Hit Them Hard: The Use of H1 and H2 Antagonists for Acute Allergic Symptoms

This is part of a recurring series examining landmark articles in Emergency Medicine, in the style of ALiEM’s 52 Articles.

This blog post reviews the article by 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):462-8.

Main Points:

  1. In this randomized, double blinded, placebo controlled trial of 91 patients presenting with acute allergic symptoms fewer patients in the active arm (ranitidine + diphenhydramine) had signs of cutaneous involvement such as urticaria at 2 hours compared to the placebo group (placebo + diphenhydramine).
  1. There was no significant difference, however, between the placebo group and active group with regards to the absence of erythema or angioedema at two hours.

Background:

Many patients present to the emergency department with acute allergic syndromes. Anti-histamines, primarily diphenhydramine, are the mainstay therapy in most mild cases and are both safe and cost effective. The addition of H2 antagonists such as ranitidine to diphenhydramine may help improve clinical outcomes and expedite management in the emergency department. The primary goals of this study were to look for resolution of urticaria and angioedema at two hours from presentation. This study was well balanced in its patient recruitment and overall provides insight into real-world application of a second agent for management of allergic symptoms.

Details:

The methodology within this study was rigorous, though the sample size was small. This trial was a randomized, double blinded, placebo controlled trial that enrolled 91 patients at an academic emergency department in New York, NY. Enrollment was based on a convenience sampling associated with the study physicians’ scheduling. Patients were enrolled in this study if they were adults who presented with acute urticaria, acute angioedema, acute unexplained stridor or acute pruritic rash following an exposure to a food, drug or contact with latex. Patients underwent vital sign monitoring, examination for physical findings such as: presence and extent of urticaria and erythema, presence of angioedema, wheezing, stridor, abdominal distention or tenderness, as well as symptom scoring. This data collection occurred at presentation, at 1 hour and 2 hours.

This study demonstrated a statistically significant difference, p=0.03, in the resolution of urticaria in the active group compared to the placebo group at two hours. One significant limitation in this study is that the treating physician was able to administer supplemental medications such as epinephrine, corticosteroids, bronchodilators and additional doses of antihistamine at their discretion with significantly more participants in the ranitidine arm receiving epinephrine, 17, compared to 9 in the placebo arm. The placebo arm had more use of additional antihistamine, 10, compared to 2 in the ranitidine arm. These additional therapies are documented in table 3; however, it is unclear if the severity of illness was equal between the two groups. The authors do note in their discussion that there was no observed covariate effect for epinephrine administration with respect to urticaria resolution.

Level of Evidence:

This study was graded a level I based on the ACEP Clinical Policy Grading Scheme

Surprises:

Within the sample groups there was significant history of asthma as well as other nonasthmatic atopic conditions which supports the theory that certain individuals are genetically predisposed to allergic syndromes.

Source Articles:

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):462-8.

Faculty Reviewer: Dr. Siket

3 thoughts on “Hit Them Hard: The Use of H1 and H2 Antagonists for Acute Allergic Symptoms

  1. Hi All. I’m not sure the conclusion from this 15 year old study should be to “Hit ‘Em Hard” with both H1 and H2 blockers. The placebo and treatment groups were NOT equal, and the one medication that significantly affects urticaria – epinephrine – was used almost twice as often in the treatment group. I would interpret this as not demonstrating a significant difference. When you add the nursing time and cost of adding another medication, I don’t think this study shows that adding the H2 blocker is worth it. So, I will be sticking with diphenhydramine and adding epi if I really want to reduce urticaria and tissue swelling.

  2. I’d tend to agree with Dr. Zink (and not just because I’m contractually obligated to).

    In addition, I’d hasten to note that the outcome, while patient-centered in terms of measuring an obnoxious symptom, is not the life-threatening outcome that we’d really like to prevent, i.e. recurrence of anaphylaxis. I’m not aware of anyone having died from hives.

  3. no, but I will tell you that, this summer when I had three separate episodes of multiple wasp stings with diffuse urticaria, I used EVERYTHING I had at home (benadryl and zantac) as I was fleeing to the CVS for steroids. There’s a desperation factor involved that made me ignore the studies….

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