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1.
J Adv Res ; 32: 27-36, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34484823

RESUMO

Introduction: In long-term induced general anesthesia cases such as those uniquely defined by the ongoing Covid-19 pandemic context, the clearance of hypnotic and analgesic drugs from the body follows anomalous diffusion with afferent drug trapping and escape rates in heterogeneous tissues. Evidence exists that drug molecules have a preference to accumulate in slow acting compartments such as muscle and fat mass volumes. Currently used patient dependent pharmacokinetic models do not take into account anomalous diffusion resulted from heterogeneous drug distribution in the body with time varying clearance rates. Objectives: This paper proposes a mathematical framework for drug trapping estimation in PK models for estimating optimal drug infusion rates to maintain long-term anesthesia in Covid-19 patients. We also propose a protocol for measuring and calibrating PK models, along with a methodology to minimize blood sample collection. Methods: We propose a framework enabling calibration of the models during the follow up of Covid-19 patients undergoing anesthesia during their treatment and recovery period in ICU. The proposed model can be easily updated with incoming information from clinical protocols on blood plasma drug concentration profiles. Already available pharmacokinetic and pharmacodynamic models can be then calibrated based on blood plasma concentration measurements. Results: The proposed calibration methodology allow to minimize risk for potential over-dosing as clearance rates are updated based on direct measurements from the patient. Conclusions: The proposed methodology will reduce the adverse effects related to over-dosing, which allow further increase of the success rate during the recovery period.


Assuntos
Anestesia , COVID-19 , Hipnóticos e Sedativos , Modelos Biológicos , SARS-CoV-2 , Idoso , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Pandemias
2.
Cochrane Database Syst Rev ; 8: CD011786, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397100

RESUMO

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence). AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.


Assuntos
Hidrato de Cloral/administração & dosagem , Técnicas de Diagnóstico Neurológico , Hipnóticos e Sedativos/administração & dosagem , Criança , Hidrato de Cloral/efeitos adversos , Humanos , Hidroxizina/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Pentobarbital/administração & dosagem
3.
Medicine (Baltimore) ; 100(29): e26576, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398011

RESUMO

BACKGROUND: Deep neuromuscular blockade is considered beneficial for improving the surgical space condition during laparoscopic surgery. Adequacy of the surgical space condition may affect the anesthetists' decision regarding titration of depth of anesthesia. We investigated whether deep neuromuscular blockade reduces the propofol requirement under bispectral index monitoring compared to moderate neuromuscular blockade. METHODS: Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to a moderate or deep group. A train-of-four count of 1-2 in the moderate group, and a post-tetanic count of 1-2 in the deep group, were maintained by continuous infusion of rocuronium. The induction and maintenance of anesthesia were achieved by target-controlled infusion of propofol and remifentanil. The dose of propofol was adjusted to maintain the bispectral index in the range of 40-50. The remifentanil dose was titrated to maintain the systolic blood pressure to within 20% of the ward values. RESULTS: A total of 82 patients were included in the analyses. The mean±SD dose of propofol was 7.54 ±â€Š1.66 and 7.42 ±â€Š1.01 mg·kg-1·h-1 in the moderate and deep groups, respectively (P = .104). The mean±SD dose of remifentanil was 4.84 ±â€Š1.74 and 4.79 ±â€Š1.77 µg kg-1 h-1 in the moderate and deep groups, respectively (P = .688). In comparison to the moderate group, the deep group showed significantly lower rates of intraoperative patient movement (42.9% vs 22.5%, respectively, P = .050) and additional neuromuscular blocking agent administration (76% vs 53%, respectively, P = .007). Postoperative complications, including pulmonary complications, wound problems and reoperation, were not different between the two groups. CONCLUSION: Deep neuromuscular blockade did not reduce the bispectral index-guided propofol requirement compared to moderate neuromuscular blockade during laparoscopic colon surgery, despite reducing movement of the patient and the requirement for a rescue neuromuscular blocking agent. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03890406).


Assuntos
Monitores de Consciência/normas , Monitoração Neuromuscular/normas , Propofol/administração & dosagem , Adulto , Idoso , Monitores de Consciência/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Bloqueio Neuromuscular/classificação , Bloqueio Neuromuscular/métodos , Monitoração Neuromuscular/métodos , Propofol/uso terapêutico , Estudos Prospectivos , República da Coreia , Estatísticas não Paramétricas
4.
Int J Mol Sci ; 22(13)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34281255

RESUMO

Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell's K+ currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 µM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 µM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of IK(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.


Assuntos
Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores , Midazolam/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Animais , Citocinas/metabolismo , Canais de Potássio de Retificação Tardia/metabolismo , Relação Dose-Resposta a Droga , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Células Jurkat , Cinética , Lipopolissacarídeos/farmacologia , Ativação Linfocitária , Microscopia Confocal , Midazolam/administração & dosagem , Técnicas de Patch-Clamp , Fito-Hemaglutininas/farmacologia , Linfócitos T/imunologia
5.
Emerg Med Clin North Am ; 39(3): 677-687, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215409

RESUMO

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.


Assuntos
Drogas Desenhadas/efeitos adversos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Canabinoides/efeitos adversos , Drogas Desenhadas/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Loperamida/administração & dosagem , Loperamida/efeitos adversos , Mitragyna/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Fenetilaminas/efeitos adversos
6.
Br J Anaesth ; 127(3): 415-423, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34246461

RESUMO

BACKGROUND: Remimazolam is a new benzodiazepine for procedural sedation and general anaesthesia. The aim of this study was to characterise its pharmacokinetic properties and safety in renally and hepatically impaired subjects. METHODS: Two separate trials were conducted in patients with hepatic (n=11) or renal impairment (n=11) compared with matched healthy subjects (n=9 and n=12, respectively). The hepatic impairment trial was an open-label adaptive 'Reduced Design' trial, using a single bolus of remimazolam 0.1 mg kg-1 i.v., whereas the renal impairment trial was an open-label trial of a single bolus dose of remimazolam 1.5 mg i.v. Remimazolam plasma concentrations over time were analysed by population pharmacokinetic modelling. RESULTS: Remimazolam pharmacokinetic properties were adequately described by a three-compartment, recirculatory model. Exposure in subjects with severe hepatic impairment was 38.1% higher (i.e. clearance was 38.1% lower) compared with healthy volunteers. This increase caused a slightly delayed recovery (8.0 min for healthy, 12.1 min for moderate, and 16.7 min for severe hepatic impairment). With renal impairment, plasma clearance was comparable with that measured in healthy subjects. Simulations of Cmax after a bolus dose of 10 mg showed no relevant impact of hepatic or renal impairment. The overall incidence of adverse events was low, and all adverse events were mild. CONCLUSIONS: As Cmax after a remimazolam bolus i.v. was not affected by hepatic or renal impairment, no dose adjustments are required. No unexpected adverse events related to remimazolam were seen in subjects with renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: Hepatic impairment trial: ClinicalTrials.gov, NCT01790607 (https://clinicaltrials.gov/ct2/show/NCT01790607). Renal impairment trial: EudraCT Number: 2014-004575-23.


Assuntos
Benzodiazepinas/farmacocinética , Taxa de Filtração Glomerular , Hipnóticos e Sedativos/farmacocinética , Nefropatias/fisiopatologia , Rim/fisiopatologia , Hepatopatias/fisiopatologia , Fígado/fisiopatologia , Adulto , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/sangue , Simulação por Computador , Monitoramento de Medicamentos , Feminino , Humanos , Hungria , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/sangue , Injeções Intravenosas , Nefropatias/diagnóstico , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos
7.
Forensic Sci Int ; 325: 110881, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34237583

RESUMO

In order to obtain fundamental information on the disposition of hypnotics into hair after a single oral dose the quantitative hair analysis of triazolam (TZ), etizolam (EZ), flunitrazepam (FNZ), nitrazepam (NZ) and zolpidem (ZP) have been performed using a validated LC-MS/MS procedure. Hair specimens (straight, black) were collected from three subjects about one month and three months after a single 0.25 mg dose of TZ, 1 mg of EZ, 2 mg of FNZ, 5 mg of NZ and 10 mg of ZP tartrate. The subjects ingested just one out of five different hypnotics on each day, each of five days in turn. All ingested hypnotics have been detected in hair from each subject both one month and three months after intake, and their concentrations were in the range of 0.023-0.043 pg/hair strand (0.077-0.36 pg/mg) for TZ, 0.11-0.63 pg/hair strand (0.44-5.2 pg/mg) for EZ, 0.14-2.6 pg/hair strand (0.56-22 pg/mg) for FNZ, 0.33-1.7 pg/hair strand (1.3-17 pg/mg) for NZ and 20-40 pg/hair strand (120-270 pg/mg) for ZP. For FNZ and NZ, not only the parent drugs but also their metabolites, 7-amino-FNZ and 7-amino-NZ, were detected in the range of 2.3-9.2 pg/hair strand (9.2-82 pg/mg) and 2.4-9.1 pg/hair strand (8.0-55 pg/mg), respectively. The calculated incorporation ratios into hair against the dose were found to exhibit similarity between the four benzodiazepines. This finding suggests the ability to apply these quantitative data to approximately estimating the amounts of other benzodiazepines, which have similar chemical structures, in hair although it should be noted that the amounts of drugs in hair varies considerably depending on the hair color. On the other hand, the incorporation ratio of ZP showed 15-29 times higher than that of TZ, indicating that lipophilic ZP was more likely to incorporate into hair than benzodiazepines. In addition, the application of the present data to a drug-facilitated sexual assault was shown.


Assuntos
Cabelo/química , Hipnóticos e Sedativos/análise , Adulto , Grupo com Ancestrais do Continente Asiático , Cromatografia Líquida , Crime , Diazepam/administração & dosagem , Diazepam/análogos & derivados , Diazepam/análise , Feminino , Flunitrazepam/administração & dosagem , Flunitrazepam/análise , Toxicologia Forense , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Espectrometria de Massas , Nitrazepam/administração & dosagem , Nitrazepam/análise , Detecção do Abuso de Substâncias , Triazolam/administração & dosagem , Triazolam/análise , Zolpidem/administração & dosagem , Zolpidem/análise
8.
J Zoo Wildl Med ; 52(2): 715-720, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130416

RESUMO

Fifty-three free-ranging moose (Alces americanus) cows were darted from a helicopter with 3-4 ml of a premix combination of butorphanol (27.3 mg/ml), azaperone (9.1 mg/ml), and medetomidine (10.9 mg/ml; BAM), equivalent to estimated dosages of: butorphanol 0.26 ± 0.08 (mean ± SD) mg/kg, azaperone 0.09 ± 0.03 mg/kg, and medetomidine 0.11 ± 0.03 mg/kg. After a mean chase time (from sighting to darting) of 6.1 ± 5.5 min, the mean induction time (from darting to recumbency) was 8.3 ± 2.6 min. This combination provided a safe and reliable sedation for minor procedures that lasted 30-60 min. Heart rate (50.4 ± 7.0 beats/min), respiratory rate (21.3 ± 11.1 breaths/minute), ETCO2 via nasal canula (43.2 ± 7.0 mmHg), and rectal temperature (38.5°C ± 0.7°C) mostly remained at expected values for wild cervid and bovid species anesthetized with this drug combination. SpO2 (90.0% ± 3.7%) was suggestive of moderate hypoxemia despite intranasal oxygen supplementation (1 L per 100 kg/min). The recovery time to standing was 6.7 ± 3.8 min after reversal with IM naltrexone (3 mg/mg butorphanol) and atipamezole (5 mg/mg medetomidine). Despite a larger volume to inject, this protocol offers an alternative to highly potent opioids, and should be considered for practical or staff safety reasons. On the basis of the results of this study, the use of 4 ml of BAM is considered a safe and effective protocol for immobilization of cow moose under comparable settings.


Assuntos
Azaperona/farmacologia , Butorfanol/farmacologia , Cervos , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestesia/veterinária , Animais , Animais Selvagens , Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Medetomidina/administração & dosagem
9.
J Zoo Wildl Med ; 52(2): 445-452, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130386

RESUMO

Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO2, oxygen saturation (SpO2), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO2, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia.


Assuntos
Injeções Intramusculares/veterinária , Medetomidina/farmacologia , Pan troglodytes , Tiletamina/farmacologia , Zolazepam/farmacologia , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Combinação de Medicamentos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares/métodos , Masculino , Medetomidina/administração & dosagem , Midazolam/farmacologia , Tiletamina/administração & dosagem , Zolazepam/administração & dosagem
10.
J Zoo Wildl Med ; 52(2): 453-459, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130387

RESUMO

Przewalski's horses (Equus ferus przewalskii) are an endangered equid species. Anesthesia administered by remote delivery is often needed to provide medical care. Behavioral and physiologic parameters were prospectively compared in 14 horses (8 females and 6 males, 3-18 yr) after a single-dart or staged two-dart anesthesia induction protocol with intramuscular medetomidine (0.06 mg/kg), butorphanol (0.05 mg/kg), thiafentanil (0.02 mg/kg), and ketamine (1 mg/kg). Seven horses were randomly assigned to receive all drugs in a single dart, and the other seven to receive medetomidine and butorphanol 10 min prior to thiafentanil and ketamine in a second dart. Induction and recovery quality were scored on a scale from 1 to 5 (worst to best), and video recordings were assessed for frequency of specific behaviors. Need for supplemental propofol was recorded. Median induction score was significantly better (P = 0.01) after two darts (4/5) compared to a single dart (3/5). Degree of muscle fasciculation (undesirable) during induction was significantly lower (P= 0.006) with the two-dart protocol. During the transition to recumbency, 71% versus 14% of horses transitioned headfirst (undesirable) after a single dart versus two darts, respectively (P= 0.07). Supplemental propofol administration was necessary in 43% of horses after two darts and in 100% of horses after a single dart (P= 0.10) to facilitate intubation and reach a working depth of anesthesia. Physiologic and recovery parameters were not significantly different between groups. Improved induction quality was observed clinically using a staged two-dart versus a single-dart protocol and should be considered when anesthetizing captive Przewalski's horses using this drug combination.


Assuntos
Analgésicos Opioides/farmacologia , Anestésicos/farmacologia , Cavalos , Hipnóticos e Sedativos/farmacologia , Analgésicos Opioides/administração & dosagem , Anestésicos/administração & dosagem , Animais , Animais de Zoológico , Esquema de Medicação , Feminino , Hipnóticos e Sedativos/administração & dosagem , Masculino
11.
J Zoo Wildl Med ; 52(2): 479-489, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130390

RESUMO

The effects of α-2 agonists on echocardiographic findings in great apes are not well documented, and knowledge of these effects would expand the understanding of cardiac examinations of chimpanzees under anesthesia with protocols using these drugs. Ten adult chimpanzees (Pan troglodytes), four males and six females, underwent echocardiographic examinations after anesthesia with dexmedetomidine, midazolam, and ketamine (phase 1). Four animals required isoflurane to achieve an adequate plane of anesthesia. Atipamezole was used to antagonize dexmedetomidine, and all remaining animals were placed on isoflurane (phase 2), and then a second echocardiogram was performed. Direct arterial blood pressure was monitored during the anesthetic event. Measurements and recordings were assessed for statistically significant differences between the two phases and sex. There were no significant differences between phases or sex for any two-dimensional echocardiographic measurement of systolic function, although interventricular septum thickness at end systole approached a significant decrease from phase 1 to phase 2 (P = 0.058) when sex was considered a between-subject factor. Left ventricular outflow tract (P = 0.017) and pulmonary artery (P = 0.028) velocities increased after reversal of the dexmedetomidine. Diastolic transmitral flow was consistent with grade 3 diastolic dysfunction (median early to late ventricular filling velocities (E/A) of 2.02, interquartile range [IQR], 1.53-2.13) with a nonsignificant decrease of E velocity and increase in A velocity and decreased E/A after reversal. Trace mitral and tricuspid regurgitation were common findings in the sample population. Arterial blood pressure significantly decreased between phase 1 and phase 2 (P < 0.01). All chimpanzees entered a hypotensive state (mean arterial pressure < 60 mm Hg) during phase 2. Although limited by the small number of chimpanzees, this study showed an increase in afterload, potential diastolic dysfunction, and a decrease in blood pressure after the antagonism of dexmedetomidine. Additional studies to further assess the effects of α-2 agonists in chimpanzees are warranted.


Assuntos
Anestesia/veterinária , Pressão Sanguínea/fisiologia , Dexmedetomidina/farmacologia , Ecocardiografia/veterinária , Imidazóis/farmacologia , Pan troglodytes , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Monitores de Pressão Arterial , Dexmedetomidina/administração & dosagem , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imidazóis/administração & dosagem , Isoflurano/administração & dosagem , Isoflurano/farmacologia , Masculino
12.
Medicine (Baltimore) ; 100(22): e25885, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087831

RESUMO

BACKGROUND: Long operation duration (>4 hours' anesthesia) of laparotomy in elderly patients would increase the risk of postoperative delirium (POD), which is characterized by acute cognitive dysfunction, changes in the level of consciousness, obvious attention disorder, emotional disorder, and sleep-waking cycle disorder. The occurrence of POD is closely related to the risk of death, and it will also seriously affect the cognitive function of patients, prolong postoperative hospital stays, and increase medical expenses. It is known that dexmetomidine could function in sedation, analgesia and anti-sympathetic effect, and it also could simulate the normal sleep state of human body, but there is still a lack of clinical study of dexmedetomidine on the incidence of POD in elderly patients undergoing long-term general anesthesia in laparotomy. METHODS: This is a single-center, double-blinded, randomized controlled study. With the approval of the Ethics Committee of Chongqing Shapingba District People's Hospital, participants who meet the requirements will be randomly divided into the treatment group (continuous infusion of dexmetomidine) and the control group (continuous infusion of 0.9% sodium chloride solution) in a ratio of 1:1. The incidence of delirium, cognitive function score, inflammatory factors, and adverse reactions will be evaluated after the operation. Finally, the data will be analyzed by SPSS 22.0. CONCLUSION: The results of this study will explore the efficacy and safety of dexmetomidine in reducing the incidence of postoperative delirium in elderly patients undergoing long-term general anesthesia in laparotomy. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/2GJY6.


Assuntos
Dexmedetomidina/uso terapêutico , Delírio do Despertar/prevenção & controle , Hipnóticos e Sedativos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Laparotomia/métodos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Projetos de Pesquisa
13.
Medicine (Baltimore) ; 100(22): e26199, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087890

RESUMO

ABSTRACT: Although dental treatment with sedation is performed increasingly in special needs patients, data on adding midazolam to intravenous propofol sedation are very limited for this group. The purpose of this study was to identify the factors and procedure time associated with the use of intravenous sedation with propofol alone or propofol combined with midazolam in dental patients with special needs.This was a retrospective data analysis. The sedation medications and relevant covariates, including demographic parameters, disability levels, oral health conditions, dental procedures, treatment time, and side effects, of 718 patients with special needs were collected between April 2013 and September 2014. The unfavorable side effects by sedation types were reported. Factors associated with procedure time and the sedation medications were assessed with multiple logistic regression analyses.Of 718 patients, 8 patients experienced unfavorable side effects (vomiting, sleepiness, or emotional disturbance) after the dental procedures; the rate was 0.6% in the 509 patients who received propofol only. In 209 patients who received propofol and midazolam, 2.4% experienced the side effects. Sedation time was associated with body mass index (BMI) < 25 (adjusted odds ratio [aOR] = 1.45, 95% confidence interval [CI]: 1.04-2.04) and the performance of multiple dental procedures (aOR = 1.44, 95% CI: 1.06-1.97) but not associated with the sedation types. A significant odds ratio for the combined use of propofol and midazolam was shown for adolescents (aOR = 2.22, 95% CI: 1.28-3.86), men (aOR = 2.05, 95% CI: 1.41-2.98), patients with cognitive impairment (aOR = 1.99, 95% CI: 1.21-3.29), and patients undergoing scaling procedures (aOR = 1.64, 95% CI: 1.13-2.39).With the acceptable side effects of the use of propofol alone and propofol combined with midazolam, multiple dental procedures increase the sedation time and the factors associated with the combined use of propofol and midazolam are younger age, male sex, recognition problems, and the type dental procedure in the dental treatment of patients with special needs.


Assuntos
Sedação Consciente/estatística & dados numéricos , Assistência Odontológica/normas , Midazolam/administração & dosagem , Propofol/administração & dosagem , Adjuvantes Anestésicos/administração & dosagem , Adjuvantes Anestésicos/efeitos adversos , Administração Intravenosa , Adolescente , Adulto , Sintomas Afetivos/induzido quimicamente , Criança , Disfunção Cognitiva/complicações , Sedação Consciente/efeitos adversos , Assistência Odontológica/estatística & dados numéricos , Raspagem Dentária/estatística & dados numéricos , Combinação de Medicamentos , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Propofol/efeitos adversos , Estudos Retrospectivos , Sonolência , Vômito/induzido quimicamente
14.
Medicine (Baltimore) ; 100(22): e26240, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087910

RESUMO

RATIONALE: There have been a few reports on the early rehabilitation of patients with coronavirus disease (COVID-19), and none on the effectiveness and adverse events of early mobilization for mechanical ventilation patients (other than COVID-19) during deep sedation. This report indicates that sitting without adverse events is possible in patients with severe COVID-19 pneumonia during deep sedation with muscle relaxation. PATIENT CONCERNS: A 65-year-old man with a history of diabetes mellitus, lacunar infarction, and Parkinson's disease was admitted to a local hospital for pneumonia due to COVID-19. After admission, the patient was managed on a ventilator under deep sedation with muscle relaxants and sedatives. Twelve days after admission, the patient was transferred to our hospital due to his worsening respiratory status. DIAGNOSIS: Pneumonia due to COVID-19 was diagnosed using a polymerase chain reaction-dependent method. INTERVENTIONS: The day following transfer, a physical therapist started passive range of motion training and sitting. OUTCOMES: The period spanning his initial rehabilitation to muscle relaxant medication interruption was 9 days, and he underwent 7 rehabilitation sessions. The patient was unable to sit during only one of the 7 sessions due to pre-rehabilitation hypoxemia. In 5 of the 6 sitting sessions, PaO2/FiO2 transiently decreased but recovered by the time of subsequent blood sampling. The patient's PaCO2 decreased during all sessions. His blood pressure did not drastically decrease in any sitting session, except the first. Sputum excretion via sputum suction increased during sitting, and peak inspiratory pressure did not change. LESSONS: The patient eventually died of pneumonia due to COVID-19. However, sitting during deep sedation with muscle relaxants did not cause any serious adverse events nor did it appear to cause obvious negative respiratory effects.


Assuntos
COVID-19/reabilitação , Sedação Profunda/métodos , Deambulação Precoce/métodos , Postura Sentada , Idoso , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Amplitude de Movimento Articular , Respiração Artificial , SARS-CoV-2
15.
Molecules ; 26(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063337

RESUMO

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.


Assuntos
Afeto/efeitos dos fármacos , Curcuma/química , Lobo Frontal/fisiologia , Alho/química , Litsea/química , Óleos Voláteis/administração & dosagem , Lobo Temporal/fisiologia , Administração por Inalação , Ondas Encefálicas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroencefalografia , Feminino , Lobo Frontal/efeitos dos fármacos , Alimento Funcional/análise , Alimento Funcional/economia , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia , Odorantes , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Descanso/fisiologia , Lobo Temporal/efeitos dos fármacos , Tailândia , Adulto Jovem
16.
Schweiz Arch Tierheilkd ; 163(6): 431-436, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34097637

RESUMO

INTRODUCTION: A mixed breed dog was anesthetized for diagnostic myelography to investigate acute onset neck pain. Instead of contrast medium, 444 µg/kg medetomidine were inadvertently injected into the cerebromedullaris cisterna owing to a human error. Severe bradycardia, undetectable peripheral pulse, respiratory arrest and loss of pupillary, palpebral and corneal reflexes were observed immediately after injection. Profound hypothermia developed and esophageal temperature, measured 20 minutes after medetomidine injection, was 33 °C. Atipamezole at 1 mg/kg im was administered, followed by a second dose of 0,5 mg/kg iv 20 minutes thereafter. In the meantime, cardiorespiratory parameters and body temperature were monitored, and supportive care that included manually assisted pulmonary ventilation, active warming, and administration of 5 µg/kg/min dopamine was initiated. The dog's clinical condition improved within one hour from the beginning of supportive care, at which time ocular reflexes and swallowing returned, spontaneous ventilation was deemed as adequate and the trachea could be extubated. The dog was discharged in good clinical conditions five days later. Human error and distraction led to a potentially life-threatening complication in the dog of this report and could have possibly been prevented with the use of checklists and with a clearer definition of roles and responsibilities of the personnel involved prior to commencing the clinical procedure. Profound cardiovascular, respiratory, and thermoregulatory depression caused by intracisternal injection of medetomidine responded to parenteral administration of its antagonist and supportive care.


Assuntos
Imidazóis/administração & dosagem , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Erros Médicos/veterinária , Mielografia/veterinária , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Cães , Hipnóticos e Sedativos/administração & dosagem , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(19): e25967, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106671

RESUMO

INTRODUCTION: Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders. PATIENT CONCERNS: An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels. DIAGNOSES: At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement. INTERVENTIONS: Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely. OUTCOMES: The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital. CONCLUSION: This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.


Assuntos
Catatonia/complicações , Catatonia/tratamento farmacológico , Hipnóticos e Sedativos/uso terapêutico , Propofol/uso terapêutico , Aspergilose Pulmonar/complicações , Fumarato de Quetiapina/uso terapêutico , Catatonia/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/diagnóstico , Propofol/administração & dosagem , Fumarato de Quetiapina/administração & dosagem , Insuficiência Renal/complicações , Esquizofrenia/complicações
18.
Br J Anaesth ; 127(1): 133-142, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33933271

RESUMO

BACKGROUND: We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. METHODS: This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min-1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min-1) or nasopharyngeal tube (5 L min-1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. RESULTS: In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, -23.4% [95% confidence interval (CI), -28.9 to -16.7]; P<0.001). Prolonged desaturation (>1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P<0.001). CONCLUSIONS: In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. CLINICAL TRIAL REGISTRATION: NCT03829293.


Assuntos
Cânula , Endoscopia Gastrointestinal/métodos , Hipnóticos e Sedativos/administração & dosagem , Hipóxia/etiologia , Hipóxia/prevenção & controle , Oxigenoterapia/métodos , Idoso , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipóxia/diagnóstico , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/instrumentação , Fatores de Risco , Método Simples-Cego
19.
Br J Anaesth ; 127(1): 41-55, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33965206

RESUMO

Anaesthesiologists and non-anaesthesiologist sedationists have a limited set of available i.v. hypnotics, further reduced by the withdrawal of thiopental in the USA and its near disappearance in Europe. Meanwhile, demand for sedation increases and new clinical groups are using what traditionally are anaesthesiologists' drugs. Improved understanding of the determinants of perioperative morbidity and mortality has spotlighted hypotension as a potent cause of patient harm, and practice must be adjusted to respect this. High-dose propofol sedation may be harmful, and a critical reappraisal of drug choices and doses is needed. The development of remimazolam, initially for procedural sedation, allows reconsideration of benzodiazepines as the hypnotic component of a general anaesthetic even if their characterisation as i.v. anaesthetics is questionable. Early data suggest that a combination of remimazolam and remifentanil can induce and maintain anaesthesia. Further work is needed to define use cases for this technique and to determine the impact on patient outcomes.


Assuntos
Benzodiazepinas/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Assistência Perioperatória/métodos , Humanos , Complicações Pós-Operatórias/prevenção & controle
20.
Best Pract Res Clin Anaesthesiol ; 35(2): 221-229, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34030806

RESUMO

Dexmedetomidine can be used for sedation and analgesia and has been approved for this use by the European Medicines Agency since 2017. It causes an arousable state of sedation, which is beneficial during neurosurgical procedures that require the patient to cooperate with neurological tests (i.e. tumor surgery or implantation of deep brain stimulators). During procedures where monitoring of somatosensory evoked potentials and/or motor evoked potentials is required, dexmedetomidine can be used as an adjunct to general anesthesia with GABAergic drugs to decrease the dose of the latter when these drugs impair the monitoring signals. The use of dexmedetomidine has also been associated with neuroprotective effects and a decreased incidence of delirium, but studies confirming these effects in the peri-operative (neuro-)surgical setting are lacking. Although dexmedetomidine does not cause respiratory depression, its hemodynamic effects are complex and careful patient selection, choice of dose, and monitoring must be performed.


Assuntos
Dexmedetomidina/administração & dosagem , Potencial Evocado Motor/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Procedimentos Neurocirúrgicos/métodos , Dexmedetomidina/efeitos adversos , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Humanos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/prevenção & controle
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