Association between neuromuscular blocking agent sensitivity during anesthesia and neuromotor synapse microanatomy in children with cerebral palsy

2015 ◽  
Vol 57 ◽  
pp. 22-22
Keyword(s):  
Cerebral Palsy ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Children With Cerebral Palsy

scholarly journals Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

2018 ◽  
Vol 129 (5) ◽  
pp. 970-988 ◽  
Author(s):  
John J. Savarese ◽  
Hiroshi Sunaga ◽  
Jeff D. McGilvra ◽  
Matthew R. Belmont ◽  
Matthew T. Murrell ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Neuromuscular Blockade ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Duration Of Action ◽  
Short Acting ◽  
Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

The Interaction Between Suxamethonium and the Succeeding Non-Depolarizing Neuromuscular Blocking Agent

1991 ◽  
Vol 35 (1) ◽  
pp. 8
Author(s):  
J. SWEN ◽  
H. W. J. ROOT ◽  
A. BENCINI ◽  
J. M. KET ◽  
J. HERMANS ◽  
...  
Keyword(s):  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent

SECTION ON CRITICAL CARE 1996 ANNUAL MEETING PROGRAM

PEDIATRICS ◽  
1996 ◽  
Vol 98 (3) ◽  
pp. 541-550
Keyword(s):  
Heart Surgery ◽  
Venous Pressure ◽  
Blocking Agent ◽  
Congenital Heart Surgery ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Hemodynamic Effects ◽  
Open Label ◽  
Maximal Increase ◽  
Hemodynamic Status

Background: Some neuromuscular blocking agents have previously been shown to have clinically significant hemodynamic effects. These agents should obviously be avoided in patients whose hemodynamic status might be considered compromised. Rocuronium bromide (ROC) is a new steroidal non-depolarizing neuromuscular blocking agent recently approved for use by the FDA. The hemodynamic effects associated with its use in critically ill pediatric patients have not been reported. Methods: In a nonrandomized open-label study 10 infants and children (ages 1 mth to 68 mths, mean 14 mths; weight 2.9-16 kg, mean 6.3 kg) were given two doses of ROC (0.6 mg/kg followed by 0.9 mg/kg) as a neuromuscular blocking agent after congenital heart surgery, once their hemodynamic status was thought to be stable (mean 20 hours after admission). All patients were sedated with morphine, fentanyl, midazolam or a combination of fentanyl and midazolam. Hemodynamic parameters including heart rate (HR), blood pressure (BP), central venous pressure, left atrial pressure and pulmonary artery pressure were recorded when possible just prior to injection and at one minute, five minutes and ten minutes. Any apparent adverse effects were also noted. Results: ROC produced small, transient increases in HR and BP at both 0.6 and 0.9 mg/kg doses. For both doses, the peak increase in BP was noted at one minute, with BP returning to baseline by five minutes. The maximal mean increase in BP for either group at any time period was 6%. The maximal increase in mean BP in any patient was 22%. Peak HR response was noted at five minutes in both groups and HR did not return to baseline by 10 minutes.

The Clinical Neuromuscular Pharmacology of 51W89 in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia 

1995 ◽  
Vol 82 (5) ◽  
pp. 1139-1145 ◽  
Author(s):  
Matthew R. Belmont ◽  
Cynthia A. Lien ◽  
Steve Quessy ◽  
Martha M. Abou-Donia ◽  
Amy Abalos ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Surgical Procedures ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Blocking Effect ◽  
Preclinical Studies ◽  
Physical Status ◽  
Elective Surgical Procedures ◽  
Recovery Index

Background Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. Methods Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length. Results The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min. Conclusions 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.

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