology of thromboses related to end-stage liver disease (ESLD), discuss causes of hypercoagulability, describe susceptible populations, and critically evaluate proposed prophylaxis and treatment of thromboses. Classically, ESLD has been regarded as a model for coagulopathy, and patients were deemed to be at high risk for bleeding complications. Patients with ESLD are not auto-anticoagulated, and they do not have a lower risk of portal vein thrombosis, intracardiac thrombus formation, pulmonary embolism or hepatic artery thrombosis. Though the cause of hypercoagulability is multifactorial, endothelial dysfunction likely plays a central role for all patients with ESLD. Some subpopulations, such as patients with nonalcoholic steatohepatitis and autoimmune conditions, are at increased risk of thrombotic events as are patients of Hispanic ethnicity. The science behind prophylaxis of different types of clotting and treatment of thromboses is developing rapidly. A number of medications, including low molecular weight heparin, unfractionated heparin, aspirin, vitamin K antagonists, and direct oral anticoagulants can be used, but clear guidelines are lacking. Acute intraoperative clotting can be associated with high mortality. Routine use of transesophageal echocardiography can be helpful in early recognition and treatment of intraoperative thrombosis. Heparin should be reserved for cases of intracardiac thrombus/pulmonary embolism without hemodynamic instability. In unstable patients, low dose of recombinant tissue plasminogen activator can be used. In this new era of heightened awareness of thrombotic events in ESLD patients, prospective randomized trials are urgently needed to best guide clinical practice.