Q:

10/19/2015
I have very few patients who react to some food or some drug with an allergic classical reaction even sometimes with an anaphylactic shock, but the amazing point is that they develop a hypertension instead of hypotension. How to explain this and what would be the place of adrenaline?

A:


Anaphylaxis is a syndrome and the manifestations show wide variability during a single episode and among individuals. The source of the allergen, the status of the affected individual prior to the event, the physiologic responses to anaphylaxis, the time course and variability as to which organ systems are most affected add to the range of clinical manifestations.

Your question specifies “anaphylactic shock” but this is not consistent with hypertension by definition. However, during a reaction, patients may initially have hypertension and subsequently develop hypotension. Peripheral vasoconstriction also varies during the course of anaphylaxis such that the hypotension occurring late in anaphylaxis is more likely due to third space loss with reduced vascular volume and myocardial contractility rather than vasodilation. In this situation, epinephrine would have limited or no benefit and the preferred treatment would be vascular volume replacement.

My approach with suspected or definite anaphylaxis with hypertension is to use lower doses of IM epinephrine (e.g. 0.05-0.1 mg for an adult) and closely observe the patient with frequent rechecks of the blood pressure. I do not think you are placing your patient at risk with low dose epinephrine and you are potentially adding risk if you delay treatment of anaphylaxis.

I will share your question with the lead author of the prior and most recent Practice Parameter: Diagnosis and Management of Anaphylaxis (2010 Anaphylaxis Practice Parameter), Dr. Phil Lieberman. Dr. Lieberman has responded. First let me concur with everything Dr. Ledford mentioned in his response to your question, and I would add the following:

First of all, in actuality, it should not be surprising that patients who have classic anaphylactic reactions characterized by skin and respiratory involvement also experience hypertension rather than hypotension. A starting point to understand that would be to review the NIAID/FAAN definition of anaphylaxis (1) which has also been adopted by the FDA in establishing whether or not an anaphylactic event has occurred during the administration of a drug under investigation for approval. For your convenience, I have copied this definition copied.

“Clinical criteria for diagnosing anaphylaxis
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP**
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's baseline

PEF, Peak expiratory flow; BP, blood pressure.
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 mm Hg + [2 × age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years.”

As you can see, anaphylaxis can exist without hypotension. The question then becomes how often this occurs, and based on a number of studies (2-9), the vast majority of anaphylactic episodes occur without hypotension. Clinical manifestations of hypotension such as dizziness or documented hypotension occur in probably somewhere around a third of reactions based upon these studies. This means of course that two-thirds occur without hypotension, but it should be clearly stated that does not mean these patients are normotensive. In fact, many are hypertensive during these events. Perhaps the majority experience elevation of blood pressure during non-hypotensive episodes. The reason for this is that during episodes of anaphylaxis, the blood pressure can become elevated because there is compensatory secretion of catecholamines, both norepinephrine and epinephrine (10, 11); activation of the angiotensin system with production of angiotensin I and angiotensin II (12); and production of endothelin-1, a potent vasoconstrictor peptide that is elevated in patients with heart failure, strokes, and hypotension as well (13). “

Unfortunately, we do not know in many cases why a given individual characteristically develops hypotension during anaphylactic episodes whereas other patients do not except for the predisposition to hypotension in patients taking beta-blockers and ACE inhibitors. Nonetheless, many patients do have hypertension accompanying respiratory and cutaneous manifestations, and as noted above, this is probably due to a stress response involving catecholamines, angiotensin, and endothelin.

References:
1. Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: summary report - second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis
Network Symposium. J Allergy Clin Immunol. 2006; 117(2):391-397.
2. Soreide E, Busrod T, Harber S. Severe anaphylactic reactions outside hospital; etiology, symptoms, and treatment. Acta Anaesthesiologica Scandinavica 1988; 32:339-344.
3. Moro M, Tejedor M, Esteban J, et al. Severity of anaphylaxis according to causes and demographic characteristics. Journal of Allergy and Clinical Immunology 2008; 121(2):S24.
4. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. Journal of Allergy and Clinical Immunology 2001; 107:891-896.
5. Braganza SC, Acworth JP, McKinnon DR, et al. Pediatric emergency department anaphylaxis: different patterns from adults. Archives of Disease in Childhood 2006; 91:159-163.
6. Simons FER, Chad ZH, Gold M. Anaphylaxis in children. Allergy and Clinical Immunology International, Journal of World Allergy Organization 2004; 1 (Supplement):242-244.
7. Simons FER. Anaphylaxis in infants: can recognition and management be improved? Journal of Allergy and Clinical Immunology 2007; 120(3):537-540.
8. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm. International Journal of Cardiology 2006; 110:7-14.
9. DeSouza RL, Short T, Warman GR, et al. Anaphylaxis associated with fibrinolysis, reversed with tranexamic acid and demonstrated by thromboelastography. Anaesthesia Intensive Care 2004; 32:580-587.
10. Fahmy NR. Hemodynamics, plasma histamine and catecholamine concentrations during an anaphylactoid reaction to morphine. Anesthesiology 1981; 55:329-331.
11. Moss J, Fahmy NR, Sunder N, et al. Hormonal and hemodynamic profile of an anaphylactic reaction in man. Circulation 1981; 63:210-213.
12. Rittweger R, Hermann K, Ring J. Increased urinary excretion of angiotensin during anaphylactoic reactions. International Archives of Allergy and Immunology 1994; 104:255-261.
13. Gawlik R, Rogala E, Jawor B. Endothelin-1 in plasma of patients with hymenoptera venom anaphylaxis. Journal of Allergy and Clinical Immunology 1998; 101 (abstract):S160.

Sincerely,
Phil Lieberman, M.D.

In summary, the combination of the variability of anaphylaxis severity, the variations during anaphylaxis, the vascular volume and vasomotor tone prior to the event, and the anxiety level associated with anaphylaxis contribute to differences in blood pressure. The assessment is further complicated by the fact that often we do not know the blood pressure prior to anaphylaxis, so that an elevated blood pressure reading may nevertheless be a decrease from the affected individual’s basal blood pressure.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI

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