Introduction
- The overall prevalence of ACE inhibitor angioedema is low (~0.2-0.7%), however it makes up the
- ACE inhibitor angioedema is caused by the buildup of bradykinin which leads to increased vascular
- ACE inhibitor angioedema can occur at any time, with the majority of cases occurring within the
- Risk factors for ACE inhibitor angioedema includes female sex, African American race, chronic
majority of visits to the ED for angioedema
permeability and the release of substance P resulting in vasodilation and fluid extravasation into
tissues
first month of therapy.
heart failure, coronary artery disease, history of smoking, and concomitant use of dipeptidyl
peptidase 4 (DPP4) inhibitors
Clinical Detail
| Fresh Frozen Plasma (FFP) | Icatibant | Tranexamic Acid (TXA) | |
|---|---|---|---|
| Dose | 2-4 units | 30 mg | 1000 mg |
| Administration | Intravenous | Subcutaneous | Intravenous |
| PK/PD | Onset: ~ 2 hours | Onset: 2 hours Duration: 6 hours | Onset: ~ 2 hours |
| Adverse Effects | Hypervolemia, TRALI, thrombosis, hyperfibrinolysis, infection | Injection site reactions, LFT elevations, dizziness | Abdominal pain, headache, musculoskeletal pain/spasms |
| Drug Interactions and warnings | Calcium administration within the same line (may produce precipitants) | None | Contraindicated in patients with SAH or active intravascular clotting |
| Compatibility | N/A | N/A | Compatible with NS, D5W, or LR |
| Comments | Takes ~ 30-45 minutes to thaw & process once ordered | Costs ~ $4,500 per 30 mg syringe (AWP) | Available in most emergency departments. Inject 1000 mg TXA in 100 mL of diluent |
Evidence
| Author, year | Design / sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Baş, 2015 | RCT (n = 27) | SubQ Icatibant 30 mg vs. prednisolone + clemastine | Time to complete symptom resolution: 8 hours vs. 27.1 hours (P=0.002). Time to onset of symptom relief: 2 hours vs. 11.7 hours (P=0.03). All patients experienced complete resolution of edema. |
| Straka, 2017 | RCT (n = 33) | SubQ Icatibant 30 mg vs placebo | Time-to-resolution (27.2 hrs vs 35.3 hrs) and amount of swelling over time were similar in placebo and icatibant treatment groups. |
| Sinert, 2017 | RCT (n = 121) | SubQ Icatibant 30 mg vs placebo | There were no difference time to meeting discharge criteria between groups (4 hrs vs 4 hrs). |
| Karim, 2002 | Case Report (n = 1) | 4 units FFP following chlorpheniramine, hydrocortisone, and epinephrine | Dramatic improvement within 2 hours following FFP administration allowing for extubation. |
| Warrier, 2004 | Case Report (n = 1) | 2 units FFP following antihistamine, corticosteroid, epinephrine, antileukotrienes, cyclosporine, and IVIG (all without improvement) | Complete resolution of symptoms within 2-4 hours following FFP administration. |
| Bolton, 2012 | Case Report (n = 1) | 2 units FFP following antihistamine and corticosteroid administration | Near complete resolution of symptoms within 2 hours following FFP administration. |
| Hassen, 2013 | Case series (n = 7) | 2 units FFP following antihistamine and corticosteroid administration | Temporal association between the administration of FFP and improvement in angioedema in 7 cases of presumed ACEI-induced angioedema that were refractory to histamine-related anaphlaxis. |
| Stewart, 2013 | Case Report (n = 2) | 2 units FFP administered | Administration of FFP resulted in rapid resolution of symptoms in both patients. |
| Beauchêne, 2018 | Case Series (n = 33) | Tranexamic Acid IV: 24 patients (73%) PO: 8 patients (24%) Unknown: 1 patient (3%) Dosage: 500 mg – 4 grams (55% received 1 g) | 81.8% patients achieved significant improvement following TXA administration alone. 39.3% patients experienced symptom improvement within 1 hr of TXA administration. |
| Wang, 2020 | Case Report (n = 1) | TXA 1000 mg IVPB over 10 minutes administered following diphenhydramine, famotidine, methylprednisolone, and epinephrine | Improvement in speech observed within 30 minutes of TXA administration with complete resolution of symptoms at 2 hrs. Patient discharged 2.5 hours following presentation to ED. |
| Manzano, 2021 | Case series (n = 11) | TXA 1000 mg IV | The median length of stay in the hospital was 1.2 days (0.4-18.2 days). No noted adverse effects related to medication administration of TXA. |
Conclusions
- Many cases of ACE inhibitor angioedema will resolve on their own with the cessation of the
- More studies are needed to evaluate the use of investigational therapies including tranexamic acid
- In severe cases of ACE inhibitor angioedema, it is reasonable to consider using tranexamic acid or
(Christian Leppert & [email protected]
offending agent.
and FFP.
FFP if icatibant is unavailable after weighing the risks versus benefits.
References
- Lexicomp Online, Hudson, Ohio: UpToDate, Inc.; 2021; April 22, 2021. Available from:
- Brown T, Gonzalez J, Monteleone C. Angiotensin-converting enzyme inhibitor-induced angioedema: a review
- Campo P, Fernandez TD, Canto G, et al. Angioedema induced by angiotensin-converting enzyme inhibitors.
- Byrd JB, Touzin K, Sile S, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor-associated
- Straka BT, Ramirez CE, Byrd JB, Stone E, Woodard-Grice A, Nian H, Yu C, Banerji A, Brown NJ. Effect of
- Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W;
- 1016/j.jaip.2017.03.003. Epub 2017 May 25. PMID: 28552382.
- Baş M, Greve J, Stelter K, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J
- Karim MY, Masood A. Fresh-frozen plasma as a treatment for life-threatening ACE-inhibitor angioedema. J
- Warrier MR, Copilevitz CA, Dykewicz MS, et al. Fresh frozen plasma in the treatment of resistant angiotensin-
- Hassen GW, Kalantari H, Parraga M, Chirurgi R, Meletiche C, Chan C, Ciarlo J, Gazi F, Lobaito C, Tadayon S,
- Bolton MR, Dooley-Hash SL. Angiotensin-converting enzyme inhibitor angioedema. J Emerg Med.
- Stewart M, McGlone R. Fresh frozen plasma in the treatment of ACE inhibitor-induced angioedema. BMJ Case
- Wang K, Geiger H, McMahon A. Tranexamic acid for ACE inhibitor induced angioedema – A case report. Am
- Beauchêne C, Martins-Héricher J, Denis D, et al. Tranexamic acid as first-line emergency treatment for
- Martinez Manzano JM, Lo KB, Patarroyo-Aponte G, Azmaiparashvili Z. The use of intravenous tranexamic acid
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