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2.
Medicine (Baltimore) ; 100(8): e24842, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663105

RESUMO

ABSTRACT: An association between animals and volatile anaesthetic requirements has been shown; however, evidence related to the postoperative outcome of human patients is lacking. Our aim was to investigate whether there is a difference in the requirement for sevoflurane among people undergoing gastrointestinal surgery.We observed 390 adult patients who underwent gastrointestinal surgery with an American Society of Anesthesiologists physical status of I or II with an expected surgery duration of > 2 hours. We used the bispectral index (BIS) to guide the regulation of end-tidal sevoflurane concentration (ETsevo). The mean ETsevo from 20 minutes after endotracheal intubation to 2 hours after the start of surgery was calculated for all patients. Differential sevoflurane requirements were identified according to ETsevo. The BIS, ETsevo, heart rate, mean arterial pressure, dose of sufentanil and cisatracurium, tracheal extubation time, incidence of intraoperative awareness, and incidence of postoperative nausea and vomiting were compared between patients with a low requirement for sevoflurane (group L) and patients with a high requirement for sevoflurane (group H).The mean ETsevo of the 390 patients was 1.55% ±â€Š0.26%. Based on our definition, patients with an ETsevo of < 1.29% were allocated to the low requirement group (group L; n = 69), while patients with an ETsevo of > 1.81% were allocated to the high requirement group (group H; n = 78). The ETsevo of group L was significantly lower than the ETsevo of group H (1.29% ±â€Š0.014% vs 1.82% ±â€Š0.017%, P < .001). There was no significant difference in the ETsevo, BIS, heart rate, mean arterial pressure, dose of sufentanil and cisatracurium, tracheal extubation time, incidence of intraoperative awareness, and incidence of postoperative nausea and vomiting. The tracheal extubation time in the L group was significantly shorter than that in the H group. No intraoperative awareness occurred.There was a significant difference in the requirement for sevoflurane in adult patients. The tracheal extubation time in group L was significantly shorter than that in group H.


Assuntos
Período de Recuperação da Anestesia , Anestesia Geral/métodos , Anestésicos Inalatórios/farmacocinética , Sevoflurano/farmacocinética , Extubação/efeitos adversos , Anestésicos Inalatórios/administração & dosagem , Estudos de Casos e Controles , Monitores de Consciência , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sevoflurano/administração & dosagem
3.
Medicine (Baltimore) ; 100(4): e23753, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530174

RESUMO

ABSTRACT: To evaluate the utility of low-concentration nitrous oxide (N2O) anesthesia in ptosis surgeryThis study was a retrospective consecutive case series that included 54 successive patients with blepharoptosis who underwent bilateral levator aponeurosis advancement and on whom skin resection performed by the same surgeon between August 2016 and July 2017. Among these patients, 27 were operated with a local anesthesia injection (air group) and 27 with a local anesthesia injection and low-concentration N2O anesthesia (N2O group). All N2O cases used a total of 6 L of gas comprising 70% oxygen and 30% N2O. Preoperative and postoperative blood pressure (BP) and heart rate (HR) and intraoperative pain, anxiety, nausea, and memory were measured immediately after surgery using visual analog scale score (VASS). Additionally, perioperative side effects were examined.There was no significant difference in age, sex, and preoperative and postoperative margin reflex distance (MRD) between the 2 groups (all P > .05). The intraoperative mean peripheral oxygen saturation was significantly higher (97.5% ±â€Š1.6% vs 99.5% ±â€Š.6%, P < .001), intraoperative HR was significantly lower (78.2 ±â€Š12.8 vs 70.7 ±â€Š11.6 bpm, P = .02), and operation time was significantly shorter (33.1 ±â€Š8.1 vs 29.4 ±â€Š10.3 minutes, P = .03) in the N2O group than in the air group.Difference between intraoperative and preoperative systolic BP (BPs) (+15.8 ±â€Š18.0 vs + 3.1 ±â€Š21.7 mm Hg, P = .02), diastolic BP (BPd) (+7.0 ±â€Š17.4 vs -2.3 ±â€Š13.6 mm Hg, P = .04), and HR (3.2 ±â€Š8.5 vs -3.9 ±â€Š9.4 bpm, P = .01) was significantly lower in the N2O group than in the air group.VASS of intraoperative pain was significantly lower in the N2O group than in the air group (49.5 ±â€Š24.7 vs 22.6 ±â€Š14.9, P < .001), whereas intraoperative anxiety and memory did not present significant differences between the groups (P = .09 and P = .45, respectively). Intraoperative nausea score was 0 for all cases in both groups. There was no other side effect.Ptosis surgery with anesthesia using 30% N2O may effectively suppress intraoperative BP and HR along with pain and shorten the operation time without side effects such as nausea.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Blefaroplastia/métodos , Blefaroptose/cirurgia , Óxido Nitroso/administração & dosagem , Óxido Nitroso/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Ansiedade/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Período Intraoperatório , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Duração da Cirurgia , Manejo da Dor , Estudos Retrospectivos , Sinais Vitais
4.
Medicine (Baltimore) ; 100(6): e23570, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578509

RESUMO

ABSTRACT: The Gas Man simulation software provides an opportunity to teach, understand and examine the pharmacokinetics of volatile anesthetics. The primary aim of this study was to investigate the accuracy of a cardiac output and alveolar ventilation matched Gas Man model and to compare its predictive performance with the standard pharmacokinetic model using patient data.Therefore, patient data from volatile anesthesia were successively compared to simulated administration of desflurane and sevoflurane for the standard and a parameter-matched simulation model with modified alveolar ventilation and cardiac output. We calculated the root-mean-square deviation (RMSD) between measured and calculated induction, maintenance and elimination and the expiratory decrement times during emergence and recovery for the standard and the parameter-matched model.During induction, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [induction (desflurane), standard: 1.8 (0.4) % Atm, parameter-matched: 0.9 (0.5) % Atm., P = .001; induction (sevoflurane), standard: 1.2 (0.9) % Atm, parameter-matched: 0.4 (0.4) % Atm, P = .029]. During elimination, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [elimination (desflurane), standard: 0.7 (0.6) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .001; elimination (sevoflurane), standard: 0.7 (0.5) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .008]. The RMSDs during the maintenance of anesthesia and the expiratory decrement times during emergence and recovery showed no significant differences between the patient and simulated data for both simulation models.Gas Man simulation software predicts expiratory concentrations of desflurane and sevoflurane in humans with good accuracy, especially when compared to models for intravenous anesthetics. Enhancing the standard model by ventilation and hemodynamic input variables increases the predictive performance of the simulation model. In most patients and clinical scenarios, the predictive performance of the standard Gas Man simulation model will be high enough to estimate pharmacokinetics of desflurane and sevoflurane with appropriate accuracy.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Desflurano/farmacocinética , Expiração/fisiologia , Ventilação Pulmonar/fisiologia , Sevoflurano/farmacocinética , Adulto , Idoso , Algoritmos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacocinética , Débito Cardíaco/fisiologia , Ensaios Clínicos como Assunto , Simulação por Computador/estatística & dados numéricos , Desflurano/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Pulmão/metabolismo , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/fisiologia , Sevoflurano/administração & dosagem
5.
Magn Reson Imaging ; 75: 134-140, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33127411

RESUMO

OBJECTIVE: Alfaxalone has been used increasingly in biomedical research and veterinary medicine of large animals in recent years. However, its effects on the cerebral blood flow (CBF) physiology and intrinsic neuronal activity of anesthetized brains remain poorly understood. METHODS: Four healthy adult rhesus monkeys were anesthetized initially with alfaxalone (0.125 mg/kg/min) or ketamine (1.6 mg/kg/min) for 50 min, then administrated with 0.8% isoflurane for 60 min. Heart rates, breathing beats, and blood pressures were continuously monitored. CBF data were collected using pseudo-continuous arterial spin-labeling (pCASL) MRI technique and rsfMRI data were collected using single-shot EPI sequence for each anesthetic. RESULTS: Both the heart rates and mean arterial pressure (MAP) remained more stable during alfaxalone infusion than those during ketamine administration. Alfaxalone reduced CBF substantially compared to ketamine anesthesia (grey matter, 65 ± 22 vs. 179 ± 38 ml/100g/min, p<0.001; white matter, 14 ± 7 vs. 26 ± 6 ml/100g/min, p < 0.05); In addition, CBF increase was seen in all selected cortical and subcortical regions of alfaxalone-pretreated monkey brains during isoflurane exposure, very different from the findings in isoflurane-exposed monkeys pretreated with ketamine. Also, alfaxalone showed suppression effects on functional connectivity of the monkey brain similar to ketamine. CONCLUSION: Alfaxalone showed strong suppression effects on CBF of the monkey brain.The residual effect of alfaxalone on CBF of isoflurane-exposed brains was evident and monotonous in all the examined brain regions when used as induction agent for inhalational anesthesia. In particular, alfaxalone showed similar suppression effect on intrinsic neuronal activity of the brain in comparison with ketamine. These findings suggest alfaxalone can be a good alternative to veterinary anesthesia in neuroimaging examination of large animal models. However, its effects on CBF and functional connectivity should be considered.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Ketamina/farmacologia , Pregnanodionas/farmacologia , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Encéfalo/irrigação sanguínea , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/administração & dosagem , Isoflurano/farmacologia , Macaca mulatta , Masculino , Pregnanodionas/administração & dosagem
6.
BMJ Open ; 10(12): e039881, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323432

RESUMO

OBJECTIVES: We compared early recovery outcomes between living kidney donors who received total intravenous (IV) propofol versus inhalational desflurane during hand-assisted laparoscopic nephrectomy. DESIGN: A single-centre, prospective randomised controlled trial. SETTING: University hospital. PARTICIPANTS: Study participants were enrolled between October 2019 and February 2020. A total of 80 living donors were randomly assigned to an intravenous propofol group (n=40) or a desflurane group (n=40). INTERVENTION: Propofol group received intravenous propofol and desflurane group received desflurane, as a maintenance anaesthetic. PRIMARY AND SECONDARY OUTCOME MEASURES: The quality of postoperative functional recovery was primarily assessed using the Korean version of the Quality of Recovery-40 (QoR-40K) questionnaire on postoperative day 1. Secondarily, ambulation, pain score, rescue analgesics, complications and total hospital stay were assessed postoperatively. RESULTS: Our study population included 35 males and 45 females. The mean age was 46±13 years. The global QoR-40K score (161 (154-173) vs 152 (136-161) points, respectively, p=0.001) and all five subdimension scores (physical comfort, 49 (45-53) vs 45 (42-48) points, respectively, p=0.003; emotional state, 39 (37-41) vs 37 (33-41) points, respectively, p=0.005; psychological support, 30 (26-34) vs 28 (26-32) points, respectively, p=0.04; physical independence, 16 (11-18) vs 12 (8-14) points, respectively, p=0.004; and pain, 31 (28-33) vs 29 (25-31) points, respectively, p=0.021) were significantly higher in the intravenous propofol group than the desflurane group. The early ambulation success rate and numbers of early and total steps were higher, but the incidence of nausea/vomiting was lower, in the intravenous propofol group than the desflurane group. The total hospital stay after surgery was shorter in the intravenous propofol group than the desflurane group. CONCLUSIONS: Intravenous propofol may enhance the quality of postoperative recovery in comparison to desflurane in living kidney donors. TRIAL REGISTRATION NUMBER: KCT0004365.


Assuntos
Anestésicos Inalatórios , Desflurano , Laparoscopia Assistida com a Mão , Rim , Propofol , Doadores de Tecidos , Anestesia Intravenosa , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Desflurano/administração & dosagem , Feminino , Humanos , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Propofol/administração & dosagem , Estudos Prospectivos
7.
Anesthesiology ; 133(4): 824-838, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773689

RESUMO

BACKGROUND: Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. METHODS: The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. RESULTS: Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel-mediated holding currents and conductance from -75.0 ± 12.9 to -130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel-mediated holding conductance. CONCLUSIONS: Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Canais Iônicos/agonistas , Proteínas de Membrana/agonistas , Neurônios/efeitos dos fármacos , Respiração/efeitos dos fármacos , Complexo Olivar Superior/efeitos dos fármacos , Animais , Feminino , Canais Iônicos/fisiologia , Masculino , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Canais de Sódio/fisiologia , Complexo Olivar Superior/fisiologia
8.
Br J Anaesth ; 125(6): 995-1001, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32861507

RESUMO

BACKGROUND: Malignant hyperthermia (MH) susceptibility is an inherited condition, diagnosed either by the presence of a pathogenic genetic variant or by in vitro caffeine-halothane contracture testing. Through a multi-dimensional approach, we describe the implications of discordance between genetic and in vitro test results in a patient with a family history of possible MH. METHODS: The patient, whose brother had a possible MH reaction, underwent the caffeine-halothane contracture test (CHCT) according to the North American MH Group protocol. Screening of the complete RYR1 and CACNA1S transcripts was done using Sanger sequencing. Additional functional analyses included skinned myofibre calcium-induced calcium release sensitivity, calcium signalling assays in cultured myotubes, and in silico evaluation of the effect of any genetic variants on their chemical environment. RESULTS: The patient's CHCT result was negative but she carried an RYR1 variant c.1209C>G, p.Ile403Met, that is listed as pathogenic by the European Malignant Hyperthermia Group. Functional tests indicated a gain-of-function effect with a weak impact, and the variant was predicted to affect the folding stability of the 3D structure of the RyR1 protein. Based on American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines, this variant would be characterised as a variant of uncertain significance. CONCLUSIONS: Available data do not confirm or exclude an increased risk of MH for this patient. Further research is needed to correlate RyR1 functional assays, including the current gold standard testing for MH susceptibility, with clinical phenotypes. The pathogenicity of genetic variants associated with MH susceptibility should be re-evaluated.


Assuntos
Genótipo , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/genética , Mutação/genética , Fenótipo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adulto , Anestésicos Inalatórios/administração & dosagem , Cafeína/administração & dosagem , Feminino , Halotano/administração & dosagem , Humanos , Reprodutibilidade dos Testes
9.
J Vis Exp ; (161)2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32716388

RESUMO

Low-flow digital vaporizers commonly utilize a syringe pump to directly administer volatile anesthetics into a stream of carrier gas. Per animal welfare recommendations, animals are warmed and monitored during procedures requiring anesthesia. Common anesthesia and physiological monitoring equipment include gas tanks, anesthetic vaporizers and stands, warming controllers and pads, mechanical ventilators, and pulse oximeters. A computer is also necessary for data collection and to run equipment software. In smaller spaces or when performing field work, it can be challenging to configure all this equipment in limited space. The goal of this protocol is to demonstrate best practices for use of a low-flow digital vaporizer using both compressed oxygen and room air, along with an integrated mechanical ventilator, pulse oximeter, and far infrared warming as an all-inclusive anesthesia and physiological monitoring suite ideal for rodents.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos/administração & dosagem , Monitorização Fisiológica/instrumentação , Nebulizadores e Vaporizadores , Ventiladores Mecânicos , Animais , Oxigênio/administração & dosagem , Roedores
10.
Curr Opin Anaesthesiol ; 33(4): 577-583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628406

RESUMO

PURPOSE OF REVIEW: Pollution and global warming/climate change contribute to one-quarter of all deaths worldwide. Global healthcare as a whole is the world's fifth largest emitter of greenhouse gases, and anesthetic gases, intravenous agents and supplies contribute significantly to the overall problem. It is the ethical obligation of all anesthesiologists to minimize the harmful impact of anesthesia practice on environmental sustainability. RECENT FINDINGS: Focused programs encouraging judicious selection of the use of anesthetic gas agents has been shown to reduce CO2 equivalent emissions by 64%, with significant cost savings. Good gas flow management reduces nonscavenged anesthetic gas significantly, and has been shown to decrease the consumption of volatile anesthetic agent by about one-fifth. New devices may allow for recapture, reclamation and recycling of waste anesthetic gases. For propofol, a nonbiodegradable, environmentally toxic agent, simply changing the size of vials on formulary has been shown to reduce wasted agent by 90%. SUMMARY: The 5 R's of waste minimization in the operating room (OR) (Reduce, Reuse, Recycle, Rethink and Research) have proven benefit in reducing the environmental impact of the practice of anesthesiology, as well as in reducing costs.


Assuntos
Anestesiologistas/ética , Anestesiologia/ética , Anestésicos Inalatórios/efeitos adversos , Mudança Climática , Poluição do Ar/prevenção & controle , Anestésicos Inalatórios/administração & dosagem , Efeito Estufa , Humanos , Salas Cirúrgicas
11.
Medicine (Baltimore) ; 99(25): e20714, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569207

RESUMO

Surgical management of cancer may induce stress and increase the likelihood of cancer metastasis and recurrence. Appropriate surgical and anesthetic techniques may affect the patient's outcome. Although numerous studies have been performed, conflicting results have been obtained regarding the effect of anesthetic techniques on the outcome of patients with cancer. We conducted this study to evaluate the association of anesthetic techniques with overall and recurrence-free survival in patients who had undergone gastric cancer surgery.This retrospective study reviewed the electronic medical records of patients, who had visited our hospital and had been diagnosed with gastric cancer between July 1st, 2006 to June 30th, 2016. Univariate analysis of the potential prognostic factors was performed using the log-rank test for categorical factors, and parameters with a P-value < .05 at the univariate step were included in the multivariate regression analysis. Propensity Score Matching was performed to account for differences in baseline characteristics: propofol or desflurane, in a 1:1 ratio.A total of 408 patients anesthetized with desflurane (218) and propofol (190) were eligible for analysis. After propensity matching, 167 patients remained in each group. The overall mortality rate was significantly higher in the desflurane group (56%) than in the propofol group (34%) during follow-up (P < .001). In addition, a greater percentage of patients in the desflurane group (41%) exhibited postoperative metastasis than those in the propofol group (19%, P < .001).The authors found some association between types of anesthesia used and the long-term prognosis of gastric cancer. Propofol-based total intravenous anesthesia improved survival and reduced the risk of recurrence and metastasis during the 5-year follow-up period after gastric cancer surgery.


Assuntos
Anestesia Intravenosa/métodos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Desflurano/administração & dosagem , Propofol/administração & dosagem , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
12.
Intensive Care Med ; 46(8): 1563-1566, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32588067

RESUMO

Hospitals worldwide are experiencing a shortage in essential intravenous sedative medications. This is attributable to high number and high sedative needs of COVID-19 critical care patients with disruption of drug supply chains. Inhaled volatile anesthetic agents are an abundant resource and readily implementable solution for providing ICU sedation. Inhaled volatile agents may also provide important pulmonary benefits for COVID-19 patients with ARDS that could improve gas exchange and reduce time spent on a ventilator. We review the use of volatile agents, and provide a technical overview and algorithm for administering inhaled volatile-based sedation in ICUs.


Assuntos
Anestésicos Inalatórios , Betacoronavirus , Infecções por Coronavirus/complicações , Hipnóticos e Sedativos/administração & dosagem , Pneumonia Viral/terapia , /terapia , Algoritmos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/provisão & distribução , Humanos , Isoflurano , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/etiologia , Sevoflurano/efeitos adversos
14.
Proc Natl Acad Sci U S A ; 117(24): 13757-13766, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32467161

RESUMO

Inhaled anesthetics are a chemically diverse collection of hydrophobic molecules that robustly activate TWIK-related K+ channels (TREK-1) and reversibly induce loss of consciousness. For 100 y, anesthetics were speculated to target cellular membranes, yet no plausible mechanism emerged to explain a membrane effect on ion channels. Here we show that inhaled anesthetics (chloroform and isoflurane) activate TREK-1 through disruption of phospholipase D2 (PLD2) localization to lipid rafts and subsequent production of signaling lipid phosphatidic acid (PA). Catalytically dead PLD2 robustly blocks anesthetic TREK-1 currents in whole-cell patch-clamp recordings. Localization of PLD2 renders the TRAAK channel sensitive, a channel that is otherwise anesthetic insensitive. General anesthetics, such as chloroform, isoflurane, diethyl ether, xenon, and propofol, disrupt lipid rafts and activate PLD2. In the whole brain of flies, anesthesia disrupts rafts and PLDnull flies resist anesthesia. Our results establish a membrane-mediated target of inhaled anesthesia and suggest PA helps set thresholds of anesthetic sensitivity in vivo.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/metabolismo , Clorofórmio/administração & dosagem , Drosophila/efeitos dos fármacos , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Isoflurano/administração & dosagem , Ácidos Fosfatídicos/metabolismo , Fosfolipase D/genética , Fosfolipase D/metabolismo , Canais de Potássio/genética , Canais de Potássio/metabolismo , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo
15.
Medicine (Baltimore) ; 99(16): e19733, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311965

RESUMO

RATIONALE: Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are progressive neuromuscular disorders caused by mutations in the dystrophin gene. The management of anesthesia in patients with BMD is complicated because they are highly sensitive to the conventional anesthetics such as volatile anesthetics and muscle relaxants. It is reported that anesthesia in patients with DMD is associated with several complications. However, a few case reports have been published on adult patients with BMD undergoing surgery with general anesthesia. Reports indicate that children with BMD may experience some serious complications with flurane-inhaled anesthesia. However, no study has yet shown that the use of flurane-induced anesthesia in adults with DMD carries high risks. PATIENT CONCERNS: We describe a 56-year-old woman with BMD who was scheduled for laparoscopic hysterectomy and bilateral adnexectomy under general anesthesia due to a mass in the uterus. The patient was diagnosed with BMD 20 years back and reported that during this period, she was able to walk slowly with help during her daily life. Additionally, she also had a history of hypertension since 4 years and type 2 diabetes mellitus since 2 years. DIAGNOSIS: The patient was postmenopausal and presented with abnormal uterine bleeding and elevated CA125. Abdominal ultrasonography revealed diffuse enlargement of the uterus and hypoechoic internal echoes. These findings were suggestive of diffuse adenomyosis with multiple uterine leiomyomas, which would have adverse effects later in her life. Therefore, the patient required surgery to address the symptoms and further confirm the diagnosis. The final diagnosis was confirmed by histopathological analysis. INTERVENTIONS: The patient was scheduled for laparoscopic hysterectomy and bilateral adnexectomy. Anesthesia was induced and maintained by a combination of intravenous and inhalation anesthetic agents, particularly cisatracurium besilate and inhaled. sevoflurane. OUTCOMES: The duration of anesthesia and postoperative period were uneventful. At the end of the operation, the patient had normal vital signs and was fully conscious. The patient was followed up for 8 months and no complications were noted during this period. LESSONS: The combination of sevoflurane and cisatracurium besilate is a safe and effective method for the anesthetic management of adult patients with BMD scheduled for laparoscopic gynecological surgery. On the other hand, it is important to be aware of even rare complications of procedures, so that necessary precautions can be undertaken. Further investigations are necessary to determine the safe dosage of volatile anesthetics specifically for this clinical scenario so that anesthesiologists can use this combination method more accurately and precisely.


Assuntos
Anestesia Geral/métodos , Distrofia Muscular de Duchenne , Anestésicos Inalatórios/administração & dosagem , Atracúrio/administração & dosagem , Atracúrio/análogos & derivados , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Laparoscopia , Pessoa de Meia-Idade , Bloqueadores Neuromusculares/administração & dosagem , Sevoflurano/administração & dosagem
16.
J Neurosci ; 40(21): 4103-4115, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32327530

RESUMO

Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.SIGNIFICANCE STATEMENT Synaptic mechanisms of general anesthesia remain unidentified. In rat brainstem slices, isoflurane inhibits excitatory transmitter release by blocking presynaptic Ca2+ channels and exocytic machinery, with the latter mechanism predominating in its inhibitory effect on high-frequency transmission. Both in slice and in vivo, isoflurane preferentially inhibits spike transmission induced by high-frequency presynaptic inputs. This low-pass filtering action of isoflurane likely plays a significant role in general anesthesia.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Tronco Encefálico/efeitos dos fármacos , Isoflurano/administração & dosagem , Neurônios/efeitos dos fármacos , Terminações Pré-Sinápticas/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Exocitose/efeitos dos fármacos , Feminino , Masculino , Camundongos , Técnicas de Patch-Clamp , Ratos , Ratos Wistar
17.
PLoS One ; 15(4): e0231955, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302373

RESUMO

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs' brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Encéfalo/fisiologia , Sevoflurano/administração & dosagem , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Cães , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino
18.
PLoS One ; 15(4): e0231571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294125

RESUMO

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.


Assuntos
Dor Aguda/tratamento farmacológico , Anestésicos Inalatórios/administração & dosagem , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/organização & administração , Metoxiflurano/administração & dosagem , Terapias em Estudo/métodos , Ferimentos e Lesões/terapia , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Tomada de Decisão Clínica/métodos , Procedimentos Clínicos , Aglomeração , Tratamento de Emergência/métodos , França , Humanos , Tempo de Internação , Modelos Organizacionais , Avaliação de Processos e Resultados em Cuidados de Saúde , Manejo da Dor/métodos , Medição da Dor , Projetos Piloto , Autoadministração , Fatores de Tempo , Ferimentos e Lesões/complicações
19.
Life Sci ; 249: 117472, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112870

RESUMO

Aim Determine changes in the expressions of the ion channel-TRPV1-and neuropeptides-NKA, NKB, calcitonin gene-related peptide (CGRP), and SP-in 14-, 21-, and 42-day-old rats after inhaling 1.5% and 2.6% sevoflurane. MAIN METHODS: A small in-house inhalation anesthesia chamber was designed to allow 14-, 21-, and 42-day-old rats inhale 1.5% and 2.6% sevoflurane, and rats in the control group inhaled carrier gas(1 L/min air +1 L/min O2). In addition, 14- and 21-day-old rats were pretreated with capsazepine, followed by inhalation of 1.5% and 2.6% sevoflurane or the carrier gas. The expression of TRPV1 in lung tissues was detected by Western blotting, whereas the expressions of NKA, NKB, CGRP, and SP in the trachea were detected by immunohistochemistry. KEY FINDINGS: After inhalation of 1.5% sevoflurane, the expression of TRPV1 in the lung tissues of 14- and 21-day-old rats was significantly increased compared with that in the control group, which was antagonized by capsazepine pretreatment. Moreover, inhalation of 1.5% sevoflurane markedly increased the expressions of NKA, NKB, CGRP, and SP in the trachea of 21-day-old rats and of NKB, CGRP, and SP in the trachea of 14-day-old rats. The expressions of these molecules were antagonized by capsazepine pretreatment. Conversely, inhalation of 2.6% sevoflurane decreased the expressions of NKA and NKB in the trachea of 42-day-old rats. SIGNIFICANCE: Sevoflurane did not upregulate the expression of TRPV1 in the airways of late-developing rats. This anesthetic may have a two-way effect on airways, resulting in considerable effects in pediatric clinical anesthesia management.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Sevoflurano/administração & dosagem , Canais de Cátion TRPV/metabolismo , Traqueia/metabolismo , Administração por Inalação , Fatores Etários , Animais , Gasometria , Peso Corporal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Neurocinina A/metabolismo , Neurocinina B/metabolismo , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Substância P/metabolismo
20.
PLoS One ; 15(3): e0230290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182262

RESUMO

BACKGROUND: Previous researches have shown that anesthetic techniques may influence the patients' outcomes after cancer surgery. Here, we studied the relationship between the type of anesthetic techniques and patients' outcomes following elective robot-assisted radical prostatectomy. METHODS: This was a retrospective cohort study of patients who received elective, robot-assisted radical prostatectomy between January 2008 and December 2018. Patients were grouped according to the anesthesia they received, namely desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival curves were presented from the date of surgery to death. Univariable and multivariable Cox regression models were used to compare hazard ratios for death after propensity matching. Subgroup analyses were performed for tumor-node-metastasis stage and disease progression. The primary outcome was overall survival, and the secondary outcome was postoperative biochemical recurrence. RESULTS: A total of 365 patients (24 deaths, 7.0%) under desflurane anesthesia, and 266 patients (2 deaths, 1.0%) under propofol anesthesia were included. The all-cause mortality rate was significantly lower in the propofol anesthesia than in the desflurane anesthesia during follow-up (P = 0.001). Two hundred sixty-four patients remained in each group after propensity matching. The propofol anesthesia was associated with improved overall survival (hazard ratio, 0.11; 95% confidence interval, 0.03-0.48; P = 0.003) in the matched analysis. Subgroup analyses showed that patients under propofol anesthesia had less postoperative biochemical recurrence than those under desflurane (hazard ratio, 0.20; 95% confidence interval, 0.05-0.91; P = 0.038) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with improved overall survival in robot-assisted radical prostatectomy compared with desflurane anesthesia. In addition, patients under propofol anesthesia had less postoperative biochemical recurrence.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Desflurano/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Propofol/efeitos adversos , Prostatectomia/métodos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Desflurano/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Propofol/administração & dosagem , Prostatectomia/efeitos adversos , Robótica/métodos , Taxa de Sobrevida
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