OBJECTIVETo study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure.

METHODSForty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve.

RESULTSOnset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure.

CONCLUSIONSAll four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.

Adult ; Androstanols ; pharmacology ; Anesthesia, General ; Atracurium ; pharmacology ; Female ; Humans ; Isoquinolines ; pharmacology ; Kidney Transplantation ; Male ; Middle Aged ; Neuromuscular Blocking Agents ; pharmacology ; Succinylcholine ; pharmacology ; Time Factors ; Vecuronium Bromide ; pharmacology

BACKGROUNDMuscles present different responses to muscle relaxants, a mechanism of importance in surgeries requiring facial nerve evoked electromyography under general anaesthesia. The non-depolarizing muscle relaxants have multiple reaction formats in the neuromuscular junction, in which pre-synaptic quantal release of acetylcholine was one of the important mechanisms. This study was to compare the pre-synaptic quantal release of acetylcholine from the neuromuscular junctions innervated by normal/damaged facial nerves and somatic nerve under the effect of rocuronium in rats in vitro.

METHODSAcute right-sided facial nerve injury was induced by nerve crush axotomies. Both sided facial nerve connected orbicularis oris strips and tibial nerve connected gastrocnemius strips were isolated to measure endplate potentials (EPP) and miniature endplate potentials (MEPP) using an intracellular microelectrode gauge under different rocuronium concentrations. Then, the pre-synaptic quantal releases of acetylcholine were calculated by the ratios of the EPPs and the MEPPs, and compared among the damaged or normal facial nerve innervated orbicularis oris and tibial nerve innervated gastrocnemius.

RESULTSThe EPP/MEPP ratios of the three neuromuscular junctions decreased in a dose dependent manner with the increase of the rocuronium concentration. With the concentrations of rocuronium being 5 µg/ml, 7.5 µg/ml and 10 µg/ml, the decrease of the EPP/MEPP ratio in the damaged facial nerve group was greater than that in the normal facial nerve group. The decrease in the somatic nerve group was the biggest, with significant differences.

CONCLUSIONSRocuronium presented different levels of inhibition on the pre-synaptic quantal release of acetylcholine in the three groups of neuromuscular junctions. The levels of the inhibition showed the following sequence: somatic nerve > damaged facial nerve > normal facial nerve. The difference may be one of the reasons causing the different sensitivities to rocuronium among the muscles innervated by the normal/injured facial nerves and the somatic nerve. The results may provide some information for the proper usage of muscle relaxants in surgeries requiring electromyographic monitoring for the pre-surgically impaired facial nerves.

Acetylcholine ; metabolism ; Androstanols ; pharmacology ; Animals ; Facial Nerve ; drug effects ; metabolism ; Male ; Neuromuscular Junction ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

In this study, we tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptors. The poly A m RNA from muscle by isolation were microinjected into Xenopus oocytes for receptor expression. Concentration-effect curves for the inhibition of Ach-induced currents were established for vecuronium, rocuranium, and isoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the isoflurane at a concentration equivalent to half the concentration producing a 50% inhibition alone. All tested drugs produced rapid and readily reversible concentration-dependent inhibition. The 50% inhibitory concentration values were 889 micromol/L (95% CI: 711-1214 micromol). 33.4 micromol (95% CI: 27.1-41.7 nmol) and 9.2 nmol (95% CI: 7.9-12.3 nmol) for isoflurane. rocuranium and vecuronium, respectively. Coapplication of isoflurane significantly enhanced the inhibitory effects of rocuranium and vecuronium, and it was especially so at low concentration of NMDRs. Isoflurane increases the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site.
Androstanols/*pharmacology ; Anesthetics, Inhalation/pharmacology ; Drug Synergism ; Isoflurane/*pharmacology ; Neuromuscular Blocking Agents/*pharmacology ; Neuromuscular Junction/drug effects ; Neuromuscular Nondepolarizing Agents/*pharmacology ; Oocytes ; Receptors, Nicotinic/*drug effects ; Vecuronium Bromide/pharmacology ; Xenopus laevis

In this study, we tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptors. The poly A m RNA from muscle by isolation were microinjected into Xenopus oocytes for receptor expression. Concentration-effect curves for the inhibition of Ach-induced currents were established for vecuronium, rocuranium, and isoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the isoflurane at a concentration equivalent to half the concentration producing a 50% inhibition alone. All tested drugs produced rapid and readily reversible concentration-dependent inhibition. The 50% inhibitory concentration values were 889 micromol/L (95% CI: 711-1214 micromol). 33.4 micromol (95% CI: 27.1-41.7 nmol) and 9.2 nmol (95% CI: 7.9-12.3 nmol) for isoflurane. rocuranium and vecuronium, respectively. Coapplication of isoflurane significantly enhanced the inhibitory effects of rocuranium and vecuronium, and it was especially so at low concentration of NMDRs. Isoflurane increases the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site.
Androstanols ; pharmacology ; Anesthetics, Inhalation ; pharmacology ; Animals ; Drug Synergism ; Female ; Isoflurane ; pharmacology ; Neuromuscular Blocking Agents ; pharmacology ; Neuromuscular Junction ; drug effects ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Oocytes ; Receptors, Nicotinic ; drug effects ; Vecuronium Bromide ; pharmacology ; Xenopus laevis

BACKGROUNDThe 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).

METHODSA 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.

RESULTSFour 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).

CONCLUSIONSSepsis 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.

Acetylcholinesterase ; metabolism ; Androstanols ; pharmacology ; Animals ; Cecum ; injuries ; Cholinesterase Inhibitors ; pharmacology ; Diaphragm ; drug effects ; metabolism ; Disease Models, Animal ; Ligation ; Male ; Neostigmine ; pharmacology ; Neuromuscular Junction ; enzymology ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Punctures ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; physiopathology

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

OBJECTIVETo evaluate the effect of dexmedetomidine (Dex) on bispectral index (BIS) and auditory evoked potential index (AAI) during anesthesia with target controlled infusion (TCI) of propofol and remifentanyl.

METHODSThirty adult patients (ASA I approximate, equalsII) who were scheduled for elective thyroidectomy were monitored with BIS, AAI, ECG, blood pressure, end-tidal CO(2), and pulse oximeter before and during anesthesia. Anesthesia was induced by TCI with propofol 4 mg/L and remifentanyl 1 mu g/kg. After loss of consciousness the patients were intubated after rocuronium 0.6 mg/kg intravenous injection, remifentanyl was then infused at 0.2 microg/(kg x min)(-1) and propofol infusion (Ct) was titrated to maintain a BIS value at 50 +/- 3. At 10 min after stabilization of anesthesia the patients were randomly and double-blindly divided into 2 groups: Group D (n=15) received Dex 0.4 mu g/kg iv administered over 5 min and Group C (n=15) received equal volume of normal saline. Values of BIS, AAI, MAP, HR were recorded every 2 min within 20 min after the administration of the drugs.

RESULTSBefore anesthesia the BIS index was 90 +/- 2 in Group D and 92 +/- 2 in Group C, AAI was 81 +/- 1 in Group D and 78 +/- 1 in Group C. In anesthesia with target controlled infusion of propofol, BIS index showed a significant decrease with the i.v. administration of Dex 0.4 microg/kg, while AAI remained unchanged. In Group C, both of BIS and AAI remained unchanged after saline injection.

CONCLUSIONDuring propofol and remifentanyl anesthesia, after the administration of Dex, BIS value demonstrates a predominant decrease, whereas AAI shows no changes.

Adrenergic alpha-Agonists ; administration & dosage ; Adult ; Androstanols ; administration & dosage ; Anesthetics, Combined ; administration & dosage ; Anesthetics, Intravenous ; administration & dosage ; Dexmedetomidine ; administration & dosage ; pharmacology ; Double-Blind Method ; Evoked Potentials, Auditory ; drug effects ; Female ; Humans ; Infusions, Intravenous ; methods ; Male ; Medetomidine ; pharmacology ; Middle Aged ; Monitoring, Intraoperative ; methods ; Neuromuscular Nondepolarizing Agents ; administration & dosage ; Piperidines ; administration & dosage ; pharmacology ; Propofol ; administration & dosage ; pharmacology ; Thyroidectomy

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.
Adult ; Androstanols/*administration & dosage/adverse effects ; Anesthetics, Intravenous/administration & dosage ; Double-Blind Method ; Female ; Histamine H1 Antagonists/*pharmacology ; Humans ; Incidence ; Injections, Intravenous ; Male ; Middle Aged ; Movement/drug effects/physiology ; Neuromuscular Nondepolarizing Agents/*administration & dosage/adverse effects ; Pain/chemically induced ; Pain Measurement ; Pheniramine/*pharmacology ; Thiopental/administration & dosage