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Three Part Question

In the [treatment of anaphylaxis] does the addition of an [H2 receptor antagonist] [improve outcome]?

Clinical Scenario

A 26 year old man presents to the emergency department with anaphylaxis. He has required intramuscular adrenaline. He has had 10mg of chlorphenamine, intravenous steroids and IV crystalloids. You wonder if the addition of an IV H2 antagonist such as ranitidine will improve outcome.

Search Strategy

The "Healthcare Databases" from the National Library for Health interface of the MEDLINE database 1950 to present was used.

{exp ANAPHYLAXIS/ OR exp DRUG HYPERSENSITIVITY/ OR exp HYPERSENSITIVITY, IMMEDIATE/ OR (anaphyla* OR allerg*).af [Limit to: Humans and English Language]} AND {exp HISTAMINE H2 ANTAGONISTS/ OR exp CIMETIDINE/ OR exp RANITIDINE/ OR (nizatidine OR famotidine).af [Limit to: Humans and English Language]}

Search Outcome

518 papers were identified.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lin R, Curry A, Pesola G, et al November 2000 USA	91 adults presenting to the ED with urticaria, acute angioedema, acute unexplained stridor or acute pruritic rash within 12 hours of ingested food or ingested, inhaled or injected drug or contact with latex.	Patients received either 50mg of diphenhydramine and placebo or 50mg of diphenhydramine and 50mg of ranitidine. Outcomes were measured at 1 hour and 2 hours.	Absence of urticaria at 2 hours	91.7% (ranitidine gp.) vs 73.8% (placebo gp.). 53 patients total, P=0.02	Wide Inclusion criteria. Patients were on less severe end of allergic spectrum of allergic syndromes: only 2 had hypotension and only 10 had stridor, tongue swelling or laryngoedema. No patients were intubated.
			Absence of angioedema or urticaria at 2 hours	70.5% (ranitidine gp.) vs 46.5% (placebo gp.). 72 patients total, P=0.02
			Mean systolic BP (mmHg) at baseline and 2 hours	125 +/- 19 and 119 +/- 15 (ranitidine gp.) Vs 132 +/- 19 and 112 +/- 18 (placebo gp.) No difference.

Comment(s)

There have been some studies that show that pretreatment with combined H1 and H2 antagonists are more effective in preventing allergic reactions than H1 blockade alone. Lin et al directly compared a H1 antihistamine to a combination of H1 and H2 antihistamines in patients with allergic reactions. They showed that there was a significant benefit in the patients with urticaria and in those with urticaria or angioedema in the H2 antagonist group. The patients however were on the less severe end of the spectrum of allergic reactions with only a small proportion having hypotension or airway compromise. Given that anaphylaxis is relatively uncommon, it is likely that a multi-centred trial would be needed to recruit the necessary numbers to answer this question.

Clinical Bottom Line

There is some evidence to support the use of H2 antagonists in anaphylaxis but the clinical significance of this is uncertain.

References

1. Lin R, Curry A, Pesola G, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists Annals of emergency medicine November 2000 36:5 462-468