RESUMO
Background and Purpose- There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods- Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results- Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49-0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50-0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, -0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, -0.08 to 0.78]). Conclusions- Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Médicos , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa/métodos , Medicina de Emergência/métodos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Ativador de Plasminogênio Tecidual/administração & dosagemRESUMO
OBJECTIVES: This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH). METHODS: Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte-macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH. RESULTS: PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent. CONCLUSION: The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways.