ACE-I Angioedema and FFP Tom Grosheider Evidence in the ED April 10, 2013

Background Angiotensin II AKA kinase II Angiotensin II AKA kinase II Accumulation of kinins thought responsible for angioedema through opaque mechanism Accumulation of kinins thought responsible for angioedema through opaque mechanism Cough is most common side effect (up to 25% of patients) Cough is most common side effect (up to 25% of patients) Angioedema occurs in 0.1%-0.7% of patients Angioedema occurs in 0.1%-0.7% of patients

Conventional Treatment Diphenhydramine, steroids, H1-blocker, and epinepherine if severe Diphenhydramine, steroids, H1-blocker, and epinepherine if severe Airway monitoring Airway monitoring Intubation Intubation Discontinue treatment and it usually gets better in hours Discontinue treatment and it usually gets better in hours

FFP Adopted from literature supporting its use in hereditary angioedema Adopted from literature supporting its use in hereditary angioedema In ACE-I AE, thought to be useful because it contains kinin II, which catalyzes the breakdown of bradykinin In ACE-I AE, thought to be useful because it contains kinin II, which catalyzes the breakdown of bradykinin Scant literature Scant literature

Article 1 Hassan, WH., Kalantari, H., Parraga, M., Chirugi, R., Meletiche, C., Chan, C., Ciarlo., J, Gazi, F., Lobaito, C., Tadayon, S., Yemane, S., Velez, C., “Fresh Frozen Plasma for Progressive and Refractory Angiotensin-Converting Enzyme Inhibitor- Induced Angioedema,” The Journal of Emergency Medicine, Vol. 44, No. 4, pp , Hassan, WH., Kalantari, H., Parraga, M., Chirugi, R., Meletiche, C., Chan, C., Ciarlo., J, Gazi, F., Lobaito, C., Tadayon, S., Yemane, S., Velez, C., “Fresh Frozen Plasma for Progressive and Refractory Angiotensin-Converting Enzyme Inhibitor- Induced Angioedema,” The Journal of Emergency Medicine, Vol. 44, No. 4, pp , 2013.

Article 1 Case series of 7 patients treated for presumed ACE-I angioedema Case series of 7 patients treated for presumed ACE-I angioedema Subset from a larger retrospective chart review delineating rate, causes, and ethnic differences from Subset from a larger retrospective chart review delineating rate, causes, and ethnic differences from Identified 7 patients with severe, refractory ACE-I AE who improved temporally with administration of FFP Identified 7 patients with severe, refractory ACE-I AE who improved temporally with administration of FFP

Article 1 Case 1Case 2Case 3Case 4Case 5Case 6Case 7 Age in years GenderFemaleMale FemaleMale EthnicityAA Hispanic AA Dose and type of ACEI40 mg lisinopril 30 mg lisinoprilEnalaprilLisinopril 10 mg enalapril Duration of use1 year 3 yearsUnknown Comorbidities DM Asthma Hepatitis C HIV FFP units2U3U2U 1U C1 esterase Normal C1 quantitative Normal C2 Normal C3 Normal C4 Normal Angioedema courseProgressive DispositionICU

Limitations Case reports Case reports No evidence of causality No evidence of causality Small sample size Small sample size Not everyone had a workup for HAE Not everyone had a workup for HAE

Article 2 Bolton, MR., Dooley- Hash, S., “Angiotensin- Converting Enzyme Inhibitor Angioedema,” Journal of Emergency Medicine, Vol 43, No. 4, pp. e , Bolton, MR., Dooley- Hash, S., “Angiotensin- Converting Enzyme Inhibitor Angioedema,” Journal of Emergency Medicine, Vol 43, No. 4, pp. e , 2012.

Article 2 Single case report of a 76 y/o gentleman with facial and tongue swelling Single case report of a 76 y/o gentleman with facial and tongue swelling Refractory to steroids and benadryl Refractory to steroids and benadryl Got better with 2u FFP Got better with 2u FFP Also, he had had a minor procedure requiring LMA earlier in the day and never had an HAE work-up Also, he had had a minor procedure requiring LMA earlier in the day and never had an HAE work-up

Article 3 Warrier, M., Copilevitz, C., Dykewicz., “Fresh Frozen Plasma in the Treatment of Resistant Angiotensin-converting Enzyme Inhibitor Angioedema,” Annals of Allergy and Innunology, 9: , Warrier, M., Copilevitz, C., Dykewicz., “Fresh Frozen Plasma in the Treatment of Resistant Angiotensin-converting Enzyme Inhibitor Angioedema,” Annals of Allergy and Innunology, 9: , 2004.

Article 3 43 y/o woman recently started on ramipril with AE 43 y/o woman recently started on ramipril with AE Resistant to steroids, benadryl, and sub-q epi x2 Resistant to steroids, benadryl, and sub-q epi x2 Improved with 2u FFP Improved with 2u FFP

HUPism ACE-I AE can be severe and life- threatening ACE-I AE can be severe and life- threatening FFP is not without risks FFP is not without risks FFP may be considered in severe, refractory cases of ACE-I AE, but the evidence is quite limited FFP may be considered in severe, refractory cases of ACE-I AE, but the evidence is quite limited