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Anesthesiology Mar 1989The effects of 3.0 mg.kg-1 fentanyl on cerebral and peripheral hemodynamics alone and when combined with subanesthetic doses of pentobarbital (4.0 mg.kg-1), were studied... (Comparative Study)
Comparative Study
The effects of 3.0 mg.kg-1 fentanyl on cerebral and peripheral hemodynamics alone and when combined with subanesthetic doses of pentobarbital (4.0 mg.kg-1), were studied in 11 unanesthetized, newborn lambs, in whom catheters had been previously inserted. After a control period, drugs were administered at 20-min intervals by intravenous bolus injection. Group 1 animals (n = 5) received fentanyl, pentobarbital, and naloxone (0.01 mg.kg-1), whereas Group 2 animals (n = 6) had the order of fentanyl and pentobarbital reversed. All animals responded to pain (withdrawal to tail clamping) and appeared conscious (eyes open, alert to sound) when either fentanyl or barbiturate was given alone. The combination of drugs, however, produced complete unresponsiveness. All of these effects were reversed by naloxone. Cardiac output did not change after either fentanyl or pentobarbital was administered individually but decreased significantly (29% in Group 1, 21% in Group 2) after administration of the combination of both. Mean arterial pressure and heart rate were unchanged. Cerebral blood flow, oxygen (O2) transport, and O2 consumption did not change after either administration of fentanyl or pentobarbital alone but decreased significantly after both (22%, 30%, 19%, respectively, in Group 1 and 35%, 40%, 38%, respectively, in Group 2). The decrease in cerebral O2 transport nearly paralleled the decrease in cerebral O2 consumption such that the ratio, the fractional O2 extraction, increased slightly. Fentanyl decreased kidney blood flow alone (24%) and in combination with pentobarbital (25%), although pentobarbital did so only when combined with fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Animals, Newborn; Brain; Cardiac Output; Cerebrovascular Circulation; Drug Interactions; Fentanyl; Hemodynamics; Naloxone; Oxygen Consumption; Pentobarbital; Sheep
PubMed: 2923293
DOI: 10.1097/00000542-198903000-00016 -
Epilepsia Feb 2002New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no... (Review)
Review
BACKGROUND
New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients.
METHODS
We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to "seizure suppression" versus "EEG background suppression").
RESULTS
Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001).
CONCLUSIONS
Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.
Topics: Anticonvulsants; GABA Modulators; Humans; Midazolam; Pentobarbital; Propofol; Status Epilepticus
PubMed: 11903460
DOI: 10.1046/j.1528-1157.2002.28501.x -
The Journal of Veterinary Medical... May 2024Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals,...
Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals, and injectable anesthetics, particularly barbiturate derivatives, are widely used due to the rapid onset of unconsciousness induced by these agents. Moreover, pharmaceutical-grade drugs should be used to eliminate undesirable side effects as much as possible. However, in Japan, the sale of pharmaceutical-grade pentobarbital sodium (PB) ended in 2019, and that of secobarbital sodium (SB) ended in 2023, leading to a demand for new pharmaceutical-grade injectable euthanasia drugs. This study evaluates thiamylal sodium (TM), a barbiturate derivative that is available domestically, as a euthanasia agent for mice. The results showed that when administered at dosages of 200 mg/kg or more, TM exhibited effects equivalent to those of PB and SB. In addition, the impact of TM administration on hematological characteristics was examined. In female mice administered TM, decreased blood chloride and calcium levels and increased aspartate aminotransferase and alanine aminotransferase levels, which are markers of liver damage, were observed. These findings suggest that high concentrations of TM may affect renal and liver function. This study revealed that TM is effective as a euthanasia agent at dosages of 200 mg/kg or more. However, considering the potential risks of renal and liver damage due to TM administration, it may be preferable to use alternative euthanasia drugs when these risks could affect the objectives or outcomes of the research.
Topics: Animals; Female; Euthanasia, Animal; Mice; Male; Pentobarbital
PubMed: 38556347
DOI: 10.1292/jvms.24-0041 -
Nutrients Mar 2023Dried (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry...
Dried (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry extract (ext) and its active substance linarin were analyzed by pentobarbital-induced sleep experiment in mice and electroencephalography (EEG), electromyogram (EMG) analysis in rats. In a dose-dependent manner, Chry ext and linarin promoted longer sleep duration in the pentobarbital-induced sleep test compared to pentobarbital-only groups at both hypnotic and subhypnotic doses. Chry ext administration also significantly improved sleep quality, as seen in the relative power of low-frequency (delta) waves when compared with the control group. Linarin increased Cl uptake in the SH-SY5Y human cell line and chloride influx was reduced by bicuculline. After administration of Chry ext, the hippocampus, frontal cortex, and hypothalamus from rodents were collected and blotted for glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) receptors subunit expression levels. The expression of α1-subunits, β2-subunits, and GAD of the GABA receptor was modulated in the rodent brain. In conclusion, Chry ext augments pentobarbital-induced sleep duration and enhances sleep quality in EEG waves. These effects might be due to the activation of the Cl channel.
Topics: Rats; Mice; Humans; Animals; Pentobarbital; Receptors, GABA-A; Sleep Quality; Rodentia; Chlorides; Neuroblastoma; Sleep
PubMed: 36986039
DOI: 10.3390/nu15061309 -
The Journal of Biological Chemistry May 2008Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated...
Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and pentobarbital current activation are distinct. Moreover, pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of pentobarbital did not alter their modification rates, suggesting that the GABA- and pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.
Topics: Amino Acid Substitution; Animals; GABA Antagonists; GABA Modulators; Ion Channel Gating; Pentobarbital; Protein Structure, Tertiary; Pyridazines; Rats; Receptors, GABA-A; Xenopus laevis; gamma-Aminobutyric Acid
PubMed: 18387955
DOI: 10.1074/jbc.M708638200 -
Biomedicine & Pharmacotherapy =... Sep 2019The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of...
The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801-induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders.
Topics: Animals; Behavior, Animal; Depression; Dizocilpine Maleate; Drug Administration Routes; Imipramine; Inhalation Exposure; Locomotion; Male; Mice, Inbred C57BL; Pentobarbital; Scopolamine
PubMed: 31177060
DOI: 10.1016/j.biopha.2019.109038 -
Anesthesiology Jun 2009Anesthetics depress both ventilatory and upper airway dilator muscle activity and thus put the upper airway at risk for collapse. However, these effects are...
BACKGROUND
Anesthetics depress both ventilatory and upper airway dilator muscle activity and thus put the upper airway at risk for collapse. However, these effects are agent-dependent and may involve upper airway and diaphragm muscles to varying degrees. The authors assessed the effects of pentobarbital on upper airway dilator and respiratory pump muscle function in rats and compared these results with the effects of normal sleep.
METHODS
Tracheostomized rats were given increasing doses of pentobarbital to produce deep sedation then light and deep anesthesia, and negative pressure airway stimuli were applied (n = 11). To compare the effects of pentobarbital with those of natural sleep, the authors chronically instrumented rats (n = 10) with genioglossus and neck electromyogram and electroencephalogram electrodes and compared genioglossus activity during wakefulness, sleep (rapid eye movement and non-rapid eye movement), and pentobarbital anesthesia.
RESULTS
Pentobarbital caused a dose-dependent decrease in ventilation and in phasic diaphragmatic electromyogram by 11 +/- 0.1%, but it increased phasic genioglossus electromyogram by 23 +/- 0.2%. Natural non-rapid eye movement sleep and pentobarbital anesthesia (10 mg/kg intraperitoneally) decreased respiratory genioglossus electromyogram by 61 +/- 29% and 45 +/- 35%, respectively, and natural rapid eye movement sleep caused the greatest decrease in phasic genioglossus electromyogram (95 +/- 0.3%).
CONCLUSIONS
Pentobarbital in rats impairs respiratory genioglossus activity compared to the awake state, but the decrease is no greater than seen during natural sleep. During anesthesia, in the absence of pharyngeal airflow, phasic genioglossus activity is increased in a dose-dependent fashion.
Topics: Anesthesia; Animals; Conscious Sedation; Diaphragm; Dose-Response Relationship, Drug; Electromyography; Hypnotics and Sedatives; Male; Pentobarbital; Polysomnography; Rats; Rats, Sprague-Dawley; Respiratory Mechanics; Respiratory Muscles; Sleep, REM; Tracheostomy; Wakefulness
PubMed: 19417601
DOI: 10.1097/ALN.0b013e3181a16337 -
Documenta Ophthalmologica. Advances in... Feb 2012We compared the suitability of pentobarbital sodium (PB) and propofol (PF) anesthetics for multifocal electroretinograms (mfERGs) in rhesus macaques. mfERGs were... (Comparative Study)
Comparative Study
We compared the suitability of pentobarbital sodium (PB) and propofol (PF) anesthetics for multifocal electroretinograms (mfERGs) in rhesus macaques. mfERGs were collected from 4 ocularly normal rhesus macaques. All animals were pre-anesthetized with intramuscular ketamine (10-15 mg/kg). Intravenous PB induction/maintenance levels were 15 mg/kg/2-10 mg/kg and for PF, 2-5 mg/kg/6-24 mg/kg/h. There were 3 testing sessions with PB anesthesia and 5-7 testing sessions with PF anesthesia. All PB sessions were carried out before PF. First-order (K1) and second-order (first slice) kernels (K2.1) response density amplitude (RDA), implicit time (IT), and root mean square signal-to-noise ratios (RMS SNR) of the low-frequency (LFC) and high-frequency (HFC) components were evaluated. The use of PF or PB anesthesia resulted in robust, replicable mfERGs in rhesus macaques; however, RMS SNR of K1 LFC in ring and quadrant analyses was significantly larger for PF than for PB. Additionally, K1 RDA under PF was significantly larger than under PB for N1, P1, and P2 components (ring and quadrant) and for N2 (quadrant). PF IT was significantly prolonged (<1 ms) relative to PB IT for N1, P1 (ring), and N1 (quadrant), while PB IT was significantly prolonged (0.8-4.2 ms) relative to PF IT for N2 and P2 (ring and quadrant). K1 HFC and K2.1 LFC did not differ significantly between PB and PF in the ring or quadrant analyses. The response differences found with PB and PF anesthesia likely arise from variable relative effects of the anesthetics on retinal γ-aminobutyric acid (GABA(A)) receptors, and in part, on glycine and on glutamate receptors. Given the advantages of a stable anesthetic plane with continuous intravenous infusion and a smoother, more rapid recovery, PF is an appealing alternative for mfERG testing in rhesus macaques.
Topics: Anesthesia; Anesthetics, Intravenous; Animals; Electroretinography; Evoked Potentials, Visual; Female; Hypnotics and Sedatives; Macaca mulatta; Pentobarbital; Propofol; Retina; Retinoscopy; Signal-To-Noise Ratio
PubMed: 22200766
DOI: 10.1007/s10633-011-9306-x -
Anesthesiology Aug 1993When compared with barbiturates, isoflurane may lack protective effects during focal cerebral ischemia. The reason for this difference is not clear. In this study,... (Comparative Study)
Comparative Study
BACKGROUND
When compared with barbiturates, isoflurane may lack protective effects during focal cerebral ischemia. The reason for this difference is not clear. In this study, regional cerebral blood flow (rCBF), arterial and venous O2 saturation, and O2 extraction were compared in the ischemic cortex and in the nonischemic brain regions of rats anesthetized with isoflurane or pentobarbital using a microspectrophotometric technique that directly measures the O2 saturation of blood in the small arteries and veins.
METHODS
Twenty-eight rats were anesthetized with 1.4% isoflurane or 50 mg/kg pentobarbital. One hour after a middle cerebral artery (MCA) occlusion, rCBF was measured in the ischemic cortex and in the nonischemic brain regions using 14C-iodoantipyrine in one-half of each group of animals. Regional arterial and venous O2 saturation were determined using microspectrophotometry in the other one-half of each group.
RESULTS
The rCBF of the ischemic cortex (IC) and the non-ischemic contralateral cortex (CC) of the isoflurane group were significantly higher than those of the pentobarbital group. The venous O2 saturation was significantly less, and the O2 extraction was significantly higher, in the IC than in the nonischemic regions in both groups of animals (pentobarbital group, IC 10.5 +/- 1.1 ml O2.100 ml blood-1, CC 6.3 +/- 0.7; isoflurane group, IC 10.8 +/- 0.6, CC 5.9 +/- 0.2). There was no significant difference between the two groups.
CONCLUSIONS
Because the rCBF was less and the O2 extraction was similar, O2 consumption in the focal ischemic area of the brain during pentobarbital anesthesia must have been less than that during isoflurane anesthesia.
Topics: Animals; Brain; Cerebrovascular Circulation; Hemodynamics; Isoflurane; Male; Oxygen Consumption; Pentobarbital; Rats
PubMed: 8342841
DOI: 10.1097/00000542-199308000-00015 -
Journal of Veterinary Internal Medicine 2015An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies...
BACKGROUND
An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death.
HYPOTHESIS/OBJECTIVES
To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity.
ANIMALS
Fifteen horses requiring euthanasia.
METHODS
Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored.
RESULTS
Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion).
CONCLUSIONS AND CLINICAL IMPORTANCE
Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred.
Topics: Animals; Blood Pressure; Brain Stem; Cerebrum; Electroencephalography; Euthanasia, Animal; Female; Horses; Hypnotics and Sedatives; Male; Pentobarbital
PubMed: 25800436
DOI: 10.1111/jvim.12570