1. Angioedema after Alteplase
Rebecca Cowie, APRN, RN, CCRN, SCRN

2. Definition
Angioedema is the swelling of deep dermis, subcutaneous, or submucosal tissue due to vascular leakage. [1, 2] Acute episodes often involve the lip, eyes, and face (see the image below); however, angioedema may affect other parts of body, including respiratory and gastrointestinal (GI) mucosa. Laryngeal swelling can be life-threatening. (Medscape, 2017)

4. Development after Administration of Alteplase
This life threatening effect has been reported in 0.9% to 5.1% treated with tPA
One meta-analysis published in 2013 (Yayan) found the following characteristics among patients who developed angioedema after administration of Alteplase:
58.5% were taking an ACE; 7.3 % were taking and ARB; 34.1% were not taking any medication prior
Symmetrical swelling of the tongue results in the highest risk for complications
Onset typically within 2 hours of administration (half life of Alteplase is ~ 7 minutes)
The site of angioedema tends to occur on the side opposite the cerebral lesion
Another analysis found that patients with total insular infarct were more likely to develop oral angioedema (Myslimi, et al., 2016).

5. Why does this occur?
The mechanisms underlying the development of angioedema are hydrolyzes of plasminogen to plasmin that activates the kinin system with occurrence of potent vasodilator bradykinin and activation of the complement system resulting in mast cell degranulation and histamine release. (Bozkurt, et al., 2015)

6. Assessment Baseline assessment of tongue
Observe for facial, tongue, or pharyngeal edema
Symptoms can be unilateral, so this symptom could be mistaken for facial weakness or dysarthria caused by initial stroke

7. Responding to Angioedema
Angioedema is a life threatening emergency
If an anaphylactic reaction (facial, tongue or pharyngeal edema) is suspected, STOP treatment immediately
Notify the physician
Administer antihistamines and corticosteroids
Prepare for possible intubation
Patients with oral angionedema did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1, mRS score of 0 to 2 , and death. (Myslimi et al., 2016)

9. Outcomes in those with angioedema versus those without
Patients with oral angionedema did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1, mRS score of 0 to 2 , and death. (Myslimi et al., 2016)

10. Staff Education
Staff should be educated on the risk of angioedema following administration of alteplase.
Signs and symptoms and frequent monitoring
Increased risk if on ACE inhibitor prior to alteplase
How to respond
Protocols or order sets in place for treatment

11. In Closing…
Educate your staff on the incidence, symptoms and treatment of oral angioedema following administration of alteplase.
Identify patients who may be at increased risk (ACE inhibitors prior to alteplase administration).
Develop order sets or protocols for rapid treatment.

12. Any Questions????

13. Find us on Facebook at fb.me/arstrokeprofessionals.
Interested in ASPECT?
Find us on Facebook at fb.me/arstrokeprofessionals.

14. References
Incidence, predictors and clinical characteristics of orolingual angio-edema complicating thrombolysis with tissue plasminogen activator for ischemic stroke. Hurford, R. Rezvani, S., Kreimei, M et all… Journal of Neurology, Neurosurgery and Psychiatry, 2014, doi: /jnnp
Lingual angioedema after alteplase treatment in a patient with acute ischemic stroke. Bozkurt, S., Arslan, E., Kose, A., Ayrik, C., Yilmaz, A., & Dundar, G. World Journal of Emergency Medicine, 2015, 6(1),
Onset of orolingual angioedema after treatment of acute brain ischemia with alteplase depends on the site of brain ischemia: a meta analysis. Yayan, J. North American Journal of Medical Sciences, 2013, 5(10).
Orolingual angioedema during or after thrombolysis for cerebral ischemia. Myslimi, F., et al. Stroke, 2016;47: DOI: /STROKEAHA