Inflammatory liver disease shortens atracurium-induced neuromuscular blockade in rats.
BACKGROUND
and objective Inflammatory liver dysfunction in rats leads to a prolonged vecuronium-induced neuromuscular blockade due to insufficient metabolism. A coexisting resistance against the drug partly counteracts this prolongation. The present study investigates the pharmacodynamics of atracurium whose metabolism does not depend on liver function.


METHODS
Male Sprague-Dawley rats (n=14; 290 +/- 30 g) were randomly allocated to either a group in which liver inflammation was induced by intravenous injection of 60 mg kg(-1) heat-killed Corynebacterium parvum or to a control group. On day 5 after injection, liver function was assessed using the aminopyrine breath test. Under propofol anaesthesia, duration of action of atracurium (4.8 mg kg(-1)) was measured by evoked mechanomyography (stimulation of the sciatic nerve; contraction of the gastrocnemius muscle). Nitric oxide concentrations, as variables for the severity of the inflammation, were assessed by measurement of nitrite/nitrate plasma concentrations.


RESULTS
In C. parvum-injected rats, nitrite/nitrate plasma concentrations were increased (972 +/- 597 vs. 25 +/- 7 micromol L(-1)), the aminopyrine turnover was depressed (1.7 +/- 0.4% vs. 3.5 +/- 0.5%), and the atracurium-induced neuromuscular blockade was shortened (372 +/- 128 s vs. 1081 +/- 234 s).


CONCLUSIONS
A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to atracurium. Further investigations are needed regarding a possible up-regulation of acetylcholine receptors or an increased protein binding of atracurium during sepsis to clarify reasons behind this phenomenon.
Mayer
B
B
Klinik für Anaesthesiologie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany.
Fink
H
H
Bogdanski
R
R
Stadler
J
J
Blobner
M
M
D000410:Alanine Transaminase / Q000097:blood; D000632:Aminopyrine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001279:Atracurium / Q000494:pharmacology*; D001772:Blood Cell Count; D001944:Breath Tests; D003354:Corynebacterium Infections / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006505:Hepatitis / Q000503:physiopathology*; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D011425:Propionibacterium acnes; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003473:Neuromuscular Nondepolarizing Agents; D000632:Aminopyrine; D001279:Atracurium; D000410:Alanine Transaminase