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Biomedical subjects

James E Caldwell

Publications and source records attributed to James E Caldwell.

6 recordsLinked to original sources

Influence of chronic phenytoin administration on the pharmacokinetics and pharmacodynamics of vecuronium.

BACKGROUND: The duration of action of vecuronium is reduced in patients receiving phenytoin. In this study, the authors examined, simultaneously, the influence of phenytoin on both the pharmacokinetics and the pharmacodynamics of vecuronium. METHODS: This study was approved by the institutional review board of the University of California, San Francisco, and patients gave written informed consent. Twenty-two patients, 11 taking phenytoin and all scheduled to undergo prolonged neurosurgical procedures with general anesthesia, participated in the study. In 12 patients (6 phenytoin, 6 control), vecuronium was infused at 7.5 microg x kg(-1) x min(-1) until the first response (T1) of each train-of-four decreased by 50%; in the remaining 10 patients (5 phenytoin, 5 control), 200 microg/kg vecuronium was infused over 10 min. Arterial blood samples were drawn at intervals over the next 5-7 h. Plasma concentrations of vecuronium and 3-desacetylvecuronium were measured by capillary gas chromatography. Pharmacokinetic and pharmacodynamic modeling was used to characterize the disposition of vecuronium and patient responses to it in the two groups. RESULTS: Clearance was typically increased by 138% (95% confidence interval, 93-183%) in patients taking phenytoin. The effect of vecuronium was well described using a sigmoid Emax model. The concentration of vecuronium giving 50% twitch depression was increased 124% (45-202%) in patients taking phenytoin. CONCLUSIONS: Chronic phenytoin therapy reduces the effect of vecuronium by mechanisms that include both increased vecuronium metabolism and reduced sensitivity of the patient to circulating concentrations of vecuronium.

Adult↗

Muscle relaxation does not alter hypnotic level during propofol anesthesia.

UNLABELLED: Electromyographic (EMG) activity can contaminate electroencephalographic signals. Paralysis may therefore reduce the Bispectral Index (BIS) by alleviating artifact from muscles lying near the electrodes. Paralysis may also reduce signals from muscle stretch receptors that normally contribute to arousal. We therefore tested the hypothesis that nondepolarizing neuromuscular block reduces BIS. Ten volunteers were anesthetized with propofol at a target effect site concentration of 3.8 plus/minus 0.4 microg/mL. A mivacurium infusion was adjusted to vary the first twitch (T1) in a train-of-four to 80%, 30%, 20%, 15%, 10%, 5%, or 2% of the prerelaxant intensity. At each randomly assigned T1, we measured BIS and frontal-temporal EMG intensity. BIS averaged 95 plus/minus 4 before induction of anesthesia, and decreased significantly to 40 plus/minus 5 after propofol administration. However, there were no significant differences at the designated block levels. Frontal-temporal EMG intensity averaged 47 plus/minus 3 dB before induction of anesthesia, and decreased significantly to 27 plus/minus 1 dB after propofol administration. However, there were no significant differences at the designated block levels. These data suggest that the BIS level and EMG tone are unaltered by mivacurium administration during propofol anesthesia. IMPLICATIONS: Neuromuscular block level did not alter Bispectral Index (BIS) during propofol anesthesia, either by reducing electromyographic artifact or by decreasing afferent neuronal input. The BIS will thus comparably estimate sedation in deeply unconscious patients who are paralyzed, partially paralyzed, or unparalyzed.

Adult↗

A comparison of three anesthetic techniques in patients undergoing craniotomy for supratentorial intracranial surgery.

UNLABELLED: Several anesthetic techniques have been used successfully to provide anesthesia for resection of intracranial supratentorial mass lesions. One technique used to enhance recovery involves changing anesthesia from vapor-based to propofol-based for cranial closure. However, there are no data to support a beneficial effect of this approach in the immediate postoperative period after craniotomy. We evaluated 3 anesthetic techniques in 60 patients undergoing elective surgery for supratentorial mass lesions. Patients were randomly assigned to three anesthesia study groups: propofol infusion, isoflurane inhalation, and these two techniques combined. In the combination group, once the dura was closed, isoflurane was discontinued and propofol infusion simultaneously started. We studied intra- and postoperative hemodynamics and several recovery variables for 2 h after the end of anesthesia. Baseline and average intraoperative blood pressure and heart rate values did not differ among the groups. Heart rate and blood pressure increased similarly in all groups in response to intubation and pin placement and postoperatively. None of the recovery event times (open eyes, extubation, follow commands, oriented, Aldrete score) or psychomotor test performance differed significantly. We conclude that the sequential administration of isoflurane and propofol did not provide earlier recovery and cognition than the intraoperative use of isoflurane alone. IMPLICATIONS: We evaluated three anesthetic techniques with and without propofol in patients undergoing elective surgery for supratentorial mass lesions by using a prospective, randomized clinical study design and found that the three anesthetics did not differ in intra- or postoperative hemodynamic stability or early postoperative recovery variables.

Adult↗

Efficacy of tactile-guided reversal from cisatracurium-induced neuromuscular block.

BACKGROUND: Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response. METHODS: Anesthesia was induced in 64 adults with 2-5 microg/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured. RESULTS: Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences). CONCLUSIONS: To achieve rapid (within 10 min) reversal to a TOF ratio of 0.7 in more than 87% of patients, three or four tactile responses should be present at the time of neostigmine administration. It was not possible within 30 min to achieve a TOF ratio of 0.9 in all patients, regardless of the number of tactile responses present at neostigmine administration.

Adolescent↗

The influence of mild hypothermia on the pharmacokinetics and time course of action of neostigmine in anesthetized volunteers.

BACKGROUND: The pharmacokinetics, maximum effect, and time course of action of neostigmine were studied in seven human volunteers. METHODS: Each volunteer was studied twice, during both normothermia and hypothermia. Anesthesia was induced with 30 microg/kg alfentanil and 3 mg/kg propofol, and was maintained with 60-70% nitrous oxide and 0.7-0.9% isoflurane. The mechanical response of the adductor pollicis to train-of-four stimulation of the ulnar nerve was recorded, and central body temperature maintained stable at either less than 34.5 degrees C or greater than 36.5 degrees C by surface cooling or warming. Before neostigmine administration, a stable 5% twitch height was obtained by an infusion of vecuronium, and the infusion rate remained unchanged thereafter. Neostigmine, 70 microg/kg, was then infused over 2 min, and blood samples for estimation of neostigmine concentrations were collected at intervals for 240 min. RESULTS: With hypothermia, the central volume of distribution of neostigmine decreased by 38%, and onset time of maximum effect increased (4.6 vs. 5.6 min). Hypothermia did not change the clearance (696 ml/min), maximum effect, or duration of action of neostigmine. CONCLUSIONS: The efficacy of neostigmine as an antagonist of vecuronium-induced neuromuscular block is not altered by mild hypothermia.

Adult↗