A Dose-ranging Study of Rapacuronium in Pediatric Patients

2000 ◽  
Vol 92 (4) ◽  
pp. 1002-1009 ◽  
Author(s):  
George H. Meakin ◽  
Olli A. Meretoja ◽  
Johann Motsch ◽  
Tomi Taivainen ◽  
Kari Wirtavuori ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Tracheal Intubation ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Infants And Children ◽  
Older Children ◽  
Duration Of Action ◽  
Intubating Conditions ◽  
Nitrous Oxide Oxygen ◽  
Train Of Four

Background The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. Methods Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. Results Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. Conclusions Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Comparison of the Intubation Conditions Provided by Rapacuronium (ORG 9487) or Succinylcholine in Humans during Anesthesia with Fentanyl and Propofol 

1999 ◽  
Vol 91 (5) ◽  
pp. 1311-1311 ◽  
Author(s):  
Neal W. Fleming ◽  
Frances Chung ◽  
Peter S. A. Glass ◽  
John B. Kitts ◽  
Hans Kirkegaard-Nielsen ◽  
...  
Keyword(s):  
Tracheal Intubation ◽  
Short Duration ◽  
Rapid Onset ◽  
Neuromuscular Function ◽  
Neuromuscular Blocking ◽  
Blocking Drug ◽  
Duration Of Action ◽  
Prospective Randomized Clinical Trial ◽  
Org 9487 ◽  
Train Of Four

Background Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. Methods This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. Results Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. Conclusions A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

Intramuscular Rapacuronium in Infants and Children 

1999 ◽  
Vol 91 (5) ◽  
pp. 1285-1285 ◽  
Author(s):  
Lynne M. Reynolds ◽  
Andrew Infosino ◽  
Ronald Brown ◽  
James Hsu ◽  
Dennis M. Fisher
Keyword(s):  
Tracheal Intubation ◽  
Pediatric Patients ◽  
Minute Ventilation ◽  
Optimal Dose ◽  
Deltoid Muscle ◽  
Rapid Onset ◽  
Infants And Children ◽  
Halothane Anesthesia ◽  
Duration Of Action ◽  
In Infants And Children

Background Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. Methods Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. Results Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. Conclusions This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.

scholarly journals Effect of Remifentanil on Tracheal Intubation Conditions and Haemodynamics in Children Anaesthetised with Sevoflurane and Nitrous Oxide

2009 ◽  
Vol 37 (4) ◽  
pp. 577-583 ◽  
Author(s):  
K. S. Park ◽  
S. Y. Park ◽  
J. Y. Kim ◽  
J. S. Kim ◽  
Y. J. Chae
Keyword(s):  
Blood Pressure ◽  
Nitrous Oxide ◽  
Tracheal Intubation ◽  
Salivary Secretion ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agents ◽  
Relative Lack ◽  
Acceptable Alternative ◽  
Intubating Conditions

This study examined the effect of remifentanil added to inhalation agents on intubating conditions in children (aged one to seven years). As is our routine, all patients were premedicated with 0.004 mg/kg glycopyrrolate intramuscularly 30 minutes before anaesthesia to prevent bradycardia and salivary secretion, and received intravenous 1 mg/kg ketamine prior to transfer into the operating room to facilitate separation of the child from the parents. Laryngoscopy was attempted after ventilation with 8% sevoflurane in 50% nitrous oxide and 50% oxygen for two minutes, and intravenous administration of either a placebo bolus of saline (Group S) or one of two doses of remifentanil, 1 μg/kg (Group R1) or 2 μg/kg (Group R2) given over 30 seconds, commenced at the beginning of the sevoflurane administration. Only 18 of 32 patients (56.3%) in Group S had acceptable intubating conditions compared with 31 of 32 patients (96.9%) in Group R1 and 32 of 32 patients (100%) in Group R2 (P <0.001). Mean blood pressure was lower in Group R1 and R2 compared with Group S (P <0.005). Our routine use of ketamine and glycopyrrolate may have influenced the relative lack of significant hypotension and bradycardia. Sevoflurane, nitrous oxide and remifentanil provided acceptable conditions for tracheal intubation in children and could be an acceptable alternative to intravenous induction and neuromuscular blocking agents.

Intramuscular Rapacuronium in Infants and Children

2001 ◽  
Vol 94 (1) ◽  
pp. 3-7 ◽  
Author(s):  
William T. Denman ◽  
Richard F. Kaplan ◽  
Nishan G. Goudsouzian ◽  
Tetsu Uejima ◽  
Sandra L. Barcelona ◽  
...  
Keyword(s):  
Tracheal Intubation ◽  
Minimum Alveolar Concentration ◽  
Randomized Study ◽  
Onset Time ◽  
Infants And Children ◽  
Halothane Anesthesia ◽  
Time Duration ◽  
Duration Of Action ◽  
Intubating Conditions ◽  
The Mean

Background This multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions. Methods Ninety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure. Results The tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children. Conclusions Only 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants.

scholarly journals Intubating Conditions with three different doses of Rocuronium in surgery of cancer patients

2017 ◽  
Vol 1 (1) ◽  
pp. 28-35
Author(s):  
Bhawana Wagle ◽  
Yogesh Regmi
Keyword(s):  
Tracheal Intubation ◽  
Surgical Procedures ◽  
Double Blind Study ◽  
Double Blind ◽  
Duration Of Action ◽  
Intubating Conditions ◽  
Elective Surgical Procedures ◽  
Train Of Four ◽  
Tactile Response ◽  
Group B

Background: This is a prospective randomized, double blind study to determine the doses of rocuronium that would give 90% and 95% probabilities of successful tracheal intubation within 60s after administration. This study evaluated intubating conditions and duration of action of 0.4 mg, 0.8 mg and 1.2 mg of rocuronium, administered intravenously in patients undergoing elective surgical procedures. Goal in this study is to define doses level of rocuronium that would provide optimal relaxation for tracheal intubation in patients in whom succinylcholine was relatively contraindicated. Methods: Sixty patients both male and female, ASA I & II, age between 18–60 years, with BMI of less that 30 who were planned for elective surgical procedures were randomized into three groups. Group A received 0.4 mg (n=20), Group B received 0.8 mg (n=20) and Group C received 1.2 mg (n=20) of rocuronium. At 60 seconds after injection of the rocuronium, laryngoscopy was initiated, with the goal being endotracheal tube passed through the patient's vocal cords and the cuff inflated within the trachea in 20s. Intubating conditions was graded excellent, good or poor according to Cooper scoring system criteria. When the patient lost consciousness, train-of-four (TOF) stimulation (at 2 Hz and repeated every 12s) were recorded. Immediately after tracheal intubation and every 5 min thereafter the investigator counted the number of tactile TOF responses. The duration of action of rocuronium was defined as the time from the end of injection of rocuronium until reappearance of first tactile response to TOF stimulation. Results: There were twelve patients in the 0.4mg/kg rocuronium group, two in the 0.8mg/kg group, and one in the 1.2mg/kg rocuronium group with an unacceptable intubation grade caused by sustained coughing at intubation. The D90 and D95 doses were 0.83(0.59 -1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D50 and D95 doses were 43min and 52 min, respectively. Conclusion: After induction with pethedine and sodium thiopentone, rocuronium in a dose of 0.8mg/kg produces equivalent intubating conditions as that of 1.2mg/kg after 60 seconds of administration

Evaluation of 51W89 for Tracheal Intubation in Surgical Patients during Nitrous Oxide/Oxygen/Propofol Anesthesia

1994 ◽  
Vol 81 (SUPPLEMENT) ◽  
pp. A1082 ◽  
Author(s):  
E. Schmautz ◽  
H. Deriaz ◽  
M. Vrillon ◽  
A. Lienhart
Keyword(s):  
Nitrous Oxide ◽  
Tracheal Intubation ◽  
Surgical Patients ◽  
Nitrous Oxide Oxygen

Evaluation of Neuromuscular and Cardiovascular Effects of Two Doses of Rapacuronium (ORG 9487) versus Mivacurium and Succinylcholine 

1999 ◽  
Vol 91 (6) ◽  
pp. 1648-1648 ◽  
Author(s):  
Rafael Miguel ◽  
Thomas Witkowski ◽  
Hideo Nagashima ◽  
Robert Fragen ◽  
Richard Bartkowski ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Cardiovascular Effects ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Open Label ◽  
Org 9487 ◽  
Train Of Four ◽  
Pressure Changes ◽  
To Receive ◽  
Nondepolarizing Muscle Relaxant

Background This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. Methods Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). Results Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P &lt; 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P &lt; 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P &lt; 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. Conclusions Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.

Early Reversal of Rapacuronium with Neostigmine 

1999 ◽  
Vol 91 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Robert Purdy ◽  
David R. Bevan ◽  
Francois Donati ◽  
Lance J. Lichtor
Keyword(s):  
Neuromuscular Block ◽  
Rapid Onset ◽  
Force Of Contraction ◽  
Mean Values ◽  
Neuromuscular Relaxant ◽  
Treatment Groups ◽  
Nitrous Oxide Oxygen ◽  
Train Of Four ◽  
To Receive ◽  
Different Doses

Background Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium. Methods One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine. Results Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine. Conclusions Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.

scholarly journals Prospective Clinical Comparative Assessment of Intubating Conditions and Neuromuscular Blocking Effects of Two Different Doses of Cisatracurium.

2020 ◽  
Vol 5 (1) ◽  
pp. 34-40
Author(s):  
Kailash Prabhudev ◽  
Channagouda Hadimani
Keyword(s):  
Study Groups ◽  
Neuromuscular Blocking ◽  
Allergic Reactions ◽  
Duration Of Action ◽  
Intubating Conditions ◽  
Elective Surgical Procedures ◽  
Blocking Effects ◽  
The Difference ◽  
Clinically Significant ◽  
Different Doses

Background: To study the effects of two different doses of cisatracurium 0.15mg/kg and 0.2mg/kg regarding intubating conditions, duration of action, hemodynamic stability and allergic reactions.Subjects and Methods:60 patients posted for elective surgical procedures under general anaesthesia in various surgical disciplines were enrolled into the study and alternatively allocated patients into one of the two study groups of 30 each to receive either 0.15mg/kg or 0.2mg/kg of cisatracurium. Intubating conditions assessed as excellent, good, poor or not possible and duration of action assessed and noted. PR and BP monitored at regular timed intervals following muscle relaxant and allergic reactions evaluated clinically.Results:4×ED 95 dose of cisatracurium had statistically significantly longer duration of action and had produced proportionately excellent intubating conditions as compared to its 3×ED 95 dose. The mean duration of action after 4×ED 95 loading dose was 53.03±5.75 minutes and 45.16±4.41 minutes after 3×ED 95 dose and the difference was statistically and clinically significant. Proportionately 4×ED 95 dose of Cisatracurium had produced excellent intubating conditions as compared to its 3×ED 95 dose (90% vs 70%). Differences in hemodynamic changes (pulse rate and blood pressure) after the above doses were clinically insignificant. And none of the patients after either dose showed allergic reactions.Conclusion:Cisatracurium at a higher dose 0.2mg/kg (4×ED 95) as compared to its lower dose 0.15mg/kg (3×ED 95) provides longer duration of action and proportionately excellent intubating conditions. Both doses produced stable hemodynamic status without clinically significant changes in PR and BP. No allergic reactions were noted at both the doses.

scholarly journals Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers

2018 ◽  
Vol 128 (6) ◽  
pp. 1107-1116
Author(s):  
Josh D. Kaullen ◽  
Joel S. Owen ◽  
Kim L. R. Brouwer ◽  
Paul M. Heerdt ◽  
Cynthia A. Lien ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Blocking Agent ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Population Pharmacokinetic ◽  
Time Data ◽  
Muscle Twitch ◽  
Concentration Data ◽  
Duration Of Action

Abstract Background CW002 is an investigational nondepolarizing, neuromuscular blocking agent with a rapid onset and intermediate duration of action in animals. This is a single ascending dose, healthy subject study exploring tolerability, pharmacokinetics, and potency. Methods Population pharmacokinetic and pharmacokinetic/pharmacodynamic models were developed using plasma drug concentration data from a previously published dose–response study in 28 healthy subjects receiving single doses of CW002 during sevoflurane anesthesia. Subjects included in the models were from five different dose cohorts (cohorts 3, 4, 5, 6, and 8 receiving 0.04, 0.06, 0.08, 0.10, and 0.14 mg/kg, respectively). Serial arterial plasma concentrations and muscle twitch heights were monitored. Results A four-compartment model was fit to the concentration–time data, whereas a transit compartment with a sigmoid Emax model was fit to the pharmacokinetic/pharmacodynamic data. The population pharmacokinetics of CW002 was linear with very low interindividual variability in clearance (10.8%). Simulations were conducted to predict the onset and offset of effect at 2×, 3×, and 4× ED95. The time to 80% block was predicted to be 1.5, 0.8, and 0.7 min for 2×, 3×, and 4× ED95 doses, respectively. The simulated 25 to 75% recovery index was independent of dose. Conclusions CW002 has predictable pharmacokinetics and is likely to have a rapid onset with an intermediate duration of action at 3× ED95. This model provides information to inform critical decisions (e.g., dose, study design) for continued development of CW002.

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