Evaluation of methohexital as an alternative to propofol in a high volume outpatient pediatric sedation service.

BACKGROUND: Propofol is a preferred agent for many pediatric sedation providers because of its rapid onset and short duration of action. It allows for quick turn around times and enhanced throughput. Occasionally, intravenous (IV) methohexital (MHX), an ultra-short acting barbiturate is utilized instead of propofol. OBJECTIVE: Describe the experience with MHX in a primarily propofol driven outpatient sedation program and to see if it serves as an acceptable alternative when propofol is not the preferred pharmacologic option. METHODS: Retrospective chart review from 2012 to 2015 of patients receiving IV MHX as their primary sedation agent. Data collected included demographics, reason for methohexital use, dosing, type of procedure, success rate, adverse events (AE), duration of the procedure, and time to discharge. RESULTS: Methohexital was used in 240 patient encounters. Median age was 4years (IQR 2-7), 71.8% were male, and 80.4% were ASA-PS I or II. Indications for MHX use: egg+soy/peanut allergy in 93 (38.8%) and mitochondrial disorder 9 (3.8%). Median induction bolus was 2.1mg/kg (IQR, 1.9-2.8), median maintenance infusion was 4.5mg/kg/h (IQR, 3.0-6.0). Hiccups 15 (6.3%), secretions requiring intervention 14 (5.8%), and cough 12 (5.0%) were the most commonly occurring minor AEs. Airway obstruction was seen in 28 (11.6%). Overall success rate was 94%. Median time to discharge after procedure completion was 40.5min (IQR 28-57). CONCLUSION: Methohexital can be used with a high success rate and AEs that are not inconsistent with propofol administration. Methohexital should be considered when propofol is not a preferred option.

Anaesthetic sensitivity of fMLP-induced cell signalling in Xenopus oocytes.

FMLP stimulation of Xenopus oocytes expressing fMLP receptors leads to a concentration-dependent biphasic inward current. To identify the evolution of these currents we have examined the effects of blocking various cell signalling pathways. In addition we have analysed the effects of three intravenous anaesthetics on these fMLP-induced currents. Xenopus oocytes were microinjected with cRNA encoding the fMLP receptor and fMLP-stimulated (100 nM) currents measured, using two-electrode voltage-clamp (-70 mV), before and after injection of heparin (120 ng ml-1), wortmannin (1 microM), U73122 (5 microM) or buffer. Concentration-response curves were established for the action on fMLP-stimulated currents of thiopentone (5-500 microM), methohexitone (0.2-200 microM) and propofol (0.5-500 microM). Heparin significantly enhanced the fast current (p<0.05). Wortmannin had no effect on either current. U73122 inhibited only the slow current (p<0.05). All anaesthetics inhibited both currents, with the maximum inhibition for the fast/slow currents 70%/100%, 60%/60% and 100%/100% for thiopentone (IC50 147/120 microM), methohexitone (IC50 4.7/2.2 microM) and propofol (IC50 33/8 microM), respectively. We suggest (a) the slow current arises via the PLC/PKC pathway because it is reduced by the PLC inhibitor U73122, (b) the PI3K- and PLD-mediated pathways are not involved because wortmannin had no effect and (c) activation of the two conductance channels must be different because U73122 reduced the slow but not the fast current. Since both currents are decreased by all three anaesthetics, their inhibition might be mediated through an action at the agonist/receptor, although, since the slow current is consistently more sensitive than the fast, there may be additionally an action on cell signalling.

Correlation of effects of general anesthetics on somatosensory neurons in the primate thalamus and cortical EEG power.

The effects of two types of general anesthetic on the neurophysiological properties of the primate somatosensory thalamus were correlated with effects on frontal cortex electroencephalographic (EEG) power and spectral properties. Graded doses of the intravenous agent methohexital sodium (METH) were studied in 12 cells in three monkeys on a halothane baseline anesthetic. Low doses of METH (0.2-1.0 mg/kg) produced a reduction of EEG power but had no effects on spontaneous or evoked thalamic activity. EEG power showed maximal attenuation after 2.0 mg/kg METH, whereas decreases in thalamic activity were first noted over a similar moderate dose range (2.0-5.0 mg/kg). The physiological parameter most sensitive to METH was the spontaneous activity, which showed initial changes in rate and moderate doses followed by marked inhibition at higher doses. Finally, the high dose of METH (10.0 mg/kg) produced marked reduction in all neurophysiological parameters with recovery over the following 30-45 min. The effects of the volatile anesthetic halothane were studied on 15 cells in four monkeys anesthetized with pentobarbital sodium. The low dose of halothane (0.25%) produced a facilitation of responses to cutaneous stimuli as well as decrease in the rate and burst patterns in the spontaneous activity. The power in the EEG was not affected at this concentration. The responses of the cells to the mechanical stimuli at moderate doses (0.5-1.0%) of halothane returned to the baseline magnitude, whereas spontaneous activity remained unaffected compared with initial effects. EEG power was reduced by 1% halothane. Finally, all neurophysiological parameters showed profound reduction at the highest halothane concentrations (2.0-3.0%) with recovery over the next 30-45 min. In conclusion, the two classes of anesthetics most commonly used for acute neurophysiological studies in the primate show well-defined thresholds at which changes in the response properties of thalamic neurons are produced. This threshold for the barbiturates and halothane can be predicted by monitoring of cortical EEG.

Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia.

OBJECTIVE: To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. DESIGN: Prospective, controlled study with open-label assignment of animals to two groups. SETTING: Laboratory. SUBJECTS: Goehingen minipigs. INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. CONCLUSIONS: Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases.

Effects of methohexitone, althesin, ketamine and droperidol on peripheral vagal transmission.

The effects of methohexitone, ketamine, Althesin and droperidol on the peripheral vagal transmission to the heart were studied in decerebrate cats by evaluating the influences of the drugs on the heart rate responses to vagal electrostimulation and the injection of acetylcholine i.v. The sites of the peripheral vagal transmission (vagal ganglia and sino-atrial pacemaker cells) were reached by the application of the drugs to the pericardial space. The bradycardia in response to vagal electrostimulation was attenuated by Althesin (2.1 x 10(-4)-3.3 x 10(-3) mol litre-1; expressed as the concentration of alphaxalone), ketamine (2.9 x 10(-4)-4.6 x 10(-3) mol litre-1) and droperidol (2.6 x 10(-5)-6.6 x 10(-4) mol litre-1) in a concentration-dependent manner, but not influenced by methohexitone (2.8 x 10(-4)-4.4 x 10(-3) mol litre-1). The bradycardia-attenuating effects were probably caused by an atropine-like action since the heart rate responses to the injection of acetylcholine i.v. were also attenuated by the same three drugs.

[Influence of curare and methohexital-Na on the content of energy-rich phosphates and substrates of glycolysis in rat liver (author's transl)]. / Der Einfluss von Curare und Methohexital-Na auf den Gehalt an energiereichen Phosphaten und Glykolysesubstraten in der Rattenleber.

Our investigations demonstrate that 7',12'-dihydroxy-6,6'-dimethoxy-2,2,2',2'-tetramethyl-tubocuraranium dihydroxide (D-tubocurarine, Curarin-Asta), in the following briefly called curare, and methohexital sodium influence glycolysis and energy metabolism of rat liver cells. Within the first 5 min after i.v. application of curare we observed a decrease of ATP levels due to either increased energy demands during cellular metabolism or to a decrease of ATP production in the respiratory chain. This effect was followed by an activation of glycolysis as demonstrated by a decrease of cytoplasmic glycogen and an increase of glucose-6-phosphate. Simultaneously, cytoplasmic lactate levels were increased and redox potentials significantly shifted. The latter effect is caused by alterations in the lactate-pyruvate ratios. In contrast, methohexital sodium induced a significant increase of cellular ATP levels. The observed low lactate-pyruvate ratio and the changes in the adenylate system following methohexital sodium suggest that this drug reduces energy consumption during cellular metabolism.

The effects of anaesthetics on the uptake and release of amino acid neurotransmitters in thalamic slices.

1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesthetics used had any detectable effect upon the spontaneous release of either amino acid. 4 Urethane and ketamine had no effect upon the K+-stimulated release of either amino acid. 5 Methohexitone and thiopentone produced a biphasic dose-response on the K+-stimulated release of both amino acids; low concentrations enhanced release, high concentrations depressed release. 6 Bicuculline hydrochloride and picrotoxin both significantly reduced the barbiturate-induced enhancement of K+-stimulated amino acid release, but did not significantly alter the depression of K+-stimulated release at higher barbiturate concentrations. 7 Baclofen, either alone (1 microM to 1 mM), or tested against the barbiturates, had no detectable effect.

A barbiturate evoked intensification of postsynaptic inhibition in the preoptic ovulatory trigger region of the hypothalamus.

Extracellular single unit recordings were used to study inhibitory synaptic responses evoked from preoptic-anterior hypothalamic neurones following arcuate-ventromedial stimulation. Intravenously administered methohexitone, pentobarbitone and thiopentone increased the duration of inhibitory synaptic responses by up to 400%. Submaximal responses to iontophoretically applied GABA but not glycine were also potentiated. Recovery from the actions of the short acting barbiturates was observed.

Unit activity in rat diencephalic islands--the effect of anaesthetics.

1. Unit activity was recorded with steel micro-electrodes from 486 hypothalamic neurones in rat diencephalic island preparations.2. The histograms of firing frequencies for populations of hypothalamic units from unanaesthetized preparations and from those under urethane anaesthesia were not significantly different. The firing rates of both were significantly faster than those observed in intact brains under urethane.3. The mean distance between stable units in unanaesthetized island preparations did not differ significantly from that in preparations anaesthetized with urethane.4. The response of individual neurones to intravenous injections of urethane was variable, and apparently not associated with the onset or maintenance of anaesthesia. Some showed transient acceleration, some deceleration and some no change in rate or pattern of discharge.5. All neurones tested were slowed or stopped by intravenous injections of subanaesthetic doses of sodium methohexitone (Brietal). The responses were highly reproducible and dose-dependent.6. Brietal also produced a fall in arterial pressure and depressed respiration. Inhalation of amyl nitrite evoked larger hypotensive responses but did not affect unit activity; nor did inhalation of CO(2) (hypercapnia) or N(2)O (hypoxia).7. It is concluded that urethane anaesthesia is not associated with any direct action on hypothalamic neurones. The depression of firing rate in hypothalamic neurones induced by Brietal may represent an important forebrain mechanism in anaesthesia by this agent.