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1.
J Spec Oper Med ; 20(1): 31-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203601

RESUMO

Ketamine's favorable hemodynamic and safety profile is motivating increasing use in the prehospital environment. Despite these advantages, certain side effects require advanced planning and training. We present a case of rapid intravenous administration of ketamine causing bradycardia and hypotension. A 46-year-old man presented to the emergency department for an exacerbation of chronic shoulder pain. Given the chronicity of the pain and multiple failed treatment attempts, ketamine at an analgesic dose was used. Despite the local protocol directing administration over several minutes, it was pushed rapidly, resulting in malaise, nausea, pallor, bradycardia, and hypotension. The patient returned to his baseline without intervention. This and other known side effects of ketamine, such as behavioral disturbances, altered sense of reality, and elevated heart rate and blood pressure, are well documented in the literature. With this report, the authors aim to raise awareness of transient bradycardia and hypotension associated with the rapid administration of ketamine at an analgesic dose.


Assuntos
Analgésicos/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Ketamina/efeitos adversos , Analgésicos/administração & dosagem , Serviço Hospitalar de Emergência , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade
2.
PLoS One ; 15(1): e0227762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929589

RESUMO

Intranasal ketamine has recently gained interest in human medicine, not only for its sedative, anaesthetic or analgesic properties, but also in the management of treatment resistant depression, where it has been shown to be an effective, fast acting alternative treatment. Since several similarities are reported between human psychiatric disorders and canine anxiety disorders, intranasal ketamine could serve as an alternative treatment for anxiety disordered dogs. However, to the authors knowledge, intranasal administration of ketamine and its pharmacokinetics have never been described in dogs. Therefore, this study aimed to examine the pharmacokinetics, absolute bioavailability and tolerability of intranasal ketamine administration compared with intravenous administration. Seven healthy, adult laboratory Beagle dogs were included in this randomized crossover study. The dogs received 2 mg/kg body weight ketamine intravenously (IV) or intranasally (IN), with a two-week wash-out period. Prior to ketamine administration, dogs were sedated intramuscularly with dexmedetomidine. Venous blood samples were collected at fixed times until 480 min post-administration and ketamine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. Cardiovascular parameters and sedation scores were recorded at the same time points. Non-compartmental pharmacokinetic analysis revealed a rapid (Tmax = 0.25 ± 0.14 h) and complete IN bioavailability (F = 147.65 ± 49.97%). Elimination half-life was similar between both administration routes (T1/2el IV = 1.47 ± 0.24 h, T1/2el IN = 1.50 ± 0.97 h). Heart rate and sedation scores were significantly higher at 5 and 10 min following IV administration compared to IN administration, but not at the later time-points.


Assuntos
Analgésicos/sangue , Dexmedetomidina/administração & dosagem , Ketamina/sangue , Administração Intranasal , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Disponibilidade Biológica , Dexmedetomidina/farmacologia , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Masculino
3.
Expert Rev Clin Pharmacol ; 13(2): 135-146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31990596

RESUMO

Introduction: The use of ketamine infusions for chronic pain has surged, with utilization exceeding the proliferation of knowledge. A proposed mechanism for the long-term benefit in chronic pain is that ketamine may alter the affective-motivational component of pain.Areas covered: In this review, we discuss the classification and various dimensions of pain, and explore the effects of ketamine on different pain categories and components. The relationship between ketamine's action at the NMDA receptor, the development of chronic pain, and the its possible role in preventing the persistence of pain are examined. We also summarize animal models evaluating the antinociceptive effects of ketamine and risk mitigation strategies of ketamine-associated side effects.Expert opinion: Although ketamine exerts most of its analgesic effects via the NMDA receptor, recent evidence suggests that other receptors such as AMPA, and active metabolites such as nor-ketamine, may also play a role in pain relief and alleviation of depression. Data from clinical studies performed in patients with chronic pain and depression, and the observation that ketamine's analgesic benefits outlast its effects on quantitative sensory testing, suggest that the enduring effects on chronic pain may be predominantly due ketamine's ability to modulate the affective-motivational dimension of pain.


Assuntos
Analgésicos/administração & dosagem , Dor Crônica/tratamento farmacológico , Ketamina/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Dor Crônica/fisiopatologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo
4.
Expert Opin Pharmacother ; 21(1): 9-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31663783

RESUMO

Introduction: In March 2019, intranasal esketamine was approved by the Food and Drug Administration (FDA) for the treatment of treatment-resistant depression (TRD) in adults. This review presents the results of clinical trials underlying the FDA approval of intranasal esketamine.Areas covered: Esketamine's efficacy and safety in TRD were assessed in 5 phase III studies: three 4-week, placebo-controlled studies, and two long-term trials. One short-term trial showed statistically significant antidepressant effects of esketamine vs placebo, while a long-term withdrawal study showed that esketamine is significantly beneficial in terms of extending time to relapse, compared to placebo. Two other short-term trials did not meet the prespecified statistical tests for showing efficacy, although improvement in depressive symptoms from baseline to the end of week 4 favors esketamine over placebo.Expert opinion: Intranasal esketamine is a new treatment option for people with TRD. The main benefit of esketamine is rapid onset of antidepressant activity, but the effects of prolonged treatment are still preliminary. The main concerns relate to the safety aspects of prolonged esketamine therapy, when considering its abuse potential. While data for esketamine use over a long period of time is lacking, its use should be carefully monitored.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Administração Intranasal , Adulto , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Humanos , Ketamina/efeitos adversos
5.
Forensic Sci Int ; 306: 110093, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816483

RESUMO

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.


Assuntos
Analgésicos Opioides/envenenamento , Ketamina/envenenamento , Metanfetamina/envenenamento , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Distribuição por Idade , Analgésicos Opioides/efeitos adversos , Intoxicação por Monóxido de Carbono/mortalidade , China/epidemiologia , Feminino , Heroína/efeitos adversos , Heroína/envenenamento , Humanos , /envenenamento , Ketamina/efeitos adversos , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Distribuição por Sexo , Suicídio/estatística & dados numéricos , Adulto Jovem
6.
Ann Ist Super Sanita ; 55(4): 338-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850860

RESUMO

INTRODUCTION: Ketamine is an essential medicine used as an anesthetic in low and middle-income countries and in veterinary medicine. Recreational use is widespread throughout the world, especially owing to its lower price compared to other substances. In Western countries its use has been mainly linked to subpopulations of young people who use drugs recreationally. Ketamine misuse is associated with amnesia, dependence, dissociation, lower urinary tract dysfunction and poor impulse control. Regular ketamine use is associated with abdominal pains. AIMS: The aims of this study are to analyze characteristics and main symptoms of ketamine abusers attending emergency departments (EDs) in the metropolitan area of Bologna, Emilia-Romagna Region, northern Italy. METHODS: We identified 74 records of ketamine-related visits: 30% female; 22% non-natives; mean age 25.6 years. Forty-two percent reported ketamine use alone, 46% reported the use of other illegal substance (cocaine 19%, heroin 18%), 26% alcohol misuse. RESULTS: The most common reported symptoms were neurological (soporous state 18%, agitation 14%, confusion 7%, panic attacks 7%, mydriasis 7%, tremors 7%), gastro-intestinal (abdominal pain 15%, vomiting 11%), urological (6.8%) and cardiac (palpitations 5%, chest pain 5%). Complications secondary to falls and cuts (7%) were the most frequent trauma complications. We highlight a significant number of visits regarding suicide attempts (10%) and overdose (4%). CONCLUSIONS: The results highlight a particular population of problematic ketamine users identified using the hospital's ICT system. In particular, poly-drug users who consume ketamine in combination with heroin or cocaine presenting to the ED represent a specific target for targeted prevention projects on non-lethal overdoses and suicide attempts.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Ketamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Adulto , Alcoolismo/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Comorbidade , Estudos Transversais , Overdose de Drogas/epidemiologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Itália/epidemiologia , Masculino , Transtornos Mentais/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Avaliação de Sintomas , Adulto Jovem
8.
Georgian Med News ; (294): 141-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687967

RESUMO

General anesthesia may cause damage of the central nervous system and cognitive dysfunction in the postoperative period. A new intranasal form of Noopept (N-Phenylacetyl-L-prolylglycine ethyl ester) was developed by our team at the Department of the medical technology (Zaporizhzhia State Medical University, Ukraine). The objectives of this investigation were the study of neuroprotective action of Noopept and to prove using in the clinic for correction of amnestic and behavioral disorders after ketamine anesthesia. We discovered that the intranasal administration of noopept after ketamine anesthesia significantly decreases anxiety and excitability, raises the animal's activity, shows an intensive antiamnesic effects and increases animal's training ability. Noopept significantly exceeds piracetam and cerebrocurin according to neuroprotective effects.


Assuntos
Amnésia/tratamento farmacológico , Ketamina/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Amnésia/induzido quimicamente , Anestesia , Anestesia Geral , Animais , Dipeptídeos/uso terapêutico , Ketamina/administração & dosagem , Transtornos Mentais/induzido quimicamente , Resultado do Tratamento , Ucrânia
10.
Psychiatr Danub ; 31(Suppl 3): 530-533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488786

RESUMO

Major depressive disorder (MDD) is a recurrent, incapacitating psychiatric illness which will be the second most disabling disease worldwide by the year 2020. There is a rising promise in a N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, which may be used in the treatment of resistant depression. Many of the studies are in favor of the drug, even in single dose application, with effects appearing in minutes to hours from administration. However, there is a need to evaluate the benefits and risks regarding psychomimetic, psychiatric, neurologic, and cognitive adverse effects of ketamine administration. The most distressing symptoms which appear most frequently during ketamine administration are dissociative symptoms, which can be quantified as a CNS adverse drug reaction. Results generally show that a single infusion of ketamine is efficacious and well-tolerated, while dissociative symptoms tend to abate within 2 hours after ketamine administration. As studies show single doses of ketamine should be definitely considered as an option in TRD patients with/without suicidal thoughts, even though it could not provide remission, or the effect could be temporary, but improving patients' quality of life by reducing depressive symptomatology should be a major asset while considering this particular procedure, particularly in inpatients.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Depressão/tratamento farmacológico , Humanos , Qualidade de Vida
11.
Psychiatr Danub ; 31(Suppl 3): 585-590, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488795

RESUMO

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Depressão/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
12.
J S Afr Vet Assoc ; 90(0): e1-e7, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31368316

RESUMO

The objective of this study was to gain better insight into factors associated with the capture-related mortality rate in cheetahs. A link to an online questionnaire was sent to zoo and wildlife veterinarians through the Species Survival Plan Programme and European Endangered Species Programme coordinators and via the 'Wildlife VetNet' Google group forum. The questionnaire consisted of 50 questions relating to the veterinarians' country of residence and experience, the medicine combinations used, standard monitoring procedures, capture-related complications and mortalities experienced in this species under different capture conditions. In addition, necropsy data from the national wildlife disease database of the National Zoological Gardens of South Africa were examined for cases where anaesthetic death was listed as the cause of death in cheetahs. A total of 75 veterinarians completed the survey, with 38 from African countries and a combined total of 37 from Europe, the United States (US) and Asia. Of these, 24% (n = 18/75) had experienced at least one capture-associated cheetah mortality, with almost all of the fatalities (29/30) reported by veterinarians working in Africa. A lack of anaesthetic monitoring and the absence of supplemental oxygen were shown to be significant risk factors for mortality. Hyperthermia, likely to be associated with capture stress, was the most common reported complication (35%). The results suggest that free-ranging rather than habituated captive cheetahs are particularly at risk of dying during immobilisation and transport. The capture-related fatalities in this species do not appear to be associated with either the veterinarian's level of clinical experience or the immobilisation agents used.


Assuntos
Acinonyx , Anestésicos Dissociativos/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Imobilização/veterinária , Mortalidade , Animais , Animais Selvagens , Animais de Zoológico , Autopsia/veterinária , Bases de Dados Factuais , Combinação de Medicamentos , Europa (Continente) , Imobilização/efeitos adversos , Imobilização/métodos , Ketamina/efeitos adversos , Modelos Logísticos , Medetomidina/efeitos adversos , Fatores de Risco , África do Sul/epidemiologia , Inquéritos e Questionários , Tranquilizantes/efeitos adversos , Médicos Veterinários
13.
J Clin Psychopharmacol ; 39(5): 446-454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433347

RESUMO

PURPOSE/BACKGROUND: As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear. METHODS/PROCEDURES: Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 µg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 µg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV). FINDINGS/RESULTS: Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits. IMPLICATIONS/CONCLUSIONS: Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.


Assuntos
Condução de Veículo , Dexmedetomidina/administração & dosagem , Fentanila/administração & dosagem , Ketamina/administração & dosagem , Adulto , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Simulação por Computador , Dexmedetomidina/efeitos adversos , Quimioterapia Combinada , Feminino , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Ketamina/efeitos adversos , Ketamina/análogos & derivados , Ketamina/farmacocinética , Masculino , Adulto Jovem
14.
Gen Physiol Biophys ; 38(5): 427-434, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31411575

RESUMO

The objective of this study is to investigate the effects of nimesulide on ketamine-induced ovarian and uterine toxicity by biochemical and histopathological examinations. Ketamine is an anesthetic agent whose use leads to overproduction of catecholamines. Nimesulide is a cyclooxygenase-2 inhibitor, which has also been reported to exert a significant antioxidant effect. Wistar albino female rats were randomly divided into three groups as follows: ketamine group (60 mg/kg), ketamine (60 mg/kg) + nimesulide (50 mg/kg) group, and a healthy control group. Then, the biochemical levels and histopathological findings in the ovaries and uteri of the rats were examined for malondialdehyde, myeloperoxidase, total glutathione and superoxide dismutase. The study demonstrated that, in the uterine and ovarian tissues of rats that have been administered ketamine, there was a decrease in the levels of total glutathione and superoxide dismutase, while malondialdehyde and myeloperoxidase was increased: however it was observed that these ratios were reversed in the ketamine+nimesulide group. It was also proved that the negative effects of ketamine can be corrected with nimesulide when the myometrial and endometrial thicknesses are compared. Antioxidants such as nimesulide may protect against the damage caused by ketamine to the genital organs in young women.


Assuntos
Antioxidantes/farmacologia , Ketamina/efeitos adversos , Ketamina/antagonistas & inibidores , Ovário/efeitos dos fármacos , Sulfonamidas/farmacologia , Útero/efeitos dos fármacos , Animais , Feminino , Glutationa/metabolismo , Malondialdeído/metabolismo , Ovário/enzimologia , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Útero/enzimologia , Útero/metabolismo
15.
J Zoo Wildl Med ; 50(2): 457-460, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260214

RESUMO

Two anesthetic protocols in adult giraffe were compared by retrospective study. Thirteen anesthesia records for medetomidine-ketamine (MK) and seven for medetomidine-ketamine with a potent opioid (MKO) were evaluated for differences in demographic, behavioral, drug, and respiratory parameters. Giraffe stood significantly more quickly with MKO vs MK though MK animals were physically restrained to preclude premature standing as part of normal recovery practices (5.5 min vs 21.4 min, P = 0.01). Regurgitation was recorded in 5/13 and resedation in 4/13 MK animals. The range of values for blood lactate was higher in MKO (5.18-11.25 mM/L) than in MK giraffe (0.78-6.08 mM/L). Despite limitations of a retrospective study, both MK and MKO giraffe anesthesia protocols exhibit benefits and side effects. Awareness and management of these factors will improve outcomes until standardized, prospective studies of giraffe immobilization offer more comprehensive guidance on protocol selection.


Assuntos
Analgésicos Opioides/farmacologia , Anestesia/veterinária , Girafas , Ketamina/farmacologia , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/efeitos adversos , Anestésicos Dissociativos/farmacologia , Animais , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Estudos Retrospectivos
16.
Int J Mol Med ; 44(3): 797-812, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257475

RESUMO

The present study investigated the methylation of CpG sites in the cyclooxygenase (COX)­2 promoter via nuclear factor (NF)­κB transcriptional regulation and elucidated its effect on the COX­2 transcriptional expression in a ketamine­induced ulcerative cystitis (KIC) animal model. The results of the present study revealed that ketamine treatment induced NF­κB p65 translocation to nuclei and activated COX­2 expression and prostaglandin (PGE)2 production in bladder tissue, whereas COX­2 inhibitor suppressed the inflammatory effect. Moreover, DNA hypomethylation of the COX­2 promoter region located from ­1,522 to ­829 bp might contribute to transcriptional regulation of COX­2 expression and induce a pro­inflammatory response in KIC. Ketamine treatment increased the binding of NF­κB and permissive histone H3 lysine­4 (H3K4)m3, but caused a decrease in the repressive histone H3K27m3 and H3K36m3 on the COX­2 promoter ranging from ­1,522 to ­1,331 bp as determined by a chromatin immunoprecipitation assay. Moreover, in the ketamine group, the level of Ten­Eleven­Translocation methylcytosine dioxygenase for demethylation as determined by reverse transcription­quantitative PCR assay was increased in comparison with the control group, but that was not the case for the level of DNA methyltransferases for methylation. The present findings revealed that there was a hypomethylation pattern of the COX­2 promoter in association with the level of COX­2 transcription in KIC.


Assuntos
Ciclo-Oxigenase 2/genética , Cistite/etiologia , Cistite/metabolismo , Metilação de DNA , Epigênese Genética , Regulação da Expressão Gênica , NF-kappa B/metabolismo , Animais , Imunoprecipitação da Cromatina , Ilhas de CpG , Cistite/patologia , Modelos Animais de Doenças , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Ketamina/efeitos adversos , Modelos Biológicos , Regiões Promotoras Genéticas , Transporte Proteico , Ratos
17.
Medicine (Baltimore) ; 98(28): e16403, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305450

RESUMO

BACKGROUND: Thoracic epidural analgesia is the preferred method for postoperative analgesia following thoracic surgery. However, intravenous patient-controlled analgesia (IVPCA) may be an effective alternative. This study was conducted because few scientific reports exist comparing fentanyl-based IVPCA including a low dose of ketamine (fk-IVPCA) with thoracic patient-controlled epidural analgesia (t-PCEA) for the treatment of postoperative pain after video-assisted thoracic surgery (VATS). METHODS: This prospective, and randomized study included 70 patients randomized into fk-IVPCA and t-PCEA groups. Pain at rest and during movement, successful and unsuccessful triggers after pressing the PCA device button, the need for rescue analgesia, drug-related adverse events, and patient satisfaction were recorded for 48 hours postoperatively. RESULTS: No significant differences in the intensity of pain at rest or during movement were observed between the 2 groups within 48 hours postoperatively. The number of unsuccessful PCA triggers in the t-PCEA group 0 to 4 hours after surgery was significantly higher than that in the fk-IVPCA group. However, the numbers of successful PCA triggers in the fk-IVPCA group at 4 to 12 and 0 to 24 hours after surgery were significantly higher than those in the t-PCEA group. The incidence of analgesic-related side effects and patient satisfaction were similar in both groups. CONCLUSIONS: Compared with t-PCEA, the addition of a subanesthetic dose of ketamine to fentanyl-based IVPCA resulted in similar pain control after VATS with no increase in the incidence of drug-related adverse effects. The results confirm that both multimodal intravenous analgesia and epidural analgesia can provide sufficient pain control and are safe strategies for treating acute post-thoracotomy pain.


Assuntos
Analgesia Epidural , Analgesia Controlada pelo Paciente , Analgésicos/administração & dosagem , Fentanila/administração & dosagem , Ketamina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Administração Intravenosa , Analgesia Epidural/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Analgesia Controlada pelo Paciente/métodos , Analgésicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Movimento , Manejo da Dor/efeitos adversos , Manejo da Dor/métodos , Satisfação do Paciente , Cirurgia Torácica Vídeoassistida , Toracotomia , Resultado do Tratamento
18.
Afr Health Sci ; 19(1): 1736-1744, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31149004

RESUMO

Background: The aim of this study was to compare the effect of propofol and ketofol (ketamine-propofol mixture) on EA in children undergoing tonsillectomy. Method: In this randomized clinical trial, 87 ASA class I and II patients, aged 3-12 years, who underwent tonsillectomy, were divided into two groups to receive either propofol 100 µg/kg/min (group p, n=44) or ketofol : ketamine 25 µg/kg/min + propofol 75 µg/kg/min (group k, n= 43). Incidence and severity of EA was evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scales on arrival at the recovery room, and 10 and 30 min after that time. Results: There was no statistically significant difference in demographic data between the two groups. In the ketofol group, the need for agitation treatment and also mean recovery duration were lower than in the propofol group (30 and 41%, and 29.9 and 32.7 min), without statistically significant difference (P value=0.143 and P value=0.187). Laryngospasm or bronchospasm occurred in 2 patients in each group and bleeding was observed in only one individual in the ketofol group. Conclusion: Infusion of ketofol in children undergoing tonsillectomy provides shorter recovery time and lower incidence of EA despite the non significant difference with propofol.


Assuntos
Anestésicos Dissociativos/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Delírio do Despertar/induzido quimicamente , Ketamina/administração & dosagem , Propofol/administração & dosagem , Tonsilectomia/métodos , Anestesia/efeitos adversos , Anestésicos Dissociativos/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Espasmo Brônquico/induzido quimicamente , Criança , Pré-Escolar , Delírio do Despertar/epidemiologia , Feminino , Humanos , Incidência , Ketamina/efeitos adversos , Laringismo/induzido quimicamente , Masculino , Propofol/efeitos adversos , Índice de Gravidade de Doença
20.
Vet Anaesth Analg ; 46(4): 466-475, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31176572

RESUMO

OBJECTIVE: To compare immobilization efficacy of a nonpotent opioid drug combination, ketamine-butorphanol-medetomidine (KBM) to the preferred etorphine-azaperone (EA) combination in zebras. STUDY DESIGN: Randomized crossover trial. ANIMALS: A group of ten adult zebra (six females and four male). METHODS: KBM and EA were administered once to the zebras in random order by dart, 3 weeks apart. Once a zebra was recumbent and instrumented, physiological parameters were measured and recorded at 5-minute intervals until 20 minutes. Antagonist drugs were administered at 25 minutes. KBM was antagonised using atipamezole (7.5 mg mg-1 medetomidine dose) and naltrexone (2 mg mg-1 butorphanol dose). EA was antagonized using naltrexone (20 mg mg-1 etorphine dose). Induction and recovery (following antagonist administration) times were recorded. Physiological parameters, including invasive blood pressure and blood gas analysis, were compared between combinations using a general linear mixed model. Data are reported as mean ± standard deviation or median (interquartile range). RESULTS: The doses of KBM and EA administered were 3.30 ± 0.18, 0.40 ± 0.02 and 0.16 ± 0.01 mg kg-1; and 0.02 ± 0.001 and 0.20 ± 0.01 mg kg-1, respectively. KBM and EA induction times were 420 (282-564) and 240 (204-294) seconds, respectively (p = 0.03). Zebras remained recumbent throughout the study procedures. Systolic blood pressure (226 ± 42 and 167 ± 42 mmHg) and oxygen partial pressure (64 ± 12 and 47 ± 13 mmHg) were higher for KBM compared to EA (p < 0.01). Recovery time, after administering antagonists, was 92 (34-1337) and 26 (22-32) seconds for KBM and EA, respectively (p = 0.03). CONCLUSIONS AND CLINICAL RELEVANCE: Compared to EA, KBM also immobilized zebras effectively. Systemic hypertension and moderate hypoxaemia are clinical concerns of KBM and severe hypoxaemia is a concern of EA. This occurrence of hypoxaemia highlights the importance of oxygen administration during immobilization.


Assuntos
Analgésicos Opioides/farmacologia , Anestésicos Dissociativos/farmacologia , Equidae , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Animais , Animais Selvagens , Azaperona/administração & dosagem , Azaperona/efeitos adversos , Azaperona/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Butorfanol/administração & dosagem , Butorfanol/farmacologia , Estudos Cross-Over , Combinação de Medicamentos , Etorfina/administração & dosagem , Etorfina/efeitos adversos , Etorfina/farmacologia , Feminino , Hipertensão/induzido quimicamente , Hipertensão/veterinária , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipóxia/induzido quimicamente , Hipóxia/veterinária , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Masculino , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Medetomidina/farmacologia , Oxigênio/administração & dosagem , Distribuição Aleatória
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