Maximum Twitch Depression Research Articles

Effect of ORM1 genetic polymorphism on time-course of muscle relaxation induced by rocuronium

Objective To evaluate the effect of ORM1 genetic polymorphism on the time-course of muscle relaxation induced by rocuronium. Methods Seventy American Society of Anesthesiologists physical status Ⅰor Ⅱ patients, aged 25-55 yr, scheduled for elective gynecological laparoscopic surgery, with body mass index of 20-25 kg/m2, were enrolled in this study.Anesthesia was induced with iv midazolam and fentanyl and target-controlled infusion of propofol.After the patients lost consciousness, neuromuscular block was assessed with TOF Watch-SX using single stimulation of the ulnar nerve.When the maximal twitch depression was achieved, tracheal intubation was facilitated with rocuronium 0.6 mg/kg.The patients were mechanically ventilated.End-tidal carbon dioxide partial pressure was maintained at 35-45 mmHg.The onset time, nonresponse time, clinical duration, 75% recovery time and recovery index of rocuronium were recorded.Peripheral venous blood samples were collected before surgery for determination of concentrations of plasma alpha1 acid glycoprotein, C-reactive protein(by enzyme-linked immunosorbent assay)and albumin(by biochemical method). ORM1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism.The patients were divided into 3 groups according to the ORM1 genotypes: wild homozygote(ORM1*F1/*F1) group (AA group), mutation heterozygote(ORM1*F1/*S) group (AG group)and mutation homozygote(ORM1*S/*S) group (GG group). Results There were 40 cases in group AA, 25 cases in group AG, and 5 cases in group GG.There were no significant differences in plasma alpha1 acid glycoprotein, albumin and C-reactive protein concentrations between the three groups(P>0.05). Compared with group AA, the clinical duration, 75% recovery time and recovery index of rocuronium were significantly prolonged(P 0.05). Conclusion ORM1 genetic polymorphism is one of the genetic factors which affect the time-course of muscle relaxation induced by rocuronium. Key words: Orosomucoid; Polymorphism, single nucleotide; Androstanols; Neuromuscular blockade; Dose-response relationship, drug

Comparison of four facial muscles, orbicularis oculi, corrugator supercilii, masseter or mylohyoid, as best predictor of good conditions for intubation

Monitoring of facial muscles after neuromuscular blockade can give an early indication of respiratory muscle readiness for tracheal intubation. To assess which facial muscle, the orbicularis oculi, corrugator supercilii, masseter or the mylohyoid, is the best predictor of readiness for intubation after rocuronium. Prospective, randomised, blinded trial. Single centre: Seoul, Korea, from August 2012 to November 2012. Two hundred and eighty-eight patients aged 22 to 64 years were randomised to one of eight study groups: orbicularis oculi, corrugator supercilii, masseter and mylohyoid for rocuronium 0.6 or 1.2 mg kg. The maximum twitch depression at the eyelid (orbicularis oculi), the superciliary arch (corrugator supercilii), the cheek (masseter) and the submental triangle (mylohyoid) was assessed after rocuronium 0.6 and 1.2 mg kg. Endotracheal intubation was performed after maximal neuromuscular blockade, and intubating conditions were appraised. The onset time of rocuronium and the quality of the intubation conditions were assessed. The onset times in the orbicularis oculi, corrugator supercilii and masseter were significantly faster than that in the mylohyoid (P < 0.001). 'Clinically acceptable' intubation conditions were significantly enhanced in the mylohyoid (94%) compared with those in the orbicularis oculi (80%) and masseter (78%) after rocuronium 0.6 mg kg (P < 0.05), and no difference with corrugator supercilii (92%). Despite differences in onset time of orbicularis oculi and masseter compared to mylohyoid (P < 0.05), intubating conditions were similar among the four muscles after rocuronium 1.2 mg kg. Following rocuronium 0.6 mg kg at similar depths of anaesthesia, the monitoring of the corrugator supercilii provided the best balance of a shorter onset time while maintaining 'clinically acceptable' intubation conditions. IRB File No.: HYUH 2012-07-009.

Calabadion

To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects. A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure. After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 ± 1.1 and 16.2 ± 3.3 min with placebo to 4.6 ± 1.8 min with neostigmine/glycopyrrolate to 15 ± 8 and 84 ± 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 ± 2.8 and 9.9 ± 1.7 min with placebo to 2.8 ± 0.8 and 7.6 ± 2.1 min with neostigmine/glycopyrrolate to 47 ± 13 and 87 ± 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h. Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.

Effects of vecuronium priming and ephedrine pretreatment on the onset time of neuromuscular blockade of vecuronium during induction period

Objective To evaluate the effect of vecuronium priming, ephedrine pretreatment, and vecuronium priming combined with ephedrine pretreatment on the onset time of neuromuscular blockade of vecuronium, intubation conditions and their hemodynamic effects during induction period. Methods Forty-eight adult patients with ASA grade Ⅰ or Ⅱ , scheduled for elective surgery were randomly allocated to four groups with 12 cases in each. Just 3 min before induction, the patients were injected with ephedrine 70 μg/kg and vecuronium priming 0.01 mg/kg in group Ⅰ , vecuronium 0.01 mg/kg in group Ⅱ , ephedrine 70 μg/kg in groupⅢ, and normal saline 0.5 ml in group Ⅳ. Followed by a four min priming or/and pretreatment interval, the intubation dose of vecuronium was injected (vecuronium 0.09 mg/kg in group Ⅰ and group Ⅱ , vecuronium 0.1 mg/kg in group Ⅲ and Ⅳ ). The neuromuscular block was monitor by acceleromyography (TOF Watch SX, Organon) using train of four stimulation (TOF) every 15 s.Endotracheal intubation was performed by a blinded investigator in 2 min. Time to maximal twitch depression was recorded, Intubation conditions were assessed, heart rate and mean blood pressure were observed and recorded as well right before the induction, 1 min after the induction and every minute after endotracheal intubation for 5 min. Results The onset times in group Ⅰ , Ⅱ , Ⅲ and Ⅳwere (99±13), (131±24), (143±20) and (185±26) s, respectively. The onset time of vecuronium in group Ⅰ , Ⅱ and Ⅲ was significantly shorter than that in group Ⅳ (P＜0.001). The onset time of vecuronium in group Ⅰ was faster than that in group Ⅱ and group Ⅲ (P＜0.005). The intubation conditions were better in group Ⅰ , Ⅱ and Ⅲ than those in groupⅣ.There were no significant change in mean blood pressure during the induction in all patients, but heart rates in group Ⅰ , Ⅲ (both with ephedrine pretreatment) were much higher( P＜0.05 ). Conclusion Either vecuronium priming or ephedrine pretreatment can shorten the onset time of vecuronium. The combination of vecuronium priming with ephedrine pretreatment accelerates the onset of vecuronium; In combination with ephedrine, it has no effect on hypotension induced by propofol injection. Key words: Vecuronium; Ephedrine; The onset time; Hemodynamics; The intubating conditions

A reply

We thank Dr Brown for her interest in our editorial. She is, of course, correct in stating that the vast majority of cases of laryngospasm are managed successfully with the application of CPAP and other simple manoeuvres. The thrust of our article was, however, the serious case of laryngospasm, when these simple manoeuvres have been tried and the situation is slipping out of control, that is, when the oxygen saturation continues to drop rapidly or the patient becomes bradycardic before intravenous access has been achieved. We did not intend to discuss those simple manoeuvres in detail. Dr Brown states that ‘complete laryngospasm can quickly progress to hypoxia and bradycardia, and intubation may become necessary’. We are aware that many anaesthetists may choose to intubate at this stage and this may resolve the situation. However, if unsuccessful, especially in the older child or adult, valuable time is wasted. We feel that it is an important principle in the management of such a situation that we must not get fixated on intubation, but on oxygenation. Is full muscle relaxation necessary to facilitate intubation? We state in our editorial that the time to maximal twitch depression for intramuscular suxamethonium is in the region of 3–4 min, but that ‘oxygenation is the initial goal, and therefore, full relaxation is probably not necessary’. This relates specifically to the ability to oxygenate by CPAP and manual inflation of the lungs, not to intubation. Dr Brown states ‘this implies that one need not wait for the full effects of suxamethonium before attempting intubation’. We have based our logic on the work of Donati [1], that central muscles such as the muscles of the larynx and diaphragm relax earlier than peripheral muscles and therefore oxygenation by the application of tight CPAP and manual inflation will be possible before full relaxation is present at the adductor pollicis muscle. Therefore, it does not necessarily follow that one can intubate at this point. We believe that when faced with this life-threatening situation one should administer suxamethonium by one of the routes discussed and maintain CPAP until laryngospasm breaks. Oxygenate and then, if necessary, intubate. Likewise, the use of topical lidocaine in this situation, although reported, could make the situation worse and, again, wastes precious time. The rapidly deteriorating child or adult allows no time to ‘consider’ different options. The anaesthetist must have a plan and act on that plan rapidly. Experience is little protection in this situation. This can happen to anyone, at any time and it is our belief that the administration of suxamethonium by the intramuscular, intra-osseous or intralingual route is of paramount importance to prevent serious complications from laryngospasm.

Time course of neuromuscular blockade with rocuronium in children with intracardiac shunts

Objective: To evaluate the time course of neuromuscular blockade after rocuronium in children with intracardiac shunts. Design: Prospective study. Setting: University hospital. Participants: Consecutive children (n = 52) with intracardiac shunts scheduled for elective cardiac surgery. Participants were allocated to 2 groups according to the direction of the shunt. Interventions: Rocuronium, 0.6 mg/kg, was administered for muscle relaxation. The ulnar nerve was stimulated at 20-second intervals with a supramaximal 2-Hz train-of-4 stimulation (TOF-Guard nerve stimulator; Biomet International, Odense, Denmark). The onset time to maximal twitch depression and the time to clinical recovery were compared between the 2 groups. Measurements and Main Results: The time to maximal block was significantly faster in children with a right-to-left shunt: 56.8 ± 5.3 seconds versus 77.1 ± 6.6 seconds (p = 0.01). There was a tendency to shorter recovery in children with a right-to-left shunt: 42.3 ± 6.1 minutes versus 55.4 ± 4.9 minutes (p = NS). Conclusion: This study shows a more rapid onset of rocuronium in children with cyanotic congenital heart disease. In these patients, rocuronium is indicated, particularly for rapid airway control. Copyright 2002, Elsevier Science (USA). All rights reserved.

A New Method of Monitoring the Effect of Muscle Relaxants on Laryngeal Muscles Using Surface Laryngeal Electromyography

A New Method of Monitoring the Effect of Muscle Relaxants on Laryngeal Muscles Using Surface Laryngeal Electromyography

SUCCINYLCHOLINE DOSE-RESPONSE IN OBESE ADOLESCENTS

S415 Introduction: Obese adolescents are at increased risk of aspiration during general anesthesia [1]. A rapid sequence induction (RSI) may be used to reduce risk. Succinylcholine (sux) has the most rapid onset of all muscle relaxants currently in use. A dose response relationship for sux in obese adolescents has not been established, thus we undertook the present study. Methods: After IRB approval and informed parental consent, 30 children, 9-15 yrs old with a body mass index (BMI)>30 were enrolled. Subjects 1-20 were randomized to receive sux 100 mcg/kg (group A) or sux 250 mcg/kg (group B). The ED50 of sux was estimated. A third group (C) of 10 children received this dose, sux 150 mcg/kg. An IV catheter was placed and blood for dibucaine number (Db) and pseudocholinesterase level (Pch) obtained 30 minutes after midazolam 0.4 mg/kg PO (max=20mg). Routine monitors and a Datex relaxograph were placed. Patients were preoxygenated for 2 minutes before induction (atropine 0.01 mg/kg IV, thiopental 5 mg/kg IV, fentanyl 3 mcg/kg IV, cricoid pressure). A baseline response of the adductor pollicis to supramaximal train of four ulnar nerve stimuli (TOF) every 10 seconds was recorded. Then, the study dose of sux was administered. After maximum twitch depression occurred, a second dose of sux was given (total dose of sux 2 mg/kg), and the patient's trachea intubated. Demographic data were analyzed by ANOVA. A linear regression was done since the data satisfied criteria for linearity and no patient had a 0% or 100% response. The variables used included the log of the study dose of sux vs the probit transformation of the maximum twitch depression during TOF [2]. ED50, ED90, and ED95 were calculated with 95% confidence intervals. Results: No difference between groups exists in age (12.2 +/- 2.2 years), weight (98.6 +/- 31.3 kgs), BMI (36.5 +/- 10), Db (85.2 +/- 3.4), or Pch (18.8 +/- 3.61 mM/L). The estimated (see Figure 1) ED50, ED90, and ED95 (with lower and upper 95% confidence intervals) in mcg/kg are: 158 (79 and 316), 293 (133 and 644), and 348 (153 and 789), respectively. Pch was > the upper limit of normal (7-19[micro sign]mol/l) in 48% of subjects tested (n=25).Figure 1: Linear regression of the log of the study dose of sux versus the probit transformation of the maximum response (% twitch depression).Discussion: Intuition mandates that the dose of sux be based on lean body mass. Adult literature suggests that altered physiology (increased Pch and extracellular fluid volume) renders this dosing inappropriate [3]. We conclude: 1) The ED90 in obese adolescents is similar to that reported in adults, 290 mcg/kg [4], and less than that reported in children, 352 mcg/kg [5]; 2) Pch may be increased in obese adolescents; and 3) The recommended dose of sux in obese adolescents should be 1.5 mg/kg (4 x ED95) of actual body mass.

Cardiovascular effects of doxacurium chloride in isoflurane-anaesthetised dogs

The cardiovascular effects of doxacurium were studied in 6 isoflurane-anaesthetised dogs. Each dog was anaesthetised twice, receiving doxacurium (0.008 mg/kg bwt) or placebo iv. Dogs were ventilated to normocapnia. Heart rate, cardiac index, systolic, diastolic, and mean arterial blood pressures, stroke volume, pulmonary vascular resistance, pulmonary artery wedge pressure, systemic vascular resistance, and pulmonary arterial pressure were determined. Neuromuscular blockade was assessed using the train-of-four technique. After recording baseline values, dogs randomly received either doxacurium or placebo iv, and data were recorded at 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 min. At 120 min, dogs treated with doxacurium received edrophonìum (0.5 mg/kg bwt iv) to antagonise neuromuscular blockade; dogs treated with placebos received saline iv. No statistically significant differences were detected after doxacurium compared to placebo. In both the doxacurium and placebo groups, significant increases in systolic arterial blood pressure, cardiac index, and stroke volume and a significant decrease in systemic vascular resistance occurred with time. Doxacurium depressed twitch tension 100% in all dogs (time to maximal twitch depression, 11 ± 7 min). First twitch tension was less than 10% of baseline values in all dogs at the time (120 min) of edrophonium administration. Additional edrophonium (1.0 ± 0.4 mg/kg iv) was required to obtain a fourth twitch to first twitch ratio of greater than 0.70. In conclusion, doxacurium is a long-acting neuromuscular blocking agent with no significant cardiovascular effects in isoflurane-anesthetised dogs. In dogs, doxacurium is indicated primarily for long surgical procedures requiring neuromuscular blockade and cardiovascular stability.

USE OF THE MUSCLE RELAXANT VECURONIUM BY DIFFERENT ADMINISTRATION TECHNIQUES IN DOGS

Different administration techniques of the muscle relaxant vecuronium were studied on the anterior tibialis muscle preparation of thiopentone, a chloralose anaesthetized dogs. The intubating dose, double intubating dose and the intubating dose after priming were studied. The time of injecting the top-up dose was chosen from our results to be at the maximal twitch depression of the priming dose. Our study demonstrated that, administration of the intubating dose (0.1 mg kg-l) of vecuronium 5 minutes after priming doses (0.01 and 0.02 mg kg-l) significantly reduced the onset time without altering the duration of action and recovery index. Likewise, the double intubating dose significantly decrease the onset time with a significant prolongation of the duration of action and recovery index. It could be concluded that, the priming appears to decrease the onset time rather than the duration of action and allowing rapid spontaneaus recovery. This is particularly important for the safety of patient's during intubation and in the immediate post-operative phase.

Effects of age on neuromuscular blockade by vecuronium as measured by accelography under sevoflurane anesthesia

We evaluated possible differential effects of age on a single bolus intravenous injection of vecuronium using accelography under sevoflurane anesthesia. Thirty anesthetized patients were divided into three groups of 10 patients as follows: group 1=age 1-5 years; group 2=age 20-40 years, and group 3=age >70 years. Vecuronium 0.1 mg·kg(-1) was given to facilitate tracheal intubation. Onset time, i.e., the time from the start of injection of the first dose of vecuronium to development of maximal twitch depression in group 1 was significantly shorter than those in groups 2 and 3 (103.5±30.4s, 166.5±32.7s, and 202.5±56.7s; mean±SD;P<0.01). Clinical duration, i.e., the time from completion of maximal block to 25% recovery of train-of-four (TOF) ratio in group 1 was significantly shorter than that in group 3 (43.6±12.0 min and 67.3±15.6 min;P<0.01). The reversal time from 25% to 75% of the TOF ratio after the administration of neostigmine in group 1 was not significantly different from those in groups 2 and 3 (172.5±73.9s, 219.0±59.7s, and 222.0±155.7s). The authors conclude that the time to maximal twitch depression after the administration of vecuronium is significantly shorter in children than that in adults, and that the fastest recovery from vecuronium is also observed in children.

Differential effects of vecuronium on the thumb and the big toe muscles evaluated by acceleration measurement.

To clarify the differential effects of vecuronium on the thumb and on the big toe, train-of-four (TOF) stimuli were applied to the ulnar nerve at the wrist and the tibial nerve at the ankle in anesthetized patients using two acceleration transducers. Ten adult patients, aged 21-55 years, were studied. Anesthesia was induced by an intravenous injection of thiopental, and vecuronium 0.1 mg·kg-1 was used for paralysis. Anesthesia was maintained with nitrous oxide (66%)-oxygen-sevoflurane (1 MAC). The duration of time to the maximal twitch depression on the thumb and the big toe was 136.5±32.5 s and 183.0±40.1 s (P<0.05), respectively. The time to 25% recovery of the twitch height on the thumb and the big toe was 48.1±17.3 min and 39.1±11.6 min, respectively; the time to 50% recovery of twitch height on the thumb and the big toe was 54.1±16.1 min and 40.0±9.2 min (P<0.05), respectively. When paralysis was reversed at 25% of TOF ratio on the thumb, the value of the TOF ratio on the big toe was 58.5±18.2% (P<0.01).

Pharmacodynamics of vecuronium in patients with and without renal failure: a meta-analysis

Eight trials comparing the effects of vecuronium in patients with either normal renal function or renal failure were subjected to a meta-analysis. Vecuronium doses were similar in the different trials, identical in the two patient groups of any given trial, and ranged from 0.05 to 0.14 mg.kg-1. Neuromuscular blockade was assessed by TOF or single twitch stimulation, and recorded by either mechanomyography or electromyography. Indices of blockade included onset time (from injection to maximal twitch depression), duration of action (from injection to recovery to 25% of control twitch) and 25-75% recovery index. Statistical analysis used Hedges method: effect size and variance were calculated for each relevant outcome, then the global effect size was estimated by pooling the effect sizes of each trial. Three separate meta-analyses were conducted. No differences were found either in onset time, or in recovery index between the two groups, whereas the duration of action was longer in the renal failure group. It is concluded that renal function is likely involved in the pharmacokinetic parameters of vecuronium.

Delayed onset of alcuronium effect in children with cyanotic congenital heart disease.

The effect of alcuronium dichloride (0.3 mg/kg) was studied in seven normal children (Group A), nine with acyanotic congenital heart disease (Group B) and eight with cyanotic disease (Group C). The onset of action was recorded using an integrated electromyograph and blood samples taken for later estimation of plasma concentrations of the drug. The mean time (SD) taken to 75% suppression of twitch height was 1.3(0.8), 1.7(1.0) and 3.8(2.8) minutes, respectively, in each of the three groups. This was significantly slower in Group C compared with both other groups (P < 0.05). While six of the Group A patients and seven from Group B reached 95% paralysis within ten minutes, only two of the cyanosed children achieved this level of relaxation. However, if times to 95% relaxation were extrapolated, there was no significant difference between the groups at 4.5(3.9), 5.8(5.7) and 10.9(6.5) minutes respectively. There was a weak but statistically significant relationship between haematocrit and time to 75% blockade. Maximum twitch depression was similar in all three groups with plasma concentrations at this time being 1.6(0.7), 1.8(0.5) and 2.3(1.4) micrograms/ml respectively. Again, there was no statistically significant difference between these values. These results confirm that the clinical onset of relaxation is delayed in children with cyanotic congenital heart disease, possibly because of delayed distribution of alcuronium.

The Effect of Lidocaine HCI Administered into Epidural Space on the Neuromuscular Blocking Action of Vecuronium

Most local anesthetics intravenously administered inhibit neuromuscular transmission or enhance the neuromuscular block of both nondepolarizing and depolarizing musde relaxants. Local anesthetics used to treat cardiac arrhythmias intraoperatively or postoperatively may, therefore, greatly augment a residual neuromuscular block. To obtain adequate balanced anesthesia and postoperative analgesia, general anesthesia with epidural anesthesia is frequently selected. In the present study we investigated the effects of lidocaine HC1 administered into epidural space on the neuromuscular blocking action of vecuronium. Eighty adult gynecological patients of ASA class I or II were studied. Patients were divided into four groups as follows ; Group I (n=20); vecuronium 0.1 mg/kg iv administered only Group II(n=20); vecuronium 0.1 mg/kg iv and lidocaine 6 mg/kg administered into epidural space Group III(n=20); vecuronium 0.1 mg/kg iv and lidocaine 8 mg/kg administered into epidural space Group IV(n=20); vecuronium 0.1 mg/kg iv and lidocaine 10 mg/kg administered into epidural space Patients of experimental groups II, III and IV were anesthetized by epidural block with 2 % lidocaine followed by general anesthesia 15 minutes later. Before induction with fentanyl(3 ug/kg), droperidol(0.04 mg/kg), thiopental sodium (5 mg/kg) and vecuronium(0.1 mg/kg) iv, neuromuscular monitoring was set by using ABM(Anesthesia and Brain activity Monitor, Datex Co, Finland) which stimulating ulnar nerve at the wrist with supramaximal stimuli at a frequency of 2 Hz and 20 seconds interval. The electromyographic response of hypothenar muscles was recorded. Following stabilization of the control twitch height, vecuronium(0.1 mg/kg) was intravenously injected, and tracheal intubation was performed when the first twitch height of the train of four twitch response(T1) was 5 % of the controL Anesthesia was maintained with O2 (2 L/min) and N2O (4 L/min). The time of onset of action (time from vecuronium iv to 0 % of T1), time of maximal twitch depression (time from loss of T1 to reappearance of T1), Recovery index (time from recovery of 25 % of T1 to 75 % of T1) and T4 ratios (ratio of the height of the fourth twitch to T1) at 25 %, 50 % and 75% of T1 were measured and compared among the groups. The results were as follows ; 1. The time of onset of action was 3.99±0.92 minutes in the control group and 2.94±0.89 minutes in the lidocaine 10 mg/kg administered group(P 0.05). These results suggest that the effect of lidocaine HC1 administered into epidural space on the neuromuscular blocking action of vecuronium showed prolonged depression and recovery time, and reduced time of the onset of action with dose larger than lidocaine 8 mg/kg.

Neuromuscular and cardiovascular effects of atracurium in isoflurane-anesthetized chickens

Summary Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered to 24 isoflurane-anesthetized domestic chickens. Birds were randomly assigned to 4 groups, and atracurium was administered at dosage of 0.15, 0.25, 0.35 or 0.45 mg/kg of body weight. The time of onset of twitch depression, the amount of maximal twitch depression, and the duration of muscular relaxation were recorded. After return to control twitch height, atracurium was further administered to achieve &gt; 75% twitch depression. When twitch depression reached 75% during noninduced recovery, 0 5 mg of edrophonium/kg was administered to reverse the muscle relaxation. Throughout the experimental period, cardiovascular, arterial blood gas, and acid-base variables were monitored. The effective dosage of atracurium to result in 95% twitch depression in 50% of birds, (ed95/50) was calculated, using probit analysis, to be 0.25 mg/kg, whereas the ed95/95, the dosage of atracurium to result in 95% twitch depression in 95% of birds, was calculated by probit analysis to be 0.46 mg/kg. The total duration of action at dosage of 0.25 mg/kg was 34.5 ± 5.8 minutes; at the highest dosage (0 45 mg/kg), total duration increased 0 47.8 ± 10.3 minutes. The return to control twitch height was greatly hastened by administration of edrophonium. Small, but statistically significant changes in heart rate and systolic blood pressure, were associated with administration of atracurium and edrophonium. These changes would not be clinically relevant. In this study, atracurium was found to be safe and reliable for induction of muscle relaxation in isoflurane-anesthetized chickens.

Prediction of Vecuronium Block Onset and Time to Maximum Twitch Depression

Prediction of Vecuronium Block Onset and Time to Maximum Twitch Depression

Effects of Succinylcholine on the Pharmacodynamics of Pipecuronium and Pancuronium

To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)

Vergleichende Untersuchungen von Atracurium und Vecuronium für mittellang dauernde operative Eingriffe bei Säuglingen und Kleinkindern

Onset time, intubation condition and recovery time after single bolus injection of atracurium (0.3 mg/kg in body weight less than 10 kg (Group 1), 0.5 mg/kg in body weight greater than 10 kg (Group 2] and vecuronium (0.05 mg/kg in body weight less than 10 kg (Group 3), 0.1 mg/kg in body weight greater than 10 kg (Group 4] were studied in 40 infants and children anaesthetised with halothane. At the end of the onset time (time from the end of the bolus injection of the muscle relaxant until the maximal twitch depression of the m. adductor pollicis) the intubation conditions were judged as good or very good in both groups. The onset time after bolus injection of atracurium (92.5 +/- 31.9 sec in Group 1, 117.0 +/- 25.2 sec in Group 2) was slightly shorter than after vecuronium (135.7 +/- 64.1 sec in Group 3, 123.3 +/- 26.8 sec in Group 4). The duration from the time of injection to 75% recovery of T1 had been longer by using atracurium (45.2 min in Group 1 + 2) than by vecuronium (36.6 min in Group 3, 34.2 min in Group 4). In infants (Group 1 + 3) the recovery time (duration from 25% to 75% recovery of control twitch height) after relaxation with atracurium as well as vecuronium was longer than in children (Group 2 + 4). Neither cardiovascular side effects nor signs of histamine release occurred after the injection of both muscle relaxants at our dosage level. It is concluded that in infants and children atracurium is a real alternative to vecuronium for relaxation for medium long surgical procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and Pharmacodynamics of Doxacurium in Young and Elderly Patients During Isoflurane Anesthesia

Preliminary disposition studies of the investigational, long-acting muscle relaxant doxacurium chloride (Nuromax) have demonstrated dual elimination by renal and hepatobiliary pathways, as well as slow hydrolysis by plasma cholinesterase. The present study compares the kinetics and dynamics of doxacurium in eight ASA physical status I or II elderly patients (67-72 yr of age) and eight ASA I or II young patients (22-49 yr of age). After institutionally approved written informed consent, kinetic and dynamic measurements were made after a 25-micrograms/kg bolus injection of doxacurium during 1.25 MAC nitrous oxide/oxygen/isoflurane anesthesia. Maximum twitch depression was similar in older patients (96.4% +/- 1.3%) to that in the young patients (96.6% +/- 1.8%). The time to achieve this level of block was significantly longer in the elderly than in the young (11.2 +/- 1.1 min versus 7.7 +/- 1.0 min, respectively). Recovery times to twitch heights of 5% and 25% of control tended to be prolonged and were more variable in the elderly (82.6 +/- 17.2 and 97.1 +/- 20.1 min, respectively) than in the young (54.8 +/- 9 and 67.5 +/- 8.2 min, respectively). Elimination half-life (96 +/- 20 min) and clearance (2.47 +/- 0.69 mL.kg-1.min-1) in the elderly patients were not statistically different from values found in the younger group. Volume of distribution at steady state in the elderly (220 +/- 80.2 mL/kg) was significantly larger than in the young (150 +/- 40.0 mL/kg).(ABSTRACT TRUNCATED AT 250 WORDS)