Anesthesia and analgesia
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Anesthesia and analgesia · Oct 2015
Several Ryanodine Receptor Type 1 Gene Mutations of p.Arg2508 Are Potential Sources of Malignant Hyperthermia.
Malignant hyperthermia (MH) is a pharmacogenetic disorder that occurs in predisposed individuals after exposure to volatile anesthetics or depolarizing muscle relaxants. Genetic mutations of ryanodine receptor 1 (RYR1), which are considered to cause MH, are found mainly in 3 regions called "hotspots." There are sometimes multiple mutations at the same site of RYR1. Although p.Arg2508 of RYR1 is located outside hotspots, several mutations or variants (including the known MH causative mutation p.Arg2508Cys) have been identified in this region. We hypothesized that any mutations or variants in RYR1 p.Arg2508 cause important changes in pathological conditions related to MH. In this study, we analyzed the functions of 4 different RYR1 variants containing mutations at p.Arg2508. ⋯ Any of these 4 mutations in RYR1 p.Arg2508 may cause important changes related to MH. Studying the effects of changes in amino acids at 2508 in RYR1 on the movement of this large protein may lead to a better understanding of the pathology of MH events.
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Anesthesia and analgesia · Oct 2015
A Recirculatory Model for Pharmacokinetics and the Effects on Bispectral Index After Intravenous Infusion of the Sedative and Anesthetic AZD3043 in Healthy Volunteers.
AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers. ⋯ AZD3043 had a high clearance and a low apparent volume of distribution, leading to a short half-life. However, the apparent volume of distribution was dose dependent (P < 0.001), leading to an increased half-life with increasing dose. The distribution to the effect site was fast and together with the short plasma half-life led to a fast onset and offset of effects.
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Anesthesia and analgesia · Oct 2015
A Bolus and Bolus Followed by Infusion Study of AZD3043, an Investigational Intravenous Drug for Sedation and Anesthesia: Safety and Pharmacodynamics in Healthy Male and Female Volunteers.
AZD3043 (THRX-918661) is an investigational phenylpropanoid sedative/anesthetic that is rapidly metabolized by esterases in blood and liver. In the first-in-man study, a 30-minute constant IV infusion of AZD3043 induced anesthesia without major safety or tolerability concerns and with rapid recovery characteristics. ⋯ AZD3043 provided rapid recovery from anesthesia with maintained ventilation. Further studies are warranted in a clinical setting.
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Anesthesia and analgesia · Oct 2015
Labor Analgesia Consumption and Time to Neuraxial Catheter Placement in Women with a History of Surgical Correction for Scoliosis: A Case-Matched Study.
Neuraxial analgesic techniques are the most effective form of labor analgesia. Small studies (9-21 patients), conducted 10 to 20 years ago, demonstrated successful neuraxial labor analgesia in only 50% to 66% of patients with surgical correction for scoliosis. Newer surgical techniques for scoliosis correction make the epidural space more accessible, but postsurgical changes may still alter the efficacy of neuraxial labor analgesia. The purpose of this prospective case-matched study was to compare hourly bupivacaine consumption and time to placement of neuraxial technique in laboring women with spinal instrumentation compared with women without previous back surgery. ⋯ The findings of this investigation suggest that previous surgery for scoliosis repair does not affect neuraxial labor analgesia consumption, but performance of the neuraxial technique is more difficult. Our findings suggest that neuraxial labor analgesia should be offered to parturients with previous surgery for scoliosis repair although informed consent should include a discussion of the possibility of technical difficulties and surgical anesthesia failure.