Abstract
The long-term outcome after acute stroke is negatively impacted by secondary complications, such as dysphagia, aspiration pneumonia, urinary tract infections and fever. In current clinical practice, these complications are treated by medication such as metoclopramide, antibiotics and paracetamol, but it is unknown if the use of these medications in the
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acute phase of stroke may prevent secondary complications and improve functional outcome. The first chapters of this thesis focus on the rationale and design of the PRECIOUS trial, which aims to answer this question. The trial may show effectiveness, particularly because of its very early treatment and focus on elderly patients with severe stroke.
The results of PRECIOUS could not be included in this thesis as a consequence of a two-year extension of the trial. One of the major delaying factors was obtaining legal and regulatory approval for the trial, especially the execution of legal agreements with each study site. Centres that were opened later were less likely to recruit patients in the first six months, possibly reflecting declining motivation of participating investigators. Multinational trials may strongly benefit from internationally accepted templates for research contracts and formal deadlines for legal review.
One of the most life-threatening complications of acute supratentorial ischemic stroke is space-occupying edema. In an individual patient data meta-analysis of randomised controlled trials surgical decompression in patients with space occupying edema strongly reduces mortality and improves the chance of a favorable functional outcome. The effect appears to be independent of the presence of aphasia, stroke severity, age, and affected vascular territory. The benefit of surgery after 48 hours and in elderly patients remains uncertain.
Most in-hospital stroke-related deaths occur after a decision to withhold life-sustaining treatments, such as cardiopulmonary resuscitation. The decision to install treatment restrictions implies that prognosis is accurate and indisputably poor. However, the results of our analysis suggest that the presence of a treatment restriction (such as a do-not-resuscitate order) is associated with mortality, even when adjustments are made for important prognostic factors. Treatment restrictions may lead to an overall milieu of nihilism that influences attitudes of care beyond the orders themselves and may have the potential of a “self-fulfilling prophecy” when estimating prognosis for stroke patients.
When death is regarded as inevitable, a transition from curative to palliative treatment is
made in many stroke patients. In after-death interviews, relatives of patients that died on the stroke unit are generally satisfied with the end-of-life phase. Negative experiences are mostly related to feeding, inability to say goodbye to loved ones, appearing not to have control and not retaining a sense of dignity. Breathing difficulties frequently occur during the dying phase, but palliative medication adequately resolves discomfort in most patients. Counseling family members on what to expect in terms of signs and symptoms during the end-of-life phase is extremely important.
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