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BACKGROUND: Cognitive impairment is common in older surgical patients and is associated with postoperative delirium. However, cognitive function is inconsistently assessed preoperatively, leading to missed opportunities to recognize vulnerable patients. We designed a prospective cohort study to assess the agreement of the Mini-Cog screening tool administered in the preoperative clinic (clinic-day test) or immediately before surgery (surgery-day test) and to determine whether a positive screening for cognitive dysfunction in the surgery-day test is associated with postoperative delirium in the postanesthesia care unit (PACU). METHODS: This was a cohort study of patients aged 65-89 years, scheduled for elective, inpatient surgery under general anesthesia between June 20, 2018 and August 3, 2018. Mini-Cog test scores were obtained during a clinic-day test and surgery-day test. The Short Confusion Assessment Method was performed in the PACU. Agreement between Mini-Cog clinic-day and surgery-day test scores was estimated using an ordinally weighted kappa statistic, κ. Multivariable logistic regression was used to determine whether there was an association between a positive screen for cognitive impairment and PACU delirium. Odds ratio analysis was performed to determine whether the Mini-Cog score was associated with PACU delirium. RESULTS: Of 128 patients meeting eligibility criteria, 80 patients were enrolled. Ten had cognitive impairment based on the Mini-Cog clinic-day test score, while 70 did not. Age, sex, race, education level, subjective memory impairment, and American Society of Anesthesiologists (ASA) physical status were equivalent in the 2 groups. The mean number of days between the clinic-day score and the surgery-day score was 8.4 days (standard deviation [SD] = 6.9). Mini-Cog clinic-day and surgery-day scores had high agreement (κ = 0.78; 95% confidence interval [CI], 0.69-0.87; P < .001), and both scores were highly predictive of PACU delirium. Patients with Mini-Cog surgery-day scores compatible with cognitive impairment (Mini-Cog scores ≤2) had an estimated 12.8 times higher odds of PACU delirium compared to patients with normal cognitive function or Mini-Cog scores >2 (odds ratio [OR] = 12.8; 95% CI, 2.6-63.8, P = .002). Similarly, patients with Mini-Cog clinic-day test scores compatible with cognitive impairment had an estimated 29 times higher odds of PACU delirium compared to patients with normal cognitive function (OR = 29.0; 95% CI, 2.6-63.8, P < .001). CONCLUSIONS: These data support the approach of using the Mini-Cog on the day of surgery to screen for cognitive impairment in older patients. Importantly, Mini-Cog surgery-day test scores compatible with cognitive impairment (≤2) were strongly associated with PACU delirium.
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Periodo de Recuperación de la Anestesia , Anestesia General/efectos adversos , Cognición , Disfunción Cognitiva/diagnóstico , Procedimientos Quirúrgicos Electivos/efectos adversos , Delirio del Despertar/etiología , Pruebas de Estado Mental y Demencia , Cuidados Preoperatorios , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/psicología , Delirio del Despertar/diagnóstico , Delirio del Despertar/psicología , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND/OBJECTIVE: Peripheral-nerve blocks (PNBs) using continuous-infusion of local anesthetics are used to provide perioperative analgesia. Yet little research exists to characterize the histopathological effects of continuous long-duration PNBs. Herein we test the hypothesis that continuous peri-neural bupivacaine infusion (3-day vs. 7-day infusion) contributes to histologic injury in a duration-dependent manner using an in vivo model of rat sciatic nerves. METHODS: We placed indwelling catheters in 22 rats for infusion with low-dose (0.5mg/kg/hr) bupivacaine or normal saline proximal to the right sciatic nerves for 3 or 7 consecutive days. Hind-limb analgesia was measured using Von-Frey nociceptive testing. At infusion end, rats were sacrificed, bilateral nerves were sectioned and stained with hematoxylin and eosin and CD68 for evaluation of inflammatory response, and eriochrome to assess damage to myelin. RESULTS: Animals receiving continuous infusion of bupivacaine maintained analgesia as demonstrated by significant decrease (50% on average) in nociceptive response in bupivacaine-infused limbs across time points. Both 7-day saline and bupivacaine-infused sciatic nerves showed significantly-increased inflammation by H&E staining compared to untreated native nerve controls (Pâ=â0.0001, Pâ<â0.0001). Extent of inflammation did not vary significantly based on infusate (7-day saline vs. 7-day bupivacaine Pâ>â0.99) or duration (3-day bupivacaine vs 7-day bupivacaine Pâ>â0.99). No significant change in sciatic nerve myelin was found in bupivacaine-infused animals compared to saline-infused controls, regardless of duration. CONCLUSIONS: Long-duration (7-day) bupivacaine infusion provided durable post-operative analgesia, yet contributed to equivalent neural inflammation as short duration (3-day) infusion of bupivacaine or saline with no evidence of demyelination.
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Bupivacaína , Bloqueo Nervioso , Animales , Axones , Bupivacaína/farmacología , Vaina de Mielina , Ratas , Ratas Sprague-Dawley , Nervio Ciático/patología , Nervio Ciático/fisiologíaRESUMEN
BACKGROUND: Numerous oxygen delivery systems are used to treat hypoxemia. It is unknown if FIO2 at the lips predicts oropharyngeal FIO2 for various oxygen mask systems. We tested whether FIO2 measurements differed between the lips and oropharynx, and whether this difference depends on the mask system. METHODS: Ten healthy volunteers had one sampling catheter positioned at the lips and another catheter in the oropharynx. FIO2 was sampled at each location while the subjects breathed normal tidal volumes with oxygen at 15 L/min via 4 delivery devices: a simple mask, a non-rebreather mask, a face mask with a diffuser that concentrates and directs O2 toward the mouth and nose (mask with diffuser), and a closed mask with a Jackson-Rees circuit. Data were analyzed by using a linear mixed model to account for subject crossover in the repeated measures design. RESULTS: FIO2 levels differed significantly for the 4 delivery mask systems (P < .001) and by sampling catheter location (P < .001). Differences in mean FIO2 between the lips and the oropharynx were observed for the mask with diffuser (difference 0.30, 95% CI 0.25-0.36; P < .001), and non-rebreather mask (difference 0.09, 95% CI 0.04-0.15; P = .001). The mean FIO2 at the oropharynx was highest for the closed mask (0.97, 95% CI 0.92-1.00), followed by the non-rebreather mask (0.76, 95% CI 0.72-0.81), simple mask (0.62, 95% CI 0.58-0.67), and the mask with diffuser (0.51, 95% CI 0.46-0.56). At the lips, the mean FIO2 was highest for the closed mask (0.97, 95% CI 0.92-1.00), followed by the non-rebreather mask (0.86, 95% CI 0.81- 0.90), OxyMask (0.81, 95% CI 0.76-0.86), and simple mask (0.67, 95% CI 0.62-0.71). CONCLUSIONS: With high oxygen flows and normal tidal volume breathing, FIO2 measurements obtained at the oropharynx or at the lips depended on the device used, with the mask with diffuser showing the most significant discrepancies. FIO2 measures at the oropharynx and the lips were only consistent for the closed mask system. (ClinicalTrials.gov registration NCT02523586.).
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Hipoxia/terapia , Máscaras , Terapia por Inhalación de Oxígeno/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Labio , Masculino , Persona de Mediana Edad , Orofaringe , Oxígeno/administración & dosificación , Volumen de Ventilación Pulmonar , Adulto JovenRESUMEN
BACKGROUND: Previous studies show that the potent, prototypical sigma(1)-receptor agonist 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) prevents cell death after oxygen-glucose deprivation (OGD) in primary cortical neuronal cultures. We tested the hypothesis that PPBP protects neurons by a mechanism involving activation of the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB). METHODS: Primary cultured cortical neurons were exposed to 2 h of OGD and allowed to recover for 24 h, and PPBP treatment was initiated 15 min before the insult in the presence and absence of the sigma(1)-receptor antagonist rimcazole and inhibitors against protein kinases known to activate signal transduction cascades that result in CREB phosphorylation, such as H89 (protein kinase A inhibitor), LY294002 (PI3K inhibitor), U0126 (MEK1/2 inhibitor), or KN62 calmodulin kinase II inhibitor). Neuronal cell death was assayed by lactate dehydrogenase measurement 24 h after OGD. CREB phosphorylation was measured by immunoblot analysis at 30 min, 1 h, and 3 h of reoxygenation. Blots were quantitatively analyzed using Quantity One image analysis software. RESULTS: PPBP increased CREB phosphorylation at 1 h after recovery from OGD, which was abolished by rimcazole (1.7 +/- 0.2 in PPBP and 0.8 +/- 0.1 in PPBP plus rimcazole with OGD compared with 0.9 +/- 0.1 in OGD alone, p-CREB/CREB). The PPBP-induced increase in CREB phosphorylation was blocked by H89 (0.5 +/- 0.07) but not U0126, KN62, or LY294002. PPBP treatment prevented OGD-induced cell death and pretreatment with H89 blocked this protection (0.18 +/- 0.02 in PPBP and 0.27 +/- 0.03 in PPBP plus H89 with OGD compared with 0.33 +/- 0.02 in OGD alone, lactate dehydrogenase assay). Pretreatment with LY294002, UO126, or KN62 had no effect on neuronal protection by PPBP. CONCLUSIONS: These data suggest that the mechanism of neuroprotection by PPBP may be linked to CREB phosphorylation.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Haloperidol/análogos & derivados , Fármacos Neuroprotectores/farmacología , Animales , Western Blotting , Butadienos/farmacología , Muerte Celular/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Células Cultivadas , Cromonas/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Glucosa/deficiencia , Haloperidol/farmacología , Isoquinolinas/farmacología , Morfolinas/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Nitrilos/farmacología , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores sigma/efectos de los fármacos , Sulfonamidas/farmacología , Receptor Sigma-1RESUMEN
OBJECTIVE: To investigate the effectiveness of the Karl Storz BERCI DCI Macintosh video laryngoscope (MVL) via the TELE PACK system for facilitating intubation by novice paramedic students in a simulation environment. We assessed the laryngeal view, measured by percentage of glottic opening (POGO), when intubating the SimMan manikin airway in different settings. The primary endpoint was the best POGO achieved by the student. Secondary endpoints included intubation times and success rate. METHOD: We enrolled 25 novice paramedic students to intubate SimMan manikins. Students were randomized to use either a conventional Macintosh 3 (Mac3) blade alone or the MVL with a Mac3 blade. Students attempted their first intubation with the manikin on a stretcher in a normal neck position and reattempted intubation with the manikin's neck stiffened. The groups then crossed over using the alternate device to repeat the attempts in the manikin with a normal neck and with a stiffened neck. The students then attempted the same sequence of four intubations with the manikin on the floor. RESULTS: The MVL significantly improved POGO in all scenarios (p < 0.05). The MVL improved mean POGO 16% +/- 6% in the manikin with a normal neck position on a stretcher and 33% +/- 7% in the manikin with a stiff neck on the floor. The improvement was significantly greater in simulated difficult scenarios. The intubation success rate (94%) was equal in the two groups, and the POGO was significantly worse in the failures. In some subgroups, intubation times were longer with the MVL. CONCLUSION: The MVL improves the laryngeal view for novice laryngoscopists in a simulated setting, and this improvement is greatest in simulated difficult scenarios.
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Técnicos Medios en Salud/educación , Simulación por Computador , Intubación Intratraqueal/métodos , Laringoscopía , Maniquíes , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Reflective practice has been identified as one way to increase participation in self-directed lifelong learning so that physicians maintain a level of current and relevant medical knowledge for their practice. This study sought to determine if reflective practice affected the readiness for self-directed learning in a sample of anesthesiology residents in the United States. METHODS: An experimental design was used to employ quantitative methods to investigate the effects of a self-guided 8-week reflective practice exercise on readiness for self-directed learning as measured by Guglielmino's Self-Directed Learning Readiness Scale/Learning Preference Assessment (SDLRS/LPA). Participants were randomly assigned into an experimental group or control group. RESULTS: Fifty-one anesthesiology residents in 3 residency programs completed this study. No significant difference was found between the posttest SDLRS/LPA scores of the control (median = 227) and experimental group (median = 225; U = 294; z = -.584; P = .559; r = 41.18) as well as the pretest and posttest scores (z = -.65; P = .518; r = -.129) of the experimental group. CONCLUSIONS: We should continue to explore ways to train physicians to engage in practices that promote self-directed lifelong learning.
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Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, larger preclinical trials. Histologic brain pathology was evaluated at 4 d after 90 min of reversible occlusion of the middle cerebral artery (MCA). MCA occlusion was accomplished by using a transorbital approach and temporary placement of an aneurysm clip. Male and female rhesus macaques 7 to 11 y of age were studied. Baseline and intraischemic blood glucose, systolic blood pressure, heart rate, oxygen saturation, end-tidal CO2, and rectal temperatures were not different among groups. The variability in injury volume was comparable to that observed in human focal cerebrovascular ischemia and in other nonhuman primate models using proximal MCA occlusion. In this small sample, the volume of injury was not different between male and female subjects, but observed variability was higher in female caudate nucleus, putamen, and hemisphere. This report is the first to compare cerebral ischemic outcomes in female and male rhesus macaques. The female rhesus macaque ischemic stroke model could be used after rodent studies to provide preclinical data for clinical trials in women.
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Ataque Isquémico Transitorio/etiología , Animales , Encéfalo/patología , Dióxido de Carbono/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/fisiopatología , Macaca mulatta , Masculino , Caracteres Sexuales , Especificidad de la EspecieRESUMEN
Administration of anesthetic agents fundamentally shifts the responsibility for maintenance of homeostasis from the patient and their intrinsic physiological regulatory mechanisms to the anesthesiologist. Continuous delivery of oxygen and nutrients to the brain is necessary to prevent irreversible injury and arises from a complex series of regulatory mechanisms that ensure uninterrupted cerebral blood flow. Our understanding of these regulatory mechanisms and the effects of anesthetics on them has been driven by the tireless work of pioneers in the field. It is of paramount importance that the anesthesiologist shares this understanding. Herein, we will review the physiological determinants of cerebral blood flow and how delivery of anesthesia impacts these processes.
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Anestésicos/farmacología , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Anestesia/efectos adversos , Anestesia/métodos , Animales , Encéfalo/metabolismo , Circulación Cerebrovascular/fisiología , HumanosRESUMEN
This review will focus on inhalational anesthetic neuroprotection during cerebral ischemia and inhalational anesthetic preconditioning before ischemic brain injury. The limitations and challenges of past and current research in this area will be addressed before reviewing experimental and clinical studies evaluating the effects of inhalational anesthetics before and during cerebral ischemia. Mechanisms underlying volatile anesthetic neuroprotection and preconditioning will also be examined. Lastly, future directions for inhalational anesthetics and ischemic brain injury will be briefly discussed.
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Anestésicos por Inhalación/farmacología , Isquemia Encefálica/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Anestésicos por Inhalación/uso terapéutico , Humanos , Precondicionamiento Isquémico/métodosRESUMEN
BACKGROUND: Sigma (sigma)-receptor agonists attenuate brain injury after experimental focal cerebral ischemia in several species. We tested the hypothesis that the potent, prototypical sigma(1)-receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), protects neurons by a mechanism involving the antiapoptotic protein bcl-2. METHODS: Primary cortical neuronal cultures were exposed to either 2 h of oxygen-glucose deprivation (OGD) or glutamate (100 microM). PPBP treatment was initiated either 15 min prior to the insult or at 15 min postinsult then continued for 24 h. In another set of experiments, cultured neurons were preincubated for 2 h prior to PPBP treatment with sigma1-receptor antagonist, rimcazole, in a dose-dependent manner. Alive and dead cells were detected with calcein-AM and propidium iodide respectively. Bcl-2 and bax expression were determined by quantitative real time reverse transcription polymerase chain reaction and western blotting, and DNA damage was detected by TUNEL staining. RESULTS: PPBP pretreatment attenuated neuronal injury induced by OGD or glutamate (50 or 100 microM). This protection was reversed with rimcazole (cell death: OGD 48 +/- 2%, OGD plus PPBP 31 +/- 3%, OGD plus PPBP with rimcazole 46 +/- 2%). PPBP treatment increased bcl-2 but not bax mRNA levels. PPBP's ability to preserve bcl-2 protein after OGD by PPBP was fully abolished by rimcazole. Lastly, PPBP reduced the number of TUNEL-positive cells after OGD, suggesting fewer cells with overt DNA damage. CONCLUSIONS: These data demonstrate that PPBP reduces cell death in vitro by a mechanism involving receptor-dependent preservation of protective genes such as bcl-2.
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Fármacos Neuroprotectores/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Receptores sigma/agonistas , Receptores sigma/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Células Cultivadas , Daño del ADN/fisiología , Relación Dosis-Respuesta a Droga , Neuronas/efectos de los fármacos , Neuronas/fisiología , Piperidinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores sigma/antagonistas & inhibidoresRESUMEN
Postischemic administration of the sigma-1 agonists reduces ischemic brain injury; however, the mechanism is unclear. We hypothesized that the sigma-1 agonist (+)isoform of pentazocine (P(+)) reduces damage in part by ameliorating cell death mediated via inducible nitric oxide synthase (iNOS) and that the (-)isoform (P(-)) lacks this effect. We compared treatment with P(+) with or without the iNOS inhibitor aminoguanidine (AG) and also the effects of P(+) in iNOS deficient (iNOSKO) mice. A possible mechanism of neuroprotection is inhibition of iNOS expression. Male C57/Bl6 mice were subjected to transient middle cerebral artery occlusion (90 min) and drugs were administered with reperfusion: 1) P(+) with AG (P+/AG), 2) P(+), 3) P(-), 4) AG, or 5) placebo. iNOSKOs were treated with either P(+) or placebo. Infarction (triphenyltetrazolium chloride histology, 72 h) was reduced by P(+) treatment in striatum by 44% and in neocortex by 23% versus placebo (P < 0.05), a reduction comparable to AG effect. P(-) did not attenuate brain injury. There was no difference in P(+)/AG treatment compared with showed the same level of neuroprotection as P(+) alone. P(+) also did not provide further neuroprotection for iNOSKOs. We conclude that postischemic administration of P(+) reduces infarct volume in mice. Because AG provides no additional benefit to P(+) treatment and iNOSKOs do not benefit from P(+), we speculate that P(+) acts by suppressing cell death resulting from iNOS toxicity.
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Inhibidores Enzimáticos/farmacología , Fármacos Neuroprotectores/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Receptores sigma/agonistas , Animales , Calcio/metabolismo , Guanidinas/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Pentazocina/farmacología , Receptor Sigma-1Asunto(s)
Terapias Complementarias/estadística & datos numéricos , Manejo del Dolor/estadística & datos numéricos , Anestesiólogos/organización & administración , Anestesiólogos/estadística & datos numéricos , Política de Salud , Humanos , Medicina Integrativa/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Lean strategies can be readily applied to health care in general and operating rooms specifically. The emphasis is on the patient as the customer, respect and engagement of all providers, and leadership from management. The strategy of lean is to use continuous improvement to eliminate waste from the care process, leaving only value-added activities. This iterative process progressively adds the steps of identifying the 7 common forms of waste (transportation, inventory, motion, waiting, overproduction, overprocessing, and defects), 5S (sort, simplify, sweep, standardize, sustain), visual controls, just-in-time processing, level-loaded work, and built-in quality to achieve the highest quality of patient care.
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Eficiencia Organizacional , Quirófanos/organización & administración , Garantía de la Calidad de Atención de Salud/métodos , Humanos , LiderazgoRESUMEN
BACKGROUND: The Foundation for Anesthesia Education and Research Resident Scholar Program (RSP) supports academically promising anesthesiology residents to attend mentoring seminars at the American Society of Anesthesiologists annual meeting. The objective of this study was to describe the career paths of RSP participants. METHODS: Prior RSP participants were surveyed regarding their academic productivity and their evaluation of the RSP experience. Univariate statistics were used to characterize the survey results. RESULTS: A total of 882 RSP participants were surveyed. The response rate was 26%. Seventy-two percent of respondents had worked in an academic institution, and 45% (95% CI: 38%-51%) were currently at an academic institution, which is higher than the national average of 18% (P<0.001). CONCLUSIONS: This program may be a model for supporting the development of future academic anesthesiologists.
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BACKGROUND AND PURPOSE: We have previously demonstrated that pretreatment with selective kappa-opioid agonist BRL 52537 hydrochloride [(+/-)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine], provides ischemic neuroprotection following transient focal ischemia in rats. The present study was undertaken to a) define "therapeutic opportunity" for ischemic neuroprotection with BRL 52537, and b) determine if BRL 52537 attenuates ischemia-evoked efflux of dopamine and its metabolites in the striatum in vivo following transient focal ischemia. METHODS: Using the intraluminal filament technique, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO). In a blinded, randomized fashion, rats were treated with saline (vehicle) or 1 mg/Kg/hr BRL 52537 infusion for 22 hours, initiated at onset, 2, 4, or 6 hours of reperfusion (Rep). In a separate set of experiments utilizing in vivo microdialysis, extracellular levels of dopamine and its metabolites were determined in the striatum during 2 hours of MCAO and 3 hours of reperfusion. RESULTS: Infarct volume (% of contralateral structure; mean +/-SEM) in cortex was significantly attenuated when BRL 52537 was administered at reperfusion (22+/-6%), 2 hours (21+/-6%), and 4 hours (18+/-5%) compared with controls (39+/-5%). In striatum, infarct volume was significantly attenuated when BRL 52537 was administered at reperfusion (38+/-9%), 2 hours (40+/-8%), 4 hours (50+/-8%), and 6 hours (46+/-9%) as compared with controls (70+/-4%). A 6- to 8-fold increase in dopamine in microdialysates occurred within 40 minutes of MCAO. Pretreatment with BRL 52537 did not alter microdialysate levels of dopamine or its metabolites in the striatum during MCAO and early reperfusion, as compared with saline controls. CONCLUSIONS: These data demonstrate that BRL 52537 provides robust ischemic neurprotection with a long therapeutic opportunity (at least 6 hours) without altering ischemia-evoked efflux of dopamine (DA) and its metabolites in striatum during ischemia and early reperfusion.
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Isquemia Encefálica/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Piperidinas/uso terapéutico , Pirrolidinas/uso terapéutico , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Cuerpo Estriado/química , Cuerpo Estriado/patología , Dopamina/análisis , Dopamina/metabolismo , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/prevención & control , Microdiálisis , Fármacos Neuroprotectores/farmacología , Piperidinas/farmacología , Pirrolidinas/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Receptores Opioides kappa/antagonistas & inhibidores , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND AND PURPOSE: Kappa-opioid receptors (KOR) have been implicated in neuroprotection from ischemic neuronal injury. We tested the effects of a selective and specific KOR agonist, BRL 52537 hydrochloride [(+/-)-1-(3,4-dichlorophenyl)acetyl-2-(1-pyrrolidinyl) methylpiperidine], on infarct volume and nitric oxide production after transient focal ischemia in the rat. METHODS: With the use of the intraluminal filament technique, halothane-anesthetized male Wistar rats (weight, 250 to 300 g) were subjected to 2 hours of focal cerebral ischemia confirmed by Doppler flowmetry. In a blinded randomized fashion, rats were treated with intravenous saline or 1 mg/kg per hour BRL 52537 infusion, initiated 15 minutes before occlusion and maintained until 2 hours of reperfusion. In a second experiment, rats were treated during reperfusion with saline or 1 mg/kg per hour BRL 52537, initiated at onset of reperfusion and continued for 22 hours. In a final experiment, in vivo striatal nitric oxide production was estimated via microdialysis by quantification of citrulline recovery after labeled arginine infusion in striatum of intravenous BRL 52537- or saline-treated rats. RESULTS: In rats treated with BRL 52537 during ischemia and early reperfusion, infarct volume was significantly attenuated in cortex (16+/-6% versus 40+/-7% of ipsilateral cortex in saline group) and in caudoputamen (30+/-8% versus 66+/-6% of ipsilateral caudoputamen in saline group). Infarct volume was also reduced by treatment administered only during reperfusion in cortex (19+/-8% in BRL 52537 group [n=10] versus 38+/-6% in saline group) and in caudoputamen (35+/-9% versus 66+/-4% in saline group). BRL 52537 treatment markedly attenuated NO production in ischemic striatum compared with saline-treated controls. CONCLUSIONS: These data demonstrate that (1) the selective KOR agonist BRL 52537 provides significant neuroprotection from focal cerebral ischemia when given as a pretreatment or as a posttreatment and (2) attenuation of ischemia-evoked nitric oxide production in vivo may represent one mechanism of ischemic neuroprotection.
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Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Óxido Nítrico/metabolismo , Piperidinas/farmacología , Pirrolidinas/farmacología , Receptores Opioides kappa/agonistas , Animales , Arginina/administración & dosificación , Arginina/metabolismo , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Citrulina/análisis , Citrulina/biosíntesis , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/patología , Masculino , Microdiálisis , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Traumatic spinal cord injury is frequently associated with brain injury and with alterations in respiratory and cardiovascular function that require critical care management. Complications include respiratory failure, atelectasis, pneumonia, neurogenic shock, autonomic dysreflexia, venous thromboembolism, and sepsis. While complications may be managed with supportive care, the goal of ameliorating neurologic outcome has proved elusive. Methylprednisolone, when instituted <8 hours after traumatic spinal cord injury, was associated in two clinical trials with statistically significant improvements in motor scores at 6 months and 1 year; however, critical reappraisal of these data raises questions about their validity and clinical relevance. Until more evidence of clinically effective therapies is available, acute management must be driven by pathophysiologic principles, with emphasis on interventions that attenuate secondary neurologic injury; these include the rational use of immobilization, cautious airway management, and promotion of cord perfusion and oxygenation with the appropriate level of hemodynamic and respiratory support. Clinical trials of pharmacologic neuroprotection have yielded disappointing results, but the ongoing elucidation of spinal cord repair and regenerative mechanisms suggests new therapeutic prospects.
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Cuidados Críticos , Atención Perioperativa , Traumatismos de la Médula Espinal/terapia , Procedimientos Quirúrgicos Operativos , HumanosRESUMEN
STUDY OBJECTIVE: To test the sterility of medication vial tops after removal of the dust cover, and to survey anesthesia providers for their perceptions surrounding medication vials and sterility. DESIGN: Experimental design and survey instrument. SETTING: Ambulatory and hospital care setting. PARTICIPANTS: Anesthesia providers in the United States. MEASUREMENTS: A two-question survey was distributed to anesthesia providers in the U.S. An experimental model was conducted on a total of 42 medication vials. The access diaphragms of medication vials were sampled after routine handling, after exposure to aerosolized contamination with the dust cover on, and after submersion into a bacterial medium with the dust cover on. MAIN RESULTS: 878 responses to Question 1 and 876 responses to Question 2 were received. Fifty-two percent of respondents declared that the access diaphragm was sterile in routine conditions, and 43% felt that (or were unsure if) the dust cover would prevent contamination when exposed to a contaminated environment. Two of the 12 vials sampled in the routine handling model had microbial contaminants on the access diaphragm. No growth was found on any of the 15 vials exposed to aerosolized E. coli. Seven of the 15 vials in the submersion model were contaminated. CONCLUSIONS: Anesthesia providers in the U.S. possess contradictory opinions of, and unclear knowledge about, the sterility of rubber stoppers used to access medications, and also the barrier capacity of a vial's dust cover. Standard anesthetic medication vial dust covers do not offer barrier protection against the growth of pathogens.