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

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

BACKGROUND: The administration of high doses of glucocorticoids can produce significant side effects including skeletal muscle atrophy, weakness and aberrant pharmacology. However, available reports have yielded conflicting results ranging from facilitatory to no change to inhibitory action of glucocoticoids on neuromuscular transmission. Also, the mechanisms for such changes are not known. Therefore, this study investigated the changes in muscle contractility and pharmacology after prednisolone administration in vivo. METHODS: With institutional approval, Sprague-Dawley rats were randomly allocated to 3 treatment groups, namely prednisolone (10 mg/kg daily for 7 days), saline control (equal volume of saline daily for 7 days) and an age-matched food-restriction group which grew at the same rate as the prednisolone group. On day 8 the rats were anesthetized, mechanically ventilated and the twitch response of the tibialis muscle to supramaximal stimulation of the sciatic nerve at 2 Hz for 2 sec every 12 sec, or at 50 or 100 Hz tetanus for 5 sec were monitored. The peak twitch and tetanic tensions were measured and tetanic fade was calculated. The cumulative dose-response curves of d-tubocurarine (d-TC) in the tibialis muscles were determined. The tibialis muscle weight relative to body weight was measured (muscle index), and the tension per unit muscle mass (i.e., specific tension) was calculated. The control and treatment groups were compared by a one way ANOVA test and P>0.05 was regarded as significant. RESULTS: Prednisolone caused a decline in growth rate and the ED50 of dTC relative to saline. Food-restriction caused a decline in growth rate and an increase in muscle index relative to saline, and a decline in tension relative to prednisolone. CONCLUSIONS: These results indicate that prednisolone can alter the sensitivity of skeletal muscles to dTC even without or before changes in neuromuscular contractility become apparent. Therefore, titration of doses of nondepolarizing neuromuscular blocking agents may be indicated in patients receiving glucocorticoid therapy.
Animals ; Atrophy ; Body Weight ; Glucocorticoids ; Humans ; Muscle, Skeletal* ; Muscles ; Neuromuscular Agents* ; Neuromuscular Blocking Agents ; Pharmacology ; Prednisolone ; Rats* ; Rats, Sprague-Dawley ; Refractory Period, Electrophysiological ; Sciatic Nerve ; Tetanus ; Tubocurarine

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

OBJECTIVETo evaluate the impact of gender differences on the dose-effect relationship of cisatracurium.

METHODSEighty ASA class I or II patients (40 male and 40 female patients) undergoing elective abdominal surgeries received a single-dose intravenous injection of midazolam and fentanyl. The male and female patients were subdivided into 4 equal groups to receive a intravenous bolus of 20, 30, 40, or 50 µg/kg of cisatracurium. The neuromuscular block was measured using a neuromuscular transmission monitor, and the responses were defined in terms of the percentages of maximum suppression in T1 of TOF of the adductor pollicis muscle. According to log-probit transformation of the data of the dose and response, the dose-response curve of cisatracurium was established through linear regression. The onset time of vecuronium was also observed.

RESULTSThe ED95 value of cisatracurium in male patients was 67.4±4.4 µg/kg, significantly higher than that in female patients (48.7±1.0 µg/kg, P<0.05). No significant variation in the onset time was found in the 4 dose groups of either male or female patients (P>0.05).

CONCLUSIONFemale patients are more sensitive to cisatracurium than male patients.

Abdomen ; surgery ; Adolescent ; Adult ; Anesthesia, General ; Atracurium ; administration & dosage ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Elective Surgical Procedures ; Female ; Humans ; Male ; Neuromuscular Blockade ; methods ; Neuromuscular Blocking Agents ; administration & dosage ; pharmacology ; Pharmacological Phenomena ; physiology ; Sex Factors ; Young Adult

Among nondepolarizing neuromuscular blocking agents, d-tubocurarine may cause blood pressure reduction due to ganglionic blockade and histamine release, while pancuronium and gallamine are associated with vagal blockade and heart rate acceleration. Metocurine, as a trimethylated derivative of d-tubocurarine synthesized by King in 1935, is known to have relatively long duration of action and produces little change in cardiovascular system. Despite its relative lack of cardiovascular effects, the accumulation of data with regard to human neuromus- cular pharmacology and the clinical use has been scant. One hundred and nine adult patients of either sex were anesthetized with thiopental sodium and 50% nitrous oxide with 1.5-2.5% enflurane. For evaluation of neuromuscular blocking effect of metocurine, train-of-four stimulation (2.0 Hz for 2 seconds) was applied at the wrist along the ulnar nerve distribution and the response was measured via ABM Datex. Systolic, diastolic blood pressure and heart rate were recorded continuously after administration of metocurine, d-tubocurarine or pancuronium. All data were analized by ANOVA, Scheffe test. The results are follows : 1) The mean onset times of metocurine 0.1, 0.2, 0.3 mg/kg groups were 119.5+/-40.0, 120.9+/-61.1, 84.8+/-61,1 seconds and the mean durations were 75.1+/-37.6, 104.9+/-42.1, 131.0+/-42.5 minutes respectively. 2) Single-bolus dose of metocurine 0.1, 0.2, and 0.3 mg/kg did not cause significant cardiovascular changes from the control values, but d-tubocurarine 0.3 mg/kg decreased mean systolic blood pressure significantly from 116.6+/-15.7 to 99.0+/-10.9 mmHg 2 minutes after injection. 3) Systolic blood pressures of metocurine 0.2 mg/kg (107.2+/-11.7 mmHg) and d-tubocurarine 0.3 mg/ kg (100.4+/-12.9 mmHg) were significantly different from that of pancuronivm 0.06 mg/kg (127.8+/-16. 0 mmHg) after 1 minute, and 2 minutes after injection, systolic blood pressure of metocurine 0.2 mg/ kg (110.2+/-14.3 mmHg) and d-tubocurarine 0.3 mg/kg (99.0+/-10.9 mmHg) were different from that of pancuronium 0.06 mg/kg (125.3+13.1 mmHg). Five minutes after injection, systolic pressure of d- tubocurarine 0.3mg/kg group (101.110.2mmHg) was significantly different from that of pancur-onium 0.06 mg/kg group (118.7+/-11.0 mmHg). 4) Diastolic blood pressure of d-tubocurarine 0.3 mg/kg (63.4+/-12.9 mmHg) was significantly differ- ent from that of pancuronium 0.06mg/kg (84.2+/-13.3mmHg) after 1 minute, and 2 minutes after injection, diastolic blood pressure or d-tubocurarine 0.3 mg/kg (65.4+/-11.3 mmHg) was different from that of pancuronium 0.06mg/kg (83.1+/-11.6mmHg). There was no significant difference among the groups with respect to heart rate. In summary, metocurine has relatively rapid onset and long duration of action, and used in a dose sufficient to provide surgical relaxation, it produces little change in cardiovascular system in contrast to d-tubocurarine or pancuronium. 1t is therefore suggested that metocurine may be recommended as a muscle relaxant for patients having cardiovascular disease.
Acceleration ; Adult ; Blood Pressure ; Cardiovascular Diseases ; Cardiovascular System ; Enflurane ; Gallamine Triethiodide ; Ganglion Cysts ; Heart Rate ; Hemodynamics* ; Histamine Release ; Humans ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Nitrous Oxide ; Pancuronium ; Pharmacology ; Relaxation ; Thiopental ; Tubocurarine ; Ulnar Nerve ; Wrist

OBJECTIVETo compare the effects of sevoflurane and propofol-remifentanil anesthesia on neuromuscular blockade produced by continuous cisatracurium infusion.

METHODSForty ASA I or II patients undergoing selective surgery were randomly divided into sevoflurane and propofol-remifentanil anesthesia groups (n=20). Neuromuscular blockade was monitored using train-of-four (TOF) stimulation by recording the contraction force of the adductor pollicis muscle with a muscle relaxation monitor. A bolus dose of cisatracurium of 0.15 mg/kg was administered to facilitate endotracheal intubation, followed by continuous infusion adjusted manually to maintain the first twitch (T1) < or = 5% of the control level. The following variables were recorded including the infusion rate, total amount of cisatracurium, spontaneous recovery index (RI), and the time interval from termination of infusion cisatracurium to recovery of TOF ratio (TOFR) to 0.9.

RESULTSWith the maintenance of a 95%-99% neuromuscular blockade, the infusion rate was significantly lower in sevoflurane group than in propofol-remifentanil group (P<0.05), and stabilized in both groups after 120 min. No significant differences were found in RI or the time to TOFR of 0.9 between the two groups (P>0.05).

CONCLUSIONDuring the maintenance of stable neuromuscular blockade by continuous cisatracurium infusion, both sevoflurane and propofol-remifentanil anesthesia can time-dependently enhance the effect of cisatracurium without producing significant differences in the recovery properties.

Adolescent ; Adult ; Aged ; Anesthetics, General ; administration & dosage ; pharmacology ; Anesthetics, Intravenous ; Atracurium ; administration & dosage ; analogs & derivatives ; pharmacology ; Drug Synergism ; Elective Surgical Procedures ; Female ; Humans ; Infusions, Intravenous ; Male ; Methyl Ethers ; administration & dosage ; pharmacology ; Middle Aged ; Neuromuscular Blocking Agents ; administration & dosage ; pharmacology ; Piperidines ; administration & dosage ; pharmacology ; Propofol ; administration & dosage ; pharmacology ; Young Adult

Neonates requiring anesthesia present unique challenges for anesthesiologists. They are very different from children and adults in the point of anatomy, cardiovascular response, respiratory system, central and autonomic nervous system, renal system and fluid balance, metabolism and thermal homeostasis, and pharmacology. In addition, they are frequently associated with congenital anomalies. The object of this study is to analyze the neonates' operation and anesthesia and to improve the outcome. We analyzed the 428 neonates who had received operation from 1979 to 1992 retrospectively. We devided them into four groups by age ; 0-1, 1-2, 2-3, and 3-4 weeks old group, and 0-1 week group is subdivided into preterm and full term one. The results were as follows ; 1. The rate of male versus female was 2.2: 1 (68.7: 31.3%) and 54.2% of them had been operated under 1 week old age. 2. The incidence of operated diseases is in order of congenital megacolon (15.9%), imperforate anus (15.9%) and pyloric stenosis (10.5%). 3. Operating time was within 2 hours in almost cases (95.7%) except tracheo-esophageal fistula (141.82+/-43.49 minutes). And the disease having operated in the shortest duration was inguinal hernia (19.29+/-16.15 minutes). 4. Patients with duodenal atresia, gastroschisis, omphalocele, diaphragmatic hemia, and tracheo -esophageal fistula were somewhat associated with congenital anomalies and the mortality was 10.5 to 33.3%. 5. Endotracheal intubation was achieved by mask inhalation in 76.4% and remains by using intravenous drugs. 6. There was not used any neuromuscular blocking agents thorough the operation procedure in 133 cases (48.4%). 7. Breathing circuit for anesthesia was Mapleson F system in all and the airway was kept with endotracheal tube (91.3%), mask (5.1%), and laryngeal mask airway (3.6%). 8. There were about 40% of patients with tracheo-esophageal fistula, sacrococcygeal anomalies, diaphragmatic hernia, omphalocele, and gastroschisis requiring special respiratory care, that is, keeping endotracheal intubation and ventilator for certain postoperative period. 9. Overall rate of emergency operation was 61%, but it was 73% in 0-1 week old neonates. 10. Mortality of operation for neonates was 7.7% and it occurred mainly in the pateints with gastroschisis, omphalocele, duodenal atresia, diaphragmatic hernia, imperforate anus, and tracheo- esophageal fistula. But there was only 1.6% mortality during 24 hours after operation. With the above results I suggested that shortening of operation time and skilled anesthesia could markedly improved the outcome of operation for neonates. And to achieve the goal all neonatal surgeons and anesthesiologists will have to get many experiences and knowledge about the neonate pathophysiologic conditions and pharmacologic responses.
Adult ; Anesthesia ; Anus, Imperforate ; Autonomic Nervous System ; Child ; Emergencies ; Esophageal Fistula ; Female ; Fistula ; Gastroschisis ; Hernia, Diaphragmatic ; Hernia, Inguinal ; Hernia, Umbilical ; Hirschsprung Disease ; Homeostasis ; Humans ; Incidence ; Infant, Newborn ; Inhalation ; Intubation, Intratracheal ; Laryngeal Masks ; Male ; Masks ; Metabolism ; Mortality ; Neuromuscular Blocking Agents ; Pharmacology ; Postoperative Period ; Pyloric Stenosis ; Respiration ; Respiratory System ; Retrospective Studies ; Ventilators, Mechanical ; Water-Electrolyte Balance