Orolingual Angioedema During or After Thrombolysis for Cerebral Ischemia

Abstract

We used data prospectively collected in a registry of consecutive patients treated with intravenous r-tPA for cerebral ischemia in the stroke center of the Lille University Hospital, from September 30, 2003 to February 4, 2015. The general organization, 4,5 eligibility criteria for thrombolysis, 2,6,7 clinical assessment, 8-10 imaging procedures, and treatment administration 7 have been previously described. 4,5 Patients from this cohort were included in previous studies of our group including one in which the occurrence of OLAE was reported 11 and in a case report. 12Background and Purpose-Orolingual angioedema (OLAE) is a life-threatening complication of intravenous thrombolysis. Our objective was to compare outcomes of patients with and without OLAE. Methods-We prospectively included consecutive patients who received intravenous thrombolysis for cerebral ischemia at Lille University Hospital. We examined tongue and lips every 15 minutes during thrombolysis and ≤30 minutes after. We evaluated the 3-month outcome with the modified Rankin scale (mRS) and compared outcomes of patients with and without OLAE. Results-Of 923 consecutive patients, 20 (2.2%) developed OLAE. None of them needed oro-tracheal intubation. They were more likely to be under angiotensin-converting enzyme inhibitors (adjusted odds ratio [adjOR], 3.9; 95% confidence interval [CI], 1.6-9.7; P=0.005) to have total insular infarcts (OR, 5.0; 95% CI, 1.5-16.5; P=0.004) and tended to develop more symptomatic intracerebral hemorrhages. Results concerning angiotensin-converting enzyme inhibitors were not modified after adjustment for propensity scores (OR, 4.4; 95% CI, 1.6-11.9; P=0.004) or matched analysis based on propensity scores (OR, 3.4; 95% CI, P=0.010). Patients with OLAE did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1 (adjOR, 0.9; 95% CI, 0.3-2.1), mRS score of 0 to 2 (adjOR, 0.8; 95% CI, 0.1-1.8), and death (adjOR, 1.1; 95% CI, 0.3-3.8). Conclusions-OLAE occurs in 1 of 50 patients who receive intravenous thrombolysis, 1 of 10 in case of total insular infarct, and 1 of 6 if they are under angiotensin-converting enzyme inhibitors. Their long-term outcome does not differ from that of other patients.

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT

“…Prevalence of OA in patients with acute ischemic stroke treated with alteplase was 4.9%, which is in accordance to previous studies [1][2][3][4]7]. We found no significant differences in the frequency of insular cortex ischemic lesions on pre-thrombolysis CT, and early signs of insular cortex ischemia were not independent predictors of OA occurrence in multivariate analysis.…”

“…Despite the well known limitation of CT for diagnosis of very early cerebral ischemic changes, early signs of insular ischemia on CT had the higher interobserver agreement among all cerebral regions evaluated in the Alberta Stroke Program Early CT Score in a relevant study by Gupta et al [8], which supports the clinical value of our findings. A recent study compared the frequency of insular infarcts in MRI in 19 patients who developed OA after thrombolysis and 77 selected patients who did not develop OA and there was no difference [4]. Despite this, these authors reported a similar frequency of small insular infarcts but a significantly higher frequency of total insular infarcts in patients with OA, which should be interpreted with caution because of the scarce number of patients with total insular infarcts.…”

“…In addition to contribute to several high order complex cerebral functions, insular cortex is known to mediate autonomic responses and it is involved in cardiac and vascular autonomic tone regulation and visceromotor control. The imbalance of sympathetic and parasympathetic control induced by insular ischemic lesions was proposed by several authors to contribute to the pathophysiology of OA [2][3][4][5]. Our aim was to study risk factors for OA occurrence in ischemic stroke patients treated with alteplase, in particular association with insular ischemia.…”

“…It consists of painless swelling of lips, tongue, face and occasionally oropharynx, occurring shortly after intravenous alteplase administration, which usually resolves during the first 24 h. Most case-control studies recognize use of angiotensin-converting enzyme inhibitors (ACE-I) as the main risk factor for occurrence of this potentially serious adverse event [1][2][3][4], and other authors found a higher frequency of insular ischemia in patients who developed angioedema [2,5]. In addition to contribute to several high order complex cerebral functions, insular cortex is known to mediate autonomic responses and it is involved in cardiac and vascular autonomic tone regulation and visceromotor control.…”

Orolingual and abdominal angioedema post thrombolysis and thrombectomy

“…Bradykinin-mediated angioedema can be a complication of recombinant tissue plasminogen activator, typically orolingual, with increased risk for patients on ACE inhibitors. 1 We speculate that the procedure of thrombectomy, acting as a mechanical stress, 2 could have been a triggering factor for the unusual presentation of abdominal edema. …”