Mobilization After rtPA Within 24 Hrs of Acute Stroke
Stroke is one of the leading causes of death in the developed world today and for those who survive the event, chronic disability is a frequent complication. Best practice clinical guidelines recommend two key treatments for acute ischemic stroke: care in a specialized stroke unit and thrombolysis with recombinant-tissue plasminogen activator (rtPA). Stroke unit care (SUC) improves outcomes such as physical independence and increases chances of survival after stroke. The most specific and biologically powerful treatment for acute ischemic stroke is thrombolysis with rtPA given within the first 4.5 hours of ischemic stroke onset. However, thrombolysis is not devoid of side effects and patients are carefully selected. Prominent among concerns is the fear of secondary symptomatic intracranial hemorrhage (sICH), which is one major reason preventing an extension of rtPA treatment to a broader spectrum of patients.
SUC is characterized by close monitoring of physiological and neurological parameters and possible complications, hydration and nutritional intake, and early rehabilitation. The initiation of rehabilitation has been suggested to be of importance both to prevent and treat complications and to improve recovery of walking. Although SUC improves outcomes after stroke, several components of SUC are ill-defined and early mobilization (out of bed activity training), often part of the early rehabilitation package, is one of these. Early mobilization is currently being tested as part of an international clinical trial, AVERT (A Very Early Rehabilitation Trial). AVERT is a large phase III randomized controlled trial testing whether very early mobilization (VEM) reduces death and disability at three months post stroke. VEM is defined as mobilization out of bed commenced within 24 hours of stroke onset and continued frequently thereafter. This intervention is performed by a physiotherapist or nurse. Participants randomized to the control arm undergo standard stroke unit care. As rtPA is part of standard care, patients treated with rtPA can be included in the trial if the physician allows.
Mobilization of thrombolysed patients concerns some clinicians, and rtPA protocols often include 24 hours of bed rest after treatment. In a previous case-crossover designed study with hypothetical case vignettes, we explored the factors likely to influence the decision to allow patients to mobilize early after treatment with rtPA. The study of fifty-four clinicians found that perceived risk of neurological decline, especially due to sICH; infection of unknown cause; severe chest infection; severe stroke (NIHSS >20); drowsiness and confusion were factors that significantly influenced the decision to mobilize. In reality we know little about what influences these decisions in every day practice.
Twenty three percent of the 1898 patients recruited to AVERT to date have been treated with rtPA (n = 447). Over 500 patients treated with rtPA are expected to be recruited by trial end, approximately half of whom will be mobilized within 24 hours of stroke. These data may broaden our understanding of the benefits or harms of combining these two treatments. However, as inclusion in AVERT is dependent on physician approval, it is likely that included patients will be selected, thus limiting our ability to generalize findings to a broader stroke population. The aim of this study therefore, was to compare the characteristics of rtPA treated patients in the AVERT trial with those not included, and to explore the factors influencing inclusion in the trial.
We hypothesized that the use of rtPA would create a selection bias in the AVERT recruitment process and therefore that thrombolysed patients included in AVERT would be different from the ones not included in the trial.
Background
Stroke is one of the leading causes of death in the developed world today and for those who survive the event, chronic disability is a frequent complication. Best practice clinical guidelines recommend two key treatments for acute ischemic stroke: care in a specialized stroke unit and thrombolysis with recombinant-tissue plasminogen activator (rtPA). Stroke unit care (SUC) improves outcomes such as physical independence and increases chances of survival after stroke. The most specific and biologically powerful treatment for acute ischemic stroke is thrombolysis with rtPA given within the first 4.5 hours of ischemic stroke onset. However, thrombolysis is not devoid of side effects and patients are carefully selected. Prominent among concerns is the fear of secondary symptomatic intracranial hemorrhage (sICH), which is one major reason preventing an extension of rtPA treatment to a broader spectrum of patients.
SUC is characterized by close monitoring of physiological and neurological parameters and possible complications, hydration and nutritional intake, and early rehabilitation. The initiation of rehabilitation has been suggested to be of importance both to prevent and treat complications and to improve recovery of walking. Although SUC improves outcomes after stroke, several components of SUC are ill-defined and early mobilization (out of bed activity training), often part of the early rehabilitation package, is one of these. Early mobilization is currently being tested as part of an international clinical trial, AVERT (A Very Early Rehabilitation Trial). AVERT is a large phase III randomized controlled trial testing whether very early mobilization (VEM) reduces death and disability at three months post stroke. VEM is defined as mobilization out of bed commenced within 24 hours of stroke onset and continued frequently thereafter. This intervention is performed by a physiotherapist or nurse. Participants randomized to the control arm undergo standard stroke unit care. As rtPA is part of standard care, patients treated with rtPA can be included in the trial if the physician allows.
Mobilization of thrombolysed patients concerns some clinicians, and rtPA protocols often include 24 hours of bed rest after treatment. In a previous case-crossover designed study with hypothetical case vignettes, we explored the factors likely to influence the decision to allow patients to mobilize early after treatment with rtPA. The study of fifty-four clinicians found that perceived risk of neurological decline, especially due to sICH; infection of unknown cause; severe chest infection; severe stroke (NIHSS >20); drowsiness and confusion were factors that significantly influenced the decision to mobilize. In reality we know little about what influences these decisions in every day practice.
Twenty three percent of the 1898 patients recruited to AVERT to date have been treated with rtPA (n = 447). Over 500 patients treated with rtPA are expected to be recruited by trial end, approximately half of whom will be mobilized within 24 hours of stroke. These data may broaden our understanding of the benefits or harms of combining these two treatments. However, as inclusion in AVERT is dependent on physician approval, it is likely that included patients will be selected, thus limiting our ability to generalize findings to a broader stroke population. The aim of this study therefore, was to compare the characteristics of rtPA treated patients in the AVERT trial with those not included, and to explore the factors influencing inclusion in the trial.
We hypothesized that the use of rtPA would create a selection bias in the AVERT recruitment process and therefore that thrombolysed patients included in AVERT would be different from the ones not included in the trial.