ACE-I Angioedema ACE-I Angioedema and FFPand FFP

Tom GrosheiderTom Grosheider

Evidence in the EDEvidence in the ED

April 10, 2013April 10, 2013

BackgroundBackground

Angiotensin II AKA kinase II Angiotensin II AKA kinase II Accumulation of kinins thought Accumulation of kinins thought

responsible for angioedema through responsible for angioedema through opaque mechanismopaque mechanism

Cough is most common side effect Cough is most common side effect (up to 25% of patients)(up to 25% of patients)

Angioedema occurs in 0.1%-0.7% of Angioedema occurs in 0.1%-0.7% of patientspatients

Conventional TreatmentConventional Treatment

Diphenhydramine, steroids, H1-Diphenhydramine, steroids, H1-blocker, and epinepherine if severeblocker, and epinepherine if severe

Airway monitoringAirway monitoring Intubation Intubation Discontinue treatment and it usually Discontinue treatment and it usually

gets better in 24-48 hoursgets better in 24-48 hours

FFPFFP

Adopted from literature supporting Adopted from literature supporting its use in hereditary angioedemaits use in hereditary angioedema

In ACE-I AE, thought to be useful In ACE-I AE, thought to be useful because it contains kinin II, which because it contains kinin II, which catalyzes the breakdown of catalyzes the breakdown of bradykininbradykinin

Scant literatureScant literature

Article 1Article 1

Hassan, WH., Kalantari, H., Parraga, M., Hassan, WH., Kalantari, H., Parraga, M., Chirugi, R., Meletiche, C., Chan, C., Chirugi, R., Meletiche, C., Chan, C., Ciarlo., J, Gazi, F., Lobaito, C., Tadayon, Ciarlo., J, Gazi, F., Lobaito, C., Tadayon, S., Yemane, S., Velez, C., “Fresh Frozen S., Yemane, S., Velez, C., “Fresh Frozen Plasma for Progressive and Refractory Plasma for Progressive and Refractory Angiotensin-Converting Enzyme Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema,” The Inhibitor-Induced Angioedema,” The Journal of Emergency Medicine, Vol. 44, Journal of Emergency Medicine, Vol. 44, No. 4, pp 764-772, 2013. No. 4, pp 764-772, 2013.

Article 1Article 1

Case series of 7 patients treated for Case series of 7 patients treated for presumed ACE-I angioedemapresumed ACE-I angioedema

Subset from a larger retrospective Subset from a larger retrospective chart review delineating rate, causes, chart review delineating rate, causes, and ethnic differences from 2003-and ethnic differences from 2003-20122012

Identified 7 patients with severe, Identified 7 patients with severe, refractory ACE-I AE who improved refractory ACE-I AE who improved temporally with administration of FFP temporally with administration of FFP

Article 1Article 1  Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7

Age in years 49 64 58 62 51 73 45

Gender Female Male Male Male Female Male Male

Ethnicity AA AA Hispanic Hispanic AA AA AA

Dose and type of ACEI 40 mg lisinopril 40 mg lisinopril 30 mg lisinopril Enalapril Lisinopril Lisinopril

10 mg enalapril

Duration of use 1 year 1 year 3 years Unknown Unknown Unknown Unknown

ComorbiditiesDM<comma>

Asthma

Hepatitis C<comma> HIV          

FFP units 2U 3U 2U 2U 2U 2U 1U

C1 esterase   Normal Normal Normal   Normal Normal

C1 quantitative       Normal   Normal  

C2   Normal   Normal   Normal  

C3       Normal   Normal  

C4   Normal   Normal   Normal  

Angioedema course Progressive Progressive Progressive Progressive Progressive Progressive Progressive

Disposition ICU ICU ICU ICU ICU ICU ICU

LimitationsLimitations

Case reportsCase reports No evidence of causalityNo evidence of causality Small sample sizeSmall sample size Not everyone had a workup for HAENot everyone had a workup for HAE

Article 2Article 2

Bolton, MR., Dooley-Bolton, MR., Dooley-Hash, S., Hash, S., “Angiotensin-“Angiotensin-Converting Enzyme Converting Enzyme Inhibitor Inhibitor Angioedema,” Angioedema,” Journal of Journal of Emergency Emergency Medicine, Vol 43, Medicine, Vol 43, No. 4, pp. e261-No. 4, pp. e261-262, 2012.262, 2012.

Article 2Article 2

Single case report of a 76 y/o Single case report of a 76 y/o gentleman with facial and tongue gentleman with facial and tongue swellingswelling

Refractory to steroids and benadrylRefractory to steroids and benadryl Got better with 2u FFPGot better with 2u FFP Also, he had had a minor procedure Also, he had had a minor procedure

requiring LMA earlier in the day and requiring LMA earlier in the day and never had an HAE work-upnever had an HAE work-up

Article 3Article 3

Warrier, M., Copilevitz, C., Dykewicz., Warrier, M., Copilevitz, C., Dykewicz., “Fresh Frozen Plasma in the “Fresh Frozen Plasma in the Treatment of Resistant Angiotensin-Treatment of Resistant Angiotensin-converting Enzyme Inhibitor converting Enzyme Inhibitor Angioedema,” Annals of Allergy and Angioedema,” Annals of Allergy and Innunology, 9: 573-575, 2004.Innunology, 9: 573-575, 2004.

Article 3Article 3

43 y/o woman recently started on 43 y/o woman recently started on ramipril with AEramipril with AE

Resistant to steroids, benadryl, and Resistant to steroids, benadryl, and sub-q epi x2sub-q epi x2

Improved with 2u FFPImproved with 2u FFP

HUPismHUPism

ACE-I AE can be severe and life-ACE-I AE can be severe and life-threateningthreatening

FFP is not without risksFFP is not without risks FFP may be considered in severe, FFP may be considered in severe,

refractory cases of ACE-I AE, but the refractory cases of ACE-I AE, but the evidence is quite limitedevidence is quite limited