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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↗

Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy.

Plasma half-lives of amobarbital were determined in newborn children of 10 mothers who had been treated with barbiturates for hypertension in pregnancy for 6 to 42 days prior to delivery. Five mothers had received amobarbital, 200 mg daily, and 5, phenobarbital, 60 to 180 mg daily. Half-lives in 7 of the babies ranged from 16.6 to 49.4 hr, comparable to those previously reported in babies of mothers who had received only a single dose of amobarbital. Thus there was no evidence of induction of amobarbital hydroxylation in these children. Two babies who had a greater than normal rise in serum bilirubin had longer half-lives (86.1 and 117.7 hr). In 1 baby whose mother had membranous glomerulonephritis, plasma amobarbital concentration did not significantly change over the period of the study.

Adult↗

Estimation of amobarbital plasma-effect site equilibration kinetics. Relevance of polyexponential conductance functions.

The time delay between drug plasma concentrations and effect has been modeled most commonly by the effect compartment approach, assuming first-order monoexponential equilibrium kinetics between plasma and effect site. So far this assumption has not been rigorously probed. The purpose of the present investigation was to model the delay between amobarbital plasma concentrations and EEG effect using a new approach based on system analysis principles. This approach models the equilibrium between plasma and effect site without assuming a specific kinetic structure. Assuming linear distribution kinetics between plasma and effect site, the relationship between the two variables may be described by a convolution type of linear operation, involving a conductance function phi(t), which is approximated by a sum of exponentials. Six male Wistar-derived rats received an iv infusion of amobarbital at a rate of 10 mg/kg per min until isoelectric periods of 5 sec or longer appeared on the EEG. Frequent arterial blood samples were obtained and EEG was continuously quantified using aperiodic analysis. The amplitudes in the 2.5-30 Hz frequency band were used as EEG effect measure. The delay between plasma concentrations and EEG effect was best modeled by a biexponential conductance function. The use of a biexponential conductance function resulted in a significant further reduction (41 +/- 10%) in hysteresis when compared to a monoexponential function, indicating that the assumption of simple first-order monoexponential equilibration kinetics is inadequate. The use of a biexponential conductance function also resulted in a significantly different shape of the effect site concentration-EEG effect relationship and hence the estimated pharmacodynamic parameters, when compared with a monoexponential function. This relationship showed a biphasic behavior, with EEG effects being maximal at amobarbital concentrations of 29.6 +/- 1.3 mg/L. At 80.2 +/- 2.0 mg/L the EEG effect was reduced 50% below baseline values. A comparison was made with the equilibration between amobarbital plasma and cerebrospinal fluid (CSF) concentrations. Six male Wistar-derived rats received an iv infusion of amobarbital, 10 mg per min for 15 min. Arterial blood and CSF samples were taken simultaneously at regular intervals. The equilibration between plasma and CSF concentrations was best fitted by a monoexponential conductance function. Significant differences in equilibration profiles of CSF and effect site with the plasma site were observed. To reach 50% equilibrium the effect site requires 2.5 +/- 0.3 min and the CSF 3.5 +/- 0.2 min, to reach 95% the values were, respectively, 90 +/- 27 and 15 +/- 1 min. This suggests that CSF is kinetically distinguishable from the effect site.

Amobarbital↗

Affective self-report during the intracarotid sodium amobarbital test: group differences.

Emotional reactions are sometimes observed during the intracarotid sodium amobarbital test. For instance, euphoric/indifference reactions can be seen during right hemisphere inactivation and catastrophic reactions may accompany left hemisphere inactivation. Less dramatic changes can also be detected in affective self-report during left and right hemisphere amobarbital tests, with more negative affect reported during left hemisphere inactivation and either neutral or mildly positive affective states reported during right hemisphere inactivation. The current study not only replicated this effect, but in addition, found significant group differences. The first group (right way) showed a pattern of affective self-report during left and right amobarbital tests entirely consistent with prior findings, while a second group (wrong way) showed results that behaved in a diametrically opposite fashion. A third group (no change) showed little, if any, difference in affective self-report during left and right amobarbital tests. The major factor distinguishing the wrong way group from the other two appeared to be an asymmetrical distribution of left and right temporal lobe lesions in the former group. In contrast, the factor differentiating the right way group from the no change group appeared to be the relative degree of left hemisphere inactivation during the left hemisphere amobarbital test. The results are discussed not only in terms of their impact on theories of cerebral lateralization for emotion, but also in terms of methodological issues in this field.

Adolescent↗

Quantitative analysis of hemispatial neglect in the intracarotid sodium amobarbital (ISA) test.

There are dramatic changes in the electroencephalogram of the inactivated hemisphere in the intracarotid sodium amobarbital test. One of the more profound behavioral changes during this procedure is left hemispatial neglect accompanying right hemisphere inactivation. The present study was designed to ascertain whether there was a clear relationship between the degree of hemispheric inactivation (as measured by the electroencephalogram) and the degree of left hemispatial neglect during this procedure. Sixty-nine participants undergoing right hemisphere intracarotid sodium amobarbital testing were presented with a random letter cancellation test at various points during the procedure. Neglect was quantified as significant, moderate, minimal, or none, based on how many target letters the patients missed. The simultaneous electroencephalogram from each of these testing points was spectrally analyzed and topographic maps were generated. The degree of neglect was then compared with the comparable topographic map. It was found that as the amobarbital-induced right hemispheric dysfunction regressed, the degree of neglect lessened in a systematic fashion, as did the profound electroencephalographic changes induced by the drug. Thus, there is a clear relation between the degree of hemispheric inactivation induced by the amobarbital and the degree of left hemispatial neglect. This relationship held regardless of side of hemispheric language dominance or epileptic focus. These results replicate previous findings that right hemisphere inactivation during the intracarotid sodium amobarbital test results in left hemispatial neglect. They extend these findings by clearly showing that neglect changes in a quantitative fashion (rather than being an all-or-none phenomenon) and further, show that there is a clear relationship between the severity of neglect and the degree of hemispheric dysfunction.

Adolescent↗

Selective posterior cerebral artery amobarbital test: its role in presurgical memory assessment in temporal lobe epilepsy.

PURPOSE: To evaluate the efficacy and risk of complications of selective posterior cerebral artery (PCA) amobarbital anesthesia in memory assessment of patients with epilepsy under consideration for temporal lobe resection. METHODS: Thirty-two candidates for temporal lobectomy in whom conclusive memory assessment could not be obtained by the standard intracarotid amobarbital procedure were submitted to a selective PCA amobarbital test. A mean dose of 75 mg amobarbital was injected via microcatheter into the P2 segment of the PCA. Ten common objects were presented for naming and remembering while the anesthesia was judged efficient. After return to neurologic baseline, recall and recognition memory were assessed. RESULTS: In all of the 32 patients, angiography and PCA anesthesia were successfully accomplished without serious adverse events. All but one of the patients remained alert and cooperative for memory testing under the anesthesia, and 28 of these patients showed adequate memory capacity of the hemisphere contralateral to the side targeted for surgery. So far, 19 patients have proceeded to surgery, and no case of global amnesia or serious, material-specific memory impairment has resulted. Three patients failed the PCA test (fewer than 67% items correctly recognized) and were excluded from surgery, partly on the basis of the PCA test results, but also supported by an overall evaluation of all the diagnostic procedures used. CONCLUSIONS: The selective PCA amobarbital test appears justifiable when performed by interventional neuroradiologists and may significantly reduce the risk of erroneously excluding patients with epilepsy from temporal resection. Further corroboration of the safety of the procedure seems warranted.

Adolescent↗

Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria.

Cardiac ischemia damages the mitochondrial electron transport chain. Irreversible blockade of electron transport at complex I by rotenone decreases ischemic damage to cardiac mitochondria by decreasing the loss of cytochrome c and preserving respiration through cytochrome oxidase. Therapeutic intervention to protect myocardium during ischemia and reperfusion requires the use of a reversible inhibitor that allows resumption of oxidative metabolism during reperfusion. Amobarbital is a reversible inhibitor at the rotenone site of complex I. We asked whether amobarbital administered immediately before ischemia protected respiratory function. Isolated rat hearts were perfused for 15 min followed by 25-min global ischemia at 37 degrees C. Amobarbital-treated hearts received drug for 1 min before ischemia. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after ischemia, and oxidative phosphorylation was measured. Amobarbital protected oxidative phosphorylation, including through cytochrome oxidase, in both SSM and IFM in a dose-dependent manner, with an optimal dose of 2 to 2.5 mM. Amobarbital also preserved cytochrome c content in both SSM and IFM. Thus, reversible blockade of the electron transport chain during ischemia protects mitochondrial respiration.

Amobarbital↗

Mapping the distribution of amobarbital sodium in the intracarotid Wada test by use of Tc-99m HMPAO with SPECT.

The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures. The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium. Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient. SPECT revealed a statistically different distribution from that predicted with conventional angiography. The distribution also often differed from that of DSA, although the difference was not significant. SPECT revealed infrequent delivery to mesial temporal lobe structures. This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.

Adolescent↗

The addition of intravenous caffeine during an amobarbital interview.

Although the amobarbital interview is an effective means of temporarily relieving catatonic mutism, some catatonic patients simply fall asleep during an amobarbital interview. We are examining the feasibility of administering intravenous caffeine benzoate during an amobarbital interview to prevent patients from falling asleep. This paper describes an open trial of the administration of 500 mg caffeine benzoate during amobarbital interviews with ten patients. The procedure was well tolerated, but further studies are needed to determine whether or not caffeine is an advantage over amobarbital alone.

Adult↗

Sequential injections of amobarbital sodium and lidocaine for provocative neurologic testing in the external carotid circulation.

PURPOSE: To present the results of a protocol for embolization in the external carotid territory that includes provocative testing with amobarbital sodium and lidocaine. METHODS: Provocative testing with sequential intraarterial injections of amobarbital sodium and lidocaine was done before embolization of 66 vascular pedicles in 26 patients with the following pathologic disorders: 8 meningiomas, 7 paragangliomas, 5 dural arteriovenous fistulas, 3 angiofibromas, 1 endolymphatic sac carcinoma, 1 metastatic renal carcinoma, and 1 Rendu-Osler-Weber syndrome. Findings during provocative testing and any postembolization deficits were recorded. RESULTS: Of the 66 vascular pedicles tested, only 1 showed positive findings on an amobarbital test, in which the patient had transient numbness in the contralateral leg. Results of lidocaine tests were positive, in 7 cases, in which cranial nerve deficits were suspected on the basis of anatomic findings. All deficits resolved within 15 minutes. If results of amobarbital or lidocaine tests were positive, large particles or coils were used for embolization. Otherwise, small particles or liquid agents were used. There were no complications after embolization. CONCLUSIONS: Provocative testing with amobarbital can reveal dangerous anastomoses. Testing with lidocaine can show vascular supply to the cranial nerves. With the use of appropriate protocols, embolization in the external carotid territory can be done with minimal risk.

Adult↗

Absence of neglect for mental representations during the intracarotid amobarbital procedure.

BACKGROUND: The unilateral suppression of right-hemisphere electrophysiological activity during the intracarotid amobarbital procedure results in left neglect on visuomotor search tasks. OBJECTIVE: To investigate whether right-hemisphere inactivation during the intracarotid amobarbital procedure also results in left neglect of the mental representation of a remembered scene. DESIGN: Before the intracarotid amobarbital procedure, 16 subjects were asked to draw a room from their homes. Following the right-hemisphere injection, subjects wee tested for the presence of left neglect of extrapersonal space using a Random Letter Cancellation Test. To test for neglect of the mental representation of a remembered scene, they were then asked to report items from the room they had drawn. RESULTS: While 10 of the 16 subjects showed left neglect on the Random Letter Cancellation Test, only one subject showed left neglect of the mental representation. The other 15 subjects recalled approximately equal numbers of items from the left and the right hemispaces. CONCLUSIONS: These results replicate previous findings of left neglect of extra personal space during the intracarotid amobarbital procedure and fail to show concurrent neglect for mental representations. They provide further evidence for the multiplicity and dissociability of the behavioral manifestations of neglect.

Amobarbital↗

Identification of 5-ethyl-5-(2-methylbutyl)barbituric acid as an impurity of manufacture in amobarbital.

Amobarbital [5-ethyl-5-(3-methylbutyl)barbituric acid], USP, was found to contain an impurity that was not associated with hydrolysis and decomposition of the barbiturate ring. The impurity was isolated by semipreparative HPLC and was identified as 5-ethyl-5-(2-methylbutyl)barbituric acid (1) by MS (electron impact and chemical ionization) and 1H NMR. The substitution pattern on the alkyl side chain was verified by using the achiral NMR shift reagent tris(6,6,7,7,8,8,8-heptafluoro-2,2- dimethyl-3,5-octanedionato)europium(III). Older samples of amobarbital, USP, contained greater than 6% of 1, whereas recent samples of amobarbital, USP, contained less than 1% of 1. Because the pharmacological profiles of 1 and amobarbital in rodents are comparable, the impurity probably does not constitute a clinically significant problem for humans.

Amobarbital↗

Enzyme induction following a single dose of amobarbital in dogs.

The elimination of amobarbital in dogs was investigated by injecting various doses of amobarbital into a given animal. At low doses (3 mg/kg) serum levels declined in a first-order fashion. Superficially, at high doses (20 mg/kg) the relationship between serum concentration and time could be quantitatively characterized by simple one-compartment saturable kinetics. Indeed, qualitatively, saturation of the amobarbital-metabolizing enzymes was indicated by a shallower initial slope of the semilogarithmic concentration--time profile at the high than at the low dose. However, in addition, an acute enzyme induction phenomenon was observed which was indicated by a shorter terminal half-life of amobarbital at the high dose than after the low dose and also by a shortening in antipyrine half-life.

Amobarbital↗

Activation of the epileptic focus during intracarotid amobarbital test. Electrocorticographic registration via subdural electrodes.

During presurgical evaluation, bilateral intracarotid amobarbital tests were performed in 21 patients (42 tests) to establish the lateralization of cerebral speech dominance as well as memory function. All patients suffered from long-standing, medically intractable, complex partial seizures. Electrocorticographic recording during the investigation was carried out via bilaterally implanted subdural electrodes. The aim of the study was to assess amobarbital-induced effects on the primary epileptic focus, determined throughout presurgical evaluation. Following the application of amobarbital the primary epileptic focus was selectively activated in 10 and preferentially activated in 3 patients suffering from temporal lobe epilepsy. Specific responses of the primary epileptic focus consisted of: (i) induction of a spike-burst-suppression pattern, mainly in the mesio-basal aspects of the focal temporal lobe (n = 13); (ii) induction of spikes or sharp waves following contralateral intracarotid injection (n = 10); (iii) late induction of spikes or sharp waves following ipsilateral injection (n = 4); (iv) loss or marked reduction of drug-induced beta activity over the primary epileptic focus (n = 14) following ipsilateral or contralateral injection. In conclusion, electrocorticographic recording during the intracarotid amobarbital test contributes valuable information about the primary epileptic focus in a high proportion of patients.

Action Potentials↗

Seizures during intracarotid methohexital and amobarbital testing.

BACKGROUND: Methohexital and amobarbital have been used as agents for Wada testing in the presurgical evaluation of patients with epilepsy. Previous experience with methohexital as an anesthetic indicates that methohexital may decrease seizure threshold and may trigger seizures. METHODS: A retrospective chart review of 760 intracarotid amobarbital and methohexital tests was performed to determine the frequency of seizures associated with preoperative intracarotid barbiturate testing for language and memory lateralization. RESULTS: Sixteen patients (2.1%) who had seizures were found. In 3 patients, seizures occurred prior to barbiturate injection, and in 13, following barbiturate injection. After injection of amobarbital, 4 of 538 patients (0.7%) had a seizure. Nine of 222 patients had a seizure after methohexital injection (4.1%) (P=0.001). CONCLUSION: Patients with a previous history of epilepsy may be at higher risk for seizures after methohexital injection as compared with amobarbital injection.

Adolescent↗

Linguistic perseveration in dominant-side intracarotid amobarbital tests.

148 patients with medically intractable complex-partial seizures received bilateral intracarotid amobarbital tests. In 21 patients (14.2%), there were inappropriate responses (intrusions: N = 10; perseverations: N = 11) to a series repetition task (counting backwards) given immediately before amobarbital injection. Five cases from the perseveration subgroup are discussed in detail. In these patients, linguistic perseveration occurred with left-sided amobarbital injection, although they were all found to have left hemispheric speech dominance according to language testing during the amobarbital procedure. It is argued that these perseverations are best explained as a right hemispheric continuation of a speech motor program previously initiated by the left hemisphere.

Adolescent↗

Amobarbital inhibits K(+)-stimulated glucose oxidation in cerebellar granule neurons by two mechanisms.

The study aimed at determining mechanism(s) by which amobarbital (amytal) suppresses glucose oxidation in cerebellar granule neurons in primary cultures, a glutamatergic preparation. When challenged with a depolarizing K(+) concentration (55 mM), the cells doubled their rate of glucose oxidation (production of 14CO(2) from U-[14C]glucose) and glycolysis (lactate accumulation). At normal K(+) concentration, amobarbital reduced 14CO(2) production with half-maximum effect at 0.5-1 mM; at 55 mM K(+), the inhibition was more potent, with more than half of the K(+)-induced stimulation abolished at 50 microM. Dixon plot analysis showed a single inhibitory mechanism at 5.4 mM K(+), but at 55 mM K(+), two kinetically different mechanisms could be distinguished. A more pronounced compensatory amobarbital-induced increase in glycolysis at 5.4 than at 55 mM K(+) suggested that amobarbital in addition to its inhibition of mitochondrial respiration inhibited K(+)-induced increase in energy demand, probably by its known suppression of stimulated glutamate release.

Amobarbital↗

The amobarbital interview.

In two apparently disoriented patients, the emergency physician's use of amobarbital quickly eliminated diagnoses of an organic etiology. Although thousands of amobarbital interviews have had no complications, the use of amobarbital should follow a thorough evaluation. The amobarbital interview is a safe and simple technique to discriminate functional from organic illness, thus avoiding unnecessary medical and surgical treatment, neglected illness, and inappropriate disposition.

Adult↗