Anesthesia and analgesia
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Anesthesia and analgesia · Apr 1998
Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep.
Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (levobupivacaine) is the subject of current clinical evaluation. We conducted partial cross-over systemic and regional pharmacokinetic studies of i.v. bupivacaine (12.5-200 mg) and levobupivacaine (6.25-200 mg) in ewes. Enantiospecific analysis of blood drug concentration-time data and of regional myocardial and brain drug mass balance data indicated that (a) there was a higher mean total body clearance of R(+)-bupivacaine than of S(-)-bupivacaine (as previously reported); (b) there were no differences in the systemic pharmacokinetics of S(-)-bupivacaine whether administered alone or as a component of bupivacaine; (c) there was no evidence of dose-dependent pharmacokinetics with either enantiomer; (d) for both enantiomers, mean calculated myocardial tissue concentrations of 1%-4% dose occurred between 3 and 5 min. Mean brain concentrations of 0.2%-1% dose occurred between 2 and 4 min after the administration of bupivacaine but between 4 and 5 min after the administration of levobupivacaine. There was no evidence that systemic toxicity induced by these local anesthetics significantly modified their pharmacokinetics, and there was no evidence of an enantiomer-enantiomer pharmacokinetic interaction for bupivacaine. ⋯ Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. As a part of its preclinical evaluation, this study considered whether levobupivacaine behaved kinetically in the body in the same way as when administered as a component of bupivacaine.
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Anesthesia and analgesia · Apr 1998
Chloral hydrate sedation: the additive sedative and respiratory depressant effects of nitrous oxide.
The combination of chloral hydrate and nitrous oxide (N2O) is often used for sedation in pediatric dentistry. The purpose of this study was to determine the extent to which N2O increases the level of sedation and respiratory depression in children sedated with chloral hydrate. Thirty-two children, 1-9 yr, received chloral hydrate, 70 mg/kg (maximum 1.5 g), and then received N2O (30% and 50%). Hypoventilation (maximal PETCO2 > 45 mm Hg) occurred in 23 (77%) children during administration of chloral hydrate alone, in 29 (94%) breathing 30% N2O (P = 0.08 versus control), and in 29 (97%) breathing 50% N2O (P = 0.05 versus control). Mean PETCO2 was increased during 30% (P = 0.007) and 50% (P = 0.02) N2O administration. Using chloral hydrate alone, 8 (25%) children were not sedated, 10 (31%) were consciously sedated, and 14 (44%) were deeply sedated. Using 30% N2O, 2 children (6%) were not sedated, 0 were consciously sedated, and 29 (94%) were deeply sedated (P < 0.0001). Using 50% N2O, 1 child (3%) was not sedated, 0 were consciously sedated, 27 (94%) were deeply sedated, and 1 (3%) had no response to a painful stimulus (P < 0.0001). We conclude that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children. ⋯ Pediatric sedation in the dental office often consists of nitrous oxide (N2O) after chloral hydrate premedication. We found that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children.
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Anesthesia and analgesia · Apr 1998
Comparative StudyThe effect of prior dural puncture on cerebrospinal fluid sufentanil concentrations in sheep after the administration of epidural sufentanil.
Sufentanil is a highly lipid soluble opioid that provides potent analgesia when administered in the subarachnoid space. Unfortunately, the penetration of sufentanil into the cerebrospinal fluid (CSF) after epidural administration is poor, and limits its effectiveness for epidural analgesia. Dural puncture may enhance the movement of epidural sufentanil into the subarachnoid space and increase its effectiveness. To determine whether the administration of epidural sufentanil adjacent to a dural puncture results in significantly greater CSF concentrations, 18 adult ewes were studied. Animals in the control group had an epidural catheter placed at the superior border of the pelvis without dural puncture. Animals in the study group had an epidural catheter placed, followed by a dural puncture performed using an 18-gauge Touhy needle. The dural puncture was performed one interspace cephalad to the epidural catheter. One hour after dural puncture, each animal received a loading dose of 0.35 microg/kg of sufentanil (5 microg/mL) through the epidural catheter, followed by an infusion of epidural sufentanil 0.15 microg x kg(-1) x h(-1) for a period of 4 h. After 4 h, CSF was sampled from a site one interspace caudad to the epidural catheter as well as at the cisterna magna. The mean CSF concentration of sufentanil at the level of the pelvis for animals with a dural puncture was 12.1 +/- 3.0 ng/mL compared with 1.8 ng/mL in controls with intact dura. Sufentanil concentrations at the cisterna magna were below the level of detection (0.08 ng/mL) for all animals in both groups. We conclude that an 18-gauge dural puncture significantly increases movement of sufentanil from the epidural to the intrathecal space. This increase in sufentanil concentration at the level of the pelvis was not associated with detectable levels of sufentanil at the brainstem. ⋯ This study addresses the effect of dural puncture on spinal fluid concentrations of sufentanil after epidural administration. A sheep model was used to measure drug concentrations in the spinal fluid at the levels of the pelvis and brainstem after epidural administration. Dural puncture significantly enhanced movement of sufentanil into the spinal fluid at the level of the pelvis, but brainstem concentrations were below the level of detection. Analgesic concentrations of spinal sufentanil in the clinical setting, as well as brainstem concentrations associated with respiratory depression, have yet to be defined.
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Anesthesia and analgesia · Apr 1998
Laryngeal mask airway position and the risk of gastric insufflation.
A potential risk of the laryngeal mask airway (LMA) is an incomplete mask seal causing gastric insufflation or oropharyngeal air leakage. The objective of the present study was to assess the incidence of LMA malpositions by fiberoptic laryngoscopy, and to determine their influence on gastric insufflation and oropharyngeal air leakage. One hundred eight patients were studied after the induction of anesthesia, before any surgical manipulations. After clinically satisfactory LMA placement, tidal volumes were increased stepwise until air entered the stomach, airway pressure exceeded 40 cm H2O, or air leakage from the mask seal prevented further increases in tidal volume. LMA position in relation to the laryngeal entrance was verified using a flexible bronchoscope. The overall incidence of LMA malpositions was 40% (43 of 108). Gastric air insufflation occurred in 19% (21 of 108), and in 90% (19 of 21) of these patients, the LMA was malpositioned. Oropharyngeal air leakage occurred in 42%, and was independent of LMA position. We conclude that clinically unrecognized LMA malposition is a significant risk factor for gastric air insufflation. ⋯ Routine placement of laryngeal mask airways does not require laryngoscopy. In our study, fiberoptic verification of mask position revealed suboptimal placement in 40% of cases. Such malpositioning considerably increased the risk of gastric air insufflation.
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Anesthesia and analgesia · Apr 1998
The influence of acute normovolemic hemodilution on the dose-response and time course of action of vecuronium.
To evaluate the influence of acute isovolemic hemodilution on the dose-response and time course of action of vecuronium, we studied 60 adult patients with and without hemodilution during surgery. The patients with hemodilution underwent major elective plastic surgery with an anticipated surgical loss of more than 600 mL. Anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 microg/kg i.v. and was maintained with 60% nitrous oxide in oxygen. Further increments of thiopental 2 mg/kg or fentanyl 2 microg/kg were given as required. Acute isovolemic hemodilution in the hemodilution group was induced by drainage of venous blood and an i.v. infusion of lactated Ringer's solution and 6% dextran, during which hematocrit and hemoglobin decreased from 45.7% to 26.2% and from 148.5 g/L to 90.2 g/L, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s, and the percent depression of T1 response was used as the study parameter. The dose-response relationships of vecuronium in the two groups were determined by using the cumulative dose-response technique. The results showed that during hemodilution, the dose-response curve of vecuronium was shifted to the left in a parallel fashion, and the potency of vecuronium was increased. There were significant differences in the 50%, 90%, and 95% effective doses between the two groups. After the i.v. administration of vecuronium 80 microg/kg, vecuronium-induced neuromuscular block was significantly longer in the patients with hemodilution than in the control patients. The duration of peak effect, clinical duration, recovery index, and total duration in the hemodilution patients were significantly different from those in the control patients. We conclude that hemodilution induces significant changes in the pharmacodynamics of vecuronium. ⋯ We found that patients with hemodilution were 20% more sensitive to vecuronium and had a longer duration of action after the administration of the same dose than the controls. This should be taken into account when vecuronium is used as a muscle relaxant during acute hemodilution.