Doses Of Pentobarbital Research Articles

Pharmacological activity of hyperforin acetate in rats.

Hyperforin, the main antidepressant component of Hypericum extract, is not stable with regard to heat and light. Therefore, we investigated a newly synthetized derivative, hyperforin acetate. Herein we demonstrate its efficacy in animal models sensitive to antidepressant and anxiolytic drugs. In the forced swimming test, triple administration of hyperforin (5-20 mg/kg) significantly reduced the immobility time of rats, while in the learned helplessness test a daily treatment of 10 mg/kg for seven consecutive days was necessary to elicit an antidepressant effect. In the elevated plus-maze and in the light-dark test, the acute administration of hyperforin acetate (3-5 mg/kg) exerted an anxiolytic activity, which, however, was smaller than that of diazepam. The effect was inhibited by the pretreatment of rats with metergoline, a serotoninergic antagonist, but not with CGS-8216, a benzodiazepine receptor antagonist. Hyperforin acetate (3-10 mg/kg) was also able to reduce locomotion in rats without eliciting myorelaxant activity. As Hypericum extract was claimed to exert a potential influence on the liver drug metabolizing system, we showed that neither acute nor repeated oral doses of hyperforin acetate altered pentobarbital sleeping time in rats. Taken together, the present results show that hyperforin acetate is a pharmacologically active derivative of hyperforin and may be a starting point from which to develop new compounds for therapeutic purposes.

A novel electroencephalographic analysis method discriminates alcohol effects from those of other sedative/hypnotics

Here we describe a mathematical and statistical signal processing strategy termed event resolution imaging (ERI). Our principal objective was to determine if the acute intoxicating effects of ethanol on spontaneous EEG activity could be discriminated from those of other sedative/hypnotics. We employed ERI to combine and integrate standard analysis methods to learn multiple signal features of time-varying EEG signals. We recorded cortical EEG, electromyographic activity, and motor activity during intravenous administration of saline, ethanol (1.0 g/kg), chlordiazepoxide (10 mg/kg), pentobarbital (6 mg/kg), heroin (0.3 mg/kg), and methamphetamine (2 mg/kg) administered on separate days in six rats. A blind treatment of one of the drugs was readministered to validate the efficacy of ERI analysis. Significant changes in spontaneous EEG activity produced by all five drugs were detected by ERI analysis with a time resolution of 5–10 s. ERI analysis of spontaneous EEG activity also discriminated, with 90–95% accuracy, an ataxic dose of ethanol versus equivalent ataxic doses of chlordiazepoxide or pentobarbital, as well as the effects of saline, a reinforcing dose of heroin, or a locomotor activating dose of methamphetamine. ERI correctly matched the ‘blind drug’ as ethanol. These findings indicate that ERI analysis can detect the central nervous system effects of various psychoactive drugs and accurately discriminate the electrocortical effects of select sedative/hypnotics, with similar behavioral endpoints, but with dissimilar mechanisms of action.

Pentobarbital for severe gamma-butyrolactone withdrawal

Study Objective: Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have become popular drugs of abuse. Acute overdose with either agent results in a well-recognized syndrome of central nervous system and respiratory depression. Recently, a withdrawal syndrome has been described for GHB. We report a severe form of GBL withdrawal, characterized by delirium, psychosis, autonomic instability, and resistance to benzodiazepine therapy. Methods: We performed a chart review of consecutive admissions for GBL withdrawal in a regional toxicology treatment center. Results: During a 6-month period, 5 patients presented with severe withdrawal attributed to abrupt GBL discontinuation. Patients manifested tachycardia, hypertension, paranoid delusions, hallucinations, and rapid fluctuations in sensorium. Test results for ethanol and routine drugs of abuse were negative. Initial treatment with high doses of lorazepam proved ineffective. Pentobarbital was then administered, resulting in excellent control of behavioral, autonomic, and psychiatric symptoms and in rapid reduction or avoidance of benzodiazepines. Median hospital stay was 5 days. No patient had respiratory depression or required mechanical ventilation. Patients were discharged on tapering doses of benzodiazepines or pentobarbital and were free of psychotic symptoms at follow-up. Conclusion: GBL discontinuation can result in severe withdrawal, necessitating ICU admission. Pentobarbital may be more effective than benzodiazepines at controlling delirium in patients with abnormal vital signs, paranoid delusions, and hallucinations as a result of GBL withdrawal. [Sivilotti MLA, Burns MJ, Aaron CK, Greenberg MJ. Pentobarbital for severe gamma-butyrolactone withdrawal. Ann Emerg Med. December 2001;38:660-665.]

Discrimination of pentobarbital doses and drug mixtures under fixed-ratio and fixed-interval reinforcement schedules.

Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 10mg/kg pentobarbital, and saline, under either fixed-interval (FI) or fixed-ratio (FR) reinforcement schedules. When baseline responding stabilized, a higher percentage of responses occurred on the key that produced the reinforcer under the FR schedule than under the FI schedule. After low doses of pentobarbital, responding shifted from the saline key to the 5 mg/kg pentobarbital key; at higher doses of pentobarbital responding shifted to the 10mg/kg pentobarbital key under both schedules. After low doses of ethanol and chlordiazepoxide, responding shifted from the saline key to the 5 mg/kg pentobarbital key, but after high doses of these drugs, responding continued to occur on the 5 mg/kg pentobarbital key under both reinforcement schedules. A 5 mg/kg dose of pentobarbital increased responding on the 10 mg/kg pentobarbital key when it was combined with pentobarbital, ethanol or chlordiazepoxide. Phencyclidine and D-amphetamine produced responding largely on the saline key under both reinforcement schedules. Under the FR schedule, pentobarbital dose-response curves were usually quantal, whereas under the FI schedule the pentobarbital dose-response curves usually were graded.

Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice

A lyophilized ethanolic aqueous extract of Papaver rhoeas petals was evaluated for its behavioral and pharmaco-toxicological effects in mice and its chemical composition was studied using thin layer chromatography (TLC). In this study, chemical analysis by TLC showed that the petals contain some anthocyanins, whereas no alkaloids were detected. The toxicological effect of alcoholic and aqueous plant extract administered intraperitoneally was determined in mice. The toxicological results obtained indicated that 2000 mg/kg is LD10 and 4000 mg/kg is LD50. Behavioral and pharmacological studies of ethanolic and aqueous extract showed that the plant extract reduced locomotory, exploratory and postural behavior of mice. This was evaluated through two specific behavioral tests; a non-familiar environment test (the Staircase test) and a familiar environment test (Free exploratory test). These behavioral and pharmacological effects are more pronounced when the solvent used for extraction is 10% ethanol and is not antagonized by benzodiazepines, opioids, dopaminergic and cholinergic compounds (flumazenil, naloxone, sulpuride and atropine). The plant extract did not induce sleep in mice after treatment with an infrahypnotic dose of pentobarbital. This finding shows that the plant extract has a sedative effect at a 400 mg/kg dosage.

Schedule control of quantal and graded dose–effect curves in a drug–drug-saline discrimination

Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 5 mg/kg morphine, and saline when responding was maintained under fixed-interval (FI) or fixed-ratio (FR) reinforcement schedules. After the discrimination was established, other drugs were substituted for the training drugs. After low doses of pentobarbital and chlordiazepoxide, responding shifted from the saline key to the pentobarbital key under both FR and FI schedules. After low doses of morphine and methadone, responding shifted from the saline key to the morphine key under both reinforcement schedules. After all doses of d-amphetamine, responding occurred largely on the saline key under both schedules. Responding also was confined largely to the saline key after phencyclidine administration under the FR schedule, but under the FI schedule, responding shifted from the saline key to the pentobarbital key at high doses of phencyclidine. When responding was maintained under the FR schedule, the dose–response curves for drugs that generalized to the training drugs were quantal in shape, while under the FI schedule, the dose–response curves for drugs that generalized to the training drugs were graded. These data extend observations that FR schedules generate quantal dose–response curves, and FI schedules generate graded dose–response curves to complex three-key drug discriminations.

No Effect of Albinism on Sedative‐Hypnotic Sensitivity to Ethanol and Anesthetics

Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS) intercrosses have found genetic linkage between Tyr albinism (c/c) and differential sensitivity to sedative-hypnotic doses of ethanol and general anesthetics. This linkage could be due to a gene or genes near Tyr or Tyr itself. With regard to the latter possibility, the absence of tyrosinase activity (encoded by Tyr) in albinos could alter tyrosine availability and thus the rate-limiting step in catecholamine synthesis. In addition, albinism is associated with altered brain development that could have pleiotropic effects on behavior. Therefore, in this study, we asked whether albinism affects sedative-hypnotic sensitivity. Loss of righting reflex (LORR) duration was measured using doses of ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and etomidate (20 mg/kg) that were previously associated with differential sensitivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were backcrossed to ISS (c/c) to compare pigmented (c/c, Tg(Tyr+)) and albino (c/c) mice in the context of an ISS-like background. ISS was also crossed with C57BL/6 (B6) mice heterozygous for a spontaneous albino mutation (c2j) to compare pigmented (c/+) and albino (c/c2j) mice. Pigmented B6 (c2j/+ and +/+) and albino B6 (c2j/c2j) mice were also compared (pentobarbital). For each sedative hypnotic, albinism had no effect on LORR duration. Each expected difference was ruled out at the 95% or 99% confidence level. For each sedative hypnotic, males were more sensitive than females even though the effect size was usually smaller than the expected albino effect size, arguing empirically that the inability to detect an albino effect was not due to systematic error or an insufficient number of mice. We conclude that the differential sensitivity associated with albinism is most likely due to a gene or genes near Tyr rather than Tyr itself.

Discriminative stimulus effects of panadiplon (U-78875), a partial agonist at the benzodiazepine site, in pentobarbital-trained rhesus monkeys

The pentobarbital-like discriminative stimulus effects of the benzodiazepine receptor partial agonist panadiplon were assessed in rhesus monkeys trained to discriminate pentobarbital (10 mg/kg) from saline. In test sessions, pentobarbital and the benzodiazepine full agonist triazolam engendered near 100% drug-appropriate responding in all monkeys, whereas panadiplon engendered near 100% drug-appropriate responding in two of four monkeys. Panadiplon pretreatment resulted in leftward shifts in the pentobarbital dose–response function but predominantly rightward shifts of the triazolam dose–response function. These results are consistent with findings that benzodiazepine partial agonists have pentobarbital-like discriminative stimulus effects in some subjects only, and further suggest that partial agonists enhance the effects of pentobarbital but antagonize the effects of a benzodiazepine full agonist.

Dominant Anti-vagal Effect of Pentobarbital on Cardiac Responses to Intracardiac Autonomic Nerve Stimulation in the Dog

The isolated canine atrium was perfused by heparinized blood of the donor dog. An adequate dose of pentobarbital that induced a potent hypotension in the donor did not produce any significant change in the atrial rate and developed tension in the isolated atrium perfused with donor's blood. Pentobarbital in doses that modified neither cardiac responses to intracardiac adrenergic nerve stimulation nor exogenously given norepinephrine or acetylcholine significantly inhibited intracardiac vagal responses. From these results, it is concluded that a large dose of pentobarbital has a dominant antivagal effect in the heart.

Developmental exposure to methylmercury alters behavioral sensitivity to d-amphetamine and pentobarbital in adult rats

Female rats were exposed to 0, 0.5, or 6.4 ppm methylmercury in their drinking water before mating, and throughout gestation and lactation. When the female offspring were 4–6 months old, they were trained to respond under a multiple differential reinforcement of high rate (DRH) 9:4 — Extinction schedule of reinforcement. No differences among exposure groups were apparent in steady-state behavior. Drug challenges were conducted with multiple doses of d-amphetamine, scopolamine, pentobarbital, haloperidol, and dizocilpine, drugs selected for their different pharmacological effects. The ED 50 values for amphetamine's reinforcement rate-reducing effects for the control, 0.5-, and 6.4-ppm groups were 3.1, 1.9, and 0.9 mg amphetamine/kg body weight, respectively, demonstrating an increased sensitivity to d-amphetamine in methylmercury-exposed rats. Rats in the 6.4-ppm group also demonstrated a relative insensitivity to pentobarbital. Further, these exposed rats exhibited an inverted U-shaped dose–effect curve under the pentobarbital dose–effect determination, while controls showed only a declining curve. Exposed rats did not respond differentially to haloperidol, scopolamine, or dizocilpine, suggesting specificity. The present data suggest an involvement of catecholaminergic and GABAergic activity in methylmercury's neurotoxicity.

Pentobarbital inhibits apoptosis in neuronal cells.

Pentobarbital inhibits apoptosis in neuronal cells. Morimoto Y, Morimoto Y, Nishihira J, Kemotsu O, Shibano T, Gando S, Shikama H. Crit Care Med 2000; 28:1899–1904. Barbiturates are known to reduce focal ischemic brain injury. The mechanisms by which this occurs remain under investigation. Cellular death in response to ischemia is likely attributable to a spectrum of mechanisms. Necrosis is believed to occur in response to chaotic perturbations in intracellular biochemistry after rapid influx of extracellular calcium. Apoptosis is believed to represent, at least in part, recapitulation of programmed molecular biologic events designed to allow ontogenetic development of the organism. Apoptotic mechanisms persist in the adult to allow clearance of injured cells. There is little data regarding the effect of anesthetic agents on apoptotic mechanisms and no data regarding effects of barbiturates. This study was conducted in a cell culture system designed to investigate neuronal apoptosis. The authors first sought to prove that their model was valid. Immortalized PC12 cells originally derived from rat pheochromocytoma were studied. Apoptosis was induced by deprivation of the cultures from fetal bovine and horse serum for several days. Apoptosis was confirmed in this study by two techniques. First, DNA from serum deprived cells was fractionated and subjected to electrophoresis. A classic laddering pattern of uniform sized DNA fragments was observed indicating selective enzymatic destruction. Second, Hoechst stained cells were examined with fluorescence microscopy. Classic patterns of apoptosis were observed, for example, condensation and fragmentation of the chromatin. Given this model, neuronal apoptosis was induced in control cultures and in cultures treated with 0.5, 5, or 50 μg/ml of pentobarbital. These concentrations were selected to span the range of blood pentobarbital concentrations known to produce electroencephalographic changes in humans. Several assays of cell viability were performed. First, leakage of intracellular lactate dehydrogenase (LDH) into the overlying medium was used to define cell death. Second, flow cytometry was used to count the percentage of cells in the different treatment groups having apoptotic DNA histograms. The fraction of cells having evidence of apoptosis increased daily after onset of serum deprivation. Cell death lagged by 2 days, however, indicating that induction of apoptotic mechanisms preceded (and therefore presumably caused) cell death. Pentobarbital itself caused no cell damage. The fraction of cells having evidence of apoptosis after 4 days of serum deprivation was reduced by pentobarbital in a dose-dependent fashion (95% of untreated cells were apoptotic vs. 62% when treated with the highest dose of pentobarbital). This paper provides intriguing evidence for an additional neuroprotective mechanism of barbiturates. There have been no in vivo studies performed to confirm inhibition of apoptosis by barbiturates against ischemic brain injury. However, given this in vitro evidence, such work seems justified. (DSW)

Pentobarbital induces nocifensive hyperrflexia, not hyperalgesia in rats

To seek behavioural, reflexive and histochemical evidence of long-lasting changes in nociceptive stimulus transmission induced by exposure to doses of pentobarbital that induce nocifensive hyperreflexia. Nocifensive hyperreflexia was induced in 12 rats with 30 mg x kg(-1) pentobarbital ip. Reflex latency times for withdrawal of the hind paw from noxious radiant heat were measured with an automated electronic timer. Subjective responses to noxious stimulation (licking or biting of the stimulated hindpaw) and the level of sedation were recorded. Histological sections of lumbar spinal cord were stained for immunoreactivity of the immediate-early-gene (IEG), c-fos, in three rats that received repeated threshold noxious radiant heat stimulation during the period of nocifensive hyperreflexia induced by 30 mg x kg(-1) pentobarbital ip. Reflex withdrawal latency decreased by 32 +/- 8% of control values (P < 0.001 ) following pentobarbital injection and returned to control values 120 min after drug injection. Once fully alert, pentobarbital-treated animals did not show any increase in nociceptive behaviour relative to saline-injected controls (P = 0.41). Sustained noxious stimulation to the hindpaw in halothane-anesthetized animals was associated with an increase in c-fos immunoreactivity in the dorsal horn of the lumbar spinal cord ipsilateral to the stimulation (P < 0.001). Threshold stimulation in the pentobarbital-treated animals was not associated with any increase in c-fos expression. During pentobarbital-induced hyperreflexia, rats did not show any reflexive, behavioural, or histochemical evidence of long-lasting enhancement of nocifensive signal transmission. The results are consistent with previous observations that, in the absence of tissue injury, nocifensive hyperreflexia induced by barbiturates is a short-lived pharmacological effect.

DRUG DISCRIMINATION UNDER TWO CONCURRENT FIXED‐INTERVAL FIXED‐INTERVAL SCHEDULES

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits.

The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30 degrees C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30 degrees C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.

Drug discrimination in rats under concurrent variable-interval variable-interval schedules.

Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased lever after pentobarbital were reinforced under VI 20 s and responses on the saline-biased lever were reinforced under VI 80 s. After saline, the reinforcement contingencies programmed on the two levers were reversed. The rats made 62.3% of their responses on the pentobarbital-biased lever after pentobarbital and 72.2% on the saline-biased lever after saline, both of which are lower than predicted by the matching law. When the schedule was changed to concurrent VI 50 s VI 50 s for test sessions with saline and the training dose of pentobarbital, responding on the pentobarbital-biased lever after the training dose of pentobarbital and on the saline-biased lever after saline became nearly equal, even during the first 2 min of the session, suggesting that the presence or absence of the training drug was exerting minimal control over responding and making the determination of dose-effect relations of drugs difficult to interpret. When the pentobarbital dose-response curve was determined under the concurrent VI 50-s VI 50-s schedule, responding was fairly evenly distributed on both levers for most rats. Therefore, 6 additional rats were trained to respond under a concurrent VI 60-s VI 240-s schedule. Under this schedule, the rats made 62.6% of their responses on the pentobarbital-biased lever after pentobarbital and 73.5% of their responses on the saline-biased lever after saline, which also is lower than the percentages predicted by perfect matching. When the schedule was changed to a concurrent VI 150-s VI 150-s schedule for 5-min test sessions with additional drugs, the presence or absence of pentobarbital continued to control responding in most rats, and it was possible to generate graded dose-response curves for pentobarbital and other drugs using the data from these 5-min sessions. The dose-response curves generated under these conditions were similar to the dose-response curves generated using other reinforcement schedules and other species.

Cerebral hemodynamic effects of pentobarbital coma in head-injured patients.

The purpose of this study was to examine the changes in cerebral hemodynamics of head-injured patients undergoing barbiturate treatment of refractory intracranial hypertension. Cerebral blood flow (CBF) and metabolism variables were measured in 67 severely head-injured patients at the following times: before the loading dose of pentobarbital; after the loading dose of pentobarbital (average pentobarbital level 28.1+/-8.3 microg/mL); and 3 days later, when the peak pentobarbital level averaged 42.5+/-17.2 microg/mL. Intracranial pressure (ICP) and mean arterial blood pressure (MAP) were decreased by the loading dose of pentobarbital by an average of 12 and 9 mm Hg, respectively. Cerebral perfusion pressure (CPP) was unchanged when the entire group was analyzed together. CBF, cerebral oxygen consumption (CMR(O)2), and arteriovenous oxygen difference (AVD(O)2) were significantly decreased after the loading dose of pentobarbital, by 20%, 31%, and 11%, respectively. The average cerebrovascular resistance (CVR) was increased by 20%. The change in CMR(O)2 with the loading dose of pentobarbital was closely related to the pretreatment value (n = 67, r2 = 0.65, p < .001). Thirty (45%) of the patients had a "good ICP response," with a reduction in ICP from 34+/-9 to 15+/-5 mm Hg after the initial loading dose of pentobarbital. Twenty-seven (40%) of the patients had a "partial ICP response," with ICP decreasing but still remaining above 20 mm Hg after the loading dose of pentobarbital. In the remaining 10 patients, ICP did not change or even increased after pentobarbital. In the 30 patients with a good ICP response, pretreatment CMR(O)2 and AVD(O)2 were greater before administration of pentobarbital, and CMR(O)2 and AVD(O)2 decreased more with the loading dose of pentobarbital, than in the patients with partial or no ICP response. The outcome was significantly better in the patients with a good or partial ICP response to pentobarbital, with 21% of these patients having a good recovery or moderate disability at 3 months after injury, compared with 100% persistent vegetative state or death in the nonresponders. In summary, barbiturate coma can be a useful treatment modality for acutely reducing ICP in selected patients. Patients with overwhelmingly severe injuries are not likely to benefit, partly because their CMR(O)2 is already markedly reduced by the injury and partly because their outcome is already predetermined by the injury. Patients with systemic hypotension are not likely to have a good response because hypotension limits the amount of barbiturates that can be given.

Powerful respiratory stimulation by thin muscle afferents

The ventilatory responses to electrical stimulation of phrenic afferents were examined in spontaneously breathing dogs at different levels of sodium pentobarbital anesthesia. High intensity stimulation (activation of all the afferents, including thin fibers) increased ventilation ( V ̇ e). The increase in V ̇ e was comparable to that of breathing 10% CO 2 and was inversely related to anesthesia level. Under light anesthesia, V ̇ e increased to 282±36% of the control value when the phrenic nerve was stimulated at 130 times the twitch threshold ( n=15; P<0.01). The increase in V ̇ e was due to increases in breathing rate (193±19%) and tidal volume (V t) (143±8%). On the other hand, inspiratory time (T i) decreased. Thus, average airflow rate (V t/T i) increased to 204±23%. After administration of 20 and 40% of the initial dose of pentobarbital, V ̇ e response was attenuated to 157±21 and 121±4%, respectively. We conclude that thin muscle afferents are capable of eliciting pronounced ventilatory stimulation. The small responses observed earlier were likely due to depth of anesthesia.

Asynchronous and asymmetric burst-suppression in a patient with a corpus callosum lesion

Introduction: Burst suppression is seen in the electroencephalograms of patients receiving high doses of pentobarbital. In such circumstances, burst suppression is characterized by bilaterally synchronous and symmetric bursts of electrical activity followed by intervals of attenuation. Methods: We report on a case of asymmetric and asynchronous pentobarbital-induced burst suppression that occurred after a corpus callosum lesion sustained during trauma. Conclusions: To our knowledge, this is the first such reported human case of asymmetric and asynchronous pentobarbital-induced burst suppression. These findings suggest that the corpus callosum may be involved in the synchronization of the burst-suppression pattern.

EEG evaluation of reflex testing as assessment of depth of pentobarbital anaesthesia in the rat.

Electroencephalography (EEG) was applied to evaluate the validity of the paw pinch reflex as an indicator of anaesthetic depth in rats which are anaesthetized with a single intraperitoneal dose of pentobarbital. After induction of the anaesthesia, characterized by the rapid loss of the animals' ability to maintain upright posture, the EEG of 10 out of 11 rats was dominated by paroxysmal (burst suppression) activity, associated with unconsciousness. In seven out of 11 rats, the paw pinch reflex was lost after onset of paroxysmal electroencephalographic activity. However, the paw pinch reflex remained present in four out of 11 animals, demonstrating that the response is independent of cortical activity. In five out of seven rats, the EEG still showed paroxysmal activity when the paw pinch reflex was regained. However, in two other rats the EEG returned to a pattern similar to that shown by awake animals, 4 and 21 min respectively, before the reflex was regained. These data indicate that in the pentobarbital-anaesthetized rat, presence of the paw pinch reflex is not related to the level of depression of electrical activity in the cerebral cortex, and consequently is probably not related to the level of consciousness. Based upon these findings it is concluded that the paw pinch reflex is unreliable as a sole indicator of anaesthetic depth.