PRACTICE ISSUES IN NEUROLOGY

CONTINUUM: Lifelong Learning in Neurology December 2008; Volume 14(6) Acute Ischemic Stroke; pp 141-144
Wechsler, Lawrence R.; Zaidi, Syed Relationship Disclosure: Dr Wechsler has received personal compensation for activities with Abbott Laboratories, Inc., Bristol-Myers Squibb Company, Forest Laboratories, Inc., NMT Medical, Inc., Nuvelo Inc., and sanofi-aventis. Dr Wechsler has received personal compensation in an editorial capacity for Journal of Neuroimaging. Dr Wechsler has received research support from NMT Medical, Inc. Dr Zaidi has nothing to disclose. Unlabeled Use of Products/Investigational Use Disclosure: Drs Wechsler and Zaidi have nothing to disclose.
A 68-year-old man is evaluated in the emergency department because of aphasia and right-sided weakness. He was at a restaurant with his wife when he suddenly stopped speaking and fell to the floor unable to move his right side. Emergency medical services were called, and he was transported immediately to the emergency department. He arrived 1 hour after the onset of the deficit. A stroke code was called. On examination, his NIH Stroke Scale (NIHSS) score is 20. He is mute and does not follow verbal commands. He has a left gaze deviation and does not respond to threat from the right. There are no movements of the right extremities. He has dense right facial weakness. He does not respond to pain on the right. He has a history of atrial fibrillation treated only with aspirin. There is no prior history of stroke or TIA. His wife is present at the bedside and provides the history. CT of the brain is performed and shows no hemorrhage or early ischemic changes. Blood pressure is 150/85 mm Hg. International normalized ratio, platelet count, and blood glucose are all normal. The patient is considered a candidate for IV tissue plasminogen activator (t-PA). Because the patient is not competent to give informed consent, the patient's wife is advised of the risks and benefits of IV t-PA, including a 6% risk of intracerebral hemorrhage possibly causing neurologic worsening or even death. She is told that, despite this risk, more patients who receive tPA recover from their strokes than those who do not. The patient's wife consents to proceeding with IV t-PA treatment, which is administered 1 hour and 40 minutes after stroke onset.

DISCUSSION
In "Consent issues in the management of cerebrovascular diseases," a position paper of the AAN's Ethics, Law, and Humanities Subcommittee (1999), three elements were considered necessary and sufficient for a valid consent: adequate decision-making capacity, presentation of adequate information for an informed consent, and freedom from coercion. Adequate decision-making capacity requires that the patient is capable of understanding the relevant issues and can accurately convey his or her responses to the examiner. Many stroke patients would fall outside of this standard, particularly in the setting of impaired consciousness, aphasia, or significant cognitive deficits. Determining the necessary information regarding IV t-PA for the consent process is a significant challenge. The AAN guidelines specify that information must be adequate for a reasonable patient to make an informed decision, including risks and benefits, choice of options, and an explanation of a recommended course of action. In the case of IV t-PA, this information should include the increased short-term risk of hemorrhage and the potential long-term benefit of improved stroke outcomes. The decision-making process must not be unduly influenced by physicians, other family members, or any outside agency. Discussion of the risks and benefits of IV t-PA may include a summary of the published studies. The National Institute of Neurological Disorders and Stroke (NINDS) t-PA trial randomized 624 patients treated within 3 hours of onset of stroke to treatment with either IV t-PA or placebo (The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995). This study found an 11% absolute increase (55% relative) in favorable outcomes (NIHSS less than 1) at 90 days despite a 10-fold increase in

intracerebral hemorrhage (6% versus 0.6%). There was no significant difference in mortality (17% versus 21%). The study has been criticized because of a baseline imbalance in stroke severity between the two groups. A subsequent reanalysis showed that even after statistical adjustment for this imbalance, patients were twice as likely to achieve a favorable outcome if they received IV t-PA (Ingall et al, 2004). Similar experience with IV t-PA has been reported for treatment of patients in community and academic hospitals outside the setting of randomized controlled trials (Albers et al, 2000; Tanne et al, 1999). Other trials of IV thrombolysis for acute stroke failed to find significant benefit, but longer time windows for initiation of treatment (6 hours) (Clark et al, 1999; Hacke et al, 1995; Hacke et al, 1998), the use of different thrombolytics (streptokinase) (Donnan et al, 1996; Multicenter Acute Stroke Trial-Europe Study Group, 1996; Multicentre Acute Stroke Trial-Italy [MAST-I] Group, 1995), and other methodologic differences make direct comparisons difficult. A pooled analysis of all prior IV t-PA trials confirmed the benefit of IV t-PA up to 3 hours after stroke onset and indicated the benefit extended to 4.5 hours (Hacke et al, 2004). The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) registry of 6483 patients treated within 3 hours of stroke onset at 285 centers also found outcomes similar to those achieved in previous randomized controlled trials with no increase in hemorrhage rate or mortality (Wahlgren et al, 2007). No general agreement exists on the extent of details necessary to properly advise a patient or surrogate regarding the risk and benefits of IV t-PA. The information included in the informed consent process varies and largely depends on the physician's level of comfort that sufficient information has been provided to allow an informed decision.

Documentation of Informed Consent for IV t-PA

Some physicians and hospitals prefer a formal written consent documenting information regarding the risks and benefits signed by the patient or surrogate. Current American Heart Association/American Stroke Association guidelines do not support the need for a formal written consent (Adams et al, 2003), but recommend a detailed discussion with the patients and their families providing potential risks and benefits associated with thrombolytic therapy. The discussion should be documented in the medical record, including the person or persons receiving the information, the content of the discussion, and the source of the consent. If consent is not given, the reasons for denial should be noted. When a surrogate is used for consent, the nature of the deficits that render the patient incapable of giving consent should be noted.

Emergency Consent
In some cases, a patient is considered incapable of giving consent, and no surrogates are available in the emergent timeframe necessary for treatment with IV t-PA. In such situations, an exemption to the informed consent process exists that justifies initiation of treatment without specific consent (Fleck and Hayes, 2002). Four conditions should be met to invoke this exemption: (1) delay in treatment would have significant adverse effects; (2) no alternatives are available that would be equally effective but allow additional time for the consent process; (3) a reasonable person, if given sufficient time to consider the evidence, would agree to the treatment; and (4) the treatment should be considered as usual care. Most would agree that the first two conditions are satisfied for IV t-PA. Differences of opinion may exist regarding the third and fourth conditions, and physicians must decide for themselves whether the evidence regarding IV t-PA and the approval of the US Food and Drug Administration satisfies these criteria.

REFERENCES
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