Treatment and treatment restrictions in patients with acute ischaemic stroke

Abstract

Acute stroke is often a devastating condition. Despite the current treatment strategies, about half of patients has a poor functional outcome. New treatments strategies are clearly needed. Therapeutic hypothermia, the intentional reduction of body temperature, is a promising new treatment for acute ischaemic stroke. In part I of this thesis, I focus on the feasibility and safety of therapeutic hypothermia as a new treatment strategy. In a multi-centre, randomized, open, phase II clinical trial, I compare standard treatment with surface cooling to 34.0°C, 34.5°C or 35.0°C in awake patients with acute ischaemic stroke. Cooling was initiated within 4.5 hours after symptom onset and maintained for 24 hours. Inclusion was terminated after 22 patients because of slow recruitment. Based on this trial, I conclude that in the majority of awake patients with acute ischaemic stroke, surface cooling to 35.0°C, but not to 34.0°C and 34.5°C, appears feasible. Furthermore, I conclude that pneumonia is the most important adverse effect of treatment with hypothermia in awake patients with acute ischaemic stroke. A systematic review and meta-analysis including 23 randomized controlled clinical trials that examine the risk of infections in patients treated with hypothermia irrespective of the indication, confirms that there is an association between therapeutic hypothermia and the risk of pneumonia. Future studies should focus on the efficacy before this treatment can be implemented. The current lack of curative treatments for most patients means that the majority of patients with acute stroke has a poor outcome. In part II I focus on the challenges that accompany the end-of-life decision making process in patients with acute stroke. Treatment restrictions are installed in most of these patients, and the majority of patients is incapacitated to participate in the end-of-life decision making process. In a study describing the current practices in the end-of-life decision making process in severe stroke patients, I found that the main reason for the installment of treatment restrictions was the physician’s prediction of a poor functional outcome. Advance directives are scarce in this patient group; proxy opinions are most often used to respect patients’ autonomy. In a prospective cohort study including 60 patients with severe stroke, I assessed the predictive accuracy of treating physicians regarding mortality and functional outcome. I conclude that in the acute phase, physicians estimate the risk of death or unfavourable functional outcome at six months precisely, but the accuracy of their estimates is not sufficient to serve as the sole basis of end-of-life decisions. In the same cohort study, I found that treatment restrictions installed several days after stroke onset were independently associated with mortality at six months. This means that the installment of a treatment restriction by itself increases the risk of death. Remarkably, quality of life was satisfactory in the majority of the survivors, despite considerable handicap. Future studies should focus on how to, in the acute stage after stroke, identify patients that will recapture a good quality of life, so that treatment restrictions are installed in the right patients.