EASL Clinical Practice Guidelines: Liver transplantation

Surgical intensive care unit (ICU) stay of greater than ten days is often described by the experienced intensivist as a ‘complicated clinical course’, and is frequently attributed to persistent immune dysfunction. ‘Systemic inflammatory response syndrome’ (SIRS) followed by ‘compensatory anti-inflammatory response syndrome’ (CARS) is a conceptual framework to explain the immunological trajectory that ICU patients with severe sepsis, trauma or emergency surgery for abdominal infection often traverse, but the causes, mechanisms and reasons for persistent immune dysfunction remain unexplained. Often involving multiple organ failure (MOF) and death, improvements in surgical intensive care have altered its incidence, phenotype and frequency, and have increased the number of patients who survive initial sepsis or surgical events and progress to a persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Often observed, but rarely reversible, these patients may survive to transfer to a long-term care facility only to return to the ICU, but rarely to self sufficiency. We propose that PICS is the dominant pathophysiology and phenotype that has replaced late MOF, and prolongs surgical ICU stay, usually with poor outcome. This review details the evolving epidemiology of MOF, the clinical presentation of PICS, and our understanding of how persistent inflammation and immunosuppression defines the pathobiology of prolonged intensive care. Therapy for PICS will require efficacy for multiple immune system defects and protein catabolism, and will involve innovative interventions for immune system rebalance and nutritional support to regain physical function and well being.

/pdf/persistent-inflammation-and-immunosuppression-a-common-2cc1rbt3l6.pdf

Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care.

▪ Abstract The potent immunosuppressive drugs FK506 and rapamycin interfere with signal transduction pathways required for T cell activation and growth. The distinct inhibitory effects of these drugs on the T cell activation program are mediated through the formation of pharmacologically active complexes with members of a family of intracellular receptors termed the FK506 binding proteins (FKBPs). The FKBP12 · FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. The FKBP12 · rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin (mTOR). Accumulating data suggest that mTOR functions in a previously unrecognized signal transduction pathway required for the progression of IL-2-stimulated T cells from G1 into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular em...

Immunopharmacology of rapamycin.

Rationale: Sustained sepsis-associated immunosuppression is associated with uncontrolled infection, multiple organ dysfunction, and death.Objectives: In the first controlled biomarker-guided immuno...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200903-0363OC

Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial.

Patients with acute on chronic liver failure display 'sepsis-like' immune paralysis

SLT presents an interesting concept to alleviate the organ shortage for children with end-stage liver disease. The procedure has, however, not gained wide acceptance. This is not only related to the complexity of the procedure, but also to the poorer results and the complications reported on the right side graft. We report on a first case in which we applied a new concept for splitting. The liver was split in situ in the heart-beating cadaveric donor with the aim of reducing the problems with the right side graft. This procedure makes splitting of the liver possible without submitting the recipient of the right side to increased risk. Therefore, in situ splitting of the liver has the potential of making splitting of liver grafts the rule rather than the exception, thus increasing the organ pool for small children presently carrying a high risk of dying on the waiting list.

In situ splitting of the liver in the heart-beating cadaveric organ donor for transplantation in two recipients.

Living related liver transplantation offers several advantages in comparison to transplantation of cadaver organs. To achieve maximal donor safety evaluation, selection criteria and complications of the donor operation were retrospectively analyzed in living donors of segmental liver transplants. Seventy-three liver donor candidates were evaluated between October 1991 and June 1994. The median age of 42 mothers and 31 fathers was 31 years (range, 19-50 years). The median volume of the left lateral liver lobe comprised 230 ml (100-350 ml). Twenty-four of 73 (33%) donor candidates were not accepted for living donation. Rejection was due to unsuitability of the donor's liver as a graft (n = 13) or due to an increased risk for living donation (n = 11). Of 35 living donations performed so far, one was a full left hemihepatectomy and 34 were left lateral segmentectomies. The length of the donor operation was, on average, 4.3 hr. No heterologous blood was needed. Postoperative complications included death due to pulmonary embolism (n = 1), seizure due to a previously undiagnosed ependymoma (n = 1), bile duct injury (n = 1), incisional hernia necessitating late revision (n = 2), and duodenal ulcer (n = 2). Long-term follow-up revealed no persistent complications. Using our standardized protocol, 33% of young, presumably healthy donor candidates were rejected for living donation.

Selection of the living liver donor.

As organ donation rates decreased in Europe, the authors started a systematic approach of liver splitting in their center in 1994. During this 1-year experience, 73 cadaveric liver transplantations were performed in 66 patients. Sixteen of these transplantations were the result of split-liver transplantation (21.9% of grafts, 24.2% of patients). Patient and graft survival rates at 3 months were 81.2% and 75%, compared with 89.1% and 76.9% for whole organs. Two modified techniques were developed, based on the technique of living related liver procurement, and applied in 10 cases. With these new techniques, patient and graft survival rates were 90% and 90%. This systematic approach allowed the total number of transplantations in our program to be maintained, despite the decrease in organ availability.

One year of experience with extended application and modified techniques of split liver transplantation.

The laryngeal mask airway: Anesthetic gas leakage and fiberoptic control of positioning

Percutaneous dilatational tracheostomy : risks and benefits

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