Electroconvulsive Therapy Anesthetic Choice and Clinical Outcomes.

OBJECTIVE: Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes. METHODS: This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations. RESULTS: Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001). CONCLUSIONS: We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.

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.

Neuroprotection in transient focal cerebral ischemia by combination drug therapy and mild hypothermia: comparison with customary therapeutic regimen.

BACKGROUND AND PURPOSE: A combined therapeutic approach has been advocated repeatedly for treatment of focal cerebral ischemia. A clinical example of combined therapy is administration of nimodipine, mannitol, dexamethasone, and barbiturates during temporary occlusion of a cerebral artery in neurovascular surgery. We have recently demonstrated outstanding neuroprotective properties of a combination therapy with magnesium (calcium antagonist and glutamate antagonist), tirilazad (antioxidant), and mild hypothermia (MTH). In this study we compared this treatment strategy with the customary treatment options in a rat model of transient focal cerebral ischemia. METHODS: Sprague-Dawley rats (n=120) were subjected to 90 minutes of middle cerebral artery occlusion by an intraluminal filament (n=10 per group). In experiment 1, the customary treatment options (nimodipine, mannitol, dexamethasone, methohexital) were evaluated as monotherapy and in combination. In experiment 2, the customary and the new combination therapy (MTH) were compared. Mild hypothermia (33 degrees C) was maintained for 2 hours. Neurological examinations were performed daily. Infarct size was assessed histologically after 7 days. RESULTS: In experiment 1, infarct volume was attenuated by 34% at maximum, with mannitol and methohexital being the most effective drugs given as monotherapy. In experiment 2, combined administration of the customary treatment options had no additive effect (infarct volume -36%). Combination therapy with MTH reduced total infarction by 73% and almost completely abolished cortical infarction (-91%). None of the animals of this group had any residual neurological deficit at the end of the observation period (P<0.05 versus all other groups). CONCLUSIONS: The efficacy of drugs (monotherapy or in combination) most commonly used for neuroprotection during neurovascular surgery is limited. The newly proposed combination therapy (magnesium, tirilazad, and mild hypothermia), which is based on pathophysiological considerations, seems to be a promising alternative for neuroprotection in cerebrovascular surgery.

Additional clinical observations utilizing bispectral analysis.

Additional observations were made in the use of the bispectral (BIS) index with the use of ketamine and in performing general anesthesia without the use of local anesthesia in nonintubated patients. Twenty-five subjects undergoing extraction procedures in an outpatient setting were analyzed using bispectral analysis with ketamine and midazolam. Despite repeated injections of midazolam during the procedure, only transient decreases of the BIS occurred to the 80s, with a low value of 77 in all but 1 patient where ketamine was used. In comparison, values in the 50-70 range are typically seen immediately after the administration of sedative doses of midazolam, propofol, or methohexital. In the second study, once propofol anesthesia was initiated, BIS readings in the 30s were commonly seen in patients during their procedure. The lowest BIS level observed was 18. Bispectral analysis was useful to trend the present anesthetic state and adjust the dose of propofol accordingly. In no case was laryngospasm or total airway obstruction observed. In 1 case, partial airway obstruction secondary to retro-positioning of the tongue occurred with a subsequent decrease in oxygen saturation to 89%. This was rectified by repositioning the patient to alleviate the obstruction. Consistent with previous studies utilizing ketamine, BIS values are consistently higher when compared with other hypnotic agents. With the subsequent injection of midazolam, the BIS level did not decrease to anticipated levels. In the final study reviewed, when local anesthesia was not used during general anesthesia, bispectral analysis was a useful adjunct in helping maintain a steady state of general anesthesia in nonintubated patients undergoing third molar extractions. Bispectral analysis offers additional information on the depth of the hypnotic state and is useful in helping control the depth of anesthesia. A limitation of the index includes the inability to titrate the level of sedation induced by hypnotic agents such as midazolam when ketamine is concomitantly administered.

Mortality and morbidity with outpatient anesthesia: the Massachusetts experience.

PURPOSE: This study documented the incidence of mortality and morbidity for outpatient anesthesia delivered by oral and maxillofacial surgeons in Massachusetts. MATERIALS AND METHODS: A questionnaire was mailed to the 151 active members of the Massachusetts Society of Oral and Maxillofacial Surgeons, and all members responded. Information regarding the incidence of specific anesthetic morbidity was reported for 1 year (1994), and the incidence of mortality for 5 years (1990 to 1994) was requested. RESULTS: Approximately 1,500,000 patients underwent office treatment in the 5-year period without an office anesthetic death. The most common complication was syncope occurring in 1 of every 142 patients receiving local anesthesia. In patients undergoing general anesthesia, laryngospasm occurred 10 times more frequently than bronchospasm. The incidence of other specific anesthetic complications are documented. CONCLUSION: The results of this study suggest that the incidence of death associated with office anesthesia, although small initially, has decreased.

The cost-effectiveness of methohexital versus propofol for sedation during monitored anesthesia care.

UNLABELLED: We designed this study to test the hypothesis that methohexital is a cost-effective alternative to propofol for sedation during local anesthesia. Sixty consenting women undergoing breast biopsy procedures under local anesthesia were randomly assigned to receive an infusion of either propofol (50 microg x kg(-1) x min(-1)) or methohexital (40 microg x kg(-1) x min(-1)). The sedative infusion rate was titrated to maintain an observer's assessment of alertness/sedation (OAA/S) score of 3 (with 1 = awake/alert to 5 = asleep). Fentanyl 25 microg i.v. was administered as a "rescue" analgesic during the operation. We assessed the level of sedation (OAA/S score), vital signs, time to achieve an OAA/S score of 3 at the onset and a score of 1 after discontinuing the infusion, discharge times, perioperative side effects, and patient satisfaction. The direct cost of methohexital was lower than that of propofol, based on the milligram dosage infused during the operation. The sedative onset (to achieve an OAA/S score of 3) and the recovery (to return to an OAA/S score of 1) times, as well as discharge times, did not differ between the two groups. Patients receiving methohexital had a significantly lower incidence of pain on initial injection compared with those receiving propofol (10% vs 23%). Because the use of methohexital (29.4 +/- 2.7 microg x kg(-1) x min(-1)) for sedation during breast biopsy procedures has a similar efficacy and recovery profile to that of propofol (36.8 +/- 15.9 microg x kg(-1) x min(-1)) and is less costly based on the amount infused, it seems to be a cost-effective alternative to propofol for sedation during local anesthesia. However, when the cost of the drug infused and drug wasted was calculated, there was no difference in the overall drug cost. IMPLICATIONS: When administered to maintain a stable level of sedation during local anesthesia, methohexital is an acceptable alternative to propofol. However, the overall drug costs were similar with the two drugs.

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.

Morbidity and mortality with outpatient anesthesia: the Massachusetts experience.

All 147 active members of the Massachusetts Society of Oral and Maxillofacial Surgeons responded to an anesthesia survey. They had treated 416,561 patients during 1989. This article reports the results of the survey and specific untoward anesthetic events as recalled by these practitioners. Use of various anesthetic agents in 1989 and 1984 are compared.

TRH analogue antagonizes anaesthetic induced depression of information transfer through the ventrobasal thalamus of the rat.

Previous studies have indicated an anti-narcotic action of TRH and its analogues. A major site of anaesthetic action is in the ventrobasal thalamus (VBT). The present experiments were performed to determine whether there was antagonism between anaesthetics and a TRH analogue on VBT transmission. It was found that the TRH analogue CG3703 reversed the depressant actions of the anaesthetics urethane, sodium pentobarbitone and sodium brietal on ventrobasal transmission. These actions were also observed at the cortical level but cuneate transmission was unaffected. These results are discussed in the context of modulation of information flow through VBT. In particular it is suggested that TRHergic input from the thalamic reticular nucleus may be an important regulator of VBT transmission.

[Anesthesia procedures for bronchoscopic intubation in a comparative study]. / Anästhesieverfahren zur bronchoskopischen Intubation im Vergleich.

In 94 patients intubation by means of the fibre-optic bronchoscope was effected in various indication. Three different methods of anaesthesia were used: local anaesthesia + mild sedation; general anaesthesia + relaxation; sedation + analgesia. The experiences made with these methods--based on clinical observation and interrogation of the patients--reveal the special usefulness of local anesthesia for bronchoscopic intubation; this is probably the method of choice in practice.

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.

Hypnosis and daycase anaesthesia. A study to reduce pre-operative anxiety and intra-operative anaesthetic requirements.

Fifty-two female patients who underwent gynaecological operations as day cases received either a short pre-operative hypnotic induction or a brief discussion of equal duration. Hypnotized patients who underwent vaginal termination of pregnancy required significantly less methohexitone for induction of anaesthesia. They were also significantly more relaxed as judged by their visual analogue scores for anxiety. Less than half of the patients were satisfied with their knowledge about the operative procedure even after discussions with the surgeon and anaesthetist. A significant correlation was found between anxiety and perceived knowledge of procedures. The results suggest that pre-operative hypnosis can provide a quick and effective way to reduce pre-operative patient anxiety and anaesthetic requirements for gynaecological daycase surgery.

Full dentition periodontal surgery using intravenous conscious-sedation. A report of 10,000 cases.

In 1980 Ceravolo, et al, reported the results of 5200 cases of periodontal surgery performed in dental offices on patients while under conscious sedation. In no instance was a major complication noted. Successful case management coupled with a high degree of patient acceptance prompted the authors to continue to perform full dentition periodontal surgery with the aid of conscious sedation plus local anesthesia. To date, 10,000 cases have been completed in this manner. As yet no major complications have been noted.

Cyanosis of the hands following the use of alphaprodine in dental anaesthesia.

A case is presented of asymptomatic cyanosis of the hands, seen four hours after dental surgery under intravenous, local and inhalational anaesthesia. Alphaprodine hydrochloride, a synthetic opiate and one of the agents used, may produce dilatation of the venous bed with passive venous pooling. Such a mechanism is thought to have occurred in this case, manifesting as cyanosis. A weakly positive intradermal skin test to alphaprodine suggests immediate type hypersensitivity as a possible underlying cause.

Some studies on the properties of the intravenous anaesthetic, propofol ('Diprivan')--a review.

Four studies have been carried out on propofol in this department, one being part of a multicentre trial. The minimum induction dose in unpremedicated patients was found to be 2.5 mg/kg. Propofol has been shown to be an acceptable induction agent, although with an incidence of pain on injection which is much higher when small veins are used. When given by continuous infusion to supplement regional anaesthesia, recovery was much more rapid than with methohexitone. The potency of propofol to thiopentone has been shown to be 1:1.604. Slight falls in cardiac output occurred following propofol 2.5 mg/kg, with significant reductions in mean arterial blood pressure and systemic vascular resistance. These changes were greater than those following an equipotent dose of thiopentone 4 mg/kg.

Effect of age on the establishment of muscle paralysis induced in anaesthetized adult subjects by ORG NC 45.

The establishment of muscle paralysis produced by a single dose of 70 micrograms . kg-1 of ORG NC 45 was studied in 30 healthy anaesthetized patients, aged 15-85 years, by recording adductor pollicis isometric mechanical activity-twitch height (TH). Significant correlations were observed between age and the latency of ORG NC 45 action, defined as the reduction of TH to 95% of its initial value (r:0.315, P less than 0.05) and between age and the onset time, defined as the time elapsing between ORG NC 45 administration and maximum TH depression observed (r:0.454, P less than 0.005). Correlation between age and maximum TH depression was not significant. These results show that if the maximum TH depression observed after a standard dose of ORG NC 45 is not altered by the age of the patient, the establishment of the paralysis is delayed by ageing.

[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.

Conscious sedation and behavioral modification with local standby anesthesia for ophthalmologic surgery.

Local and retrobulbar block anesthesia in combination with a brief span of amnesia - not general anesthesia -- produced by minute doses of four intravenous sedative drugs, has made it possible to perform ophthalmologic surgery without the memory of the pain of the retrobulbar block, followed by an ensuing quiescence augmented by behavioral modification for the duration of the operation. Patients are awake, rational, cooperative, calm and relaxed, and because of behavioral modification, are highly motivated to guarantee not only their own survival, but to feel a part of the team effort to preserve the integrity of their eye.