**5. Diagnosing**

It is often difficult to recognize anaphylaxis, and many cases go undiagnosed [80, 81]. Early intervention in acute anaphylaxis reduces risk of severe reaction and

**85**

*Anaphylactic Shock*

**5.1 Diagnostic criteria**

and at least one:

baseline

**Table 3.**

blood pressure

a. Respiratory compromise

b. Respiratory compromise

a. Involvement of the skin-mucosal tissue

d. Persistent gastrointestinal symptoms

c. Reduced blood pressure or associated symptoms

*Clinical criteria for diagnosing anaphylaxis, modified from [3, 87].*

**5.2 Differential diagnosis**

and syncope [50, 88].

and fluids [86, 90, 91].

**6.1 Principal treatment**

**6. Management**

*DOI: http://dx.doi.org/10.5772/intechopen.88284*

Anaphylaxis is likely when one of the following criteria is fulfilled:

b. Reduced blood pressure or symptoms of end-organ damage

need for hospitalization [82]. In order to aid in diagnosis of anaphylaxis, diagnostic criteria have been developed (**Table 3**). In the clinic or emergency department, it may be unclear if the patient had been exposed to an allergen. In the ICU or operating room, rapid development of symptoms after administering medication makes recognizing anaphylaxis easier. Following the acute phase of anaphylaxis, serum tryptase and histamine should be measured to aid immunologist in confirming the diagnosis of anaphylaxis during follow-up care [83, 84]. Plasma tryptase remains elevated for 6 h following the onset of symptoms, but histamine levels remain elevated for just 1 h [85, 86]. Urinary histamine metabolites remain elevated for a longer period and may therefore be more useful than plasma histamine for confirming anaphylaxis [86].

1.Acute onset of an illness (minutes to several hours) with involvement of the skin and/or mucosal tissue

2.Two or more of the following that occur rapidly after exposure to a likely allergen for that patient

3.Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours) a. Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% decrease from that person's

b. Infants and children: low systolic blood pressure (age-specific) or greater than 30% decrease in systolic

There are several conditions which may mimic certain characteristics of anaphylaxis. Acute anxiety can present as dyspnea and near syncope with hyperventilation. Hypoglycemia can precipitate an altered sensorium and syncope. Vasovagal episodes can involve nausea with vomiting, hypotension, pallor, bradycardia, diaphoresis and syncope. Additional considerations include severe reactive airway disease, vocal cord dysfunction and non-allergy mediated angioedema. Vasovagal episodes can involve nausea with vomiting, hypotension, pallor, bradycardia, diaphoresis

There is a general lack of evidence basis for the treatment of anaphylaxis [89], but multiple expert guidelines highlight the chief treatment as epinephrine, oxygen,

Epinephrine is the first line treatment of anaphylaxis, and delayed administration increases the likelihood of poor outcomes [54, 55, 92]. Despite this, use of

*Anaphylactic Shock DOI: http://dx.doi.org/10.5772/intechopen.88284*

need for hospitalization [82]. In order to aid in diagnosis of anaphylaxis, diagnostic criteria have been developed (**Table 3**). In the clinic or emergency department, it may be unclear if the patient had been exposed to an allergen. In the ICU or operating room, rapid development of symptoms after administering medication makes recognizing anaphylaxis easier. Following the acute phase of anaphylaxis, serum tryptase and histamine should be measured to aid immunologist in confirming the diagnosis of anaphylaxis during follow-up care [83, 84]. Plasma tryptase remains elevated for 6 h following the onset of symptoms, but histamine levels remain elevated for just 1 h [85, 86]. Urinary histamine metabolites remain elevated for a longer period and may therefore be more useful than plasma histamine for confirming anaphylaxis [86].

## **5.1 Diagnostic criteria**

*Clinical Management of Shock - The Science and Art of Physiological Restoration*

died from anaphylaxis [63].

**4.2 Respiratory changes**

in a matter of minutes [59, 60]. Vascular smooth muscle relaxation causes vasodilation and a rapid decrease in SVR [61, 62]. Rapid drop in measured CVP suggests that venodilation plays a major as well. The combined effects as extravasation and venodilation cause significant reduction in preload. This can be severe enough to cause Empty ventricle syndrome, has been documented in autopsies of patients who

Compensatory response to these changes includes rise in heart rate, ejection fraction,

The entire respiratory tract can be affected in anaphylaxis, involving the upper airway and/or lower airway [69]. Upper airway symptoms develop due to fluid extravasation causing mucosal edema [70]. Some symptoms of upper airway involvement include angioedema, stridor, dysphagia, and rhinorrhea [50, 71]. Lower airway obstruction occurs due to mucosal edema, bronchospasm, and mucous plugging [70]. Oxygen saturation may decrease secondary to respiratory effects of anaphylaxis limiting airflow. When there is diffuse lower respiratory tract involvement, decreased oxygen saturation can persist despite endotracheal intubation [72]. When PaO2 is adequate, tissue oxygenation can still be compromised causing anaerobic metabolism. In one study on rats, tissue oxygenation of muscle decreased faster in anaphylaxis compared to nicardipine induced hypotension. The anaphylactic group also showed a greater increase in lactate and lactate-pyruvate

Mucocutaneous symptoms (e.g. flushing, pruritus, angioedema, and urticaria) are common in anaphylaxis, however in cases of shock cutaneous symptoms are often absent. Vasodilation and increased vasculature permeability leads to flushing and angioedema [74]. In addition to vascular changes, urticaria develops due inflammatory cell infiltration and neuropeptide release from sensory nerves [75]. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal pain [76]. These symptoms are likely due to intestinal smooth muscle contraction and alterations in water and electrolyte absorption [77, 78]. Neurologic changes are mostly secondary to hypotension and decreased perfusion and may manifest as dizziness, confusion, syncope/presyncope, or headache [50]. More serious effects

It is often difficult to recognize anaphylaxis, and many cases go undiagnosed [80, 81]. Early intervention in acute anaphylaxis reduces risk of severe reaction and

and cardiac index [61, 62]. Although Tachycardia is typical in anaphylaxis, although bradycardia may be seen as well. Bradycardia occurs due to a compensatory *Bezold-Jarisch* reflex, and has been found to have lower mortality rates when compared to cases of anaphylactic shock with tachycardia [66, 67]. Atropine therefore should not be administered, as it would counteract this protective effect and may increase mortality [68].

Arrhythmias and myocardial infarction can also be seen in anaphylaxis. Arrhythmias may develop due to the combined direct effect of mediators, and hemodynamic changes previously described. Myocardial infarctions seen in anaphylaxis may be due to decreased venous return and direct effects of mediators on coronary arteries

causing vasospasm or disruption of atherosclerotic plaques [64, 65].

ratio indicating depletion of intracellular energy storage [73].

**4.3 Mucocutaneous, gastrointestinal, and neurologic changes**

including seizure and stroke may also be seen but are rare [74, 79].

**84**

**5. Diagnosing**

Anaphylaxis is likely when one of the following criteria is fulfilled:

	- a. Respiratory compromise
	- b. Reduced blood pressure or symptoms of end-organ damage
	- a. Involvement of the skin-mucosal tissue
	- b. Respiratory compromise
	- c. Reduced blood pressure or associated symptoms
	- d. Persistent gastrointestinal symptoms
	- a. Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% decrease from that person's baseline
	- b. Infants and children: low systolic blood pressure (age-specific) or greater than 30% decrease in systolic blood pressure

#### **Table 3.**

*Clinical criteria for diagnosing anaphylaxis, modified from [3, 87].*

#### **5.2 Differential diagnosis**

There are several conditions which may mimic certain characteristics of anaphylaxis. Acute anxiety can present as dyspnea and near syncope with hyperventilation. Hypoglycemia can precipitate an altered sensorium and syncope. Vasovagal episodes can involve nausea with vomiting, hypotension, pallor, bradycardia, diaphoresis and syncope. Additional considerations include severe reactive airway disease, vocal cord dysfunction and non-allergy mediated angioedema. Vasovagal episodes can involve nausea with vomiting, hypotension, pallor, bradycardia, diaphoresis and syncope [50, 88].

### **6. Management**

There is a general lack of evidence basis for the treatment of anaphylaxis [89], but multiple expert guidelines highlight the chief treatment as epinephrine, oxygen, and fluids [86, 90, 91].

#### **6.1 Principal treatment**

Epinephrine is the first line treatment of anaphylaxis, and delayed administration increases the likelihood of poor outcomes [54, 55, 92]. Despite this, use of

epinephrine in anaphylaxis is infrequent and often delayed [80]. There are no contraindications for use of epinephrine in anaphylaxis, and it should still be administered in patients with history of heart disease [93].

Epinephrine exerts its effects via alpha and beta adrenergic receptors in a dosedependent response where beta receptors effects are dominant at low doses, but alpha receptors effects are seen at higher doses. The α1 receptors cause vasoconstriction increasing peripheral vascular resistance and blood pressure and improving coronary and cerebral perfusion. The β1 receptors exert positive chronotropic and inotropic effects which improves cardiac output and increases blood pressure. In the respiratory system, β2 receptors stimulation results in bronchodilation, and relief and respiratory symptoms. β receptors also inhibit release of mediators from mast cells and basophils, via increased cAMP production [94].

In most situations intramuscular administration is preferred, but IV epinephrine can be used in the ICU. IM epinephrine should be given in 0.2–0.5 mg doses (1:1000 dilution), and repeated every 5 min depending on the resolution of symptoms [86]. Studies showed that peak epinephrine concentrations were higher when epinephrine was given IM into the thigh, compared to IM administration in the arm or subcutaneous administration [95]. Multiple doses of epinephrine may be required to reverse symptoms [96]. Care should be taken to closely monitor pulse and blood pressure when epinephrine is administered intravenously as there is greater risk of severe adverse effects compared to intramuscular administration including arrhythmias and myocardial infarctions [97].

Following epinephrine administration, patients should continue to be assessed for worsening signs of anaphylaxis. Patients should be placed on pulse oximeter and given high flow oxygen as needed. Patients in anaphylactic shock should be placed in supine or Trendelenburg position to increase blood return to the heart. Patients who are sitting upright can have a significant decrease in preload leading to empty ventricle syndrome and PEA [98].

Due to the intravascular depletion, fluid is often necessary to maintain pressure. Crystalloids or colloids may be used, although physicians should be aware of the anaphylactic potential of some colloid solutions. Normal saline (0.9% saline) should be chosen over other crystalloids as it remains in the intravascular space longer than dextrose solutions [86, 99]. Caution should taken while giving fluids to patients with heart failure to prevent fluid overload.

#### **6.2 Adjunct treatments**

Antihistamines are often given as adjunct therapy in anaphylaxis, however there is no evidence to support or advise against their use in anaphylaxis [100]. Steroids may be used to prevent biphasic anaphylaxis [86], although there is no evidence to support the use of steroids in acute treatment of anaphylaxis [101, 102].

Nebulized albuterol or other beta-2 agonists may be useful to treat respiratory distress due to bronchoconstriction. While there is no clinical trial on use of these medications in anaphylaxis, their effectiveness in treating other allergic diseases offers some basis for their use [90].

#### **6.3 Additional consideration**

Beta blockers may complicate the treatment of anaphylaxis, as some of the beneficial effects of epinephrine will be diminished [103]. In patients on betablockers who do not respond to epinephrine and fluids, other vasopressors should be considered. Glucagon has been reported to be a successful treatment in several case reports of patients on beta blockers who experienced anaphylactic shock [104].

**87**

*Anaphylactic Shock*

**6.4 Follow up**

**7. Conclusions**

**Abbreviations**

mechanical support can be used.

Ig immunoglobulin

WAO World Allergy Organization

response on its own

haptens

*DOI: http://dx.doi.org/10.5772/intechopen.88284*

tor, along with education on how to use it [87].

ing the blocked adrenergic receptors.

myocardial dysfunction [106].

Glucagon mechanism of action is via direct activation of adenylate cyclase, bypass-

Vasopressin or phenylephrine can be used to increase systemic vascular resistance without further increasing heart rate. Dopamine or norepinephrine can be added in cases of relative bradycardia [105]. Mechanical support with ECMO has been reported to be successful at treating refractory anaphylaxis with profound

Methylene blue has been reported to be an effective treatment in cases of severe anaphylaxis not responding to epinephrine [88], as well as cases of anaphylaxis without hypotension. Methylene blue inhibits NO mediated vasodilation via competitive inhibition of guanylate cyclase decreasing cyclic GMP production and subsequent vasodilation [107]. This mechanism acts independent of adrenergic receptors, and may be effective in patients with refractory anaphylactic shock [108].

Before discharging a patient that experienced anaphylaxis, they should be referred to an immunologist for a thorough evaluation. Labs to assess for anaphylaxis (i.e. tryptase, histamine) should be drawn to assist allergist in making a diagnosis. Patients should also receive a prescription for an epinephrine autoinjec-

Anaphylaxis is a rapidly acting life-threatening hypersensitivity reaction. Diagnosis of anaphylaxis can be difficult, and early recognition and treatment is essential to prevent development of shock. Shock is more common in cases due to medication compared to food, although shock can occur. The primary treatment in anaphylactic shock is epinephrine, fluids, and oxygen. Additional medications including antihistamines, steroids, and inhaled beta-agonist should be used as needed. In patients who do not respond to epinephrine, other vasopressors or

AAAAI American Academy of Allergy, Asthma and Immunology ACAAI American College of Allergy, Asthma and Immunology EAACI European Academy of Allergy and Clinical Immunology

Antigen molecule capable of interacting with Ig, includes immunogens and

Immunogen molecule that can interact with Ig and cause an immune response Hapten molecule that can interact with Ig, but cannot cause immune

### *Anaphylactic Shock DOI: http://dx.doi.org/10.5772/intechopen.88284*

Glucagon mechanism of action is via direct activation of adenylate cyclase, bypassing the blocked adrenergic receptors.

Vasopressin or phenylephrine can be used to increase systemic vascular resistance without further increasing heart rate. Dopamine or norepinephrine can be added in cases of relative bradycardia [105]. Mechanical support with ECMO has been reported to be successful at treating refractory anaphylaxis with profound myocardial dysfunction [106].

Methylene blue has been reported to be an effective treatment in cases of severe anaphylaxis not responding to epinephrine [88], as well as cases of anaphylaxis without hypotension. Methylene blue inhibits NO mediated vasodilation via competitive inhibition of guanylate cyclase decreasing cyclic GMP production and subsequent vasodilation [107]. This mechanism acts independent of adrenergic receptors, and may be effective in patients with refractory anaphylactic shock [108].
