Thiopental For Induction Of Anesthesia Research Articles

Intravenous (non-opioid) anesthesia

Intravenous anesthetics are used for induction and maintenance of anesthesia (eg, total intravenous anesthesia), as well as for sedation during local anesthesia (ie, regional anesthetic techniques and monitored anesthesia care [MAC]). The most commonly used IV anesthetics are propofol and thiopental. In addition, methohexital is used for ECT and etomidate is used in hemodynamically unstable patients. Finally, ketamine is increasingly used as an adjuvant to propofol and thiopental for induction of anesthesia, and for sedation-analgesia as an alternative to opioid analgesics.

Textbook of Intravenous Anesthesia

Textbook of Intravenous Anesthesia

Comparison of Rocuronium, Succinylcholine, and Vecuronium for Rapid-sequence Induction of Anesthesia in Adult Patients

Succinylcholine has been the agent of choice when clinical conditions require emergency airway protection during a rapid-sequence induction of anesthesia. Rocuronium, a new nondepolarizing muscle relaxant with a brief onset of action, but devoid of the adverse reactions associated with succinylcholine, may be an alternative to succinylcholine. To test this hypothesis, the authors compared rocuronium with succinylcholine and vecuronium for rapid-sequence induction of anesthesia. Fifty patients, ASA 1-3, were randomly designated to receive one of three intravenous doses of rocuronium (0.6, 0.9, and 1.2 mg/kg), vecuronium (0.1 mg/kg), or succinylcholine (1.0 mg/kg). Patients were premedicated with midazolam and fentanyl, and received 2-7 mg/kg thiopental for induction of anesthesia. Sixty seconds after receiving a muscle relaxant, intubation of the trachea was attempted by a clinician who was blinded to the muscle relaxant administered. Neuromuscular monitoring was established before administration of the muscle relaxant. The time from injection of muscle relaxant until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded. Tracheal intubating conditions were evaluated, and the presence or absence of fasciculations was noted. Onset times for patients receiving 0.9 mg/kg (75 +/- 28 s) and 1.2 mg/kg rocuronium (55 +/- 14 s), and succinylcholine (50 +/- 17 s) were similar. Onset times for the groups given 0.6 mg/kg rocuronium (89 +/- 33 s) and vecuronium (144 +/- 39 s) were significantly longer. Clinical duration of action was longest with 1.2 mg/kg rocuronium, similar with 0.6 and 0.9 mg/kg rocuronium, and vecuronium, and least with succinylcholine. There is a dose-dependent decrease in onset time with rocuronium. The onset times for the two larger doses of rocuronium were similar to that for succinylcholine, but clinical duration of action with rocuronium was significantly longer. The brief onset time achieved with rocuronium indicates that administration of 0.9-1.2 mg/kg is an acceptable alternative to succinylcholine for rapid-sequence induction of anesthesia.

A Comparison between Propofol and Thiopental for Induction of Anesthesia for Elective Caesarean Section

A Comparison between Propofol and Thiopental for Induction of Anesthesia for Elective Caesarean Section

Population Pharmacokinetics and Pharmacodynamics of Thiopental

The authors have previously attributed the mechanism for the 50-67% decrease in the required dose of thiopental for induction of anesthesia in aged human patients to a decrease in the initial distribution volume for thiopental. Using a larger group of patients and volunteers studied in the laboratory, the authors have re-examined thiopental pharmacokinetics and EEG pharmacodynamics relative to age. A population data analysis approach (NONMEM), using a three-compartment model, was used to analyze bolus and rapid iv infusion thiopental serum concentration versus time data from 64 subjects. A one-compartment model was also used on the first 10 min of serum concentration data to focus only on the initial distribution phase. The population pharmacokinetic analysis demonstrated that when thiopental is administered via an iv bolus injection, traditional pharmacokinetic models limit the accurate characterization of thiopental distribution phenomena. Using the rapid iv infusion data, the pharmacokinetic mechanism for the decreased thiopental dose requirement in the elderly was a decreased rapid intercompartment clearance. Thiopental distribution from the central compartment of the three-compartment model to the rapidly equilibrating compartment (rapid intercompartment clearance) decreased 27% between the ages of 35-80 yr and decreased 34% in the one-compartment analysis. EEG spectral edge versus time data from 37 subjects was analyzed with a semiparametric modelling approach to remove the disequilibrium between thiopental serum concentration and the spectral edge. A population data analysis (NONMEM) was performed with several pharmacodynamic models. There was no age-related change in brain responsiveness or pharmacodynamics when the spectral edge is used as a measure of drug effect.

Etomidate versus Thiopental for Induction of Anesthesia

Hemodynamic changes and side effects of anesthesia induction with etomidate or thiopental were evaluated in 83 ASA class I or II patients. Patients were randomly assigned to one of 12 groups according to pretreatment drug (fentanyl, 100 micrograms, or normal saline intravenously), induction agent (etomidate, 0.4 mg/kg, or thiopental, 4 mg/kg), and maintenance anesthetic technique (isoflurane-oxygen, isoflurane-nitrous oxide-oxygen, or fentanyl-nitrous oxide-oxygen). The purpose of this experiment, of factorial design, was to evaluate the combined effects of two or more experimental variables used simultaneously and to observe interaction effects. There were significant increases in heart rate in all groups, especially after tracheal intubation. These increases were attenuated but not eliminated by fentanyl pretreatment. Systolic arterial blood pressure increased significantly after intubation and was not affected either by fentanyl pretreatment or by the induction agent. Patients in whom anesthesia was induced with etomidate had a greater incidence of pain on injection and myoclonus and a lesser incidence of apnea than patients in whom anesthesia was induced with thiopental. Fentanyl pretreatment significantly decreased the incidence of pain on injection and myoclonus, but it increased the incidence of apnea when anesthesia was induced with etomidate. The incidence of postoperative nausea and vomiting was similar after thiopental and etomidate and was unaffected by fentanyl pretreatment. (ABSTRACT TRUNCATED AT 250 WORDS)

Midazolam: the first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia.

Midazolam is a 1,4-benzodiazepine derivative with a unique chemical structure: depending on environmental pH, the drug can produce highly water-soluble salts (pH less than 4) or exist in lipophilic diazepine ring-closed form (pH greater than 4). This characteristic contributes to rapid onset of action and to good local tolerance after parenteral administration. After both oral and parenteral administration, midazolam has a fast absorption rate and is rapidly excreted, with a half-life of only about 2 hours. A reasonably good correlation has been found between plasma levels and clinical effects, indicating a fast but brief response. As a hypnotic, midazolam is mainly indicated in insomniac patients with difficulties in falling asleep or having a pathologic sleep pattern during the first half of the night. No marked hangover effects are present the next morning. In anesthesiology, midazolam appears to be a useful, short-acting, sedative-anxiolytic and amnesic premedicant after both oral and parenteral administration. In minor surgery, however, the slow, unpredictable onset and variable duration of action, as compared with thiopental, may inhibit its routine use as an induction agent, especially in young patients, without heavy premedication. In major surgery, midazolam is an alternative to thiopental for induction of anesthesia in spite of its slow, variable induction time. Its advantages include good cardiovascular stability, transient and mild respiratory depression, low frequency of venous irritation, production of anterograde amnesia and short duration of action in comparison with other benzodiazepines.

Pharmacokinetics and Anesthetic Potency of a Thiopental Isomer

□ In developing a high-performance liquid chromatographic assay for thiopental [5-ethyl-5-(l-methylbutyl)-2-thiobarbituric acid], a thiopental isomer [5-ethyl-5-(l-ethylpropyl)-2-thiobarbituric acid] was found. This isomer occurs (6–7%) in supposedly pure thiopental and in the commercially available thiopental sodium administered to patients for induction of anesthesia. A similar type of isomer also occurs in pentobarbital, the oxybarbiturate analogue of thiopental. Because the disposition and anesthetic potency of the isomer is unknown, its pharmacokinetic properties were determined in humans and its anesthetic potency in mice. In five surgical patients, the terminal elimination halflife, clearance, and volume of distribution at steady state of the isomer were not statistically different from those of thiopental. In mice, the isomer proved to be as effective as thiopental for induction of anesthesia. The LD50 and sleep time at one-half the LD50 did not statistically differ between the two compounds in mice. The close structural similarity of thiopental and the isomer results in similar pharmacokinetic and anesthetic properties. It does not appear critical that the isomer be separated from thiopental in subsequent pharmacological research.

Low-Dose Fentanyl Blocks Circulatory Responses to Tracheal Intubation

The effect of fentanyl, 8 micrograms/kg, used as an adjunct to thiopental for induction of anesthesia, on the circulatory response to tracheal intubation was investigated in 36 patients undergoing major vascular surgery. Patients were randomly assigned to receive either thiopental, 6 mg/kg, alone (N = 18), or thiopental, 3 mg/kg, along with fentanyl, 8 micrograms/kg (N = 18), for induction of anesthesia. The electrocardiogram, arterial pressure, pulmonary capillary wedge pressure, cardiac output, and central venous pressure were measured during induction of anesthesia, laryngoscopy, and intubation. Mean arterial blood pressure increased more following intubation in patients given thiopental than in patients given fentanyl-thiopental, reaching a peak value of 144 +/- 4 torr in patients receiving thiopental only, compared with 108 +/- 6 torr in those receiving fentanyl and thiopental (p less than 0.0001). Increases in systolic blood pressure, diastolic blood pressure, and pulmonary capillary wedge pressure with intubation were also significantly greater following administration of thiopental than following fentanyl-thiopental. Doses of fentanyl that are low enough to cause little postoperative respiratory depression significantly blunt postintubation hypertension when used as an adjunct to thiopental.

Comparison of Thiopental and Midazolam on the Neuromuscular Responses to Succinylcholine or Pancuronium in Humans

Midazolam (0.3 mg/kg) was compared to thiopental (4.0 mg/kg) for possible interactions with succinylcholine or pancuronium when used for induction of anesthesia. Neuromuscular function was monitored by recording the force of thumb adduction in response to ulnar nerve stimulation. Following induction of anesthesia with either midazolam (N = 10) or thiopental (N = 10), stable muscle-twitch tension was obtained and succinylcholine (1 mg/kg) was given intravenously. The duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam or thiopental. An additional group of patients anesthetized and monitored in the same manner received pancuronium (0.025 mg/kg) in incremental doses until a 99% depression of muscle-twitch tension was obtained. Dose-response curves for pancuronium, duration of blockade, and adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam (N = 10) or thiopental (N = 10). We conclude that the neuromuscular blockade produced by succinylcholine or pancuronium was no different in patients receiving either midazolam or thiopental for induction of anesthesia.

Low-Dose Fentanyl Blunts Circulatory Responses to Tracheal Intubation

The effect of fentanyl, 8 μg/kg. used as an adjunct to thiopental for induction of anesthesia, on the circulatory response to tracheal intubation was investigated in 36 patients undergoing major vascular surgery. Patients were randomly assigned to receive either thiopental, 6 mg/kg, alone (N = 181, or thiopental, 3 mg/kg, along with fentanyl, 8 μg/kg (N = 181, for induction of anesthesia. The electrocardiogram, arterial pressure, pulmonary capillary wedge pressure, cardiac output, and central venous pressure were measured during induction of anesthesia, laryngoscopy, and intubation. Mean arterial blood pressure increased more following intubation in patients given thiopental than in patients given fentanyl-thiopental, reaching a peak value of 144 ± 4 torr in patients receiving thiopental only, compared with 108 ± 6 torr in those receiving fentanyl and thiopental (p < 0.0001). Increases in systolic blood pressure, diastolic blood pressure, and pulmonary capillary wedge pressure with intubation were also significantly greater following administration of thiopental than following fentanyl-thiopental. Doses of fentanyl that are low enough to cause little postoperative respiratory depression significantly blunt postintubation hypertension when used as an adjunct to thiopental.

Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section.

This study was undertaken to investigate the effect of pregnancy on the disposition of thiopental and to determine the major factors which influence the placental transfer of the drug to the fetus. Maternal venous (MV) and umbilical venous (UV) and arterial (UA) blood samples were collected at delivery from 11 pregnant women at term who received thiopental for induction of anesthesia for elective cesarian section. A detailed study of the pharmacokinetics of thiopental was carried out in 7 of these subjects and blood samples were collected for 80 to 100 hours following thiopental administration. A transient rise in thiopental plasma concentration was observed at delivery. Mean values of pharmacokinetic parameters (plus or minus SD) were: initial distribution volume (V1) 17.31 (plus or minus 8.5), apparent volume of distribution (Vdbeta) 564 1 (plus or minus 343), volume of distribution at steady state (Vss) 2881 (plus or minus 180), systemic plasma clearance (Clp) 0.286 l/min (plus or minus 0.156), rate of change of volume of distribution at zero time (RVd0) 1.03 l/min (plus or minus 0.36) and elimination half-life (t1/2) 26.1 h (plus or minus 12.6). Comparison of these data with our previously reported data in nonpregnant surgical patients shows that Vdbeta, Vss, T1/2 are significantly greater at cesarian section (P less than 0.05) and that systemic plasma clearance shows a similar trend. UA and UV values at delivery were similar within individuals. There was no correlation between the ratio UV/MV at delivery and the dosing-delivery interval (delta t), or between UV and the administered dose or delta t. There were good correlations between UV (corrected for dose) and the reciprocals of V1, Vdbeta, Vss, and plasma clearance of thiopental. This demonstrates that differences in maternal distribution and elimination characteristics of thiopental may be more important determinants of intersubject differences in fetal drug exposure than differences in dose or delta t.

Diazepam vs thiopental for induction of anesthesia, : RUBIN A., ALLEN G. D. and EVERETT G. B. Dent. Abstr. 23 (1978) 518–519

Diazepam vs thiopental for induction of anesthesia, : RUBIN A., ALLEN G. D. and EVERETT G. B. Dent. Abstr. 23 (1978) 518–519