Sugammadex/Neostigmine and Liver Transplantation

Cirrhotic patients undergoing liver transplantation are at very high risk of post operative complication such as post-operative residual curarization. Rocuronium is a neuromuscular blocking agent that nowadays can be safely and rapidly antagonized with sugammadex. No one study compared sugammadex versus neostigmine after rocuronium infusion during liver transplantation.

It is known that major abdominal surgery is associated with increased risk of morbidity and postoperative mortality. The complexity and the duration of the procedure as well as the failure to antagonize neuromuscular blocking agents at the end of surgical procedure are risk factors for postoperative complications. Muscle relaxation plays an important role that is to facilitate intubation and to allow a better surgical condition. For this reason it is necessary to maintain, during the surgery, a deep neuromuscular block. Deep block at the level of the adductor muscle of the thumb is obtained by measuring 1-2 responses during post-tetanic stimulation (the so-called Post-Tetanic Count or PTC). The maintenance of a deep neuromuscular block requires further doses of neuromuscular blockers and, therefore, the need of long recovery times regardless of the drug used. Pharmacodynamics and pharmacokinetics of neuromuscular blocking and reversals commonly used in clinical practice can undergo significant changes due to the presence of alterations in organ function such as hepatic and renal insufficiency. In these patients we see more frequent adverse events such as prolonged neuromuscular blockade and postoperative residual curarization. In the literature it is considered suitable a recovery from neuromuscular block if the relationship between the fourth and first contraction during Train of Four (TOF) is greater than 0.9 (TOF-ratio> 0.9). This may take a long time so the reversal of blocking agents at the end of the surgical procedure is the solution to reduce this waiting period. The importance of an adequate recovery from neuromuscular block at the end of anesthesia is related to avoid postoperative residual paralysis (PORC) and reducing the risk of postoperative respiratory complications potentially fatal. Rocuronium is characterized by an increase in half-life and an increase in the recovery time of neuromuscular transmission (TOF ratio of 0.9) in cirrhotic patients compared to controls healthy people. To prevent residual neuromuscular blockade and all the complications that it brings with it it could be resorted the use of anti-cholinesterase drugs (neostigmine) to antagonize indirectly the action of non-depolarizing neuromuscular blocking agents. Neostigmine works by increasing the availability of acetylcholine at the neuromuscular junction. The administration of neostigmine may however cause bronchospasm, abdominal pain, nausea, cardiac arrhythmias and can not be used if the neuromuscular blockade is deep. Recently the use of sugammadex, a new drug that can act as an antidote to a comparison of non-depolarizing muscle relaxants amino-steroidal (rocuronium, vecuronium) showed good clinical impact. This drug works by encapsulating the muscle relaxant molecule in the plasma with a high affinity and binding to the complex thus formed which is then eliminated by the kidney. Sugammadex is characterized by the absence of adverse effects at the recommended doses and may be administered at correct dosage, even at deep neuromuscular blockade. Several studies have shown that the recovery from neuromuscular blockade induced by rocuronium is significantly faster after administration of sugammadex compared with neostigmine both when used in moderate block levels and deep. In literature there are no data and studies that assessed the recovery time of neuromuscular transmission (TOF ratio> 0.9) with the use of sugammadex verus neostigmine in patients undergoing liver transplantation after rocuronium infusion.

at the end of surgery administration of 2 mg/kg of sugammadex after the third T2 twitch at Train of Four (TOF) stimulation

at the end of surgery administration of 50 mcg/kg of neostigmine after the third T2 twitch at Train of Four (TOF) stimulation

Recovery time from moderate neuromuscular block to a TOF ratio more than 0.9 after administration of sugammadex or neostigmine using TOF-Watch SX.

Any episode PORC (defined as TOF ratio less than 0.9) within 20 minutes after extubation of the patient using TOF-Watch SX.

Inclusion Criteria: American Society of Anesthesiology status (ASA) III Ability to give a written informed consent Liver transplantation Exclusion Criteria: Any allergy to medications involved in the study Any disease involving neuromuscular transmission Any therapy with toremifene, flucloxacillin or fusidic acid Renal disease with glomerular filtration rate less than 30 ml/min/1.73m2 Hyperthermia maligna Anticonceptional therapy Pregnancy Core body temperature less than 35°C or skin temperature less than 32°C at the end of surgery

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