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1.
J Clin Ultrasound ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900022

ABSTRACT

OBJECTIVE: Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia-reperfusion injury in rats. METHODS: Adult rats were randomly assigned to a renal ischemia-reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end-diastolic velocity, and resistance index. RESULTS: The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end-diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. CONCLUSION: Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi-quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole-body hemodynamic changes in rats.

2.
Pain Ther ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900409

ABSTRACT

INTRODUCTION: Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe (a) the effect of intravenous (IV) SP infusion on pain and sensory abnormalities, and (b) its utility in the diagnosis and management of patients with chronic pain. METHODS: A narrative review of barbiturate applications for chronic pain was followed by a pragmatic study of 176 consecutive patients admitted to an inpatient pain unit (2004-2009). We collected demographic information upon admission, diagnoses retrieved from chart review, and pain ratings and sensory abnormalities at baseline and after blinded infusion of normal saline (NS) followed by SP. RESULTS: The study group consisted of 83 men and 93 women (mean age 41 ± 11 years); the mean NS dose was 7.8 ± 2.3 (range 2-10 ml), the SP dose was 223.8 ± 88 mg (range 40-420), and the numeric rating scale (NRS) baseline pain score was 6.0 ± 2. The mean reduction in NRS reached both statistical and clinical significance in 150 responders to either NS/SP or SP only. Collectively, we found (a) an extremely high rate of response to IV SP irrespective of the underlying pathology, (b) greater response for pain than for sensory abnormalities (sensory gains or deficits), (c) greater response for sensory gain than for sensory deficit, and (d) greater response for allodynia than for pinprick hyperalgesia. Illustrative case reports are also presented. DISCUSSION: IV SP infusion is a diagnostic tool that assists in elucidating pain generators and the nature of sensory abnormalities (central vs. peripheral), with effects similar to those of IV sodium amytal. The test cannot be viewed as a tell-all diagnostic modality and must be used in conjunction with clinical judgment, investigations, and psychological reports.

3.
Am J Vet Res ; 85(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38569538

ABSTRACT

OBJECTIVE: To assess the efficacy of transmucosal euthanasia solution to induce euthanasia. ANIMALS: 6 bearded dragons (Pogona vitticeps). METHODS: An initial dose of euthanasia solution containing pentobarbital and phenytoin sodium was administered transmucosally in conscious lizards (100 mg/kg pentobarbital dose), followed by a second dose 20 minutes later (400 mg/kg pentobarbital dose). The presence of movement, leakage of euthanasia solution, behaviors consistent with oral irritation, respiratory rate, heart rate, palpebral and corneal reflex, and response to noxious stimuli were recorded until death, confirmed by the absence of Doppler cardiac flow and cardiac electrical activity. The time to loss of all parameters was calculated. Postmortem evaluation allowed for histopathologic evaluation of the oral cavity and gastrointestinal tract to detect potential mucosal damage from the alkaline euthanasia solution. RESULTS: The median time to death was 300 minutes (range, 300 to 360 minutes), median time to respiratory arrest was 30 minutes (range, 30 to 50 minutes), and median time to loss of deep pain response was 30 minutes (range, 20 to 50 minutes). Signs consistent with oral irritation occurred in 4 of 6 (66.7%) lizards, including 2 lizards that exhibited whole-body spasms after euthanasia solution administration. Histopathologic changes indicating peracute mucosal ulceration, suspected to be from caustic causes, were identified in 1 (1/6 [16.7%]) lizard. CLINICAL RELEVANCE: Transmucosal euthanasia solution administration resulted in clinical euthanasia within 6 hours. This method should be utilized only after premedication with analgesic and/or anesthetic medications due to the potential for acute mucosal ulceration and behaviors that may be distressing in client-owned animals.


Subject(s)
Euthanasia, Animal , Lizards , Pentobarbital , Phenytoin , Animals , Phenytoin/administration & dosage , Pentobarbital/administration & dosage , Euthanasia, Animal/methods , Male , Female , Administration, Mucosal , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology
4.
J Vet Med Sci ; 86(5): 480-484, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38556347

ABSTRACT

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.


Subject(s)
Euthanasia, Animal , Animals , Female , Mice , Male , Pentobarbital
5.
J Pediatr Pharmacol Ther ; 29(1): 32-36, 2024.
Article in English | MEDLINE | ID: mdl-38332954

ABSTRACT

OBJECTIVE: Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when the first-line agents become -insufficient. METHODS: In this retrospective chart-review study, we report our center's experience in using intermittent doses of enteral pentobarbital as an adjunct sedative in 13 difficult to sedate critically ill and mechanically ventilated children. We compare the average sedation score and cumulative doses of other -sedatives (opioids, benzodiazepines and alpha-2 agonists) in the 24 hours before and 24 hours after enteral -pentobarbital initiation. RESULTS: The addition of enteral pentobarbital was associated with lower State Behavioral State (SBS) scores in 8 out of the 13 patients and on average smaller doses of opioids (decreased by 11%), benzodiazepines (BZD) (decreased by 5%) and alpha-agonists (decreased by 20%). No adverse effects were noted attributable to pentobarbital administration. CONCLUSION: Enteral pentobarbital seems to be safe and effective agent in the difficult to sedate critically ill child.

6.
Article in English | MEDLINE | ID: mdl-38279726

ABSTRACT

INTRODUCTION: Ziziphus mauritiana, sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have analgesic, antipyretic, potent analgesic, anti-inflammatory, and anti-emetic properties. AIMS & OBJECTIVES: The aim of this study is to investigate the sedative and anticonvulsant activities of Ziziphus mauritiana extract by governing 200 and 400 mg/kg body weight orally. MATERIALS AND METHODS: The leaves are extracted with ethanol and lukewarm water with a soxhlet apparatus for 72 hours. After that acute extract toxicity study was performed and then locomotor activity, pentobarbital induced sleeping time and anticonvulsant activity were performed with the extract. RESULTS: Oral administration of extract at dosages of 200 & 400 mg/kg was employed after an immediate toxicity test. At a dosage of 400 mg/kg, the number of locomotions was reduced significantly lengthened the period of time spent sleeping and there was showed a dosage-dependent reduction in all phases of an epileptic episode. CONCLUSION: In this study, the extract reduced locomotor activity, however, it had a superior profile for an antiepileptic action than phenytoin since it decreased locomotor activity to a lesser level. The considerable increase in pentobarbitone sleep hours with the extracts at a higher dose supported the sedative action of Z. mauritiana.


Subject(s)
Anticonvulsants , Hypnotics and Sedatives , Plant Extracts , Sleep , Ziziphus , Animals , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Ziziphus/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Hypnotics and Sedatives/pharmacology , Mice , Male , Rats , Sleep/drug effects , Plant Leaves/chemistry , Female , Seizures/drug therapy , Rats, Wistar
7.
Article in English | MEDLINE | ID: mdl-37980655

ABSTRACT

BACKGROUND: Pentobarbital and isoflurane are commonly used veterinary anesthetics. Due to the dangers of overdose by repeat-bolus regimen of pentobarbital, isoflurane has been recommended. However, literature suggests isoflurane-induced inhibition of cytokine and adhesion molecule release, impacting leukocyte adhesion. OBJECTIVE: This study aims to characterize the impacts of pentobarbital versus isoflurane on leukocyte interactions within the intestinal microcirculation with and without endotoxin challenge. METHODS: Female BALB/c mice were subjected to pentobarbital or isoflurane (N = 20) and challenged with endotoxin or saline by intraperitoneal injection. The mice were kept under anesthesia for 2 hours. Fluorochromes, rhodamine-6 G and fluorescein isothiocyanate, were injected intravenously. To visualize leukocyte adhesion within the intestinal microcirculation, laparotomy and intravital microscopy was performed. Leukocyte rolling and adhesion was quantified offline in a blinded fashion. RESULTS: Within collecting venules, leukocyte rolling and adhesion showed no significant differences between pentobarbital and isoflurane anesthesia under basal conditions. Endotoxin challenge caused a similar response in both anesthetic groups. Within postcapillary venules, no statistical differences between the two anesthetics were found for adhering leukocytes under basal conditions or following endotoxin challenge either. However, leukocyte rolling after LPS-challenge was significantly decreased in postcapillary venules during isoflurane anesthesia compared to pentobarbital anesthesia. CONCLUSIONS: Isoflurane anesthesia showed only minor differences in the immune response to endotoxin within the intestinal microcirculation compared to pentobarbital anesthesia. Due to the superior safety profile of volatile anesthetics, immunological studies may choose isoflurane over pentobarbital as the veterinary anesthetic of choice.

8.
Animals (Basel) ; 13(18)2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37760220

ABSTRACT

Refinement is one of the principles aiming to promote welfare in research animals. The techniques used during an experimental protocol, including euthanasia selection, must prevent and minimize suffering. Although the current euthanasia methods applied to laboratory rodents are accepted, the controversial findings regarding the potential stress/distress they can cause is a field of research. The objective was to assess the thermal response of Wistar rats during various euthanasia methods using infrared thermography (IRT) to determine the method that prevents or diminishes the stress response and prolonged suffering. Pentobarbital (G1), CO2 (G2), decapitation (G3), isoflurane (G4), ketamine + xylazine (G5), and ketamine + CO2 (G6) were evaluated at five evaluation times with IRT to identify changes in the surface temperature of four anatomical regions: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). Significant differences (p < 0.05) were found in G2 and G4, registering temperature increases from the administration of the drug to the cessation of respiratory rate and heart rate. Particularly, isoflurane showed a marked thermal response in T°ocu, T°ear, T°dor, and T°tai, suggesting that, in general, inhalant euthanasia methods induce stress in rats and that isoflurane might potentially cause distress, an effect that must be considered when deciding humane euthanasia methods in laboratory rodents.

9.
Am J Surg ; 226(6): 864-867, 2023 12.
Article in English | MEDLINE | ID: mdl-37532593

ABSTRACT

INTRODUCTION: Traumatic brain injury (TBI) results in the death of over 50,000 and the permanent disability of 80,000 individuals annually in the United States. Much of the permanent disability is the result of secondary brain injury from intracranial hypertension (ICH). Pentobarbital coma is often instituted following the failure of osmotic interventions and sedation to control intracranial pressure (ICP). The goal of this study was to evaluate the efficacy of pentobarbital coma with respect to ICP management and long-term functional outcome. METHODS: Traumatic brain injury patients who underwent pentobarbital coma at a level 1 trauma center between 2014 and 2021 were identified. Patient demographics, injury characteristics, Glasgow Coma Scale (GCS) scores, intracranial pressures (ICPs), and outcomes were obtained from the trauma registry as well as inpatient and outpatient medical records. The proportion of ICPs below 20 for each hospitalized patient-day was calculated. The primary outcome measured was GCS score at the last follow-up visit. RESULTS: 25 patients were identified, and the majority were male (n â€‹= â€‹23, 92%) with an average age of 30.0 years â€‹± â€‹12.9 and median injury severity score of 30 (21.5-33.5). ICPs were monitored for all patients with a median of 464 (326-1034) measurements. The average hospital stay was 16.9 days â€‹± â€‹11.5 and intensive care stay was 16.9 â€‹± â€‹10.8 days. 9 (36.0%) patients survived to hospital discharge. Mean follow-up time in months was 36.9 â€‹± â€‹28.0 (min-max 3-80). 7 of the 9 surviving patients presented as GCS 15 on follow-up and the remaining were both GCS 9. Patients presenting at last follow-up with GCS 15 had a significantly higher proportion of controlled ICPs throughout their hospitalization compared to patients who expired or with follow-up GCS <15 (GCS 15: 88% â€‹± â€‹10% vs. GCS <15 or dead: 68% â€‹± â€‹22%, P â€‹= â€‹0.006). A comparison of the daily proportion of controlled ICPs by group revealed negligible differences prior to pentobarbital initiation. Groups diverged nearly immediately upon pentobarbital coma initiation with a higher proportion of controlled ICPs for patients with follow-up GCS of 15. CONCLUSION: Patients that do not have an immediate response to pentobarbital coma therapy for ICH universally had poor outcomes. Alternative therapy or earlier palliation should be considered for such patients. In contrast, patients whose ICPs responded quickly to pentobarbital had excellent long-term outcomes.


Subject(s)
Brain Injuries, Traumatic , Brain Injuries , Intracranial Hypertension , Humans , Male , Female , Adult , Coma/complications , Pentobarbital/therapeutic use , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/therapy , Glasgow Coma Scale , Intracranial Hypertension/etiology , Intracranial Hypertension/complications , Intracranial Pressure
10.
J Am Vet Med Assoc ; 261(11): 1707-1715, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37562784

ABSTRACT

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.


Subject(s)
Pentobarbital , Veterinarians , Animals , Humans , Euthanasia, Animal , Animals, Wild , Surveys and Questionnaires
11.
Animals (Basel) ; 13(13)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37443914

ABSTRACT

This study was designed to determine how veterinarians define a good euthanasia experience. This information is used to generate a working definition of companion animal euthanasia that aligns with animal welfare standards and pet owners' expectations. An electronic survey distributed via veterinary-related social media (Facebook, Instagram) and listservs were completed by 249 veterinarians who perform feline and/or canine euthanasia. Our results suggest that very few veterinarians feel their veterinary school training adequately prepared them for euthanasia. When veterinarians were asked to rank a list of physiologic conditions and anatomical traits in order of euthanasia-related concerns, respiratory distress was ranked the highest, while the most concerning physical changes were reported to be indications or impressions of seizures or pain. The most commonly reported euthanasia injection technique performed by participants was intravenous administration of pentobarbital sodium (97%), and most veterinarians preferred having owners present (57%) or having no preference (38%) during euthanasia. Results suggest that veterinarians want a pain-free, anxiety-free experience for the patient, appreciate the use of sedatives before euthanasia, and feel that when available and appropriate, home euthanasia offers several benefits. This understanding of the numerous aspects involved in a good euthanasia experience can help inform the creation of an updated definition of companion animal euthanasia that strives to prioritize the welfare of the patient as well as the needs and expectations of the pet owner.

12.
Front Pharmacol ; 14: 1196565, 2023.
Article in English | MEDLINE | ID: mdl-37292155

ABSTRACT

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 µg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs.

13.
Cureus ; 15(3): e36498, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37090268

ABSTRACT

Concomitant prescriptions of psychotropic drugs such as sleeping pills, antidepressants, and anti-anxiety medications are common. The relationship between the number of psychotropic drug prescriptions and the incidence of drug overdose has not been reported. However, efforts have been made to reduce the number of concomitant prescriptions hoping that fewer prescriptions of multiple drugs will lower the incidence of drug overdoses. Furthermore, among sleeping pills, prescriptions of barbiturates have been gradually decreasing due to the risk of severe side effects and addiction. This report features a case of an overdose of pentobarbital tablets that caused the classic medical triad (impaired consciousness, hypotension, and hypothermia) of barbiturate intoxication under the characteristics of borderline personality disorder.

14.
Theriogenology ; 205: 1-8, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37084499

ABSTRACT

Postmortem and pre-euthanasia oocyte retrieval provides the last opportunity to preserve the genetic material in mares. Pentobarbital (PB) is the most common euthanasia agent; however, its effect on the developmental competence of oocytes has not been determined. Here, we evaluated the concentration of PB in equine follicular fluid (FF) and investigated its effect on the developmental competence of oocytes using a bovine IVF model to overcome the low availability of equine oocytes. The concentration of PB was measured by gas-chromatography/mass-spectrometry in FF collected from mare ovaries immediately after euthanasia (n = 10), 24 h post-euthanasia (n = 10), and from the ovaries collected by ovariectomy (negative control; n = 10). The serum concentration of PB was also evaluated as a positive control. PB was detected in all FF samples with an average concentration of 56.5 µg/ml. Next, bovine cumulus-oocyte complexes (COC) were held in holding media with PB for 6 h at 60 µg/ml (H60, n = 196), 164 µg/ml (H164, n = 215) or without PB (control; n = 212). After holding, the oocytes were matured and fertilized in vitro, followed by in vitro culture to the blastocyst stage. The cumulus expansion grade, cleavage rate, blastocyst rate, embryo kinetic rate and the blastocyst cell numbers were compared among the experimental groups of bovine COC. Higher rates of Grade 1 cumulus expansion were found in controls (54%, 32-76%; median, min-max) in comparison to H60 and H164 (24%,11-33% and 13%, 8-44%; P < 0.001). The cleavage rate was higher in the controls than in H164 (64% vs. 44%; P < 0.01). Blastocyst rates (blastocyst/cleaved oocytes) and total cell number were not different among the groups (control 29%, H60 25%, and H164 24%). In a preliminary study, equine oocytes (n = 28) were exposed to PB in vitro for 6 h followed by intracytoplasmic sperm injection (ICSI) and in vitro embryo production. Exposed oocytes showed a numerically lower maturation rate (43% Vs 52%; P > 0.05) in comparison to the laboratory-established rate during the same timepoints. Overall, we showed that PB reaches the FF immediately after euthanasia, exposing oocytes to this drug. This exposure affected cumulus expansion and cleavage rates in a bovine model, suggesting initial damage caused by PB that may not completely impede the formation of embryos, although lower overall embryo numbers might be obtained.


Subject(s)
Pentobarbital , Semen , Animals , Horses , Female , Male , Cattle , Pentobarbital/pharmacology , Euthanasia, Animal , Oocytes , Embryo, Mammalian , Blastocyst , In Vitro Oocyte Maturation Techniques/veterinary , In Vitro Oocyte Maturation Techniques/methods , Fertilization in Vitro/veterinary
15.
J Avian Med Surg ; 36(4): 394-399, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36935211

ABSTRACT

Intravenous lipid emulsion (ILE) therapy has shown promise as a treatment option for a variety of lipophilic toxins. Two birds presented for suspected ingestion of a toxic substance. A blue-and-gold macaw (Ara ararauna) presented after chewing a block of bromethalin rodenticide without overt clinical signs at the time of presentation. Additionally, a free-ranging bald eagle (Haliaeetus leucocephalus) was found weak and depressed near a municipal landfill after presumptive ingestion of pentobarbital. Both birds were treated with ILE therapy for potential intoxication without any adverse events. The macaw was clinically normal after 3 days of hospitalization and at a 1-week reevaluation. The eagle was transferred to a rehabilitation center after markedly improved mentation and strength and was released 7 days later. Clinicians should consider ILE therapy for the treatment of lipophilic toxicities; however, monitoring is recommended for persistent lipemia and other adverse effects that have been reported in the veterinary literature.


Subject(s)
Bird Diseases , Eagles , Parrots , Animals , Emulsions , Bird Diseases/chemically induced , Bird Diseases/therapy , Bird Diseases/diagnosis , Phospholipids , Soybean Oil
16.
Nutrients ; 15(6)2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36986039

ABSTRACT

Dried Chrysanthemum morifolium (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)65/67 and gamma-aminobutyric acid (GABA)A receptors subunit expression levels. The expression of α1-subunits, ß2-subunits, and GAD65/67 of the GABAA 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.


Subject(s)
Neuroblastoma , Pentobarbital , Rats , Mice , Humans , Animals , Pentobarbital/pharmacology , Receptors, GABA-A , Sleep Quality , Rodentia , Chlorides/metabolism , Sleep
17.
Pharmaceutics ; 15(3)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36986615

ABSTRACT

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (-63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS.

18.
J Neurotrauma ; 40(23-24): 2552-2565, 2023 12.
Article in English | MEDLINE | ID: mdl-36785968

ABSTRACT

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain.


Subject(s)
Anesthetics , Contusions , Isoflurane , Spinal Cord Injuries , Humans , Rats , Animals , Pentobarbital , Isoflurane/pharmacology , Pain/drug therapy , Pain/etiology , Spinal Cord Injuries/complications , Anesthesia, General/adverse effects , Hemorrhage , Contusions/complications
19.
Article in English | MEDLINE | ID: mdl-36815742

ABSTRACT

OBJECTIVE: To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication. CASE SUMMARY: A 10-year-old, male intact Jack Russell Terrier was referred for management of refractory status epilepticus and presented dead on arrival. After 7 minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, but the dog remained comatose, apneic, and lacked brainstem reflexes on neurological examination 6 hours following resuscitation. Magnetic resonance imaging showed polioencephalomalacia consistent with prolonged epileptiform activity, and EEG was initially concerning for electrocerebral inactivity. Following supportive care that included short-term mechanical ventilation, the dog made a full recovery and was discharged from the hospital alive 7 days postresuscitation. It was later revealed that the dog had been administered an unknown amount of pentobarbital during transportation, which likely contributed to the OHCA, clinical, and EEG findings. NEW INFORMATION PROVIDED: This is the first report to describe the full recovery and hospital discharge of a dog suffering OHCA and the first description of EEG findings in a clinical veterinary patient following cardiopulmonary arrest and successful resuscitation. Factors likely contributing to successful patient outcome and potential benefits and limitations of EEG in monitoring postcardiac arrest patients are discussed.


Subject(s)
Cardiopulmonary Resuscitation , Dog Diseases , Drug Overdose , Heart Arrest , Male , Dogs , Animals , Pentobarbital , Heart Arrest/chemically induced , Heart Arrest/therapy , Heart Arrest/veterinary , Cardiopulmonary Resuscitation/veterinary , Cardiopulmonary Resuscitation/methods , Drug Overdose/veterinary , Hospitals , Dog Diseases/chemically induced , Dog Diseases/therapy
20.
J Appl Anim Welf Sci ; 26(1): 4-14, 2023.
Article in English | MEDLINE | ID: mdl-33843357

ABSTRACT

This prospective study evaluated oral transmucosal pentobarbital sodium at three doses in 110 wild-caught wild birds requiring euthanasia. Birds received transmucosal pentobarbital at five (430 mg/kg), six (516 mg/kg), and seven times (602 mg/kg) the intravenous dose for mammals. Time to first effects and loss of consciousness, presence of pupillary light and corneal reflexes, apnea, and asystole were recorded each minute. When asystole was not achieved at 5 minutes, IV pentobarbital was administered. Combining data for all doses, loss of consciousness occurred at a median (range) of 2 minutes (0-4.75 min), apnea at 3 minutes (0-6 min), and asystole at 4 minutes (0.5-5 min). Loss of consciousness and apnea occurred significantly faster in the 602 mg/kg dose group than in the 430 mg/kg group (p = 0.009, difference of 0.6 ± 0.2 min; p = 0.024, difference of 0.7 ± 0.3 min), respectively. Apnea and asystole were achieved in 80/110 birds within 5 minutes. Oral transmucosal pentobarbital results in rapid loss of consciousness and respiratory arrest and provides a reliable alternative euthanasia method compared to intravenous administration.


Subject(s)
Hypnotics and Sedatives , Pentobarbital , Animals , Hypnotics and Sedatives/pharmacology , Apnea/veterinary , Prospective Studies , Euthanasia, Animal , Animals, Wild , Birds , Administration, Mucosal , Unconsciousness/veterinary , Mammals
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