01 January 2025 : Review article
Impact of Liver Disease on Use of Muscle Relaxants in Anesthesia: A Comprehensive Review
Paweł Radkowski
123ABCDEFG, Maciej Szewczyk 4ABCDEFG*, Anna Łęczycka5BEF, Kacper Kowalczyk5BEF, Mariusz Kęska 12BEF, Tomasz Stompór 6DG
DOI: 10.12659/MSM.945822
Med Sci Monit 2025; 31:e945822
Introduction
Liver Function Tests and Assessment of Liver Function
AST and ALT
The De Ritis Ratio
Chronic Liver Disease
Liver Cirrhosis
Steatotic Liver Disease
Acute Liver Failure
Acute-On-Chronic Liver Failure
Characteristic of Succinylcholine
Impact of Hepatic Insufficiency on Succinylcholine Use
Characteristics of Benzylisoquinolones
Atracurium Characteristic and Its Use in Hepatic Insufficiency
Cisatracurium Characteristic and Its Use in Hepatic Insufficiency
Mivacurium Characteristic and Its Use in Hepatic Insufficiency
Aminosteroids Charateristics
Pipecuronium Characteristics and Uses in Liver Insufficiency
Pancuronium Characteristics and Use in Patients with Hepatic Insufficiency
Vecuronium Characteristic and Its Use in Hepatic Insufficiency
Rocuronium Characteristic and Its Use in Hepatic Insufficiency
Neostigmine and Its Use in Hepatic Insufficiency
Sugammadex Characteristic and Its Use in Hepatic Insufficiency
Summary of Neuromuscular Blocking Agents Use in Hepatic Insufficiency and Actual Recommendations
Future Directions
Conclusions
References
Table 4 Use of NMBAs in hepatic insufficiency depending on drug metabolism and its elimination pathway.
| Drug | Metabolic and elimination pathway | Clinical impact in hepatic insufficiency |
|---|---|---|
| Succinylcholine | Metabolized by plasma butyrylcholinesterase; only 10% excreted in unchanged form in urine | Extended the activity time of succinylcholineProlonged muscle relaxation in cirrhotic patients |
| Pipecuronium | Undergoes predominantly renal elimination with a minor biliary pathway (2% in 24 hours) | Onset of neuromuscular block can be longer in cirrhotic patients |
| Rocuronium | Depends mostly on liver uptake and biliary excretion, with a minor renal pathway (10–30%). It partially undergoes hepatic metabolism producing a metabolite, which possess significant neuromuscular blocking activity | Increased onset and duration of actionRecovery time is significantly prolonged in cirrhotic patientsHigh variability in response to rocuronium in patients with hepatic insufficiency |
| Pancuronium | Excreted into both urine and bile, with kidneys constituting the primary pathway | Larger doses of the drug are needed to achieve muscle relaxationLonger elimination timeTwo times longer half-time in patients with biliary obstruction compared to other patientsHepatic disease severely impacts pancuronium properties, resulting in limited application of the drug |
| Vecuronium | Metabolized in the liver and eliminated mainly via the bile (60%). Metabolite – 3-hydroxy vecuronium excreted via kidneys | Time of elimination and neuromuscular block are significantly prolonged in patients with cirrhosis, cholestasis, and liver failure after a bolus dose of 0.2 mg/kg and after prolonged administrationThere are reports suggesting that alcoholic liver disease does not affect vecuronium’s properties when administered in a bolus dose of 0.1 mg/kg, and that a bolus dose of 0.15 mg/kg in cirrhotic patients may present a recovery rate similar to patients without liver diseaseCaution is necessary when using vecuronium in patients with liver disease due to changes in its pharmacological properties, especially at higher doses |
| Atracurium | Hoffman elimination followed by ester hydrolysis via plasma esterases; metabolism of laudanosine depends on liver function | No impact of hepatic insufficiency. In the case of concomitant renal failure, laudanosine concentrations may increase significantly |
| Cisatracurium | Hofmann elimination; cisatracurium metabolites are further excreted into urine | Can be deemed a safe and favorable muscle relaxant in hepatic disordersNo accumulation in administration of repeated dosesCisatracurium in a dose of 2×ED95 ensures optimal muscle relaxation for patients subjected to living donor liver transplantation |
| Mivacurium | Metabolized by butyrylcholinesterase | Extended time the action up to 3 times depending on severity of hepatic insufficiencyProlonged neuromuscular block |
| Sugammadex | Renal excretion | No prolongation of neuromuscular recovery and recurrence of the block when using sugammadexSugammadex may be deemed a better choice in reversal in comparison to neostigmine |
| Neostigmine | Metabolized by plasma acetylcholinesterase and hepatic microsomal enzymesApproximately 50% of neostigmine is excreted unchanged with urineAround 20% of the drug is bound to plasma proteins | Dose adjustments are currently not recommended in patients with hepatic dysfunction |
| NMBAs – neuromuscular blocking agents. | ||