Q:

3/12/2012
This patient is an 11-1/2-year-old boy who has had a documented allergic reaction to peanut butter characterized by facial swelling and hives. He did not have respiratory distress or other systemic signs of anaphylaxis. He does not have asthma. He has a history of prolonged QT syndrome for which he takes nadolol therapy. Peanut RAST 9.64. Peanut avoidance measures have been instituted. What is the appropriate emergency treatment for this patient. Does the benefit of epinephrine outweigh any possible risk of Toursades given his prolonged QT syndrome? Should I consider glucagon instead of epinephrine?

A:

Thank you for your inquiry.

This is indeed a difficult question, and unfortunately I do not have a definitive answer. We have received similar inquiries previously, and the answer to your question would be identical to the response to such inquiries. For your convenience, I have copied below a similar question and our response, and have also included the abstract from which part of this response was taken.

I wish I could tell you that this response would give you some solace as to the "proper approach," but the problem is indeed not solvable in an axiomatic fashion. It remains, as it was at the time we responded to the previous inquiry, one of debate.

It is clearly one which I would discuss with his cardiologist. My statements regarding the potential adverse effect of glucagon were drawn from a basic knowledge of pharmacology and physiology, but I could not find any studies looking at the effect of glucagon in patients with prolonged QT syndrome. It may be that the cardiologist has further insight in this regard, and glucagon might be more acceptable. However, based upon the information that I have been able to glean from the literature, I am not sure that glucagon would be a better choice. Thus more than likely it will remain a clinical decision based on risk/benefit ratio as to whether to administer epinephrine to this boy should he experience a systemic response to the ingestion of peanut. Since there is no definitive answer, I think that the best approach would be to discuss the issue with his cardiologist who could probably give you the best opinion as to the risk of epinephrine, and then together make a decision with the input of the parents.

Thank you again for your inquiry and I am sorry that we could not be of more definitive help with this difficult question.

Previous inquiry and response:
Management of large local reaction to insect sting in a child with prolonged QT syndrome on a beta-blocker

Question:
I am seeing a 7 year-old female with prolonged QT syndrome referred because of large local reactions to hymenoptera stings. Her skin tests are positive only to honeybee and IgE Rasts to the other venoms are pending. Normally, neither skin testing nor venom immuntherapy would be indicated in this child. However, epinephrine is contraindicated and her risk of a systemic reaction is at least slightly increased because of the large local reactions. She is also on a beta-blocker for her prolonged QT. My main question is whether venom immunotherapy is indicated. I would would like any other suggestions for management. Would she benefit from a glucagon kit? Because she is so high risk, should I inquire with the ped cardiologist about the possibilty of an implantable defibrillator?

Answer:
Thank you for your recent inquiry.

You have analyzed the difficult management decisions quite well regarding the patient you describe. Unfortunately, there are no true, in my opinion, "right or wrong" answers to the questions you posed. This is simply because, for the most part, there are not enough data in the literature to allow you to make an evidence-based or even a consensus-based decision in answering these questions.

Thus, in the final analysis, each answer will be determined mainly by your best analysis of risk versus benefit, and by you and your patient's personal philosophy as to how you might proceed.

Thus, I can only give you a personal perspective regarding these questions, and perhaps some assistance in analyzing the available literature to help you make a final decision.

I will save your major question regarding venom immunotherapy until last. First a comment regarding glucagon.

You quite correctly considered glucagon as an alternative to epinephrine since your patient is on a beta-blocker. You also pointed out correctly that epinephrine is contraindicated in a patient with prolonged QT syndrome. It might help, to answer your question, to better understand why epinephrine is contraindicated.

As you know, epinephrine is both a beta and alpha adrenergic agent. It is important to understand which of these two components is perhaps more responsible for the tachyarrhythmias that can occur in a patient with prolonged QT interval given an adrenergic agent. There is at least one study in this regard which compares the effect of epinephrine (beta and alpha adrenergic agent) with phenylephrine (an alpha adrenergic agent). Both of these agents, in this investigation, were given by infusion to sixteen patients with congenitally prolonged QT intervals and9 healthy controls. Epinephrine, but not phenylephrine, increased the QT dispersion, suggesting that the beta-adrenergic stimulation provoked the arrhythmias.

The authors concluded that beta-adrenergic stimulation by aggravating "nonhomogeneity of ventricular repolarization" is responsible for arrhythmias to a far greater extent that alpha stimulation. This is important because glucagon administration clearly produces changes similar to that of a beta-adrenergic agent including increases in cardiac index, stroke power index, mean left ventricular ejection, maximum rise of left ventricular pressure, and also heart rate. Thus, even though glucagon might be successful in treating an anaphylactic event more so than epinephrine in a significantly beta-blocked individual, it may well be capable of provoking the same type of tachyarrhythmia in a patient with prolonged QT interval as epinephrine.In addition glucagon is not the initial drug of choice even in patients on a beta-blocker. Epinephrine remains the drug of choice with glucagon an option if there is no response. Thus, the same admonition you mention against the administration of epinephrine in this child probably exists for the administration of glucagon as well. I am of course not expert in this area, and you would certainly want to discuss this issue with the cardiologist, but based upon the known actions of glucagon, I would surmise that it would be relatively contraindicated in a patient with a prolonged QT interval.

In addition, one might consider also, in making this decision, whether the risk of a fatal anaphylactic episode would be greater than the risk of a fatal reaction to an arrhythmia produced by glucagon. As you know, the risk of fatality in anaphylactic events is quite low. I am not aware of the risk of fatalities to tachyarrhythmias in patients with prolonged QT intervals, but I would assume it would be perhaps greater than that caused by an anaphylactic episode. The vast majority of episodes of anaphylaxis are non-fatal.

In addition, one must consider in giving glucagon, the difficulties patients normally have in drawing up accurate doses of medication during stress, the need to keep a bottle and separate syringe with the patient at all times, the inaccuracies in dosing that may occur during stress, and the psychological effect on the child and parent on being told that a sting might well be fatal and the patient should be equipped with this treatment at all times (even though the child has only experienced local reactions).

Unfortunately, I have no helpful comment regarding the decision as to whether or not to suggest an implantable defibrillator. There is of course no data in the literature that addresses this specific issue, and I think perhaps the best way to approach it might be by simply asking the question, "Would you implant a defibrillator in your own child under these circumstances?". I know of no way to approach this problem other than to discuss it with the parents and the cardiologist.

Your final and major question was whether or not the child should receive immunotherapy. Again, there is no definitive answer, but one can get some sense of perspective by looking at some available data that we have.

We know based upon well done studies that the risk of an anaphylactic reaction in this child is 10% or less. We also know that the risk of systemic symptoms occurring in patients receiving venom immunotherapy is 5 to 15% during the initial weeks of treatment, regardless of the regimen used. You might decrease that by pretreatment with antihistamines during immunotherapy. However, a risk still remains.

Thus, one could argue that the risk of a systemic reaction is equivalent for administering immunotherapy and not administering immunotherapy. One might favor immunotherapy, however, since the reaction would occur in office, and medical personnel would be available for management. On the other hand, the mandate for "primum non nocere" is one caution in this regard.

Based on these observations, I can only give you an opinion as to how I might approach this issue. My strategy in this regard would probably be to follow the "party line" for patients with large local reactions who have no complicating issues such as a prolonged QT interval. I would still, based upon the present guidelines, probably choose not to perform immunotherapy in this patient because her reactions were limited to large locals. In addition, she is also on a beta-blocker, another relative contraindication to immunotherapy.

However, I am sure that if you presented this issue to a number of experts in this area, you might get several other opinions. These could well be contrary to mine, and as stated above, I think the final analysis can only be made by a discussion between you, the parents, and the cardiologist regarding the problems you outline.

Abstract:
Journal of the American College of Cardiology
Volume 31, Issue 6, May 1998, Pages 1400-1405
Clinical Studies
Effects of Epinephrine and Phenylephrine on QT Interval Dispersion in Congenital Long QT Syndrome
Abstract
Objectives: Measurement of QT interval dispersion during pharmacologic adrenergic stimulation was used to assess the effect of alpha- and beta-adrenergic stimulation on arrhythmic vulnerability in familial long QT syndrome (LQTS).
Background: Nonhomogeneity in the ventricular action potential duration causes electrical instability leading to life-threatening ventricular arrhythmias and is markedly increased in LQTS. QT interval dispersion measured from the electrocardiogram (ECG) can be used as an index of nonhomogeneous ventricular repolarization.
Methods: Sixteen symptomatic patients with LQTS and nine healthy control subjects were examined at baseline and during epinephrine (mainly beta-adrenergic agonist, 0.05 ìg/kg body weight per min) and phenylephrine infusions (alpha-adrenergic agonist, mean 1.4 ìg/kg per min). QT interval dispersion was determined from a 12-lead ECG as interlead range and coefficient of variation measured to the end (QTend) and apex (QTapex) of the T wave.
Results: At baseline QTend dispersion was greater in patients with LQTS compared with control subjects (mean [±SD] 68 ± 34 vs. 36 ± 7 ms, p = 0.001). QTend dispersion was markedly increased in patients with LQTS by use of epinephrine (from 68 ± 34 to 90 ± 36 ms, p = 0.002), but remained unchanged in control subjects. Phenylephrine did not affect QT dispersion in either group (all p = NS). Atrial pacing to achieve comparable heart rates during baseline and epinephrine and phenylephrine infusions did not influence the magnitude of QT dispersion in either group. QTapex dispersion analysis gave congruent results.
Conclusions: Epinephrine but not phenylephrine increased QT dispersion, suggesting that beta-adrenergic stimulation provokes arrhythmias in patients with LQTS by aggravating nonhomogeneity of ventricular repolarization, whereas alpha-adrenergic stimulation is less important for arrhythmic vulnerability. The results also suggest that rapid pacing may not reduce vulnerability to arrhythmias in congenital LQTS.

Thank you again for your inquiry and we hope this response is helpful .

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology