Anaphylactic shock: the great mimic.

Abstract: Anaphylaxis, acute coronary syndrome and pulmonary embolism are conditions commonly seen in the acute medical setting which can be difficult to diagnose. Delay in establishing the correct diagnosis can result in either delayed or inappropriate treatment, and subsequent morbidity and mortality. The cases we present highlight the necessity of good clinical assessment when evaluating such patients.

Key Words: anaphylaxis, acute coronary syndrome, pulmonary embolism, troponin, D-dimer

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Anaphylaxis, acute coronary syndrome and pulmonary embolism are conditions commonly seen in the acute medical setting which can be difficult to diagnose. Delay in establishing the correct diagnosis can result in either delayed or inappropriate treatment, and subsequent morbidity and mortality.

We present two cases of anaphylaxis which highlight the necessity of good clinical assessment when evaluating such patients.

Case Reports

Patient 1

A 59-year-old woman presented with acute appendicitis. At induction of general anesthesia for an appendicectomy, she was given thiopental, fentanyl and suxamethonium. Within minutes of this, she became tachycardic and hypotensive, with her blood pressure dropping as low as 50/30 mm Hg. No swelling or rash was noted at that time. She was treated with metaraminol and gelofusine and improved. Postoperatively, an electrocardiogram showed lateral ST depression and troponin T was elevated at 0.11 ng/mL (normal range <0.1 ng/mL). Serial electrocardiograms showed inferior T wave inversion. While an inpatient, she developed a diffuse erythematous rash 24 hours after the operation, which was diagnosed as eczema and treated with topical steroids and antihistamines.

The patient was initially presumed to have had an acute coronary event in view of the electrocardiogram changes and elevated troponin level, and plans were made to investigate her further with coronary angiography. However, a serum tryptase performed retrospectively on a sample taken 1 hour after onset of symptoms was elevated at 117 ng/mL (normal range 2-14 ng/mL), which returned to 2.7 ng/mL. Consequently, allergy testing for anesthetic agents was performed. This showed a suxamethonium specific IgE of 0.62 kUA/L and negative skin prick and intradermal tests for fentanyl and thiopental. These results were thought to be consistent with anaphylaxis due to suxamethonium, complicated by transient myocardial ischemia presumably due to hypoperfusion. In addition, she had a myocardial perfusion scan which showed no coronary obstruction and a low likelihood of future coronary events.

Patient 2

A 44-year-old man presented with two episodes of syncope. After the second episode, he complained of dyspnea and noticed a rash over both lower legs. He denied any chest pain, palpitations, headache, neurologic disturbance, fever or precipitating events.

On examination, extremities were cool, and there was an urticarial rash involving the lower limbs. His heart rate was 90 bpm and regular, his blood pressure was 60/40 mm Hg and his respiratory rate was 28/min. Physical examination was otherwise unremarkable.

Laboratory investigations revealed elevated D-dimer (7832 [micro]g/L, normal range <200) and fibrinogen (5.1 g/L, normal range 1.5-4.5) with normal prothrombin time, full blood count, blood film and serum biochemistry. Arterial blood gases demonstrated type I respiratory failure (pO2 8kPa). Chest x-ray and ECG were normal. In view of these findings, pulmonary embolus was suspected but excluded after CT pulmonary angiography.

He admitted taking a single 75 mg diclofenac tablet approximately ten hours previously for gout. He had no other medical conditions. However, one month before presentation he had experienced a self-limiting urticarial rash over the lower limbs after a 2-week course of diclofenac 75 mg b.i.d. for the first presentation of gout.

A diagnosis of anaphylaxis was then made. The patient was treated with IV fluid, steroids, antihistamines and IM epinephrine. An IV epinephrine infusion was subsequently required to maintain hemodynamic stability. The patient was discharged from the hospital one day after presentation.

Discussion

Epidemiologic studies estimate that severe anaphylaxis affects 1 to 3 per 10,000 people, but has a higher incidence in the United States and Australia. (1) It is estimated to cause death in 1 to 3 per million people. Pathophysiologically, it is mediated by substances released systemically during mast cell and basophil degranulation, which cause increased vascular permeability, tachycardia, bronchospasm, pruritus, rhinorrhea, vasodilation, hypotension, flushing and headache. (2)

The main cardiovascular changes in anaphylaxis are fluid extravasation and vasodilation, which result in a mixed distributive-hypovolemic shock pattern. The increased vascular permeability in anaphylaxis can result in transfer of 50% of intravascular fluid into the extravascular space within 10 minutes. (3) In the lung, bronchospasm, tissue edema and hypotension all contribute to impaired gas exchange resulting in hypoxia.

Anaphylactic reactions have been reported to trigger cardiovascular events, including myocardial infarction and acute coronary syndromes, even in patients with normal coronary vasculature. (4) There is evidence to suggest that the chemical mediators of anaphylaxis have a direct effect on the heart, and the main proposed mechanism for allergy-induced acute coronary syndromes is coronary artery spasm. It is difficult to ascertain how large a contribution this has to cardiac dysfunction when the usual cause of poor cardiac output is poor venous return, and diastolic hypotension and hypoxia may result in myocardial ischemia. (5)

Serum tryptase assay can be utilized in distinguishing anaphylaxis from other conditions with similar clinical manifestations. (6) However, these levels should be obtained 1 to 2 hours after the onset of symptoms. If levels are high, they can occasionally be obtained 6 to 12 hours after presentation. (7)

Diagnosis of anaphylaxis under general anesthesia is difficult unless there is severe bronchoconstriction or hypotension, as cutaneous manifestations can be obscured by drapes; drug-induced hypotension is common and respiratory signs can be masked by inhalational anesthetics. In our first patient, this was the case as there was no marked bronchoconstriction or immediate skin reaction perioperatively. The most prominent abnormalities were the ECG changes and elevated troponin level, which resulted in the delay in diagnosis.

Pulmonary embolism can present with a wide range of clinical features, including dyspnea, tachypnea, pleuritic pain, apprehension, tachycardia, cough and hemoptysis. Many of these features can also be seen in anaphylaxis and were seen in our patient. Both guidelines on pulmonary embolism and anaphylaxis emphasize the need for careful assessment of probability in making the diagnosis. D-dimer testing is useful in excluding pulmonary embolism in patients when used with assessment of clinical probability. However, it has poor specificity and is elevated in a variety of settings, including anaphylaxis, due to activation of the coagulation pathway by allergic mechanisms. (8) It is not surprising that high levels of D-dimer were found in the second case we report here.

Conclusion

Anaphylaxis can present with similar features to other life-threatening medical emergencies with the cardinal features of hemodynamic compromise, cardiac dysfunction and hypoxia, as well as abnormal investigation results. Careful clinical assessment is important so that appropriate treatment can be instituted promptly to avoid further morbidity and mortality. Epinephrine is the first and most important treatment for anaphylaxis; considering its relative safety, when in doubt, epinephrine should be administered.

References

1. Moneret-Vautrin DA, Morisset M, Flabbee J, et al. Epidemiology of life-threatening and lethal anaphylaxis: a review. Allergy 2005;60:443-451.

2. Lieberman PL. Specific and idiopathic anaphylaxis: pathophysiology and treatment. In: Bierman CW, Pearlman DS, Shapiro GG, et al, eds. Allergy, Asthma and Immunology From Infancy to Adulthood Third edition. Philadelphia, WB Saunders, 1996, pp 297-319.

3. Fisher MM. Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse. Anaesth Intensive Care 1986;14:17-21.

4. Wasserman S. The heart in anaphylaxis. J Allergy Clin Immunol 1986;77:663-666.

5. Brown SG. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol 2005;5:359-364.

6. Schwartz LB, Metcalf DD, Miller JS, et al. Tryptase levels as an indicator of mast cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med 1987;316:1622-1626.

7. LaRoche D, Vergnaud M, Sillard B, et al. Biochemical markers of anaphylactoid reactions to drugs: comparison of plasma histamine and tryptase. Anesthesiology 1991;75:945-949.

8. van der Linden PW, Hack CE, Struyvenberg A, et al. Controlled insect-sting challenge in 55 patients: correlation between activation of plasminogen and the development of anaphylactic shock. Blood 1993;82:1740-1748.

Patrick F. K. Yong, MBChB, MRCP, Jonathan Birns, BSc, MRCP, and Mohammad A. A. Ibrahim, PhD, MRCPath

From the Departments of Clinical Immunology and Medicine, Kings College Hospital, London, United Kingdom.

Reprint requests to Patrick F. K. Yong, Clinical Immunology, Denmark Hill, Kings College Hospital, London SE5 9RS. Email: [e-mail]

Accepted August 22, 2006.

RELATED ARTICLE: Key Point

* Anaphylaxis can mimic other medical emergencies and should be considered in the differential diagnosis.