ABSTRACT
Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS
Subject(s)
Humans , Male , Female , Adult , Patients/classification , Respiratory Distress Syndrome, Newborn/diagnosis , Pharmaceutical Preparations/analysis , Conscious Sedation/adverse effects , Midazolam/agonists , Propofol/agonists , Cytokines/administration & dosage , Dexmedetomidine/agonistsABSTRACT
Pentameric glycine receptors (GlyRs) couple agonist binding to activation of an intrinsic ion channel. Substitution of the R271 residue impairs agonist-induced activation and is associated with the human disease hyperekplexia. On the basis of a homology model of the α1 GlyR, we substituted residues in the vicinity of R271 with cysteines, generating R271C, Q226C, and D284C single-mutant GlyRs and R271C/Q226C and R271C/D284C double-mutant GlyRs. We then examined the impact of interactions between these positions on receptor activation by glycine and modulation by the anesthetic propofol, as measured by electrophysiological experiments. Upon expression in Xenopus laevis oocytes, D284C-containing receptors were nonfunctional, despite biochemical evidence of successful cell surface expression. At R271C/Q226C GlyRs, glycine-activated whole-cell currents were increased 3-fold in the presence of the thiol reductant dithiothreitol, whereas the ability of propofol to enhance glycine-activated currents was not affected by dithiothreitol. Biochemical experiments showed that mutant R271C/Q226C subunits form covalently linked pentamers, showing that intersubunit disulfide cross-links are formed. These data indicate that intersubunit disulfide links in the transmembrane domain prevent a structural transition that is crucial to agonist-induced activation of GlyRs but not to modulation by the anesthetic propofol and implicate D284 in the functional integrity of GlyRs.
Subject(s)
Propofol/chemistry , Propofol/pharmacology , Protein Subunits/chemistry , Protein Subunits/metabolism , Receptors, Glycine/chemistry , Receptors, Glycine/metabolism , Stiff-Person Syndrome/genetics , Stiff-Person Syndrome/metabolism , Anesthetics, Intravenous , Animals , Disulfides/chemistry , Dithiothreitol/chemistry , Humans , Ligand-Gated Ion Channels/agonists , Ligand-Gated Ion Channels/chemistry , Ligand-Gated Ion Channels/metabolism , Mutation/drug effects , Neurotransmitter Agents/chemistry , Neurotransmitter Agents/metabolism , Oocytes/chemistry , Oocytes/drug effects , Propofol/agonists , Protein Binding/drug effects , Protein Binding/genetics , Protein Structure, Tertiary/drug effects , Protein Subunits/genetics , Stiff-Person Syndrome/physiopathology , Up-Regulation/drug effects , Xenopus laevisABSTRACT
STUDY OBJECTIVE: To evaluate the influence of aging on lidocaine requirements for propofol-induced pain on injection. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: The study was undertaken at a University hospital. PATIENTS: 160 ASA physical status I and II adult patients scheduled for elective surgery with general anesthesia. INTERVENTIONS: Patients received placebo (saline) or lidocaine intravenously at three different doses (10, 20, or 40 mg), with venous occlusion for two minutes, followed by injection of propofol 0.5 mg/kg into a dorsal hand vein. MEASUREMENT AND MAIN RESULTS: Pain during injection of propofol was evaluated. For young patients, the frequency of propofol-induced pain was 70% in patients receiving lidocaine 10 mg (P = not significant); 50% in those receiving lidocaine 20 mg (P = not significant); and 30% in those receiving lidocaine 40 mg (P < 0.05), compared with placebo (80%). For elderly patients, 15 patients (75%) complained of pain in the placebo group, compared with 13 (65%) in the lidocaine 10 mg group (P = not significant); 5 (25%) in the lidocaine 20 mg group (P < 0.05); and 4 (20%) in the lidocaine 40 mg group (P < 0.05). CONCLUSIONS: A lidocaine dose of 40 mg for young patients and 20 mg for old patients, with venous occlusion for two minutes, is sufficient to reduce pain on injection of propofol.
