RESUMEN
BACKGROUND: Estimates of neuronal loss in acute ischemic stroke show that the typical patient may lose 1·9 million neurons each minute that treatment is delayed. Consequently, significant emphasis has been placed on early evaluation and thrombolysis with tissue plasminogen activator (TPA), the only approved thrombolytic therapy. TPA should be administered as a bolus followed by an immediate infusion because of its short half life. However, in the real life clinical situation, delays in starting the infusion after the bolus can occur. Similarly, once infusion has started, interruptions in the infusion of TPA can also occur. These scenarios may result in lower serum concentrations which could decrease the effectiveness of thrombolysis. We sought to simulate, the influence of bolus infusion delays and also the influence of different intervals of interruptions in the infusion of TPA on serum TPA concentrations. METHODS: We simulated the effect of multiple intervals of delay after the bolus on serum TPA concentrations using known pharmacokinetics parameters of TPA. The effect of different intervals of interruptions in the infusion of TPA was also determined. The effect of rebolusing with TPA on serum concentrations in the event of significant bolus to infusion delays or significant infusion interruption was also simulated. RESULTS: Our data show that delays in starting the infusion may have significant effects on serum TPA concentrations. After the initial bolus, there is a rapid decrease in serum TPA concentrations unless the infusion is started immediately. Greater than 5 min delays in starting the infusion results in a slow gradual increase in serum TPA levels and levels stay well below the target concentrations for significant periods of time. Similarly, interruptions in the infusion of TPA lasting longer than 5 min can also significantly influence TPA levels. Rebolusing with TPA in these scenarios rapidly restores TPA levels to target concentrations. CONCLUSION: Because of its short half life, TPA should be administered as a bolus followed by an immediate infusion. Bolus to infusion delays or interruptions in the infusion of TPA after the bolus may significantly impact serum TPA levels and may reduce the efficacy of thrombolysis. Protocols or administration regimens should be employed to prevent delays or interruptions in the infusion. When delays do occur, rebolusing of TPA may be needed to rapidly restore TPA to target levels.
Asunto(s)
Fibrinolíticos/sangre , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/métodos , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/sangre , Simulación por Computador , Fibrinolíticos/farmacocinética , Humanos , Modelos Biológicos , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/farmacocinéticaRESUMEN
BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classifications are widely used for the assessment of major ischaemic stroke. We explored their intra- and inter-observer reliability in the classification of outpatient minor stroke. METHODS: Four physicians of differing seniority and training backgrounds classified minor stroke using clinical data from 90 patients. RESULTS: For both the OCSP and TOAST classifications, the intra-observer reliability varied from moderate to excellent (kappa = 0.48-0.83). The inter-observer reliability was good (kappa = 0.64) for the OCSP and moderate (kappa = 0.42) for the TOAST. Thus, neither classification was consistently reliable. CONCLUSIONS: Our results may reflect the limited validity of these classifications in a typical minor stroke outpatient population and variable observer expertise.