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Comparison of recovery tests after intravenous sedation with diazepam-methohexital and diazepam-methohexital and fentanyl.

A model for the assessment of recovery to street fitness from two commonly used techniques for intravenous sedation is described. Well-known psychometric research methods and simple paper-and-pencil tests that could be given by interested clinicians were used. The speed of recovery from diazepam-methohexital, and diazepam-methohexital and fentanyl (with naloxine reversal), did not differ significantly. Psychomotor skills were recovered before both perceptual and cognitive functions. Two simple paper-and-pencil tests easily identified perceptual and cognitive deficits at least three hours postoperatively.

Adult

[Dose-response relationship and serum concentrations of methohexital and hydroxymethohexital following rectal anesthesia induction with 1% and 5% methohexital solutions in children].

Dose-response-curves for rectal induction of anaesthesia in children with 1%- or 5%-methohexitone-solutions and dosages of 5, 10, 15, 20 and 25 mg/kg body wt. were obtained in 10 groups of 20 children. Methohexitone and hydroxy-methohexitone serum-levels were compared in another 23 children after application of 1%- or 5%-methohexitone-solutions at dosages of 15 and 20 mg/kg body wt. The sleep induction quota after 1%-methohexitone-solution in the 20 and 25 mg/kg body wt.-dosages was significantly higher, 20% and 25% respectively, and the mean sleep induction time shorter, 37% and 45% respectively compared with results after 5%. The change after 15 mg/kg body wt. was not significant. A study of dosages 5 and 10 mg/kg body wt. was discontinued due to insufficient effect. Methohexitone serum-levels ranged from 0.7-8 mg/l. All of the children after the use of 1%-methohexitone-solution, and only 60% after 5%-methohexitone had serum concentrations above the sleep inducing "borderline" concentration of 2 mg/l. The differences between mean methohexitone and hydroxy-methohexitone-serum-levels were not significant due to the small groups and the wide range of results. We conclude that individual dosages of 15 or 20 mg/kg body wt. 1%-methohexitone-solution should be applied according to clinical criteria such as physical and psychic status of the child.

Anesthesia, Rectal

Dissolving methohexital in a lipid emulsion reduces pain associated with intravenous injection.

Pain often accompanies intravenous injection of 1% methohexital. The aim of the present study was to test whether pain on injection could be reduced by dissolving methohexital in a lipid emulsion (study A) and whether this would affect anesthetic potency (study B). In study A, 24 healthy volunteers, 36 +/- 1 yr (mean +/- SE), were given 1 ml 1% methohexital in saline, 1 ml 1% methohexital in lipid emulsion, and 5 ml 0.1% methohexital in saline in random order. The injections were given in a small vein in the forearm at 5-min intervals. One minute after each injection, the subject was asked to assess the injection pain on a visual analog scale (0-100 mm). The pain score (median [range]) was 44.5 (0-77) after 1% methohexital in saline, 0.5 (0-26) after 1% methohexital in a lipid emulsion, and 1.0 (0-26) after 0.1% methohexital in saline. The pain score for 1% methohexital in saline was significantly greater than those for the other two solutions (P less than 0.001 for each comparison). In study B, 42 patients, 41 +/- 3 yr, were given 1% methohexital in lipid emulsion (n = 22) or 1% methohexital in saline (n = 20). A bolus of either solution was administered over 10 s, and the patient was considered asleep if there was no gross movement or response to verbal command 40-70 s after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Magnetic motor evoked potentials during methohexital anesthesia in the dog.

Magnetic motor evoked potentials (MMEPs) were recorded from the right cranial tibial muscle after magnetic stimulation of the left motor cortex in six dogs sedated with oxymorphone. Anesthesia was induced with an intravenous bolus of 5.5 mg/kg of methohexital and maintained with a methohexital infusion. The dogs inspired 100% oxygen during anesthesia. Blood pressure, heart rate, respiratory rate, esophageal temperature, and end-tidal carbon dioxide tension were recorded. The depth of anesthesia was increased until the amplitude of the MMEP was less than 5% of the control value, and the dogs were then allowed to recover. Every 5 minutes during anesthesia, a blood sample was taken for methohexital assay and at the same time, four replicate MMEPs were recorded. Plasma methohexital levels were significantly (P < 0.05) correlated with heart rate (p = 0.38) and end-tidal carbon dioxide tension (p = 0.49) and negatively correlated with respiratory rate (p = 0.74). There was no significant correlation between blood pressure and methohexital levels. The dogs regained consciousness at a plasma methohexital level of 10.4 +/- 3.8 micrograms/ml (mean +/- SD). The amplitude of the MMEP decreased significantly with increasing methohexital levels. In four dogs, the relationship was reasonably linear. The MMEP disappeared at a plasma methohexital level of 23 +/- 6.6 micrograms/ml. The latency of onset of the MMEP increased significantly from its control value of 14.7 +/- 1.0 ms to 17.5 +/- 1.3 ms at the highest methohexital levels at which MMEPs were recordable. This study demonstrated that MMEPs can be reliably recorded under methohexital anesthesia.

Anesthesia, General

Drug modification of ECT: methohexital and diazepam. II.

A systematic comparison of methohexital and diazepam as anesthetics in the drug modification of ECT was done by holding atropinizaton, succinylcholine-depolarizing neuromuscular blockade, and resuscitation constant while monitoring four ECT in each of 24 patients. Each patient served as his own control, and two dosages of each drug (0.25 and 0.35 mg/kg diazepam, 0.9 and 1.1 mg/kg methohexital) were given each patient in all possible orderings (4! = 24) in a scheduled experimental design in which methohexital was given by very rapid (5 sec) and diazepam was given by the recommended slower (60 sec) infusion. The data revealed significant differences and methohexital was superior. Eight of 48 (17%) EKGs were abnormal post-ECT with methohexital, 18 of 48 (38%, phi = 5.3, p < 0.025) with diazepam. Five of 24 (21%) patients had an abnormal post-ECT EKG with methohexital, 15 of 24 (60%, phi 8.6, p < 0.005) with diazepam. Significantly more ventricular premature contractions (VPCs) occurred after diazepam. Diazepam records contained both more numerous and more extensive EKG abnormalities. Methohexital induction was clinically superior as well; there was little of the induction restlessness seen in seven treatments with diazepam (phi2 7.6, p < 0.01). The differences were less marked than in a previous study in which diazepam was given as rapidly as methohexital. Methohexital has been demonstrated to be the anexthesia of safety and choice for ECT when compared to diazepam.

Diazepam

Oral self-administration of methohexital in baboons.

Oral self-administration of methohexital was generated in baboons that were food-restricted but not water-deprived. Stable intake of an 8% ethanol solution (two baboons) or water (two baboons) was first established in 3-h-sessions. Increasing concentrations of methohexital (0.005-10 mg/ml) then were substituted with a return to the ethanol or water baseline condition between methohexital conditions. For one baboon in the ethanol baseline condition, drinking was initially suppressed by methohexital substitution, but increased under a food-induced drinking procedure. For all baboons, an inverted U-shaped function generally described the relation between methohexital concentration and volume consumed. Anesthetization was observed at concentrations of 1.6 mg/ml and above. In two-bottle choice tests, three baboons generally drank greater volumes of methohexital than water at concentrations of 0.8 mg/ml and above. After a methohexital-free period of 1-3 months methohexital self-administration was readily reestablished.

Animals

Anesthetic modulation of the cardiovascular response to microlaryngoscopy. A comparison of propofol and methohexital with special reference to leg blood flow, catecholamines and recovery.

The modulating effects of propofol versus methohexital on the cardiovascular response to microlaryngoscopy were studied in 35 patients divided into four equal groups (one patient participated twice). Heart rate (HR), mean arterial blood pressure (MAP, cardiac output (CO; impedance cardiography), leg blood flow (LBF; occlusion plethysmography) and concentrations of arterial catecholamines were measured. After administration of atropine and fentanyl (2 micrograms.kg-1), anesthesia was induced by either an injection of propofol (2.0 mg.kg-1) followed by a low (6 mg.kg-1.h-1; n = 9) or a high (12 mg.kg-1.h-1; n = 9) dose propofol infusion or an injection of methohexital (1.5 mg.kg-1) followed by a low (5 mg.kg-1.h-1; n = 9) or a high (10 mg.kg-1.h-1; n = 9) dose methohexital infusion. The low methohexital infusion dose was insufficient to control MAP, which increased 41% during microlaryngoscopy compared to the awake state. The HR increased in all groups but the increase was most prominent in the low dose methohexital group. There were no statistically significant changes in CO in any group, whereas LBF increased consistently in all groups except in patients anesthetized with the low dose of methohexital. The increases of LBF in the propofol groups were intermediate and not dose dependent. The methohexital low dose group showed increases in norepinephrine levels compared to awake values and in epinephrine levels compared to the other groups. Propofol seems to differ from methohexital in modulation of peripheral vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Induction of anesthesia in children following administration of methohexital into the sigmoid colon.

The authors evaluated the sigmoidal administration of methohexital, the effect of methohexital concentration (1% versus 2%), the effect of dosage (25 mg/kg versus 15 mg/kg) on sleep-success rate, administration - sleep time, recovery time and the effect of aspirating the residual methohexital on recovery time. The study demonstrated that both 1% solution and 25 mg/kg of sigmoidal methohexital were independently associated with significantly higher sleep success rate and faster onset of sleep compared with 2% and 15 mg/kg of sigmoidal methohexital solution respectively. The recovery time was significantly affected by the dose of methohexital and was not significantly affected by the concentration of methohexital solution. Aspiration of the residual methohexital did not significantly affect the recovery time.

Catheterization

Stability of reconstituted methohexital sodium.

The purpose of this study was to determine the stability of reconstituted solutions of methohexital sodium over a 6-week period. Stability of methohexital was examined using reversed-phase high-performance liquid chromatography. The results indicate that reconstituted methohexital is extremely stable for up to 6 weeks when stored at 4 degrees C. When stored at room temperature, reconstituted solutions of methohexital contained increasing levels of degradation products and showed a corresponding decrease in methohexital over a 6-week period. However, the rate of degradation of the drug was slow, with less than 10% of the methohexital undergoing breakdown. In addition, tests for microbial contamination of the solutions stored at room temperature and under refrigeration were negative for up to 6 weeks. This study demonstrates that methohexital, when stored under refrigeration for up to 6 weeks, is virtually chemically identical to a freshly reconstituted solution of the drug. When stored at room temperature, there is some degradation of the drug, but it is not known whether the small amount of degradation is clinically significant. This study emphasizes the importance of obtaining scientific data to support changes in guidelines related to handling and storage of drugs.

Analysis of Variance

Cardiovascular effects of rectal methohexital in children.

STUDY OBJECTIVE: To define the cardiovascular effects of rectal methohexital in children with normal cardiac function. DESIGN: Cardiovascular evaluation of each patient was performed before and after medication. Each patient's predrug results were used as control measurements for comparison with measurements made after methohexital administration. SETTING: Inpatient operating room induction area in a privately endowed philanthropic children's hospital. PATIENTS: Forty-seven children age 35 +/- 22 months (mean +/- SD) scheduled for elective orthopedic or plastic surgery, free of cardiac or pulmonary disease, and receiving no medication with central nervous system activity. INTERVENTIONS: Control measurements of heart rate (HR), blood pressure (BP), and echocardiographic evaluations were obtained on the day before scheduled surgery. Repeat measurements were performed after the onset of methohexital-induced sleep. The time span of the measurements was designed to include the period of peak plasma methohexital concentration. In the preoperative holding area, 30 mg/kg of a 10% methohexital solution was administered rectally. If sleep did not occur in 15 minutes, an additional 15 mg/kg was given. MEASUREMENTS AND MAIN RESULTS: HR increased markedly after rectal methohexital [126 +/- 23 beats per minute (bpm) to 144 +/- 21 bpm, p less than 0.001], and stroke volume (SV) decreased (24 +/- 9 ml to 21 +/- 8 ml, p less than 0.01). There were no significant changes in BP or cardiac index. The shortening fraction and ejection fraction remained within the normal range for this age-group. CONCLUSIONS: Rectal methohexital induces sleep in healthy pediatric patients with minimal cardiovascular side effects. The primary effects are increased HR and decreased SV.

Anesthesia, Rectal

Electroconvulsive therapy-induced cardiac arrhythmias during anesthesia with methohexital, thiamylal, or thiopental sodium.

STUDY OBJECTIVE: To determine the frequency of electroconvulsive therapy (ECT)-induced arrhythmias under methohexital, thiamylal, or thiopental sodium anesthesia with and without atropine premedication. DESIGN: A randomized, double-blind study, placebo-controlled for atropine. SETTING: The inpatient psychiatric unit at a university medical center. PATIENTS: Forty-nine patients scheduled for ECT. INTERVENTIONS: Atropine 0.6 mg intravenously (IV) or an equal volume of normal saline IV was given before IV induction of anesthesia with methohexital 0.5 to 1.0 mg/kg, thiamylal 1.5 to 2.5 mg/kg, or thiopental sodium 1.5 to 2.5 mg/kg. MEASUREMENTS AND MAIN RESULTS: Single-lead electrocardiogram (ECG) recordings were made for 1 minute before induction, during induction of anesthesia, and for 5 minutes after the ECT stimulus. Each ECG was evaluated for arrhythmias and evidence of ischemia in a blinded fashion. Blood pressure and ECG evidence of ischemia did not differ among the groups. Seizure duration was significantly (p less than 0.05) prolonged by a mean of 5 seconds during methohexital anesthesia compared with thiopental sodium and thiamylal (47.6 +/- 18.6 seconds, 42.7 +/- 13.2 seconds, and 42.7 +/- 15.2 seconds, respectively). The frequency of sinus bradycardia was decreased (p less than 0.05) with methohexital (8%) compared with thiopental sodium (20%) and thiamylal (20%). The frequency of premature atrial contractions was decreased (p less than 0.05) with methohexital (43%) compared with thiamylal (61%) but not with thiopental sodium (57%). The frequency of premature ventricular contractions was decreased (p less than 0.05) with methohexital (27%) compared with thiopental sodium (44%) but not with thiamylal (40%). Atropine decreased the frequency of bradycardia (9% vs. 24%) and premature atrial contractions (47% vs. 61%) and increased the frequency of sinus tachycardia (88% vs. 75%). CONCLUSIONS: These data suggest that anesthesia for ECT therapy should be induced with methohexital to minimize the possibility of potentially life-threatening cardiac arrhythmias. Atropine premedication may further decrease the frequency of premature atrial contractions and bradycardia, while increasing the frequency of tachycardia.

Adult

Effective therapeutic infusions produced by closed-loop feedback control of methohexital administration during total intravenous anesthesia with fentanyl.

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital delivery during total intravenous anesthesia with fentanyl in 11 surgical patients. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Based on previous investigations a median frequency from 2-3 Hz was chosen as the desired EEG set point. In addition to methohexital, patients were given a 10-min loading infusion of 0.5 mg of fentanyl followed by a constant-rate infusion of 0.22 mg/h. In agreement with an earlier similar study in volunteers given only methohexital and aiming at the same set point, identical distribution of EEG power was achieved in the current study. The decrease of median EEG frequency to 2-3 Hz was primarily induced by an increase in fractional power in the 0.5-2- Hz frequency band to 46 +/- 4%. The average requirement of methohexital during the first 2 h was 675 +/- 250 mg. The authors conclude that model-based feedback control of intravenous methohexital delivery can help establish and quantitate methohexital requirements during total intravenous anesthesia with fentanyl.

Adolescent

Rectal methohexital: concentration and length of the rectal catheters.

In the study, the authors evaluated the concentration of rectal methohexital (1% vs 10%) and the length of the rectal catheter (3.8 vs 12.7 cm), on sleep-success rate, administration-sleep time, methohexital plasma concentrations, and recovery time in 85 healthy children scheduled for elective ophthalmic or ear, nose, or throat operations lasting approximately 1 h. At a dose of 25 mg/kg, the 1% solution of rectal methohexital was associated with a significant (P less than 0.05) higher sleep-success rate (95% vs 70%), shorter administration-sleep time (5.7 +/- 1.9 vs 7.0 +/- 2.0 min), higher methohexital plasma concentrations at 20 min (6.5 vs 4.7 ng/mL) and at 30 min (5.3 vs 3.7 ng/mL), and prolonged recovery time (53.2 +/- 31.1 vs 32.4 +/- 18.5 min). The length of the rectal catheters did not significantly affect sleep-success rate, administration-sleep time, methohexital plasma concentrations, or recovery time. The use of 25 mg/kg of 1% rectal methohexital solution to induce anesthesia in children is superior to the use of 25 mg/kg of 10% methohexital solution for induction of anesthesia in children, particularly in operations 1 h or longer in duration.

Anesthesia Recovery Period

Induction and maintenance of anesthesia in dogs by intravenous administration of methohexital.

OBJECTIVE: To devise and test an i.v. methohexital infusion regimen for induction and maintenance of surgical anesthesia in dogs from which they would rapidly recover. DESIGN: Dose-response and plasma concentration-effect study. ANIMALS: 11 clinically normal dogs. PROCEDURE: Bolus methohexital pharmacokinetic variables were determined in ketamine- and pentobarbital-anesthetized dogs. Plasma methohexital concentrations required to inhibit purposeful movement in response to painful stimuli were determined during a stepped methohexital infusion in the same dogs on a second occasion. These pharmacokinetic/pharmacodynamic data were next used to design a bolus and two-stage infusion regimen that would result in stable plasma methohexital concentrations with prolonged infusion. This regimen was tested in a second group of dogs. RESULTS: Mean steady-state volume of distribution of methohexital in the anesthetized dogs was 1.50 L/kg of body weight and mean elimination clearance was 10.2 ml/kg/min. Mean plasma concentrations required to prevent movement response to a noxious stimulus and at which the dogs could be extubated were 11.8 and 6.9 micrograms/ml, respectively. After a 6-hour infusion, recovery of airway reflexes sufficient to allow extubation required 67 minutes. CONCLUSIONS: An easily implemented i.v. methohexital infusion regimen for induction and maintenance anesthesia in dogs was developed. During a 6-hour infusion, hemodynamic variables did not change. Use of this regimen resulted in anesthesia of sufficient depth to prevent withdrawal in response to noxious stimuli and in reliable and acceptable emergence times for use in canine survival studies in a cost-effective manner.

Anesthesia, General

Self-administration of orally-delivered methohexital in rhesus monkeys with phencyclidine or pentobarbital histories: effects of food deprivation and satiation.

Orally-delivered methohexital was demonstrated to function as a reinforcer for rhesus monkeys with either phencyclidine or pentobarbital self-administration histories. The effects of food deprivation and food satiation were compared across a wide range of methohexital concentrations. Initially, three monkeys were trained to orally self-administer phencyclidine (0.25 mg/ml) and water, and three were trained to orally self-administer pentobarbital (0.5 mg/ml) and water under concurrent fixed-ratio (FR) schedules during daily 3-hr sessions. Liquid deliveries during the session (drug and water) and intersession (water) were contingent upon lip contact responses on solenoid-operated drinking spouts. The monkeys were first tested while food deprived by maintaining them at 85% of their free-feeding body weights. Methohexital concentrations were presented in the following order, and each concentration was held constant until at least five or six sessions of stable behavior were obtained: 2, 2.8, 4, 2 (retest), 1, 0.5, (plus 0.25 and 0.125 in monkey M-W) and 2 (retest) mg/ml. The monkeys were then food satiated by allowing them unlimited access to food, and the methohexital concentration series was repeated. During food deprivation, the concentration-response functions generally resembled an inverted U. Concurrent water-maintained responding was generally low, but it increased in some monkeys as methohexital concentrations increased in some monkeys. During food satiation, methohexital-maintained responding was not different from water-maintained responding in some monkeys, but in others it was substantially higher than water-maintained responding. Maximum drug intake ranged from 20.4 to 93.8 mg/kg during food deprivation and from 6.4 to 64.2 during food satiation among the six monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Comparison of the ventilatory effects of etomidate and methohexital.

Using a dual-isohypercapnic technique, the authors determined the effect of equipotent doses of methohexital (1.5 mg/kg) and etomidate (0.3 mg/kg) on the ventilatory response to CO2 (VERCO2) in six healthy volunteers. Speed of induction and duration of hypnosis did not differ significantly between the two drugs. Within 2 min after injection, the slope of VERCO2 decreased significantly after both methohexital (from 2.52 to a minimum of 0.15 l . min-1 . mmHg-1, P less than 0.05) and etomidate (from 2.56 to a minimum of 0.62 l . min-1 . mmHg-1, P less than 0.05); the magnitude of this depression did not differ significantly between the drugs. Methohexital also caused a significant decrease in minute ventilation at end-tidal PCO2 of 46 mmHg (VE 46) from 14.6 to 4.3 l . min-1 within 60 s after injection (P less than 0.05). In contrast, after etomidate VE 46 gradually increased from 17.9 1 . min-1 to a maximum of 31.6 l . min-1 at 3.5 min after injection (P less than 0.05); respiratory rate increased significantly, while changes in tidal volume were not significant. Effects of etomidate and methohexital on VE 46 differed significantly (P less than 0.001). These data indicate that, while etomidate and methohexital similarly depress the medullary centers that modify ventilatory drive in response to changing CO2 tensions, ventilation at any given CO2 tension is greater after etomidate than after methohexital. This indicates that etomidate may cause a CO2-independent stimulation of ventilation, suggesting its use for induction of anesthesia in cases where maintenance of spontaneous ventilation is desirable.

Adult

Methohexital plasma concentrations in children following rectal administration.

Despite the increasing use of rectal methohexital as a premedicant-induction agent in pediatric anesthesia, there are no data to confirm the assumption that low plasma methohexital concentrations are the cause of inadequate sedation of children and that high concentrations are associated with the loss of consciousness. Plasma methohexital concentrations were determined in 20 ASA Class I children, ages 2-7 yr, after the rectal administration of methohexital (25 mg/kg). Seventeen of the 20 children in this study fell asleep after receiving the drug and achieved peak plasma concentrations greater than 2 micrograms/ml. The maximum plasma methohexital concentration in children that did not fall asleep was less than 2 micrograms/ml. The mean time to the onset of sleep after drug administration was 8.3 min (at which time the mean plasma concentration was 4.4 micrograms/ml). The mean peak plasma concentration and the mean time to peak plasma concentration were 4.7 micrograms/ml and 13.9 min, respectively. Loss of consciousness after rectal administration of methohexital correlates well with the plasma concentration of the drug.

Anesthesia, Inhalation