Anaphylaxis

What is the initial dose and route of epinephrine?

- IM in the anterior thigh - with the more concentrated 1:1000 dose at 0.01 mg/kg - generally 0.3-0.5 mg every 5 minutes for up to a total of 3 doses

What ways can epinephrine be administered?

- IM or IV

What two things are the next steps in treating a patient with anaphylaxis?

- a definitive airway needs to be immediately established in the face of impending airway obstruction - the pt's cardiovascular compromise must be treated with epinephrine

Name 5 central nervous system symptoms that can occur with anaphylaxis.

- a sense of impending doom - headache - dizziness - confusion - altered mental status

What 3 things does epinephrine do?

- acts as a vasopressor for hemodynamic support - a bronchodilator to relieve wheezing - counteracts released mediators to prevent their further release

What are the 2 most important therapeutic interventions during anaphylaxis?

- administration of epinephrine - control of the airway Nearly all deaths caused by anaphylaxis are a result of airway compromise.

Name 4 skin symptoms that manifest in 80-90% of patients with anaphylaxis.

- angioedema - urticaria (hives) - erythema - pruritus

Decreased vascular tone and increased capillary permeability cause what 2 things?

- cardiovascular compromise - hypotension

What 2 things lead to cardiovascular compromise and hypotension?

- decreased vascular tone - increased capillary permeability

The cardiovascular system is also affected in anaphylaxis, primarily as a result of what 2 things? What do these 2 things lead to?

- decreased vasomotor tone - capillary leakage These things lead to: - hypotension - tachycardia

What 3 things does successful treatment of anaphylaxis require?

- early recognition of the symptoms of anaphylaxis - airway support - rapid epinephrine administration

What could make intubation difficult?

- edema of the pharynx and larynx

What types of medications should be administered to a pt with anaphylaxis?

- epinephrine - nebulized beta agonists - corticosteroids - antihistamines: H1 and H2 blockers

Hypotension results from what 2 things?

- extravasation of fluid from the vasculature - loss of vasomotor tone

Critical criteria: How may hypotension present in a patient?

- faintness - altered mental status

IV administration of epinephrine can cause what 4 side effects?

- hypertension - tachycardia - dysrhythmias - myocardial ischemia

What 2 things cause wheezing, and therefore increase the work of breathing?

- increased bronchial secretions - increased smooth muscle tone

Critical criteria: name the skin symptoms that are included under critical criteria.

- itching - redness - hives - generalized urticaria (hives) - mucosal edema

Critical criteria: respiratory manifestations

- laryngeal stridor - bronchospasm - bronchorrhea - hypoxia

What are the most feared and difficult to manage aspects of anaphylaxis?

- lower respiratory tract symptoms, in combination with: edema of the upper respiratory tract

What are two systemic steroids that are used as adjuvants?

- methylprednisolone - prednisone Steroids will not take action for at least 6 hours, but will blunt further immune responses. Steroids should be continued for days after the reaction, and may or may not be tapered.

Aside from peanuts and other tree nuts, what are 7 other foods that commonly cause allergic reactions?

- milk - eggs - shellfish - fish - soybean - sesame - mangos But, any food can be responsible.

Name 4 gastrointestinal symptoms that may be seen with particularly severe anaphylactic reactions.

- nausea - vomiting - cramping - diarrhea

Name 7 risk factors for severe anaphylaxis and a poor outcome.

- peanut allergy, tree allergy - pre-existing cardiovascular disease - asthma - advanced age - pregnancy - use of beta blockers, ACE inhibitors - delayed administration of epinephrine

What are 4 signs that indicate impending airway obstruction and respiratory failure?

- perioral cyanosis - diffuse wheezing - stridor - hypoxia

Respiratory compromise of both the upper and lower airways is common in anaphylaxis. Respiratory compromise is associated with what 9 things?

- rhinorrhea - sneezing - throat tightness - stridor - tachypnea - dyspnea - bronchospasm - bronchorrhea - wheezing

What are helpful pharmacologic adjuvants for managing the many symptoms of anaphylaxis?

- steroids - antihistamines - beta agonists

What are two other signs a pt is suffering from anaphylaxis?

- swelling of the tongue - labored breathing

What things occur that can increase the work of breathing?

- watery eyes - rhinorrhea - increased bronchial secretions - increased smooth muscle tone

How many patients who have been hospitalized for anaphylaxis die during their hospital stay?

0.3% (low mortality rate)

Radiographic intravenous contrast agents can also cause an anaphylactoid response. Overall, how many fatal reactions occur per 100,000 patients exposed to intravenous contrast?

0.9 fatal reactions per 100,000 patients The incidence of serious reaction skyrockets to 60% in patients who have had a prior exposure and reaction.

Name 6 pitfalls in anaphylaxis management.

1. Failure to recognize the symptoms of anaphylaxis. 2. Underestimating the severity of laryngeal edema, and failure to secure the airway early. 3. Reluctance to administer epinephrine early in the course of the illness. 4. Forgetting to remove the allergen (ex. the IV drip of penicillin, or a bee stinger). 5. Lack of appropriate patient education. 6. Failure to prescribe an epinephrine auto-injector prior to patient discharge.

Name 4 cytokines that are known key components in an anaphylaxis reaction.

1. Leukotriene C4 2. Prostaglandin D2 3. Histamine 4. Tryptase

Name 3 culprit medications known to cause anaphylaxis reactions.

1. antibiotics (esp penicillins) 2. NSAIDs 3. biological agents (chemotherapy and monoclonal antibodies)

Name the 3 most common causes of anaphylaxis.

1. medications 2. insect bites 3. food allergies

What estimated number of ED visits happen every year for adverse food reactions, some of which may be anaphylactic in nature?

30,000 per year

Anaphylaxis from stings results in how many deaths per year in the US?

50 deaths per year

What is anaphylaxis?

A rapidly progressive, life-threatening, severe allergic reaction. It can compromise the airway, breathing, and circulation.

What is true anaphylaxis?

A type 1 hypersensitivity reaction occurring after a previous sensitizing exposure. In its purest form, it is an IgE immune-mediated activation of basophils and mast cells with subsequent release of prostaglandins, leukotrienes, and histamine.

The emergent approach to anaphylaxis: ABCDE - define these.

Airway Breathing Circulation Deliver Epinephrine

What is the only clinical significance of the difference between true anaphylaxis and an anaphylactoid reaction?

Anaphylactoid reactions can occur without prior sensitization.

What is the clinical criteria for diagnosing anaphylaxis? These criteria were developed to best identify anaphylaxis early and accurately.

Anaphylaxis is highly likely if ANY ONE of the following 3 diagnostic criteria exist: 1. Acute onset (minutes to hours) with reaction of the skin and/or mucosal tissue, in addition to respiratory symptoms or hypotension. 2. Two or more of the following occurring rapidly (minutes to hours) after exposure to a likely allergen: involvement of the skin-mucosal tissue, respiratory symptoms, hypotension, or GI symptoms (abdominal pain, cramping, or diarrhea). 3. Hypotension occurring rapidly (minutes to hours) after exposure to a known allergen for that patient. Hypotension may present as faintness or altered mental status.

Epinephrine should be given when?

At the first sign of respiratory distress or cardiovascular compromise.

Patients taking what kind of medication may be less responsive to standard therapy, and therefore also require administration of glucagon?

Beta blockers

What happens when a patient is first exposed to a substance?

Binding antibodies trigger class switching and regulatory changes in gene expression, effectively priming the immune system for its next encounter with the offending agent. In certain cases, this leads to immunoglobulin (IgE) binding to mast cells and basophils.

Question 1: An 18-year-old woman is brought to the ED with suspected anaphylaxis. Which of the following symptoms is most specific for anaphylaxis rather than a simple allergic reaction? A Itching B Watery eyes C Blood pressure of 80/40 mm Hg D Hives E Headache

C Blood pressure of 80/40 mm Hg Hypotension indicates a systemic reaction and cardiovascular compromise, thereby classifying this allergic reaction as anaphylaxis. The other options may all be part of an anaphylactic response but may also just be simple allergic reactions.

How is the diagnosis of anaphylaxis made?

Clinically

What type of volume resuscitation should be given to a pt with anaphylaxis?

Crystalloid solution (Normal saline or lactated ringers)

Question 2: A 26-year-old woman with a known peanut allergy is brought to the ED after accidentally consuming salad with a peanut dressing. She is wheezing and reports abdominal cramping. Which of the following should be the first intervention? A Endotracheal intubation B Normal saline 20 cc/kg IV C Examination of the skin D Epinephrine 0.3 mg intramuscular E Nebulized epinephrine

D Epinephrine 0.3 mg intramuscular Intramuscular epinephrine should be administered immediately. If there is significant respiratory or airway compromise, then the patient's airway should be controlled. Subsequent interventions include fluid resuscitation for hypotension, as well as H2 blockers and systemic steroids to mitigate further histamine and cytokine release.

Question 4: A 65-year-old man collapsed in a park and is brought to the ED by paramedics. He was stung by a bee and known to be highly allergic. He appears cyanotic and had extreme stridor in the ambulance. Severe laryngeal edema is notable. Which of the following is the best treatment? A Nebulized albuterol, H1 and H2 antagonists, corticosteroids, and crystalloids. B Intramuscular epinephrine , H1 and H2 antagonists, and corticosteroids. C Rapid sequence intubation, intramuscular epinephrine , and corticosteroids. D Intramuscular epinephrine , rapid sequence intubation, and corticosteroids. E Nebulized albuterol, H1 and H2 antagonists, IV fluid resuscitation, and reassessment for improvement.

D Intramuscular epinephrine , rapid sequence intubation, and corticosteroids. This patient has severe anaphylaxis, and epinephrine should be administered immediately. If intravenous dosing is not immediately available, then intramuscular epinephrine should be given. One caution is that dosing errors have been noted with IV epinephrine and delay in getting IV access and equipment tubing etc; for this reason, some centers only use IM epinephrine to treat anaphylaxis. Attention should then be turned to managing the airway. Because of the significant laryngeal edema, endotracheal intubation will be nearly impossible; hence, cricothyroidotomy may be required. After securing the airway, fluids, steroids, beta agonists, and H1 and H2 antagonists should be administered.

Question 3: Risk factors for severe anaphylaxis include: A Heavy consumption of nuts B Well-controlled asthma C Extremely young age D Prior antibiotic use E Pregnancy

E Pregnancy Risk factors for severe anaphylaxis include a history of poorly controlled asthma or other chronic lung disease (eg, COPD), advanced age, pregnancy, and taking β-blockers and ACE inhibitors. Each subsequent exposure to an allergen may be worse than the prior allergic reaction.

What is the primary initial therapy for anaphylaxis?

Epinephrine

What is the most common cause of anaphylaxis in children?

Food allergies

What are the most commonly used H1 and H2 blockers?

H1 blocker: diphenhydramine (Benadryl) H2 blocker: Ranitidine (Zantac)

A patient with anaphylaxis requires rapid resuscitation and stabilization. While preparing for intubation, what should be administered to the pt? What else should be done?

High-flow oxygen therapy. Her lower extremities should be elevated to improve venous return.

What cytokine can cause urticaria (hives) and angioedema?

Histamine

What is another name for bee and wasp stings, which can be a cause of anaphylaxis?

Hymenoptera

After the initial dosing of epinephrine has been administered, and there is no response, or if the pt is already demonstrating cardiovascular compromise, what should be done? What about in pediatrics?

IV administration of epinephrine should be started immediately, at a dose of 2-10 micrograms/minute. (pediatric dosing: 0.1-0.3 micrograms/kg/minute).

In patients taking ACE inhibitors presenting with angioedema, what medication has been shown promise for treatment? What is the drug class for this medication, and what does it do?

Icatibant It is a bradykinin receptor antagonist, and reduces inflammation.

The early stages of some anaphylactic reactions involve what?

Increased secretions by mucous membranes: - watery eyes - rhinorrhea

What medication is indicated for wheezing?

Inhaled beta agonists

How should the first dose of epinephrine be administered?

Intramuscularly (IM) in the anterolateral thigh. In the setting of a severe reaction, moving quickly to IV infusion of epinephrine is recommended.

What medication has been proposed for individuals on beta blockers, since the response to epinephrine may be blunted? What does it do?

Intravenous glucagon given in addition to epinephrine. Glucagon may overcome hypotension by activating adenyl cyclase, independent of the beta adrenergic receptor.

What is an anaphylactoid reaction?

It includes the release of prostaglandins, leukotrienes, and histamine, but through non-immune mediated pathways.

What should you do after you've started your initial resuscitation of a pt with anaphylaxis?

Look for causes of anaphylaxis

Patients may lose over what percent of their blood volume to extravasation in the first 10 minutes of their allergic reaction.

May lose over 30% of their blood volume in the first 10 minutes

Extra caution must be taken with which patients when administering epinephrine?

Patients with known coronary artery disease

What should be removed, if applicable, for a pt with anaphylaxis?

Removal of any remaining antigen (ex. bee stinger)

Why is subcutaneous administration of epinephrine no longer recommended?

SQ epinephrine has been proven less effective than IM administration.

True or false: Patients can manifest systemic symptoms of anaphylaxis, WITHOUT mucosal and skin involvement.

TRUE

After recognizing a pt's presentation of anaphylaxis, what is the most critical intervention?

The administration of epinephrine

In the classic anaphylactic reaction, what occurs physiologically?

The antigen again (for another time) encounters the immune system, and binds to IgE on mast cells and basophils. This releases a flood of cytokines that sets the clinical response in motion.

What occurs physiologically in an anaphylactoid reaction?

The antigen causes a direct release of cytokines by mast cells and basophils, without need for prior sensitization.

What is extravasation?

The leakage of blood, lymph, or other fluid from a blood vessel into the tissue around it. It is also used to describe the movement of cells out of a blood vessel into tissue during inflammation or metastasis.

Why should H1 and H2 blockers be taken?

To blunt histamine release and systemic response.

True or false: Because the spectrum of allergic responses is so broad, anaphylaxis is under-recognized. As a result, it is difficult to calculate a precise incidence of this disease.

True

True or false: Other medications aside from epinephrine, while safe and easy to administer, are not first line agents, and will not counteract immediate respiratory and cardiovascular compromise.

True

True or false: There are NO absolute contraindications to epinephrine administration in suspected anaphylaxis.

True

True or false: With anaphylactic and anaphylactoid reactions, the end result is the same, and is clinically indistinguishable.

True

True or false: Millions of people present to the ED every year with allergic symptoms ranging from minor rashes to multi-organ system anaphylaxis. Most of the time, it is difficult if not impossible to identify the trigger.

True

True or false: The airway should be secured early and often. It is much easier to extubate a patient without severe laryngeal edema than to intubate a patient with an occluded posterior oropharynx.

True

True or false: Some studies suggest as many as 1 in 500 exposures to penicillin will result in anaphylaxis.

True 1 in 500

True or false: Overall, the number of cases of arthropod anaphylaxis seen by physicians is small compared to the number of iatrogenic cases.

True But because arthropod exposures can often occur miles from medical treatment, they can have serious outcomes.

True or false: In the US, the number of admissions for anaphylactic reactions has slowly increased.

True But, mortality rates have remained low.

True or false: There are numerous cytokines involved in the immunologic cascade following antigen exposure, and no one major substance is felt to be primarily responsible.

True In a nutshell: no one cytokine is primarily responsible for anaphylaxis.

True or false: Regardless of the underlying mechanism, the effects of true anaphylaxis and an anaphylactoid reaction are similar, and early recognition will determine successful clinical management in these patients.

True In a nutshell: the effects of both of similar, and early recognition is key.

Airway management in a pt with edema of the pharynx and larynx may require what procedure if endotracheal intubation fails?

cricothyroidotomy - an incision made through the skin and cricothyroid membrane to establish a patent airway during certain life-threatening situations.

What medication has been hypothesized to decrease laryngeal edema?

nebulized racemic epinephrine

What foods are the most common cause of serious allergic reactions?

peanuts and other tree nuts

What is the most commonly affected organ system during anaphylaxis?

the skin (integumentary system)