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1.
Can J Surg ; 67(3): E252-E260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38925858

RESUMO

BACKGROUND: Prescription opioid use places a considerable economic burden on health care systems. Older patients undergoing surgical procedures for painful conditions commonly receive opioids pre- and postoperatively, and are susceptible to adverse reactions. This study explores predictors of prolonged postoperative opioid use among older patients after lumbar spine surgery and the consequences in terms of health care utilization and costs. METHODS: We conducted a retrospective population-based cohort study using Ontario administrative data from older adults undergoing spine surgery between 2006 and 2017. Data were analyzed from 90 days preoperatively to 1 year after hospital discharge, with last postoperative opioid prescriptions stratified into 90-day increments. We used multivariable ordinal logistic regression to identify predictors of long-term opioid use and generalized linear modelling to examine resource utilization and health care costs (2021 Canadian dollars). RESULTS: Of 15 109 patients included, 40.8% received preoperative opioid prescriptions. Preoperative opioid use strongly predicted prolonged postoperative use (odds ratio [OR] 4.47, 95% confidence interval [CI] 4.16-4.79), with 48.3% of patients who received preoperative opioids continuing to use opioids for longer than 9 months, relative to 12.7% of those without preoperative use. Several other risk factors for prolonged use were identified. Patients receiving long-term postoperative opioids incurred greater health care costs relative to those with opioids prescribed for fewer than 90 days (OR 1.49, 95% CI 1.44-1.54). CONCLUSION: Among older adults undergoing spine surgery, preoperative opioid use was a strong predictor of prolonged postoperative use, which was associated with increased health care costs. These results form an important baseline for future studies evaluating strategies to reduce opioid use targeting older surgical populations.


Assuntos
Analgésicos Opioides , Vértebras Lombares , Dor Pós-Operatória , Humanos , Ontário , Analgésicos Opioides/uso terapêutico , Idoso , Masculino , Feminino , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Idoso de 80 Anos ou mais , Alta do Paciente/estatística & dados numéricos , Estudos de Coortes
2.
Can J Anaesth ; 69(8): 963-973, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35314993

RESUMO

PURPOSE: Postoperative opioid use may be associated with increased healthcare utilization and costs. We sought to examine the relationship between duration of postoperative opioid prescriptions and healthcare costs and resource utilization in senior patients following hip and knee replacement. METHODS: We conducted a historical cohort study evaluating postoperative opioid use and healthcare costs in patients over the age of 65 yr undergoing primary total hip or knee arthroplasty over a ten-year period from 1 April 2006 to 31 March 2016. The last follow-up date was 31 March 2017. We identified preoperative and postoperative opioid prescriptions, patient characteristics, and healthcare costs using deidentified Ontario administrative databases (Institute of Clinical Evaluative Sciences). Duration of postoperative opioid use was divided into four categories: short-term (1-90 days), prolonged (91-180 days), chronic (181-365 days), and undocumented. RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Although the initial hospitalization accounted for the greatest cost in all patients, over the following year patients in the short-term opioid use group incurred the lowest average costs, and those in the chronic group incurred the highest (hip, CAD 17,528 vs CAD 26,736; knee, CAD 16,043 vs CAD 23,007), driven by increased healthcare resource utilization. CONCLUSION: Chronic opioid use after arthroplasty was associated with higher resource utilization and healthcare costs during the year following surgery. These results can be used to develop predictors of longer opioid use and higher costs. Further research is planned to determine whether recently implemented opioid reduction strategies can reduce healthcare resource utilization.


RéSUMé: OBJECTIF: L'utilisation postopératoire d'opioïdes peut être associée à une augmentation de l'utilisation et des coûts des soins de santé. Nous avons cherché à examiner la relation entre la durée des ordonnances d'opioïdes postopératoires, les coûts des soins de santé et l'utilisation des ressources chez les patients âgés après une arthroplastie de la hanche et du genou. MéTHODE: Nous avons réalisé une étude de cohorte historique évaluant la consommation postopératoire d'opioïdes et les coûts des soins de santé chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans allant du 1er avril 2006 au 31 mars 2016. La dernière date de suivi était le 31 mars 2017. Nous avons identifié les ordonnances pré- et postopératoires d'opioïdes, les caractéristiques des patients et les coûts des soins de santé à l'aide de bases de données administratives de l'Ontario désidentifiées (ICES). La durée de la consommation d'opioïdes postopératoires était divisée en quatre catégories : à court terme (1 à 90 jours), prolongée (91 à 180 jours), chronique (181 à 365 jours) et non documentée. RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Bien que l'hospitalisation initiale ait représenté le coût le plus élevé chez tous les patients, au cours de l'année suivante, les patients du groupe de consommation d'opioïdes à court terme ont encouru les coûts moyens les plus bas et ceux du groupe chronique les coûts les plus élevés (hanche, 17 528 CAD vs 26 736 CAD; genou, 16 043 CAD vs 23 007 CAD) en raison de l'utilisation accrue des ressources de soins de santé. CONCLUSION: La consommation chronique d'opioïdes après une arthroplastie a été associée à une augmentation de l'utilisation des ressources et des coûts des soins de santé au cours de l'année suivant la chirurgie. Ces résultats peuvent être utilisés pour développer des modèles de prédiction d'une consommation prolongée d'opioïdes et de coûts plus élevés. D'autres recherches sont prévues pour déterminer si les stratégies de réduction de la consommation d'opioïdes récemment mises en œuvre pourront réduire l'utilisation des ressources en soins de santé.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Humanos , Dor Pós-Operatória/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos
3.
Can J Anaesth ; 69(8): 934-944, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34435322

RESUMO

PURPOSE: Canadian seniors who undergo hip and knee arthroplasty often experience significant postoperative pain, which could result in persistent opioid use. We aimed to document the impact of preoperative opioid use and other characteristics on postoperative opioid prescriptions in elderly patients following hip and knee replacement before widespread dissemination of opioid reduction strategies. METHODS: We conducted a historical cohort study to evaluate postoperative opioid use in patients over 65 yr undergoing primary total hip and knee replacement over a ten-year period from 1 April 2006 to 31 March 2016, using linked de-identified Ontario administrative data. We determined the use of preoperative opioids and the duration of postoperative opioid prescriptions (short-term [1-90 days], prolonged [91-180 days], chronic [181-365 days], or undocumented). RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Eighteen percent of hip and 21% of knee replacement patients received an opioid prescription within 90 days before surgery. Postoperatively, 51% of patients filled opioid prescriptions for 1-90 days, while 24% of hip and 29% of knee replacement patients filled prescriptions between 6 and 12 months, with no impact of preoperative opioid use. Residence in long-term care was a significant predictor of chronic opioid use (hip: odds ratio [OR], 2.64; 95% confidence interval [CI], 1.93 to 3.59; knee: OR, 2.46; 95% CI, 1.75 to 3.45); other risk factors included female sex and increased comorbidities. CONCLUSION: Despite a main goal of joint arthroplasty being relief of pain, seniors commonly remained on postoperative opioids, even if not receiving opioids before surgery. Opioid reduction strategies need to be implemented at the surgical, primary physician, long-term care, and patient levels. These findings form a basis for future investigations following implementation of opioid reduction approaches.


RéSUMé: OBJECTIF: Les aînés canadiens subissant une arthroplastie de la hanche ou du genou éprouvent souvent une douleur postopératoire importante, ce qui pourrait entraîner la consommation persistante d'opioïdes. Nous avons cherché à documenter l'impact d'une utilisation préopératoire d'opioïdes et d'autres caractéristiques sur les prescriptions postopératoires d'opioïdes chez les patients âgés suivant un remplacement de hanche ou de genou avant l'utilisation répandue de stratégies de réduction d'opioïdes. MéTHODE: Nous avons réalisé une étude de cohorte historique pour évaluer la consommation postopératoire d'opioïdes chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans du 1er avril 2006 au 31 mars 2016, à l'aide de données administratives dépersonnalisées et codées de l'Ontario. Nous avons déterminé la durée des ordonnances préopératoires et postopératoires d'opioïdes (à court terme [1-90 jours], prolongées [91-180 jours], chroniques [181-365 jours] ou non documentées). RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Dix-huit pour cent des patients ayant subi une arthroplastie de la hanche et 21 % des patients ayant subi une arthroplastie du genou ont reçu une ordonnance d'opioïdes dans les 90 jours précédant leur chirurgie. En période postopératoire, 51 % des patients ont utilisé leurs ordonnances d'opioïdes pendant 1 à 90 jours, tandis que 24 % des patients d'arthroplastie de la hanche et 29 % des patients d'arthroplastie du genou ont utilisé leurs ordonnances entre six et 12 mois. Le fait d'habiter dans un établissement de soins de longue durée était un prédicteur important de consommation chronique d'opioïdes (hanche : rapport de cotes [RC], 2,64; intervalle de confiance [IC] à 95 %, 1,93 à 3,59; genou : RC, 2,46; IC 95 %, 1,75 à 3,45); le sexe féminin et l'augmentation des comorbidités constituaient d'autres facteurs de risque. CONCLUSION: Bien que l'un des principaux objectifs de l'arthroplastie articulaire soit le soulagement de la douleur, les personnes âgées continuent généralement à consommer des opioïdes en période postopératoire, même si elles ne prenaient pas d'opioïdes avant leur chirurgie. Il est nécessaire de mettre en œuvre des stratégies de réduction des opioïdes qui s'adressent aux chirurgiens, aux médecins traitants, aux soins de longue durée et aux patients. Ces constatations constituent la base d'études futures réalisées à la suite de la mise en œuvre d'approches de réduction des opioïdes.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Transtornos Relacionados ao Uso de Opioides , Idoso , Analgésicos Opioides/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Ontário/epidemiologia , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
5.
Cardiovasc Ultrasound ; 13: 3, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25582221

RESUMO

BACKGROUND: Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. FINDINGS: We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. CONCLUSIONS: While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.


Assuntos
Aorta/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia Transesofagiana , Embolia Aérea/diagnóstico por imagem , Monitorização Intraoperatória/instrumentação , Software , Algoritmos , Embolia Aérea/etiologia , Humanos , Modelos Cardiovasculares
7.
Can J Anaesth ; 61(6): 543-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24844200

RESUMO

PURPOSE: To develop and validate a parent questionnaire to aid in predicting which children are likely to exhibit significant adverse behaviour at anesthetic induction. METHODS: Parents of 209 children, ages two to 13 yr, completed a brief questionnaire prior (13 items) to their child's anesthetic induction for surgery. The questionnaire included content drawn from both the literature and clinical experience. Results from the questionnaire were compared with the Induction Compliance Checklist (ICC), a validated tool to measure adverse behaviour at induction. Analyses assessing the correlation between each of the items and the total questionnaire score and between each item and the ICC score resulted in three items being removed from the questionnaire because they provided no predictive power. The association between the resulting ten-item parent questionnaire and the ICC was re-assessed using correlation. Hierarchical regression was used to evaluate the added value of our tool compared with the modified Yale Preoperative Anxiety Scale (mYPAS) in the prediction of ICC scores. RESULTS: The Cronbach's alpha reliability coefficient for the ten-item parent questionnaire was 0.73. The Pearson product-moment correlation between the ten-item questionnaire and the ICC was 0.34 (P < 0.001) for all children and 0.38 (P < 0.001) for children not preoperatively sedated. Values represent medium effect sizes for the new questionnaire's predictive power. The parent questionnaire provided added value relative to the mYPAS in terms of correlation with the ICC. CONCLUSION: Adverse behaviour at anesthesia induction is significantly predicted by our new parent questionnaire. Further refinement may improve predictive power beyond the observed medium effect size.


Assuntos
Anestesia/psicologia , Ansiedade/etiologia , Inquéritos e Questionários , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pais , Valor Preditivo dos Testes , Análise de Regressão
8.
Can J Anaesth ; 61(4): 340-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24452883

RESUMO

BACKGROUND: Ultrasound visualization of neck vessels is the standard method used to assist with internal jugular vein (IJV) central line placement. Nevertheless, this practice has not eliminated the risk of carotid puncture and/or inadvertent arterial cannulation. Transesophageal echocardiography (TEE) effectively verifies wire placement within the heart but is invasive and not always available. We examined the feasibility and potential utility of using transthoracic echocardiography (TTE) to verify the distal wire in the right atrium (RA) before dilation and cannulation of the IJV. METHODS: Following institutional Research Ethics Board approval and signed consent, 100 patients scheduled for elective cardiac surgery were recruited. As per standard practice at our institution, all patients were to have a central line inserted under general anesthesia with TEE visualization of the guidewire. Transesophageal echocardiography (apical or subcostal four-chamber images) was performed by one of four operators while another anesthesiologist performed central line placement. Following IJV puncture, blood was rapidly aspirated and reinjected to produce microbubbles. Subsequently, a 0.035-inch j-tipped flexible guidewire was inserted and visualized with TEE. The wire was then reinserted into the RA under TTE visualization. RESULTS: Overall, the RA was viewed 94% (95% confidence interval [CI] 87 to 98) of the time with TTE, and both the microbubbles and guidewire were detected 91% (95% CI 84 to 96) of the time. The subjects in whom the guidewire could not be well visualized had a higher mean body mass index (33.6 vs 28.8; P = 0.01). CONCLUSIONS: Transthoracic echocardiography [corrected] is a feasible, noninvasive, and potentially useful method to confirm appropriate placement of the guidewire before dilation and cannulation of the IJV.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cateterismo Venoso Central/métodos , Ecocardiografia Transesofagiana/métodos , Idoso , Anestesia Geral/métodos , Índice de Massa Corporal , Estudos de Viabilidade , Feminino , Átrios do Coração , Humanos , Veias Jugulares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
CJC Open ; 6(2Part A): 72-81, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38585676

RESUMO

Background: People living with frailty are vulnerable to poor outcomes and incur higher health care costs after coronary artery bypass graft (CABG) surgery. Frailty-defining instruments for population-level research in the CABG setting have not been established. The objectives of the study were to develop a preoperative frailty index for CABG (pFI-C) surgery using Ontario administrative data; assess pFI-C suitability in predicting clinical and economic outcomes; and compare pFI-C predictive capabilities with other indices. Methods: A retrospective cohort study was conducted using health administrative data of 50,682 CABG patients. The pFI-C comprised 27 frailty-related health deficits. Associations between index scores and mortality, resource use and health care costs (2022 Canadian dollars [CAD]) were assessed using multivariable regression models. Capabilities of the pFI-C in predicting mortality were evaluated using concordance statistics; goodness of fit of the models was assessed using Akakie Information Criterion. Results: As assessed by the pFI-C, 22% of the cohort lived with frailty. The pFI-C score was strongly associated with mortality per 10% increase (odds ratio [OR], 3.04; 95% confidence interval [CI], [2.83,3.27]), and was significantly associated with resource utilization and costs. The predictive performances of the pFI-C, Charlson, and Elixhauser indices and Johns Hopkins Aggregated Diagnostic Groups were similar, and mortality models containing the pFI-C had a concordance (C)-statistic of 0.784. Cost models containing the pFI-C showed the best fit. Conclusions: The pFI-C is predictive of mortality and associated with resource utilization and costs during the year following CABG. This index could aid in identifying a subgroup of high-risk CABG patients who could benefit from targeted perioperative health care interventions.


Contexte: Les personnes dont l'état de santé est fragilisé sont susceptibles de connaître des issues défavorables et de générer des coûts plus élevés pour le système de santé après un pontage aortocoronarien. Aucun instrument n'a été établi pour définir la fragilité dans la recherche populationnelle en contexte de pontage aortocoronarien. Les objectifs de l'étude étaient les suivants : 1) concevoir un indice de fragilité préopératoire en vue d'un pontage aortocoronarien (preoperative frailty index for CABG surgery, pFI-C) en utilisant des données administratives de l'Ontario; 2) évaluer la capacité de cet indice à prédire les issues cliniques et économiques; et 3) comparer la valeur prédictive de cet indice avec celle d'autres indices. Méthodologie: Une étude de cohorte rétrospective a été menée à partir de données médico-administratives portant sur 50 682 patients ayant subi un pontage aortocoronarien. Le pFI-C comprenait 27 déficits de santé liés à la fragilité. Des liens entre les scores de l'indice et la mortalité, l'utilisation des ressources et les coûts de soins de santé (en $ CA de 2022) ont été évalués à l'aide de modèles de régression multivariable. La capacité du pFI-C à prédire la mortalité a été évaluée à l'aide de la statistique de concordance; la qualité de l'ajustement des modèles a été évaluée en fonction du critère d'information d'Akaike. Résultats: Selon l'évaluation par le pFI-C, 22 % de la cohorte vivait avec une fragilité. Le score de l'indice était fortement corrélé à la mortalité par tranche d'augmentation de 10 % (rapport de cotes de 3,04; intervalle de confiance à 95 % de 2,83 à 3,27) et était corrélé de manière significative à l'utilisation des ressources et aux coûts. La valeur prédictive du pFI-C, des indices de Charlson et Elixhauser, et de Johns Hopkins Aggregated Diagnostic Groups était similaire, et les modèles de mortalité contenant le pFI-C affichaient une valeur statistique C de 0,784. Les modèles de coûts contenant le pFI-C affichaient le meilleur ajustement. Conclusions: Le pFI-C est un facteur prédictif de mortalité et est corrélé à l'utilisation des ressources et aux coûts engagés durant l'année qui suit un pontage aortocoronarien. Cet indice pourrait faciliter la détection d'un sous-groupe de patients subissant un pontage aortocoronarien et présentant un risque élevé qui pourraient bénéficier de soins périopératoires ciblés.

10.
Anesth Analg ; 114(3): 690-3, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22190548

RESUMO

We evaluated the antinociceptive effects of acute and chronic morphine administered spinally via lumbar puncture in intrathecally catheterized and sham-surgery rats. The effects of acute morphine did not differ between groups. Catheterized rats developed tolerance to chronic morphine more rapidly, compared with sham and naive rats. Therefore, catheter presence facilitated development of opioid antinociceptive tolerance. Spinal astrogliosis, determined by measurement of 3-dimensional cell volumes, was observed in catheterized rats as indicated by significantly larger cell volumes compared with surgery-naive controls. Gliosis induced by chronic intrathecal morphine administered to surgery-naive animals was comparable to that observed in saline-treated catheterized rats.


Assuntos
Cateteres de Demora , Tolerância a Medicamentos/fisiologia , Morfina/administração & dosagem , Medição da Dor/efeitos dos fármacos , Raquianestesia/métodos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/fisiologia , Cateterismo/métodos , Injeções Espinhais , Masculino , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley
11.
Anesth Analg ; 112(6): 1500-3, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21543786

RESUMO

Ultralow-dose opioid antagonists prolong opioid antinociception and block tolerance. In this study we determined whether low doses of the α-2 adrenergic receptor (A2-R) antagonist, atipamezole, similarly influenced A2-R-induced antinociception and tolerance. In rats, intrathecal norepinephrine (NE) or clonidine in combination with atipamezole was tested using tail-flick and paw pressure tests. Acute tolerance to NE was induced by serial injections. Low-dose atipamezole significantly prolonged NE and clonidine-induced antinociception. Coadministration of atipamezole with A2-R agonists also prevented loss of agonist potency in the acute tolerance model. This study demonstrates paradoxical effects of low-dose A2-R antagonists augmenting A2-R agonist-induced analgesia.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgesia/métodos , Sinergismo Farmacológico , Norepinefrina/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgésicos/administração & dosagem , Animais , Clonidina/administração & dosagem , Imidazóis/administração & dosagem , Masculino , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
12.
Mol Pain ; 6: 22, 2010 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-20398374

RESUMO

BACKGROUND: The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. RESULTS: Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. CONCLUSION: Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.


Assuntos
Gliose/induzido quimicamente , Gliose/tratamento farmacológico , Morfina/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Animais , Tolerância a Medicamentos , Imageamento Tridimensional , Imuno-Histoquímica , Masculino , Morfina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo
13.
Can J Anaesth ; 57(4): 337-42, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20112079

RESUMO

PURPOSE: Drug effects can be unpredictable during cardiac surgery due to factors that may influence drug concentration, such as extracorporeal oxygenation and hemodilution. The primary aim of the current investigation was to determine whether plasma gabapentin concentration is altered by cardiopulmonary bypass (CPB). METHODS: Following approval from the Research Ethics Board and written informed consent, we conducted this open-label prospective cohort investigation. A convenience sample of 16 patients, who were scheduled for coronary bypass surgery, received oral gabapentin 600 mg as follows: 90 min prior to induction of anesthesia, following tracheal extubation, and then every eight hours for a total of four doses. Plasma gabapentin concentration, as well as pain and sedation scores, were documented. RESULTS: Plasma gabapentin concentrations were unaltered during CPB (31.9 +/- 12.7 mumol.L(-1) prior to CPB, 35.6 +/- 12.9 to 37.2 +/- 9.6 mumol.L(-1) during CPB). However, using the current protocol, drug accumulation (reflected by increased drug concentrations) was observed following the third (58.2 +/- 19.5 micromol.L(-1)) and the fourth (71.9 +/- 34.3 micromol.L(-1)) doses. Pain and sedation scores and opioid requirements were comparable with those found in other studies. CONCLUSION: Plasma gabapentin concentration is unaltered during CPB following preoperative administration. Drug accumulation following third and fourth postoperative doses suggests the need for therapeutic drug monitoring in future trials. Gabapentin is well established as an effective adjunct analgesic in a number of surgical settings. Randomized controlled trials are necessary to evaluate analgesic efficacy, optimal dosing, and adverse effects in the setting of cardiac surgery.


Assuntos
Aminas/sangue , Analgésicos/sangue , Ponte Cardiopulmonar/efeitos adversos , Ácidos Cicloexanocarboxílicos/sangue , Ácido gama-Aminobutírico/sangue , Idoso , Aminas/administração & dosagem , Analgésicos/administração & dosagem , Estudos de Coortes , Ácidos Cicloexanocarboxílicos/administração & dosagem , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Pré-Operatórios , Fatores de Tempo , Resultado do Tratamento , Ácido gama-Aminobutírico/administração & dosagem
15.
Stem Cells ; 25(11): 2874-85, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17702982

RESUMO

Injury to the spinal cord or peripheral nerves can lead to the development of allodynia due to the loss of inhibitory tone involved in spinal sensory function. The potential of intraspinal transplants of GABAergic cells to restore inhibitory tone and thus decrease pain behaviors in a rat model of neuropathic pain was investigated. Allodynia of the left hind paw was induced in rats by unilateral L5- 6 spinal nerve root ligation. Mechanical sensitivity was assessed using von Frey filaments. Postinjury, transgenic fetal green fluorescent protein mouse GABAergic cells or human neural precursor cells (HNPCs) expanded in suspension bioreactors and differentiated into a GABAergic phenotype were transplanted into the spinal cord. Control rats received undifferentiated HNPCs or cell suspension medium only. Animals that received either fetal mouse GABAergic cell or differentiated GABAergic HNPC intraspinal transplants demonstrated a significant increase in paw withdrawal thresholds at 1 week post-transplantation that was sustained for 6 weeks. Transplanted fetal mouse GABAergic cells demonstrated immunoreactivity for glutamic acid decarboxylase and GABA that colocalized with green fluorescent protein. Intraspinally transplanted differentiated GABAergic HNPCs demonstrated immunoreactivity for GABA and beta-III tubulin. In contrast, intraspinal transplantation of undifferentiated HNPCs, which predominantly differentiated into astrocytes, or cell suspension medium did not affect any behavioral recovery. Intraspinally transplanted GABAergic cells can reduce allodynia in a rat model of neuropathic pain. In addition, HNPCs expanded in a standardized fashion in suspension bioreactors and differentiated into a GABAergic phenotype may be an alternative to fetal cells for cell-based therapies to treat chronic pain syndromes.


Assuntos
Transplante de Tecido Encefálico/métodos , Transplante de Tecido Fetal/métodos , Dor/cirurgia , Medula Espinal/cirurgia , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/fisiologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Transgênicos , Dor/patologia , Medição da Dor/métodos , Estimulação Física/métodos , Ratos , Ratos Wistar , Medula Espinal/patologia , Raízes Nervosas Espinhais/lesões
16.
Semin Thorac Cardiovasc Surg ; 30(1): 26-33, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29055710

RESUMO

Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury after cardiovascular surgery. However, it is unclear whether RIPC has a positive impact on clinical outcomes. We performed a blinded, randomized controlled trial to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was performed on the control group. Patients were recruited who were undergoing (1) high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were at high risk of ischemic complications. The primary end point was a composite outcome of mortality, myocardial infarction, stroke, renal failure, respiratory failure, and low cardiac output syndrome, and the secondary end points included the individual outcome parameters that made up this score, as well as troponin-I values. A total of 436 patients were randomized and analysis was performed on 215 patients in the control group and on 213 patients in the RIPC group. There were no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual components that made up the composite outcome. Additionally, we did not observe any differences between the groups in troponin-I values, the length of intensive care unit stay, or the total hospital stay. RIPC did not have a beneficial effect on clinical outcomes in patients who had cardiovascular surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Extremidade Superior/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/mortalidade , Feminino , Humanos , Precondicionamento Isquêmico/efeitos adversos , Precondicionamento Isquêmico/instrumentação , Precondicionamento Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/mortalidade , Fluxo Sanguíneo Regional , Fatores de Risco , Fatores de Tempo , Torniquetes , Resultado do Tratamento , Troponina I/sangue , Procedimentos Cirúrgicos Vasculares/mortalidade
18.
Eur J Health Econ ; 18(4): 471-479, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27167229

RESUMO

An obesity paradox has been described, whereby obese patients have better health outcomes than normal weight patients in certain clinical situations, including cardiac surgery. However, the relationship between body mass index (BMI) and resource utilization and costs in patients undergoing coronary artery bypass graft (CABG) surgery is largely unknown. We examined resource utilization and cost data for 53,224 patients undergoing CABG in Ontario, Canada over a 10-year period between 2002 and 2011. Data for costs during hospital admission and for a 1-year follow-up period were derived from the Institute for Clinical Evaluative Sciences, and analyzed according to pre-defined BMI categories using analysis of variance and multivariate models. BMI independently influenced healthcare costs. Underweight patients had the highest per patient costs ($50,124 ± $36,495), with the next highest costs incurred by morbidly obese ($43,770 ± $31,747) and normal weight patients ($42,564 ± $30,630). Obese and overweight patients had the lowest per patient costs ($40,760 ± $30,664 and $39,960 ± $25,422, respectively). Conversely, at the population level, overweight and obese patients were responsible for the highest total yearly population costs to the healthcare system ($92 million and $50 million, respectively, compared to $4.2 million for underweight patients). This is most likely due to the high proportion of CABG patients falling into the overweight and obese BMI groups. In the future, preoperative risk stratification and preparation based on BMI may assist in reducing surgical costs, and may inform health policy measures aimed at the management of weight extremes in the population.


Assuntos
Ponte de Artéria Coronária/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Obesidade/economia , Magreza/economia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Bases de Dados Factuais , Feminino , Recursos em Saúde/economia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ontário , Cirurgia Torácica/economia
19.
Anesth Analg ; 102(3): 859-64, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16492841

RESUMO

We assessed the attitudes of residents and program directors (PD) toward research training in Canadian anesthesiology residency programs. Questionnaires were sent to all 476 anesthesiology residents in Canada and a modified questionnaire was sent to the PD of each of the 16 anesthesiology programs between November 2003 and April 2004. There was a 60% response rate to the resident questionnaire and 95% from the PDs. Eighty-one percent of programs have mandatory research activity, although only 41% of residents think research should be mandatory. A majority of residents were recently involved in a research project. There was a discrepancy between PDs' and residents' views about the availability of some resources to facilitate research. Residents regard the time needed to learn clinical anesthesia, schedule conflicts, inadequate faculty support, and a lack of protected research time as the top barriers to undertaking a research project. PDs do not consider schedule conflicts or a lack of time as important barriers for resident research. Seventy-five percent of residents would prefer to do another academic activity, such as learning transesophageal echocardiography or taking postgraduate programs in education, rather than completing a research project during their residency.


Assuntos
Anestesiologia/educação , Atitude , Pesquisa Biomédica/educação , Docentes de Medicina , Internato e Residência , Canadá , Humanos
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