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Journal of Pharmacological and... 2015Sodium pentobarbital (Nembutal) is a barbiturate used in research as an anesthetic in many animal models. The injectable form of this drug has lately become difficult to...
INTRODUCTION
Sodium pentobarbital (Nembutal) is a barbiturate used in research as an anesthetic in many animal models. The injectable form of this drug has lately become difficult to procure and prohibitively expensive. Due to this lack of availability, researchers have begun to compound injectable sodium pentobarbital from so-called "nonpharmaceutical" pentobarbital. Some oversight agencies have objected to this practice, claiming a lack of quality control and degradation of the drug. We sought with this study to establish both: 1) a protocol for the preparation of injectable sodium pentobarbital, and 2) standard operating procedures to monitor the quality of the preparation and degradation of the drug over time.
METHODS
Our preparation consists of a mixture of sodium pentobarbital in alkaline aqueous solution, propylene glycol, and ethanol. Pentobarbital content in this preparation was assayed by high-pressure liquid chromatography (HPLC). We also assayed pentobarbital content over time in preparations of various ages up to 6 years old.
RESULTS
We determined that the drug degraded at a maximum of 0.5% per year in our preparation (alkaline water/propylene glycol/ethanol) when stored in the dark at room temperature. A yellow discoloration developed after about 2 years, which we have arbitrarily determined disqualifies the preparation from use as an anesthetic. Attempts to spectroscopically assay this discoloration were not successful.
CHEMICALS
Pentobarbital sodium (CID: 14075609).
Topics: Adjuvants, Anesthesia; Animals; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Injections; Pentobarbital; Spectrophotometry, Ultraviolet; Time Factors
PubMed: 26234474
DOI: 10.1016/j.vascn.2015.07.012 -
International Journal of Experimental... Feb 2021This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were...
This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol, pentobarbital sodium and HB groups. After anaesthesia, rabbit blood was collected from the tail vein. Haematological analysis (platelets) and an ELISA was used to measure the thrombopoietin (TPO) and 5-hydroxytryptamine (5-HT). Flow cytometry was used to determine expression of P-selectin and PAF. The expression of 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was determined in the tumour itself or in vascular tissues obtained from the rabbits. The platelet content in the disoprofol group. The content or expression of TPO, 5-HT, P-selectin, PAF, 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was significantly higher in the disoprofol group compared to pentobarbital sodium and HB groups. Expression of these molecules was much higher in the pentobarbital sodium group compared with the HB group. These findings suggest that disoprofol anaesthesia can promote HB development via the mTOR/p70S6K1 and FRAP signalling pathway.
Topics: Animals; Hepatoblastoma; Hypnotics and Sedatives; Liver Neoplasms; Pentobarbital; Platelet Activation; Propofol; Rabbits; Signal Transduction
PubMed: 33410572
DOI: 10.1111/iep.12378 -
Neurological Research Nov 2022To establish safe and straightforward anesthesia used in experiments, we examined the effect of ketamine, ketamine/xylazine, urethane, chloral hydrate, pentobarbital,...
AIM
To establish safe and straightforward anesthesia used in experiments, we examined the effect of ketamine, ketamine/xylazine, urethane, chloral hydrate, pentobarbital, isoflurane, dexmedetomidine, and dexmedetomidine/ketamine on epileptiform activity in genetic absence epilepsy (WAG\Rij) rats.
MATERIALS AND METHOD
Sixty-three male WAG/Rij rats weighing (170-190 g) were used. Tripolar electrodes were inserted into the skull. After ECoG activities were recorded for each animal for 2 hours as controls, , the anesthetic substances were administered and the recording continued for another 2 hours. All the anesthetic substances were administered intraperitoneally except isoflurane, which was administered by inhalation.The PowerLab system was used for electrophysiological activity recording and analysis.
RESULTS
The administration of ketamine (90 mg/kg), ketamine/xylazine (90/10 mg/kg), urethane (1.25 g/kg), chloral hydrate (175 mg/kg), pentobarbital (50-90 mg/kg), isoflurane (induction 5%, maintaining 3-4%), dexmedetomidine (0.5-1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg), significantly decreased the total number of SWD, the total number of spikes, and the SWD duration (p < 0,05). The mean duration of SWD was not affected in pentobarbital (50-90 mg/kg), isoflurane (induction 5%, maintaining 3-4%), dexmedetomidine (0.5-1 mg/kg), and Dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05). Time scale showed a significant decrease in the total number of SWD in the first 20 minutes (P < 0.001) for all groups except dexmedetomidine (0.5-1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05).
CONCLUSION
The anesthetics we used significantly reduced the epileptiform activity immediately after the administration, except dexmedetomidine and dexmedetomidine/ketamine groups, so we recommend using dexmedetomidine and Dexmedetomidine/ketamine in electrophysiological studies accompanied by anesthetics.
Topics: Animals; Male; Rats; Isoflurane; Xylazine; Ketamine; Anesthetics, General; Dexmedetomidine; Epilepsy, Absence; Pentobarbital; Anesthetics; Anesthetics, Intravenous; Chloral Hydrate; Urethane
PubMed: 35786420
DOI: 10.1080/01616412.2022.2095706 -
Paediatric Anaesthesia May 2017Many children with Trisomy 21 have neurologic or behavioral problems that make it difficult for them to remain still during noninvasive imaging studies, such as... (Observational Study)
Observational Study
BACKGROUND
Many children with Trisomy 21 have neurologic or behavioral problems that make it difficult for them to remain still during noninvasive imaging studies, such as transthoracic echocardiograms (TTEcho). Recently, intranasal dexmedetomidine sedation has been introduced for this purpose. However, dexmedetomidine has been associated with bradycardia. Children with Trisomy 21 have been reported to have a higher risk of bradycardia and airway obstruction with sedation or anesthesia compared to children without Trisomy 21.
OBJECTIVE
Our aim was to quantify the incidence of age-defined bradycardia and other adverse effects in patients with Trisomy 21 under sedation for TTEcho using a variety of sedation and anesthesia techniques available and utilized at our institution in this challenging patient population, including intranasal dexmedetomidine, oral pentobarbital, general anesthesia with propofol, and general anesthesia with sevoflurane. Our primary hypothesis was that intranasal dexmedetomidine sedation would result in a significantly higher risk of bradycardia in patients with Trisomy 21, compared with other sedative or anesthetic regimens.
METHODS
This is a retrospective, observational study of 147 consecutive patients with Trisomy 21 who were sedated or anesthetized for transthoracic echocardiography. Efficacy of sedation was defined as no need for rescue sedation or conversion to an alternate technique. Lowest and highest heart rate, systolic blood pressure, oxygen saturation, and PR interval from formal electrocardiograms were extracted from the electronic medical record. These data were compared to age-defined normal values to determine adverse events.
RESULTS
Four methods of sedation or anesthesia were utilized to perform sedated transthoracic echocardiography: general anesthesia with sevoflurane by mask, general anesthesia with sevoflurane induction followed by intravenous propofol maintenance, oral pentobarbital, and intranasal dexmedetomidine. Intranasal dexmedetomidine 2.5 mcg·kg was an effective sedative as a single dose for TTEcho in 37 of 41 (90%) cases. Oral pentobarbital 5 mg·kg as a single dose for young children with Trisomy 21 was effective in 55 of 75 (73%) cases. Intranasal dexmedetomidine sedation was not associated with a significantly higher risk of bradycardia in patients with Trisomy 21, compared with other sedative or anesthetic regimens, when compared to oral pentobarbital for patients under 2 years of age and general anesthesia for children 3 years and older. The two general anesthesia groups showed lowest heart rates of 66.9 ± 15.9 min for sevoflurane and 69.0 ± 11.5 min for sevoflurane-propofol. Hypotension was present in all groups ranging between an incidence of 56% in the sevoflurane group to 11% in the oral pentobarbital group. Oxygen saturation and clinically significant desaturation occurred in 14% of the oral pentobarbital group.
CONCLUSION
Intranasal dexmedetomidine sedation was not associated with a significantly higher risk of bradycardia in patients with Trisomy 21, compared with other sedative or anesthetic regimens.
Topics: Administration, Intranasal; Blood Pressure; Child, Preschool; Conscious Sedation; Dexmedetomidine; Down Syndrome; Echocardiography; Electrocardiography; Female; Heart Defects, Congenital; Heart Rate; Humans; Hypnotics and Sedatives; Infant; Male; Oxygen; Retrospective Studies; Treatment Outcome
PubMed: 28181351
DOI: 10.1111/pan.13120 -
Drug and Chemical Toxicology 2016Theanine, an additive, holds several effects on the central nervous system without toxicity and affects CNS drugs. Theanine bilaterally alters β wave of the EEG with or...
CONTEXT
Theanine, an additive, holds several effects on the central nervous system without toxicity and affects CNS drugs. Theanine bilaterally alters β wave of the EEG with or without caffeine and pentobarbital-induced locomotor activity. Theanine also enhances hypnosis of pentobarbital sodium (PB) and antidepression of midazolam, suggesting there are complicated interactions between theanine and CNS drugs. On the other side, theanine induces glycine release. Glycine potentiates the strychnine toxicity via NMDA receptor activation. Moreover, PB facilitates GABAA receptor activation by GABA, and it is commonly prescribed for strychnine poison. However, what the role that theanine plays in the anticonvulsion of PB against strychnine poison is still unknown.
MATERIALS AND METHODS
Theanine, pentobarbital sodium or strychnine was injected intraperitoneally. EEG was monitored by BIOPAC 16 EEG amplifiers. LD50 of strychnine and hypnotic ED50 of pentobarbital sodium with or without theanine for mice were tested according to Bliss' case.
RESULTS
(1) Theanine enhanced the strychnine toxicity. Both theanine and strychnine 1.0 mg/kg increased the power of the β wave. Theanine aggravated that of strychnine 1.0 mg/kg. Theanine attenuated the LD50 of strychnine. (2) Theanine enhanced the anticonvulsion of PB. Theanine increased the power of α, β wave and decreased hypnotic ED50 of PB; PB attenuated strychnine-induced EEG excitation and mortality with or without theanine, and theanine enhanced the effects of PB. Further, theanine enhanced the anticonvulsion of PB dose-dependently against the strychnine toxicity but not the lethal toxicity of strychnine.
DISCUSSION AND CONCLUSIONS
These results indicated theanine interacted with PB and strychnine. Theanine enhanced both the strychnine toxicity and anticonvulsion of PB against strychnine poison.
Topics: Animals; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Female; Glutamates; Hypnotics and Sedatives; Lethal Dose 50; Male; Mice, Inbred ICR; Pentobarbital; Seizures; Strychnine
PubMed: 26330182
DOI: 10.3109/01480545.2015.1080264 -
International Journal of Surgery Case... 2020Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there...
INTRODUCTION
Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there are known complications associated with this treatment, and as such it is typically reserved for the most severe cases. One such sequela of barbiturate induced coma therapy is refractory hypokalemia and subsequent rebound hyperkalemia.
PRESENTATION OF CASE
This case report discusses a patient who experienced hypokalemia during pentobarbital induced coma for unmanageable elevations in intracranial pressure and was treated conservatively to avoid rebound hyperkalemia depicting successful deployment of permissive hypokalemia.
DISCUSSION
It is vital that clinicians understand the possible adverse effects associated with barbiturate induced coma therapy, and that a careful balance be struck between hypokalemia and potassium supplementation to avoid rebound hyperkalemia.
CONCLUSION
Given that the risk of rebound hyperkalemia is of significant concern in patients who experience hypokalemia on barbiturate induced coma therapy, permissive hypokalemia can be a viable treatment option achieved by lowering the potassium replacement target threshold in such patients.
PubMed: 32492644
DOI: 10.1016/j.ijscr.2020.05.032 -
PloS One 2020Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor...
Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.
Topics: Anesthetics; Animals; Cell Movement; GABA Modulators; Ketamine; Male; Mice; Mice, Transgenic; Microglia; Pentobarbital; Receptors, N-Methyl-D-Aspartate; Thiopental; Xylazine
PubMed: 32760073
DOI: 10.1371/journal.pone.0236594 -
Clinical NeuropharmacologyIntracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial...
OBJECTIVE
Intracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial hypertension has been studied in the general population, this study is the first reported case of pentobarbital coma use in a pregnant patient.
METHODS
We performed a retrospective chart review of a pregnant patient with refractory intracranial hypertension and reviewed the current literature on the role of pentobarbital coma.
RESULTS
We present the case of a 35-year-old woman at 26 weeks of gestation who developed refractory intracranial hypertension secondary to rupture of a dural arteriovenous fistula. The patient was taken to surgery for decompressive hemicraniectomy, clot evacuation, and dural arteriovenous fistula resection. Subsequently, the patient was treated with pentobarbital coma for 5 days and achieved adequate control of her intracranial pressures. The patient and fetus were closely monitored by the obstetrics team with no apparent harm to fetal well-being during her hospital stay. The patient underwent planned cesarean delivery at term, and both the mother and newborn were discharged in stable condition with no known pentobarbital-related complications.
CONCLUSIONS
Thus, we present the first case report demonstrating that pentobarbital coma may be a safe and efficacious option for treating pregnant patients with life-threatening refractory intracranial hypertension. We also provide dosing information for pentobarbital administration. Additional studies and reports involving pregnant patients are needed to better understand the impact of pentobarbital on both the mother and fetus. Furthermore, long-term follow-up of both the mother and newborn is critical to identifying any delayed sequelae of neonatal exposure to pentobarbital.
Topics: Adult; Central Nervous System Vascular Malformations; Coma; Female; Humans; Infant, Newborn; Intracranial Hypertension; Pentobarbital; Pregnancy; Retrospective Studies
PubMed: 35195548
DOI: 10.1097/WNF.0000000000000496 -
Journal of the American Veterinary... Nov 2023To assess (1) veterinarians' knowledge and practices regarding disposal of euthanized animals, (2) the extent to which veterinarians communicate with their clients about...
OBJECTIVE
To assess (1) veterinarians' knowledge and practices regarding disposal of euthanized animals, (2) the extent to which veterinarians communicate with their clients about potential risks of rendering pentobarbital-euthanized animals, and (3) the extent to which veterinarians communicate potential relay toxicosis and environmental risks of pentobarbital-euthanized animals to clients.
SAMPLE
A stratified random sample of AVMA members.
METHODS
Over a 3-week period in early 2021, 16,831 of the AVMA's 99,500 members were surveyed, with 2,093 responses (a 12% response rate). Respondents were assigned to 1 of 3 categories on the basis of their answers: veterinarians euthanizing only food-producing species, veterinarians euthanizing only non-food-producing species, and veterinarians euthanizing both food-producing and non-food-producing species (ie, veterinarians euthanizing mixed species).
RESULTS
Veterinarians responding to this survey appeared to be aware of the major methods of animal disposal, and about 89% reported communicating the method of euthanasia with clients to help ensure appropriate animal disposal. However, the need for additional education on local, state, and federal laws and rendering, as well as on risks of relay toxicosis including wildlife predation and environmental impacts, was reported.
CLINICAL RELEVANCE
Survey results identified gaps in veterinarians' knowledge regarding animal disposal following pentobarbital euthanasia. Further education on this topic may be beneficial, particularly for early- and midcareer veterinarians who euthanize non-food-producing species and for veterinarians who euthanize mixed species in urban and suburban communities.
Topics: Animals; Humans; Pentobarbital; Euthanasia, Animal; Veterinarians; Animals, Wild; Surveys and Questionnaires
PubMed: 37562784
DOI: 10.2460/javma.23.03.0161 -
Neurochemistry International Jan 2019Midazolam and ketamine-induced anesthesia were recently shown to induce a disruption of MEK/ERK sequential phosphorylation with parallel upregulation of p-FADD in the...
Pentobarbital and other anesthetic agents induce opposite regulations of MAP kinases p-MEK and p-ERK, and upregulate p-FADD/FADD neuroplastic index in brain during hypnotic states in mice.
Midazolam and ketamine-induced anesthesia were recently shown to induce a disruption of MEK/ERK sequential phosphorylation with parallel upregulation of p-FADD in the mouse brain. The present study was designed to assess whether other structurally diverse anesthetic agents (pentobarbital, ethanol, chloral hydrate, isoflurane) also impair brain p-MEK to p-ERK signal and increase p-FADD during the particular time course of 'sleep' in mice. Pentobarbital (50 mg/kg)-, ethanol (4000 mg/kg)-, chloral hydrate (400 mg/kg)-, and isoflurane (2% in O)-induced anesthesia (range: 24-60 min) were associated with unaltered or increased p-MEK1/2 (up to +155%) and decreased p-ERK1/2 (up to -60%) contents, revealing disruption of MEK to ERK activation in mouse brain cortex. These anesthetic agents also upregulated cortical p-FADD (up to +110%), but not total FADD (moderately decreased), which resulted in increased neuroplastic/survival p-FADD/FADD ratios (up to +2.8 fold). The inhibition of pentobarbital metabolism with SKF525-A (a cytochrome P450 inhibitor) augmented barbiturate anesthesia (2.6 times) and induced a greater and sustained upregulation of p-MEK with p-ERK downregulation, as well as prolonged increases of p-FADD content and p-FADD/FADD ratio (effects lasting for more than 240 min). Pentobarbital also upregulated significantly the cortical contents of other markers of neuroplasticity such as the ERK inhibitor p-PEA-15 (up to +46%), the transcription factor NF-κB (up to +27%) and the synaptic density protein PSD-95 (up to +20%) during 'sleep'. The results reveal a paradoxical stimulation of p-MEK without the concomitant (canonical) activation of p-ERK (e.g. with pentobarbital and isoflurane), for which various molecular mechanisms are discussed. The downregulation of brain p-ERK may participate in the manifestations of adverse effects displayed by most hypnotic/anesthetic agents in clinical use (e.g. amnesia).
Topics: Anesthetics; Animals; Brain; Fas-Associated Death Domain Protein; Hypnotics and Sedatives; Ketamine; MAP Kinase Kinase Kinases; Male; Mice; Neuronal Plasticity; Pentobarbital; Transcriptional Activation; Up-Regulation
PubMed: 30423425
DOI: 10.1016/j.neuint.2018.11.008