rocuronium and Sepsis

The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).. A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.. Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET).. Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

Topics: Acetylcholinesterase; Androstanols; Animals; Cecum; Cholinesterase Inhibitors; Diaphragm; Disease Models, Animal; Ligation; Male; Neostigmine; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Punctures; Random Allocation; Rats; Rats, Sprague-Dawley; Rocuronium; Sepsis

Neuromuscular blockade in ICU patients has become less popular, in particular since non-invasive methods of artificial respiration have been introduced. Succinylcholine has numerous side effects. Due to its short onset, Rocuronium may be an alternative. The advantage of Atracurium and Cis-Atracurium is a largely organ-independent metabolism. In ICU patients, neuromuscular monitoring should be applied. Prolonged action and critical illness neuropathy are the most prominent side effects of neuromuscular blockade.

Topics: Androstanols; Atracurium; Critical Illness; Humans; Hypothermia, Induced; Intensive Care Units; Motor Endplate; Nervous System Diseases; Neuromuscular Blockade; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pneumonia; Rocuronium; Sepsis; Succinylcholine; Thromboembolism; Vecuronium Bromide

Sepsis attenuates the muscle-relaxing effects of nondepolarizing neuromuscular blockers. The authors investigated the effects of acute late sepsis on neuromuscular transmission and neuromuscular actions of rocuronium to clarify the mechanisms by which sepsis attenuates the effects of nondepolarizing neuromuscular blockers.. Sepsis was induced by cecal ligation and puncture operation. Endplate potentials, acetylcholine potentials, and electrotonic potentials were recorded from the motor endplates of isolated diaphragms from acute late septic and nonseptic rats.. (1) Sepsis did not influence the effect of rocuronium to decrease endplate potential amplitude, which was increased by sepsis itself; (2) sepsis facilitated the effect of rocuronium to decrease quantal acetylcholine release, which was increased by sepsis itself; (3) sepsis did not influence the effect of rocuronium to decrease acetylcholine sensitivity, which was decreased by sepsis itself; (4) sepsis decreased critical depolarization, and rocuronium did not influence critical depolarization.. These results indicate that acute late sepsis facilitates endplate potentials and enhances excitability of the muscle membrane, indicated by a decrease of critical depolarization. It is thought that these elicit the sepsis-induced attenuation of the muscle-relaxing effects of rocuronium.

Topics: Acute Disease; Androstanols; Animals; Electric Stimulation; Electrophysiology; In Vitro Techniques; Male; Membrane Potentials; Motor Endplate; Neuromuscular Nondepolarizing Agents; Rats; Rats, Wistar; Rocuronium; Sepsis; Synaptic Transmission

We investigated the effects of early and late sepsis on the actions of nondepolarizing neuromuscular blockers by using a rat sepsis model induced by cecal ligation and puncture. Isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Rocuronium, pancuronium, and d-tubocurarine dose-dependently decreased the twitch tensions of the nonseptic, early septic, and late septic diaphragms (P < 0.01 each by analysis of variance [ANOVA]). Late sepsis shifted the concentration-twitch tension curves rightward from those of nonsepsis to larger degrees than did early sepsis, as indicated by increases in 50% inhibitory concentration (IC(50)) values (P < 0.01 each by ANOVA and P < 0.01 or 0.05 by the Scheffe F test). The standardized rightward shifts in early and late sepsis were largest for pancuronium, second largest for rocuronium, and smallest for d-tubocurarine (5.741, 2.979, and 1.660 times in late sepsis, respectively; P < 0.01 each by ANOVA and the Scheffe F test). Sepsis-induced increases in IC(50) values did not accompany the decreases in slopes. The results indicate that sepsis induces hyposensitivities to nondepolarizing neuromuscular blockers, the degree of which depends on the stage of sepsis and on the kind of neuromuscular blocker.

Topics: Androstanols; Animals; Diaphragm; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Muscle Contraction; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Pancuronium; Rats; Rats, Wistar; Rocuronium; Sepsis; Tubocurarine