Administration Of Methohexital Research Articles

Methohexital-Induced Seizures During Electroconvulsive Therapy

Methohexital is a common anesthetic agent used for electroconvulsive therapy. In the adult literature, there are a few case reports of tonic-clonic seizures occurring immediately after the administration of methohexital. However, to date, there are no reports of this occurrence in children or adolescents. This case documents a generalized tonic-clonic seizure in a 15-year-old girl after receiving 60 mg of methohexital and numerous prior episodes of bitemporal electroconvulsive therapy.

Methohexital zur Therapie des erhöhten intrakraniellen Drucks

Barbiturate coma therapy is a useful method to control increased intracranial pressure (ICP) in patients with severe brain damage if standard measures have failed to lower ICP. Pentobarbital (not available in Germany) and thiopental (in Germany only approved for induction of anesthesia) have frequently been used in patients with intracranial hypertension and the effects and side-effects are well-described. However, little is known about the effect of methohexital (the only barbiturate in Germany approved for maintaining anesthesia) in lowering increased ICP. Therefore, the effect of methohexital on ICP was studied in patients where standard measures had failed to control intracranial hypertension. A retrospective observational study was carried out with the inclusion criteria of patient age ≥18 years and methohexital therapy for 12h or more with ICP monitoring in place. Methohexital was administered following a standardized algorithm to patients for whom standard measures, such as deep anesthesia, normoventilation, cerebral perfusion pressure (CPP) >65mmHg, osmotherapy, neurosurgical evacuation of mass lesions, had failed to lower ICP. Methohexital was used if the ICP had risen above 20-25mmHg for more the 20-30min and otherwise manageable causes for the ICP increase had been ruled out. Methohexital was given continuously in addition to standard analgesia and sedation in doses of 2-4-6mg/kg body weight (BW), depending on the ICP lowering effect. The records of the patient data management system from the years 2008/2009 were used to compare the ICP and CPP before and during methohexital administration. For statistical analyses Student's t-test was applied for measured values and the χ(2)-test was applied for percentage values whereby p<0.05 was defined as being statistically significant. During the study period 36 patients required methohexital therapy and 30 fulfilled the inclusion criteria. In 26 out of 30 patients the data were complete and these 26 patients were included in the data analyses. Of the patients 6 (23%) died due to elevated intracranial hypertension and 20 patients (77%) survived. In all patients methohexital lowered the ICP from 25.2mmHg (standard deviation, SD ±4.3mmHg) to 19.8mmHg (SD ±12.5mmHg) within the first 24h, this result closely failed to reach a level of significance. In the 20 survivors methohexital lowered the ICP from 25.88mmHg (SD ±4.8mmHg) to 14.25mmHg (SD ±6.9mmHg) within the first 24h, which is statistically highly significant. In non-survivors the ICP had risen from 24mmHg (SD ±2.6mmHg) to 32mmHg (SD ±16.3mmHg) within the first 24h despite all efforts. Due to the CPP driven volume and vasopressor therapy no significant changes in the CPP during methohexital administration were observed. No significant changes in brain temperature (as possible cause for the decrease of the ICP) were observed. Non-survivors received significantly more methohexital due to increased ICP and required significantly more vasopressor therapy to maintain a sufficient CPP. Methohexital showed a clear trend for decreasing ICP in patients with intracranial hypertension refractory to standard therapeutic measures. In survivors the effect was highly significant. Patients not responding to methohexital therapy seemed to have an unfavorable outcome.

The use of methohexital during chest tube removal in neonates.

The aim of the study was the evaluation of the effect of methohexital during chest tube removal (CTR) in neonates. Evaluation was based on the degree of sedation (grades 1-4) and relaxation (grades 1-4) and trends in vital signs heart rate, mean arterial blood pressure (MAP), oxygen saturation at time points (-10, -5, -3, -1, 0, 1, 3, 5, and 10 min) before and after administration of methohexital. A multidimensional pain scale [Leuven Neonatal Pain Scale (LNPS)] was used to evaluate pain expression. Effective sedation and relaxation (grade >2) would enable the physician to perform CTR without difficulties. Paired Wilcoxon was used to compare vital signs and pain expression before and after the procedure. Twenty-two procedures in 22 infants were recorded. Eleven infants were ventilated and 21 infants were having intravenous analgesics during CTR. Birth weight was 2645 g (range 1235-4500 g). Postnatal age was 6 days (range 1-80 days). Methohexital had no effect on ventilatory weaning, MAP or oxygen saturation. Heart rate increased from 144 (49) to 162 (43) (P = 0.012) b.min(-1). Sedation and relaxation were effective (>grade 2) and lasted for <5 min. No major side effects were documented. Adequate analgesia by LNPS was more difficult to evaluate as clinical pain evaluation was not feasible during full muscular relaxation. Administration of methohexital for CTR resulted in adequate sedation and relaxation without major side effects in neonates. This approach should be compared with other strategies.

Response to Electroconvulsive Therapy in a Quadriplegic Patient

Response to Electroconvulsive Therapy in a Quadriplegic Patient

FDA's role in anesthetic drug development.

FDA's role in anesthetic drug development.

A prospective evaluation of the safety and efficacy of methohexital in the emergency department

A prospective observational study in an inner-city teaching hospital was conducted to evaluate the safety and efficacy of intravenous methohexital (MTX) in the emergency department (ED). Pulse oximetry, vital signs and Glasgow Coma Scale (GCS) scores were recorded serially for 30 minutes after the administration of MTX to 76 adult patients. Likert scales of 1 to 5 were used to record the physician's assessment of the adequacy of sedation and the patient's assessments of recall and pain of the procedure. Patients received an average of 88 ± 21 mg of MTX for a variety of indications (orthopedic procedures, 78%; sedation for other procedures, 14%; intubation, 5%; and psychiatric interview, 3%). No patient had clinically significant changes in heart rate or blood pressure. Eight (10.5%) had apnea, although only one patient had oxygen saturations of less than 90%. Each episode was brief and easily managed with bag-valve-mask ventilation. Risk factors for apnea included a history of alcoholism ( P = .0003) and recent recreational narcotic use ( P = .0139). Patients were maximally sedated in an average of 37 ± 42 seconds. In the subset of initially alert patients, GCS scores decreased from 15 at baseline to 5.9 ± 4.5. The physician's assessment of the adequacy of sedation was excellent (4.7 ± 0.7). Patients reported little recall (1.3 ± 0.9) or pain (1.3 ± 0.8). It was concluded that MTX caused clinically insignificant changes in hemodynamics or oxygenation, although respiratory depression did occur; significant respiratory depression was brief and easily managed. MTX provided rapid and excellent levels of sedation with little or no patient recall or pain.

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

Abstract Objective To devise and test an IV 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 μg/ml, respectively. After a 6-hour infusion, recovery of airway reflexes sufficient to allow extubation required 67 minutes. Conclusions An easily implemented IV 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. (Am J Vet Res 1996;57:1044–1049)

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 mglkg of a 10% methohexital solution was administered rectally. If sleep did not occur in 15 minutes, an additional 15 mglkg was given. Measurements and Main Results: HR increased markedly after rectal methohexital [126 ± 23 beats per minute (bpm) to 144 ± 21 bpm, p < 0.0011, and stroke volume (SV) decreased (24 ± 9 ml to 21 ± 8 ml, p < 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.

Physician-Administered Office Anesthesia

Surgeons who administer office anesthesia accept a serious responsibility for the well-being of their patients. Each must be thoroughly familiar with the agents they employ and prepared to deal with any complications or untoward events that might arise out of their use. Patients who are healthy or have well-controlled mild systemic disease are generally suitable for office procedures. Overly apprehensive patients, those with a history of anesthetic difficulties, or any patient with significant medical problems should be provided an anesthesiologist or competent Certified Registered Nurse Anesthetist (CRNA). It is irresponsible and dangerous to administer anesthesia in a substandard facility or with an inadequate or inexperienced staff. All staff members should be BCLS (Basic Cardiac Life Support) qualified, and key individuals should be encouraged to obtain ACLS (Advanced Cardiac Life Support) certification. Proper pharmacologic preparation of the patient will allay anxiety, increase comfort, and reduce the overall quantity of anesthetic needed. Particularly useful agents include benzodiazepines (Valium and Versed) and diphenhydramine (Benadryl). Medication is not, however, a substitute for human contact, genuine concern, or timely reassurance. All patients receiving anything more than a small quantity of local anesthetic should be monitored by transcutaneous pulse oximetry, noninvasive sphygmomanometry, and real-time electrocardiography. Each provides important information on the patient's physiologic condition. Of these three monitors, the most important information is provided by the pulse oximeter. It is capable of detecting a problem before serious physiologic compromise has occurred and should be considered an indispensible part of each patient's care. A brief period of deep sedation for the administration of local anesthetic can safely be achieved using carefully titrated quantities of the short-acting barbiturate methohexital (Brevital). Gauging the proper end point of methohexital administration is accomplished through skilled observation of the patient. As the proper threshold is reached, a characteristic slackening of the jaw occurs usually in conjunction with a distinctive relaxation of the face. In the majority of cases, no change in the SaO2 will occur.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Cardiovascular and respiratory effects of three rapidly acting barbiturates in dogs

SUMMARY The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (sv) decreased; heart rate (hr), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (ci), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (map) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except hr had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values. Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, map decreased at 15 seconds, and sv decreased at all measurement times. Cardiac index increased at 30 seconds, 1 minute, and 2 minutes; myocardial contractility increased at 1, 2, and 2.5 minutes; and blood-gas and pH had returned to baseline by 12.5 minutes. To determine differences between drugs, the cardiovascular and respiratory values for each drug were compared at each measurement time. Changes in hr and sv induced by the 3 drugs were similar at all measurement times. Mean arterial pressure at 15 and 30 seconds was lower following methohexital administration than after thiopental or thiamylal administration. Cardiac index was higher at 1 minute following methohexital administration, compared with that after thiamylal administration, whereas systemic vascular resistance was higher at 1 minute following thiamylal administration, compared with that after methohexital administration. The increase in left atrial pressure was greater following thiamylal administration than after thiopental administration at 30 seconds to 5 minutes or after methohexital administration at 1 to 5 minutes. Mean pulmonary arterial pressure was significantly higher at 2 to 4 minutes following thiamylal administration than after methohexital administration. Pulmonary vascular resistance was higher at 1 minute following thiamylal administration, compared with that after thiopental and methohexital administration. At 1 and 2 minutes, myocardial contractility was significantly higher following methohexital administration, compared with that after thiobarbiturate administration. Arterial oxygen tension was lower at 12.5 minutes following administration of the thiobarbiturates, compared with that after methohexital administration. When compared with methohexital administration, arterial carbon dioxide tension was higher at 7.5 and 12.5 minutes following thiamylal administration. The decrease in pH following thiamylal administration was greater at all measurement times, compared with that after thiopental and methohexital administration.

Effects of Delayed Administration of Methohexital and Ketamine on Posthypoxic Cell Damage of Primary Neuronal Cultures

Primary neuronal cultures from chick embryo cerebral hemispheres received NaCN (cytotoxic hypoxia) for 120 min and were then allowed to recover. Methohexital (300 mumol/l) or ketamine (30 mumol/l) given either before or during the hypoxic period elevated adenosine triphosphate (ATP) content of the cultures 15 min after hypoxia. Prehypoxic administration of ketamine also preserved the structural integrity and ATP content of neurons 20 h later, while methohexital did not. Ketamine elevated ATP content as measured 20 h after hypoxia even when administered 15 min after beginning of recovery. Pharmacokinetic reasons for contradictory effects of ketamine on neuronal cell loss in vivo ischemia studies and our in vitro experiments are discussed.

Effect of the barbiturate methohexital on cerebral vessels and intracranial pressure.

Reactions of pial arteries and veins as well as intracranial pressure (ICP) and mean arterial pressure during intravenous administration of methohexital were observed in two groups of cats totaling 24 animals in order to investigate hypothesized direct barbiturate effects on cerebral vascular volume. Group 1 had bolus injection of 1 mg/kg followed by infusion of 0.1 mg/kg/min over 60 minutes. This induced a 6 to 7% arterial dilatation at 50 to 60 minutes (not significant); a 20% reduction of pial vein calibers was observed (P less than 0.01). In Group 2, the same treatment protocol administered under conditions of ICP elevation to 20 mm Hg by the cisternal infusion of mock cerebrospinal fluid resulted again in consistent, although less extensive, venous caliber reduction (5 to 7%, P less than 0.01). In Group 2 controls, pial arteries dilated by 15 to 20%; this reaction was suppressed in the methohexital-treated animals. After stopping methohexital, however, arteries in the methohexital group dilated to almost the same extent as in controls. Mean arterial pressure remained stable in both groups. ICP was not reduced by methohexital. EEG-activity was slightly increased during treatment. We conclude that methohexital has a direct effect on vessel caliber and thus cerebral blood volume via absolute diminution of venous vessels and suppression of ICP-induced autoregulative arterial dilatation. This direct vascular effect, however, seems to be counterbalanced by unknown intracranial mass effects that prevent a reduction in ICP.

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.

Etude électroencéphalographique de l'anesthésie pédiatrique au méthohexital intramusculaire

Intramuscular methohexital was used in paediatric anaesthesia to carry out special investigations. There seemed to be few side effects but twitches or seizures have been reported. An electroencephalographic study was performed in normal children. The electroencephalogram showed periods of increased amplitude. The authors discussed the problem of side effects following the intramuscular administration of methohexital in the normal child, and proscribed its use in the epileptic.

Similarity between effects of general anesthetics and dinitrophenol on cortical neurones.

In lightly anesthetized cats, a brief administration of methohexital (intravenously), or halothane, methoxyflurane, or other gaseous anesthetics (by inhalation) causes a temporary, selective depression of the spontaneous firing and acetylcholine-evoked responses of deep pericruciate neurones, but relatively little change or even an enhancement of glutamate-evoked firing. These effects are very similar to those produced by local application of dinitrophenol, and therefore support the idea that anesthetics act by inhibiting aerobic metabolism.

Electroencephalographic activation with sleep and methohexital. Comparative usefulness in the diagnosis of epilepsy.

Two types of electroencephalographic activations were observed in 41 epileptics during sleep and intravenous administration of methohexital sodium. Type 1 was the induction of specific paroxysmal discharges (SPD) in an otherwise normal tracing; it occurred in four patients during sleep and in two patients during methohexital. Type 2 was an increase of 30% or more in the frequency of SPD in a preexisting abnormal tracing; it occurred in 20 patients during sleep and in 15 during methohexital administration. Type 1 activation improved the sensitivity of electroencephalography as a diagnostic tool by 10%. However, this was achieved mainly with sleep, because whenever methohexital elicited a type 1 response a similar activation had already been obtained during sleep. Methohexital activation shows no further effectiveness than sleep and had little value in the diagnosis of the epilepsies.