Angioedema Following tPA Administration for Acute Cerebrovascular Accident
Since bradykinin is broken down by several enzymes, including ACE, degradation is therefore delayed in patients on ACE-I.10 The alternate pathway for bradykinin degradation in the absence of ACE may also result in formation of des-Arg bradykinin, another similar active metabolite that mimics the effects of bradykinins.9 The formation of bradykinin through the proteolytic effects of tPA, in combination with the delayed breakdown in patient’s taking an ACE-I, likely plays a significant role in the development of angioedema.
In addition to the direct proteolytic effect of tPA resulting in angioedema, the underlying ischemic insult may also predispose patients to angioedema. As was the case with our patient, angioedema preferentially affects the ipsilateral side of the patient’s deficit.2,11,12 Theories suggest this is due to the lack of autonomic compensatory responses in the setting of ischemic insult.2 Interestingly, the development of angioedema in relation to the use of recombinant-tPA (eg, alteplase) in the setting of MI has not been as well described and may be related to the effect of central nervous system insult.3
Treatment
Although hemorrhagic complications of tPA therapy for cerebrovascular accident are well known, the risk for angioedema as a complication is less recognized. In most cases, angioedema is transient, and very few patients require aggressive support.3,12 Treatments that have previously been described include antihistamines and steroids.1,11,13 Epinephrine has been reported in one case study as an adjunct treatment of tPA-induced angioedema; however, it was given in combination with steroids and antihistimines.14 Therefore, caution should be taken regarding the use of epinephrine in this setting as there may be a theoretical precipitation of intracranial hypertension or hemorrhage.2
Given the likely significant role of the bradykinin-mediated pathway in tPA-induced angioedema, the true efficacy of these agents is unknown. Our patient had significant labial and lingual involvement, and given the concern for impending airway compromise, fiber optic intubation was performed. The decision to intubate and the technique employed must be carefully considered as a failed airway and need for a surgical airway is a concerning prospect in the setting of fibrinolytics. Successful cricothyroidotomy without significant complications has been described in the setting of streptokinase-induced angioedema when given for MI.15
Conclusion
The use of tPA for the treatment of ischemic stroke has been increasing over the last decade.16,17 Given the high prevalence of ACE-I use in patients who are also at risk for ischemic stroke, physicians administering tPA must be aware of the risk of tPA-associated angioedema. Patients with a known history of angioedema or anaphylaxis to tPA should be counseled on these risks and should not be given this medication, but rather considered for potential endovascular or mechanical clot retrieval therapy if they meet inclusion criteria for its use.
