The document discusses anaphylaxis, including its definition, signs and symptoms, causes, pathophysiology, diagnosis, treatment and differentiation from other conditions. Some key points: - Anaphylaxis is a serious allergic reaction that is rapid in onset and potentially life-threatening. Common triggers are foods, medications, insect stings or bites. - It involves immune system mediators like histamine that cause symptoms affecting the skin, respiratory tract, gastrointestinal tract and cardiovascular system like hives, low blood pressure, breathing difficulties. - Prompt treatment with epinephrine injection is critical to counteract the effects. Airway management and fluid resuscitation may also be needed. Antihistamines

1. PHUNG HUY HOANG, MD
Resident in Internal Medicine
Pham Ngoc Thach University of Medicine
April 2017
ANAPHYLAXIS

2. • A rapid onset, serious, generalized allergic or hypersensitivity reaction.
• Potentially life-threatening.
• Difficult in recognize (mimic other conditions, variable in presentation).
• Features of both distributive (vasodilatory) and hypovolemic shock.
• Foods followed by medications (eg, antibiotics and NSAIDs) are the most common
cause of anaphylaxis in the outpatient setting.
• Medications, for example, antibiotics, muscle relaxants, blood products, and
radiocontrast media, are common causes of anaphylaxis in the hospital.
• Prompt recognition is critical in anaphylaxis.
OVERVIEW

3. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

4. • Anaphylaxis: IgE-dependence
• Anaphylactoid reaction: IgE-independence
• Immunologic anaphylaxis
▫ IgE mediated
▫ IgG mediated
▫ Immune complex/complement-mediated
• Non-immunologic anaphylaxis
TERMINOLOGY
Clinical indistinguishable
The World Allergy Organization (WAO)

5. • Immunologic
▫ IgE mediated
▫ IgG mediated (not identified in human yet)
▫ Immune complex/complement-mediated
• Non-immunologic
▫ Activation of complement, in the absence of immune complex formation (drugs that were
solubilized in the diluent Cremophor EL)
▫ Direct activation of mast cells and/or basophils (vancomycin/”red man syndrome”)
▫ Direct mast cell degranulation (opiate medications)
▫ Cold urticaria
PATHOPHYSIOLOGY

6. Frederic F. Little H. M. H. (2012), Irwin and Rippe’s Intensive Care Medicine, James M.
Rippe Richard S. Irwin, Editor, Lippincott Williams & Wilkins, pp. 2031-43

7. Frederic F. Little H. M. H. (2012), Irwin and Rippe’s Intensive Care Medicine, James M.
Rippe Richard S. Irwin, Editor, Lippincott Williams & Wilkins, pp. 2031-43

9. Vinay Kumar A. K. A., Jon C. Aster (2013), Elsevier Saunders, pp. 29-73

10. Vinay Kumar A. K. A., Jon C. Aster (2013), Elsevier Saunders, pp. 29-73

11. Vinay Kumar A. K. A., Jon C. Aster (2013), Elsevier Saunders, pp. 29-73

12. Vinay Kumar A. K. A., Jon C. Aster (2013), Elsevier Saunders, pp. 29-73

13. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

14. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

15. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

16. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

17. Vinay Kumar A. K. A., Jon C. Aster (2013), Elsevier Saunders, pp. 29-73

18. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse
B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

19. • Direct mediator effects on the myocardium
▫ Histamin H1 receptors: coronary artery vasoconstriction, vasospasm, increases vascular
permeability. H2 receptors: increase atrial and ventricular inotropy, atrial chronotropy, coronary
artery vasodilation. The interaction of H1 and H2 receptor stimulation  decreased diastolic
pressure, increased pulse pressure.
▫ Platelet-activating factor (PAF) decreases coronary blood flow, delays atrioventricular conduction,
negative inotropic effects on the heart
• Exacerbation of pre-existing myocardial insufficiency by the hemodynamic stress of
anaphylaxis
• Endogenous epinephrine released from the adrenal medulla in response to stress
• Exogenously-injected epinephrine.
CARDIOVASCULAR ABNORMALITIES

20. • Skin and mucosa (90%): generalized hives, itching or flushing, swollen lips-tongue-
uvula, periorbital edema, or conjunctival swelling
• Respiratory (70%): nasal discharge, nasal congestion, change in voice quality, sensation
of throat closure or choking, stridor, shortness of breath, wheeze, or cough.
• Gastrointestinal (45%): nausea, vomiting, diarrhea, and crampy abdominal pain.
• Cardiovascular (45%): hypotonia (collapse), syncope, incontinence, dizziness,
tachycardia, and hypotension.
SIGNS AND SYMPTOMS
DEATH

21. Frederic F. Little H. M. H. (2012), Irwin and Rippe’s Intensive Care Medicine, James M. Rippe Richard S. Irwin, Editor, Lippincott Williams & Wilkins, pp. 2031-43

22. !
Symposium sponsored by the National Institute of Health and the Food
Allergy and Asthma Network (2005/6) proposed 3 scenerios for diagnosis.
DIAGNOSTIC CRITERIA

23. DIAGNOSTIC SCENERIOS (1 in 3)
1
Acute onset of an illness (minutes to several hours) involving the skin, mucosal
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at
least one of the following:
• Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak
expiratory flow, hypoxemia).
• Reduced blood pressure (BP)
• Associated symptoms and signs of end-organ malperfusion (eg, hypotonia [collapse]
syncope, incontinence).
Skin symptoms and signs are present in up to 90 percent of anaphylactic episodes.
This criterion will therefore frequently be helpful in making the diagnosis.

24. DIAGNOSTIC SCENERIOS (1 in 3)
2
Two or more of the following that occur rapidly after exposure to a LIKELY allergen for that
patient (seconds to several hours):
• Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-
tongue-uvula).
• Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak
expiratory flow, hypoxemia).
• Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence).
• Persistent gastrointestinal symptoms and signs (eg, crampy abdominal pain, vomiting)
Skin symptoms or signs are absent or unrecognized in up to 20 percent of anaphylactic
episodes. Criterion 2 incorporates gastrointestinal symptoms in addition to skin symptoms,
respiratory symptoms, and reduced BP. It is applied to patients with exposure to a substance
that is a likely allergen for them.

25. DIAGNOSTIC SCENERIOS (1 in 3)
3
Reduced BP after exposure to a KNOWN allergen for that patient (minutes to several
hours)
Scenerio 3 is intended to detect anaphylactic episodes in which only one organ system is
involved and is applied to patients who have been exposed to a substance to which they are
known to be allergic (for example, hypotension or shock after an insect sting)

26. • Biphasic anaphylaxis:
▫ recurrence of symptoms, following the apparent resolution of the initial anaphylactic
episode (with no additional exposure to the causative agent).
▫ typically occur within 12 hours after resolution of the initial symptoms (up to 72 hours later
reported).
• Protracted anaphylaxis
▫ anaphylactic reaction that lasts for hours, days, or even weeks.
• Delayed anaphylaxis
▫ onset of anaphylaxis will be delayed, ie, beginning hours rather than minutes.
OTHER SCENERIOS

27. • Reluctant to diagnose anaphylaxis in the absence of hypotension or shock, (not
required for the diagnosis according to criterion 1 or 2; or compensated by tachycardia;
or obtain after epinephrine administration, age-appropriate BP standards esp in children)
• Skin symptoms and signs are absent or unrecognized in up to 20 percent of all episodes
(patient taken H1-antihistamine, undressed or nor full examination)
• Mistaken for an asthma exacerbation, and vice versa.
• Comorbidities and medications.
DIAGNOSTIC PITFALLS

28. Kemp S. F. (2017), "Pathophysiology of anaphylaxis", UpToDate

29. DIFFERENTIATION (1)
Kemp S. F. (2017), "Pathophysiology of anaphylaxis", UpToDate

30. DIFFERENTIATION (2)
Kemp S. F. (2017), "Pathophysiology of anaphylaxis", UpToDate

31. DIFFERENTIATION (3)
Kemp S. F. (2017), "Pathophysiology of anaphylaxis", UpToDate

32. LABORATORY FINDINGS
Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A.
Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

33. PHUNG HUY HOANG, MD
Resident in Internal Medicine
Pham Ngoc Thach University of Medicine
April 2017
TREATMENT OF
ANAPHYLAXIS

34. Impossible to predict how severe it will become or how rapidly it will
progress. For these reasons, early and definitive treatment of
suspected anaphylaxis is indicated

35. INITIAL MANAGEMENT
• Removal of the inciting antigen.
• Epinephrine.
• Airway management
• Volume resuscitation with IV fluids.
• Posture.
• Supplemental oxygen.
PRINCIPLES
ADJUNCTIVE MANAGEMENT
• H1 and H2 antagonists
• Glucocorticoid
• Glucagon
• Other vasopressors
(Norepinephrine, Dopamine)

36. IMMEDIATE MANAGEMENT
Epinephrine (1)
α1
• Increased vasoconstriction
• Increased peripheral
vascular resistance
• Decreased mucosal edema
(eg, in the upper airway)
β2
• Increased bronchodilation
• Decreased release of mediators of
inflammation from mast cells and
basophils
β1
• Increased inotropy
• Increased chronotropy

37. • There are no absolute contraindications to epinephrine use in anaphylaxis!
• Intramuscular (IM) injection of epinephrine at the earliest opportunity, followed by
additional epinephrine by IM or intravenous (IV) injection.
• 0.01 mg/kg (max 0.5mg)  0.3 to 0.5 mg (1:1000 = ampule 1mg/1ml)
intramuscularly (preferably in the mid-outer thigh)  repeat every 5 to 15 minutes
(or more frequently) as needed (usually maximum 3 doses).
IMMEDIATE MANAGEMENT
Epinephrine (2)

38. • Intravenous epinephrine by slow bolus (avoid or use only with caution)  associated
with significantly more dosing errors and cardiovascular complications than IM.
• The dose is 1/10th or less of the IV epinephrine dose used in cardiac arrest 
1:10.000 (1 ampule 1mg/1mg = 1/1.1000 with 9ml NaCl 0.9%) = 0.5 to 1 mL of 0.1
mg/mL
• If symptoms are severe  an IV continuous infusion (beginning at 0.1
mcg/kg/minute  titrate according to blood pressure, cardiac rate and function,
oxygenation).
IMMEDIATE MANAGEMENT
Epinephrine (3)

39. • Intubation should be performed immediately if marked stridor or respiratory arrest is
present
• Preparations for early intubation should be made if there is any airway involvement or
significant edema of the tongue, oropharyngeal tissues, including the uvula, or if voice
alteration
• An emergency cricothyroidotomy may be required to secure the airway if upper airway
edema prevents access to the glottic aperture
• Inhaled bronchodilators (eg, albuterol, salbutamol) (not prevent or relieve mucosal
edema or shock)
IMMEDIATE MANAGEMENT
Airway management

40. • Massive fluid shifts can occur rapidly due to increased vascular permeability
• 1 to 2 liters of normal saline at the most rapid flow rate possible in the first minutes of
treatment
▫ Lactated Ringer's (LR) solution can potentially contribute to metabolic alkalosis, although large
volumes of normal saline can cause hyperchloremic metabolic acidosis, so some clinicians
change from normal saline to LR if very large volumes are proving necessary.
▫ Dextrose is rapidly extravasated from the circulation into the interstitial tissues.
▫ Colloid solutions (eg, albumin or hydroxyethyl starch) confer no survival advantage in patients
with distributive shock and are more costly
IMMEDIATE MANAGEMENT
Volume resuscitation

41. • Placement of the patient in the supine position with the lower extremities elevated.
• Prominent upper airway swelling prompting the patient to remain upright (and often leaning
forward)
• If the patient is vomiting, placement of the patient semi-recumbent with lower
extremities elevated may be preferable.
• Place pregnant patients on their left side.
IMMEDIATE MANAGEMENT
Postures

42. • Relieve itching and urticaria.
• Endogenous production of epinephrine and other compensatory mediators (other
catecholamines, angiotensin II, and endothelin I)
• DO NOT relieve upper or lower airway obstruction, hypotension or shock, and in standard
doses, do not inhibit mediator release from mast cells and basophils.
• Onset too slow to mediate immediate effect.
ADJUNCTIVE MANAGEMENT
Anti-histamine H1 (1)

43. • Only first-generation H1 antihistamines are available in parenteral formulations, and rapid IV
administration may increase hypotension
▫ Diphenhydramine, 1.25 mg/kg to maximum of 50 mg, IV or IM
▫ Promethazine 50mg
• For oral treatment, second-generation H1 antihistamines (eg, cetirizine) offer certain
advantages over first-generation agents
ADJUNCTIVE MANAGEMENT
Anti-histamine H1 (2)

44. • An H2 antihistamine given with an H1 antihistamine may provide some additional relief of hives.
• DO NOT relieve upper or lower airway obstruction or shock
• Eg, Ranitidine 50mg.
ADJUNCTIVE MANAGEMENT
Anti-histamine H2

45. • Theoretically prevent the biphasic (up to 72 hours after initiation) or protracted reactions.
• Onset of action takes several hours.
• Hydrocortisone and cortisone have the strongest effects, followed by prednisone
• Methylprednisolone and dexamethasone have the lowest mineralocorticoid effect and
produce less fluidretention than hydrocortisone and cortisone  preferred for the elderly and for
those in whom fluid retention would be problematic
• Hydrocortisone 5mg/kg, maximum 200mg IV every 4-6h up to 72h.
• Methylprednisolone 1-2mg/kg (or equivalent) (IV or PO).
ADJUNCTIVE MANAGEMENT
Glucocorticoid

46. Ohannes W.G. Jacobs J. W. J. B. (2013), Kelley’s Textbook of Rheumatology, Ralph C. Budd Gary S. Firestein, Sherine E. Gabriel, Editor, Elsevier Saunders, pp. 894-916

47. • Absorption of parenterally introduced antigens (e.g., stinging insect venom, vaccines) may be
retarded by infiltrating the site with approximately half the dose of epinephrine (0.1-
0.3ml/1:1000). Unless anatomic region with terminal circulation, e.g., fingertip.
• Tourniquet application proximal to the site of antigen exposure that is sufficient to occlude
venous and lymphatic returns without interfering with arterial blood flow may also retard
absorption of the antigen.
• The tourniquet should be loosened for approximately 15 to 30 seconds every 10 to 15
minutes.
ADJUNCTIVE MANAGEMENT
Tourniquet

48. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-79

49. • Patients receiving beta-blockers may be resistant to treatment with epinephrine and
can develop refractory hypotension.
• Glucagon: inotropic and chronotropic effects not mediated through beta-receptors.
• 1 to 5 mg slow IV bolus over five minutes
• May be followed by an infusion of 5 to 15 mcg/minute titrated to effect
GLUCAGON

50. Timothy J. Bedient M. H. K. (2012), The Washington Manual Of Critical Care, Warren Isakow Marin H. Kollef, Editor, Lippincott Williams & Wilkins, pp. 23-6

51. Timothy J. Bedient M. H. K. (2012), The Washington Manual Of Critical Care, Warren Isakow Marin H. Kollef, Editor, Lippincott Williams & Wilkins, pp. 23-6

52. 1. Brian H. Rowe T. J. G. (2016), "Anaphylaxis, Allergies, and Angioedema", Tintinalli’s Emergency Medicine A Comprehensive
Study Guide, J. Stephan Stapczynski Judith E. Tintinalli, O. John Ma, Editor, McGraw Hill Education, pp. 74-8
2. Debendra Pattanaik J. C. Y., Phil Lieberman (2015), "Anaphylactic and Anaphylactoid Reactions", Principles of Critical Care,
Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1269-7
3. Timothy J. Bedient M. H. K. (2012), "Anaphylactic Shock", The Washington Manual Of Critical Care, Warren Isakow Marin H.
Kollef, Editor, Lippincott Williams & Wilkins, pp. 23-6
4. Frederic F. Little H. M. H. (2012), "Anaphylaxis", Irwin and Rippe’s Intensive Care Medicine, James M. Rippe Richard S. Irwin,
Editor, Lippincott Williams & Wilkins, pp. 2031-43
5. Ronna L Campbell J. M. K. (2017), "Anaphylaxis: Emergency treatment", UpToDate
6. Ronna L Campbell J. M. K. (2017), "Anaphylaxis: Acute diagnosis", UpToDate
7. Kemp S. F. (2017), "Pathophysiology of anaphylaxis", UpToDate
8. Ohannes W.G. Jacobs J. W. J. B. (2013), "Glucocorticoid Therapy", Kelley’s Textbook of Rheumatology, Ralph C. Budd Gary S.
Firestein, Sherine E. Gabriel, Editor, Elsevier Saunders, pp. 894-916
9. Vinay Kumar A. K. A., Jon C. Aster (2013), "Inflammation and Repair", Robbin's Basic Pathology, Elsevier Saunders, pp. 29-73
10. Murphy H. S. (2015), "Inflammation", Rubin’s Pathology, Jeffrey E. Saffitz David S. Strayer, Alan L. Schiller, Editor, Wolters
Kluwer, pp. 55-94
References