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Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Adolescent↗

Absence of correlation between amobarbital distribution as assessed with SPECT brain perfusion imaging and behavioral manifestations during the intracarotid amobarbital procedure (Wada test).

1. The IAP is used presurgically in patients with temporal lobe epilepsy to predict the effects on LTM and language of the planned temporal lobectomy. This prognosis presumes that a similar pattern of perfusion will result in anesthesia of the same cerebral regions in most patients. 2. Coinjection of Tc-99m HMPAO with the barbiturate during the IAP has been used to ascertain whether this actually is true, with variable results. Moreover, most studies document only unilateral IAPs and do not report on behavioral performance. 3. The authors coinjected Tc-99m HMPAO and amobarbital in 33 IAPs from 18 patients (15 injected bilaterally, 3 unilaterally) to clarify this and to evaluate the relationship of the perfusion pattern to behavioral performance; SPECT results were also compared to angiographic evaluation obtained at the time of catheter placement. 4. SPECT perfusion data was rated for presence/absence and intensity of perfusion to the ACA, MCA, PCA territories and to H, i or c to the injection site. V, STM and LTM were graded according to a standardized protocol. 5. MCAi was perfused in 100% of cases, ACAi in 91%, PCAi in 21% and Hi in only 6%. Cross-over flow was shown in 9 studies; 50% of the patients in whom both sides were injected (on different days) had crossover, involving the ACAc territory in 80% of cases. As expected, injection on the non-ES was associated with a significantly worse LTM performance than on the ES (p = 0.006). There was no relationship between the perfusion pattern and the V level of the patients (a potential confounding variable in memory/language evaluation) during IAP, nor between perfusion pattern and LTM. STM was significantly adversely affected by the presence of crossover perfusion. Angiography in general overestimated the extent of cerebral perfusion demonstrated by SPECT, most probably because of the markedly different injection conditions. 6. Despite the best efforts to standardize injections, the perfusion pattern has been mostly unpredictable in the patients. Moreover, it has little bearing on their behavioral performance, except for the prediction of poor STM performance (the clinical implications of this remaining dubious). Marked LTM alterations after non-ES injections confirm remote hippocampal effects in the presence of only rare direct perfusion of that region. Tc-99m HMPAO/Amobarbital coinjection was unhelpful from a clinical perspective, most probably because a large part of the effects of amobarbital arise from deafferentation of regions not directly perfused by the anesthetic agent.

Adult↗

HPLC analysis for amobarbital N-glycosides in urine.

A study was undertaken to determine if humans excrete both amobarbital N-glucuronides and N-glucosides in urine after an oral dose of amobarbital. Amobarbital N-glucuronides were synthesized and characterized. A reverse phase LC method using post-column pH adjustment and UV detection at 240 nm was developed and used for the quantification of the amobarbital N-glucosides and N-glucuronides in human urine. Amobarbital was administered orally to seven male subjects and the total urine was collected for a period of 48-53 h after dosing. After filtration, the urine was injected directly onto the HPLC column to analyze for the presence of metabolites. The previously identified (5S)-amobarbital N-glucoside was detected in all seven subjects. The (5R)-amobarbital N-glucoside was detected at lower concentrations in only four of the subjects. At the levels at which amobarbital N-glucosides were detected, there was no evidence for the formation and excretion of the amobarbital N-glucuronides. Amobarbital N-glucuronidation is not a quantitatively significant pathway for the biodisposition of amobarbital in humans.

Adult↗

Contralateral EEG slowing and amobarbital distribution in Wada test: an intracarotid SPECT study.

PURPOSE: To relate the occurrence of contralateral electroencephalogram slowing (CES) to amobarbital distribution, we performed electroencephalogram (EEG) monitoring and intracarotid single photon emission computed tomography (SPECT) during an intracarotid amobarbital procedure (IAP). METHODS: IAP was performed on 22 patients with temporal lobe epilepsy. CES was defined as the occurrence of significant EEG slowing on the contralateral hemisphere (>50% of the ipsilateral hemisphere slowing) after amobarbital injection. To map the distribution of the amobarbital, we injected a mixture of amobarbital and (99m)technetium-ethylcysteinate dimer (99mTc-ECD) into the internal carotid artery and performed a brain SPECT 2 h later. In the SPECT images, regions of interest were determined by ipsilateral and contralateral anterior cerebral artery territories (iACA, cACA), ipsilateral and contralateral middle cerebral artery territories (iMCA, cMCA), and ipsilateral and contralateral posterior cerebral artery territories (iPCA, cPCA), as well as ipsilateral and contralateral anterior and posterior mesial temporal regions (iAMT, cAMT, iPMT, cPMT). The perfusion of amobarbital was interpreted visually in each region. RESULTS: Amobarbital was distributed in the iMCA in all the patients; in the iACA in 20 (90.9%) patients; in the iAMT in 14 (63.5%); and in the iPCA and iPMT in only two (9.1%). CES was observed in 13 (59.1%) patients. Cross-perfusion of amobarbital in limited areas of the cACA were observed in only four of 13 patients. Wada retention memory scores (WRMS) showed no significant difference between the CES- (n = 9) and CES+ (n = 13) groups. CONCLUSIONS: Amobarbital rarely perfused the iPCA territory and the iPMT region and was rarely delivered to the contralateral hemisphere. The occurrence of CES was not related to the cross-perfusion of amobarbital. CES appears to be produced by a transient functional disconnection from the ipsilateral hemisphere.

Adolescent↗

Controlled investigation of the amobarbital interview for catatonic mutism.

OBJECTIVE: Clinical reports over the last 60 years suggest that the amobarbital interview is effective in relieving catatonic symptoms. This has never been substantiated with methodologically sound trials. The authors postulated that a randomized blind comparison of intravenous amobarbital and saline would demonstrate the superiority of amobarbital in relieving catatonic mutism. METHOD: The subjects were 20 inpatients with catatonic mutism. They were randomly assigned to either saline (N = 10) or a 5% amobarbital solution (N = 10), and the infusions were administered intravenously at a rate of 1 cc/min or less over 10 minutes by a blinded physician. A second blinded physician administered a semistructured interview during the infusion to control for the effect of suggestion. A third blinded physician rated patient responsiveness, reactivity, and arousal. Any patient who was unresponsive to the initial infusion was crossed over to the other infusion. Interviews were videotaped for determination of interrater reliability. RESULTS: In the initial infusions, six of 10 patients responded to amobarbital and zero of 10 responded to saline. Four of the saline nonresponders responded when given amobarbital. Response was evident by the 4th minute of the amobarbital infusion. Interrater reliability was high. The responders and nonresponders differed significantly in the variance of the weight-adjusted amobarbital dose, and the responders tended to be older and female. CONCLUSIONS: Intravenous amobarbital is superior to saline in relieving catatonic mutism, although only 50% of these patients responded. The nonresponders were distinguished from the responders by a greater variance in the weight-adjusted dose of amobarbital.

Adult↗

The anterior and posterior selective temporal lobe amobarbital tests: angiographic, clinical, electroencephalographic, PET, SPECT findings, and memory performance.

The techniques, results, and problems of three types of selective temporal lobe (TL) amobarbital procedures (balloon technique with temporary occlusion of the internal carotid artery distal to the origin of the anterior choroidal artery (acha) [n = 19]; selective anterior catheterization of the acha [n = 20]; and selective catheterization of the peduncular P2-segment of the posterior cerebral artery [n = 5]) are described in a group of 40 patients with medically refractory complex partial seizures of mesial TL origin. Selective amobarbital tests were carried out before surgery to predict the memory deficit after an intended selective amygdalohippocampectomy. The effects of selective anaesthetization of TL were correlated with clinical data, pattern and duration of amobarbital induced EEG changes, and performance on verbal and nonverbal memory tasks measured during the test. In 4 patients the effect of selective amobarbital injection on regional and global metabolism was studied with 18F-FDG-PET, with the PET tracer being injected intravenously immediately after amobarbital. More recently in 2 patients the vascular territory perfused by amobarbital in the acha test was studied with SPECT using 99m Tc ECD injected immediately prior to the amobarbital into the acha. Whereas the PET studies showed a rather widespread and bilateral amobarbital-induced decrease of metabolism, the SPECT studies confirmed the selective distribution of the tracer in the vascular territory of the acha, i.e., in amygdala and hippocampus. The comparison of selective TL amobarbital test performance with postoperative neuropsychological performance showed that the predictive value of this test is rather good for the postoperative verbal memory but underestimates postoperative nonverbal ("figural") memory performance.

Adult↗

Anatomic correlates of memory from intracarotid amobarbital injections with technetium Tc 99m hexamethylpropyleneamine oxime SPECT.

OBJECTIVE: To better identify regions of the brain affected by intracarotid amobarbital injections and to more precisely predict whether resections of specific brain regions will cause postoperative memory deficits. DESIGN: We modified the standard intracarotid amobarbital procedure by adding a radioactive tracer to the amobarbital injection, thereby providing better correlation between behavior and deactivated brain region. SETTING: Tertiary-care hospital center with a dedicated program for medical and surgical treatment of epilepsy. PATIENTS: We studied 39 patients with medically intractable epilepsy drawn from a regional referral base. INTERVENTION: Intracarotid injection of 125 mg of sodium amobarbital with 37 MBq of technetium Tc 99m hexamethylpropyleneamine oxime (HMPAO), followed by language and memory testing. MAIN OUTCOME MEASURES: The distribution of amobarbital as measured by single photon emission computed tomographic imaging of HMPAO and patient performance on memory tasks. RESULTS: Medial temporal regions were irrigated by the amobarbital in only 28% of the injections. Overall, findings suggest that medial temporal and lateral neotemporal cortex play a role in memory. CONCLUSIONS: The regions involved in memory function vary by individual, as does the distribution of amobarbital. Thus, the most accurate method of determining correlation of brain region with memory function during intracarotid amobarbital injection involves the use of a tracer such as HMPAO.

Adolescent↗

Amobarbital--a probe of hepatic drug oxidation in man.

Some aspects of the fate of amobarbital were investigated since this drug is being used as a probe to gauge drug oxidation in man. The mean ratio of orally available over intravenously injected amobarbital was established as 0.99 +/- 0.11 (SD), by comparing integrated concentration-time curves, indicating complete absorption and absence of a first-pass effect. One subject ingested 200 mg of amobarbital sodium, and amobarbital concentrations in serum were monitored for 5 days thereafter. Elimination of amobarbital under these conditions followed first-order kinetics. One subject ingested amobarbital 7 times over a period of 3 yr; plasma clearances (32.1 +/- 1.8 [SD]ml/min) exhibited remarkable constancy, while biologic half-lives (26.5 +/- 3.1 hr) and distribution volumes (73.6 +/- 8.0 L) showed some fluctuation. The distribution of parameters of amobarbital elimination was investigated in 36 unrelated subjects. Amobarbital half-lives (23.8 +/- 6.7 hr) appeared to be normally distributed, while the clearances (36.7 +/- 10.0 ml/min) might not follow a normal distribution.

Adolescent↗

Stereochemical characterization of the diastereomers of the amobarbital N-glucosides excreted in human urine.

The stereochemistry associated with the amobarbital N-glucoside diastereomers (1a and 1b) that are excreted by humans in urine is unknown. Using X-ray crystallography, the absolute configuration of 1b was determined to be S (C-5 position of the barbiturate ring). Following oral administration of amobarbital to Caucasians and Orientals, from 5 to 25% of the dose of amobarbital was excreted in the urine as 1b. The other diastereomer, 1a, accounted for less than 0.1 to 0.2% of the dose in four individuals, with none detected in nine individuals. The rate constants, kf,1b, determined from the urinary excretion of 1b were lower than those previously reported for unresolved amobarbital N-glucosides. However, based on the urinary excretion of 1b, the rate constants, K, for elimination of amobarbital in Caucasians and Orientals were similar to those previously determined from the serum levels of amobarbital and the urinary excretion of unresolved amobarbital N-glucosides. In previous studies of the N-glucosylation of amobarbital, it is likely that a single N-glucose diastereomer, 1b, was being observed.

Adult↗

Selective amobarbital test for the determination of language function in patients with epilepsy with frontal and posterior temporal brain lesions.

PURPOSE: Selective amobarbital tests with selective temporary inactivation of the left frontal operculum and/or the left parietotemporal cortex were performed in 5 patients with left-hemispheric epileptogenic lesions in or adjacent to classical Broca's and/or Wernicke's area. The aim was to assess language functions in these brain regions before surgery, to tailor the surgery according to the individual functional importance of these brain regions, and to predict postoperative outcome. METHODS: Amobarbital was injected by transfemoral selective catheterization of the arteries supplying the target areas. Along with neuropsychological and neurological testing during the amobarbital procedure, EEG recordings were performed in all patients, and [99mTc]HMPAO-single photon emission computed tomography (SPECT) in 2 patients. RESULTS: After the amobarbital injection into the left frontal opercular region, there was no recognizable language dysfunction in 3 patients. In these 3 patients, the lesions in or adjacent to the frontal operculum were completely resected without postoperative language impairment. In the remaining 2 patients, temporary language impairment after the amobarbital injection into the left frontoopercular and Wernicke's region, respectively, suggested language functions in these areas. Surgery was restricted to the left mesiotemporal lobe in 1 patient. In the other patient, the tumor infiltrating the frontal operculum was restrictively resected. Postoperatively, the first patient had no language impairment, but the latter had transient global aphasia, from which she recovered. CONCLUSIONS: Selective temporary amobarbital inactivation of brain regions that may be associated with language has clearly indicated the presence or absence of language functions in these regions. The test contributed substantially to planning of the surgical approach in each patient. The predictive value of the amobarbital test was demonstrated by the postoperative outcome.

Adolescent↗

Salivary excretion of amobarbital in man.

The concentrations of amobarbital in saliva and serum were determined in 5 normal adults following ingestion of 120 mg of sodium amobarbital. There was excellent linear relationship between amobarbital concentrations in saliva and serum (r = 0.993); salivary levels were 36.1% of serum levels. Since the pH of saliva was generally lower than that of blood in man, the degree of ionization of amobarbital in serum and saliva had to be taken into consideration. Estimation of the protein binding of amobarbital in serum from concentrations of amobarbital in saliva and serum was in good agreement with the in vitro data of equilibrium dialysis.

Adult↗

SATSCOM--Selective amobarbital test intraarterial SPECT coregistered to MRI: description of a method assessing selective perfusion.

For evaluation of potential functional deficits, an intraarterial amobarbital test is performed prior to neurosurgical or neuroradiological interventions. To visualize individual amobarbital perfusion patterns, simultaneous injection of (99m)Tc-HMPAO was performed previously. The present study describes for the first time a method of coregistration of intraarterial SPECT during selective amobarbital test to MRI. Three patients undergoing selective amobarbital test of the posterior cerebral artery were included. SATSCOM (Selective amobarbital test intraarterial SPECT coregistered to MRI) was performed by skull extraction in SPECT and MRI followed by surface matching. In all three patients, SATSCOM revealed accurate matching results. With this functional-anatomical mapping, suppression of higher cortical functions can be correlated to anatomical regions. Furthermore, a more precise mapping of amobarbital effect improves planning invasive interventions, particularly those close to eloquent areas.

Adult↗

Multiple effects of amobarbital on Ehrlich ascites tumor cells. Inhibition of pyruvate dehydrogenase.

The inhibition of the proliferation of hyperdiploid Ehrlich ascites tumor cells in suspension cultures by amobarbital is coupled to an increased glycolytic activity as shown by lactic acid production and glucose consumption; higher concentrations of amobarbital than 1 mM enhance the ATP/ADP ratio of the total cell. The actual activity of pyruvate dehydrogenase of intact cells is completely inhibited in the presence of 2 mM amobarbital as was shown by the 14CO2 evolution from [114C]pyruvate or the incorporation of 14CO2 into the total lipid fraction of the cells from [U-14C]lactate. The pyruvate dehydrogenase complex from Ehrlich ascites tumor cells is completely inhibited by 1 mM amobarbital in vitro. The activity of alpha-oxoglutarate dehydrogenase is inhibited by amobarbital, too, as well as shown by measuring the 14CO2 evolution from [1-14C]glutamate with intact cells. It is suggested that the inhibition of pyruvate dehydrogenase in the presence of amobarbital is the result of a direct action on the enzyme as well as the consequence of a change in the cellular redox state or its energy charge.

Adenosine Diphosphate↗

The amobarbital interview revisited: a review of the literature since 1966.

The amobarbital interview has been a diagnostic and therapeutic tool for almost 70 years. Because safer alternatives, namely benzodiazepines, have become available over the past 30 years, its clinical use merits reexamination. Toward this end, the psychiatric literature on the amobarbital interview is reviewed. A Medline search using the key words "amobarbital interview" generated papers published in English since 1966. Most of the literature demonstrating utility of the amobarbital interview consists of uncontrolled case series or case reports on a variety of clinical applications. One controlled study in patients with catatonia demonstrated clear superiority of amobarbital over placebo in promoting verbalization and alertness, but six other controlled studies using various doses in heterogeneous patient groups failed to find differences between this drug and placebo. Additional rigorous, controlled studies comparing amobarbital with placebo and with possible alternatives such as benzodiazepines in specific patient populations are needed to define the place of this agent in the psychiatric armamentarium.

Amobarbital↗

Potential toxic effects of superselective injection of amobarbital sodium on microvasculature: a study in an animal model.

PURPOSE: To determine whether microvascular damage occurs from superselective intraarterial injection of amobarbital sodium using the swine endovascular embolization model. METHODS: Thirty-four swine underwent percutaneous femoral puncture for superselective catheterization of the proximal artery of the rete. Varying concentrations of amobarbital sodium were prepared (12.5 to 100 mg/mL solution) in either normal saline or sterile water (105 mOsm/L to 1138 mOsm/L) of which one concentration was infused slowly into one ipsilateral rete. Control infusions were also performed. Histopathologic changes were evaluated at 30 minutes and 10 days after infusion, using standard light and electron microscopy techniques. RESULTS: Moderate vasospasm occurred only in three swine at 100 mg/mL amobarbital sodium in normal saline. Light microscopy showed no significant histologic changes in the retia at any of the tested concentrations of amobarbital sodium. Electron microscopy showed ultrastructural alterations in the intima only at the higher amobarbital sodium concentrations. CONCLUSIONS: Concerns for inducing significant damage to cerebral microvasculature by superselective injection of amobarbital sodium at the usually recommended concentrations and doses are probably not justified.

Amobarbital↗

The Response to an Amobarbital Interview as a Predictor of Therapeutic Outcome in Patients with Catatonic Mutism.

Intravenous amobarbital temporarily relieves catatonic mutism. The older psychiatric literature reported that response to amobarbital is associated with eventual good therapeutic outcome, whereas nonresponse may indicate poor outcome. This study investigated the short-term outcome of 20 patients with catatonic mutism after an amobarbital interview. A blind review of the charts was conducted at the patients' discharge, and patients were rated as either having good or poor outcome. The patients who did not respond to amobarbital improved during hospitalization as often as those patients who did respond to amobarbital. We conclude that a negative amobarbital interview is an unreliable prognosticator of poor response in these patients.

Journal Article↗

Correlates of arterial-filling patterns in the intracarotid amobarbital procedure.

OBJECTIVE: To determine behavioral correlates of anterior cerebral artery (ACA) and posterior cerebral artery (PCA) perfusion patterns in the intracarotid amobarbital sodium procedure. DESIGN: Multivariate analysis of covariance and partial correlations of behavioral measures to ACA crossflow and PCA filling. SETTING: Angiography and the intracarotid amobarbital procedure at a comprehensive epilepsy center. SUBJECTS: Forty-two patients with intractable epilepsy (right-hemisphere seizure focus [n-23]; left-hemisphere seizure focus [n = 19]). MEASUREMENTS: Internal carotid angiography was performed both at a standard injection rate (8 mL of contrast per second) and at 1 mL/s, which matched the rate of the subsequent amobarbital injection. The degree of ipsilateral PCA and contralateral ACA filling were graded on a seven-point scale and compared with postinjection behavior, language, and memory measures. RESULTS: The ACA crossflow did not correlate significantly with that of any measure. The degree of PCA-filling pattern correlated significantly only with the level of consciousness (r = .31, P < .004), but it was not significant after accounting for the effects of seizure laterality, injection side, and amobarbital dosage. Neither ACA crossflow nor PCA filling correlated significantly with memory. The degree of ACA and PCA filling was overestimated at standard angiography (8 mL of contrast medium per second) injection rates. CONCLUSIONS: Although the degree of PCA filling correlates mildly with the level of consciousness postinjection, possibly by perfusion of thalamic or mesencephalic branches, it is not reliably predictive and is less contributory than the injection side and seizure laterality. The PCA filling is not required to produce valid memory assessment in the intracarotid amobarbital procedure, and ACA crossflow is not predictive of behavioral responses.

Adult↗