ANAPHYLACTIC SHOCK

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ANAPHYLACTIC SHOCK:

ANAPHYLACTIC SHOCK Dr. Ubaidur Rahaman M.D. (Medicine), European Diploma in Intensive Care

IMMUNE SYSTEM:

PROTECTION/ IMMUNITY FROM MICROORGANISMS AGENTS IMMUNE SYSTEM

SERUM SICKNESS:

SERUM SICKNESS

ANAPHYLAXIS:

ANAPHYLAXIS Ana+Phylaxis = Contrary to Protection

IMMUNE SYSTEM: DOUBLE EDGED SWORD:

IMMUNE SYSTEM: DOUBLE EDGED SWORD

ALLERGY:

ALLERGY Allos (other or different) + ergia (energy or action) change in reactivity or capacity to react

ALLERGY: LOST MEANING:

ALLERGY: LOST MEANING

HYPERSENSITIVITY REACTION:

HYPERSENSITIVITY REACTION 1923, Arthur F. Coca and Robert A. Cooke ALLERGY KILLING SELF

HYPERSENSITIVITY REACTION:

HYPERSENSITIVITY REACTION 1963 COOMB AND GELL

TYPES OF HYPER SENSITIVITY REACTIONS:

TYPES OF HYPER SENSITIVITY REACTIONS

ANAPHYLAXIS: TYPE I HYPERSENSITIVY REACTION:

ANAPHYLAXIS: TYPE I HYPERSENSITIVY REACTION

PATHOPHYSIOLOGY:

PATHOPHYSIOLOGY

SIGNS & SYMPTOMS:

SIGNS & SYMPTOMS SKIN Eyes MUCOSA

SIGNS & SYMPTOMS: Respiratory System:

SIGNS & SYMPTOMS: Respiratory System

SIGNS & SYMPTOMS: Cardiovascular System:

SIGNS & SYMPTOMS: Cardiovascular System

SIGNS & SYMPTOMS: GIT:

SIGNS & SYMPTOMS: GIT

SIGNS & SYMPTOMS: CNS:

SIGNS & SYMPTOMS: CNS

MANIFESTATIONS OF ANAPHYLAXIS:

MANIFESTATIONS OF ANAPHYLAXIS

ETIOLOGY:

ETIOLOGY

PATTERNS OF ANAPHYLAXIS:

20 PATTERNS OF ANAPHYLAXIS Uniphasic Isolated reaction producing signs and symptoms within minutes (typically within 30 minutes) of exposure to an offending stimulus Biphasic Late-phase reactions that can occur 1 to 72 hours (most within 10 hours) after the initial attack (1%-23%) Protracted Severe anaphylactic reaction that may last between 24 and 36 hours despite aggressive treatment

UNIPHASIC ANAPHYLAXIS:

UNIPHASIC ANAPHYLAXIS 21 Antigen Exposure Treatment Initial Symptoms Time 0

Slide22:

Antigen Exposure Treatment Treatment 8 to 12 hours 1 Classic Model 30 minutes to 72 hours 2 Time Symptom Score First Phase Second Phase Asymptomatic BIPHASIC ANAPHYLAXIS 22 1. Lieberman P. J Allergy Clin Immunol . 2005;115:S483-S523. 2. Lieberman P. Allergy Clin Immunol Int . 2004;16(6):241-248.

PROTRACTED ANAPHYLAXIS:

PROTRACTED ANAPHYLAXIS 23 Antigen Exposure Initial Symptoms Up to 32 hours 1 Time 1. Lieberman P, et al. J Allergy Clin Immunol . 2005;115:S483-S523 . 0

DIAGNOSIS: CLINICAL CRITERIA :

24 OR OR DIAGNOSIS: CLINICAL CRITERIA Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both 2 of the following that occur rapidly after exposure to a likely allergen (minutes to several hours): Reduced BP after exposure to known allergen (minutes to several hours): AND AT LEAST 1 OF THE FOLLOWING Respiratory compromise ( eg , dyspnea, wheeze- bronchospasm) Reduced BP or associated symptoms of end-organ dysfunction Involvement of the skin-mucosal tissue ( eg , generalized hives, itch-flush, swollen lips-tongue-uvula) b. Respiratory compromise c. Reduced BP or associated symptoms d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) Infants and children: low SBP* (age specific) or >30% decrease in SBP b. Adults: SBP of <90 mm Hg or >30% decrease from that person’ s baseline * Low SBP for children is defined as <70 mm Hg from 1 month to 1 year, <70 mm Hg plus (2x age) from 1 to 10 years, and <90 mm Hg from 11 to 17 years. BP, blood pressure; SBP, systolic blood pressure.

SHOCK: CLASSIFICATION:

SHOCK: CLASSIFICATION PULSE PRESSURE= SBP – DBP PULSE PRESSURE STROKE VOLUME    

MANAGEMENT:

MANAGEMENT AIRWAY BREATHING CIRCULATION

LIFE THREATENING ISSUES:

LIFE THREATENING ISSUES AIRWAY – swelling, hoarseness, stridor BREATHING –rapid breathing, wheeze, fatigue, cyanosis, SpO2 < 92%, confusion CIRCULATION – pale, clammy, low blood pressure, faintness, drowsy/coma Weak or absent central pulsE

MANAGEMENT :

MANAGEMENT Administer IM epinephrine quickly Repeat every 5 to 10 minutes if necessary Place patient in supine position with legs elevated Consider oxygen for all patients Treatment in order of importance is: epinephrine, patient position, oxygen, IV fluids, nebulized therapy, vasopressors, antihistamines, corticosteroids, and other agents Evaluate hypotension and need for IV fluids Individualize observation 28 Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480. IM, intramuscular; IV, intravenous.

ADMINISTER EPINEPHRINE IMMEDIATELY!!!:

ADMINISTER EPINEPHRINE IMMEDIATELY!!! Failure to administer epinephrine promptly is the most important factor contributing to death in patients with anaphylaxis The vasopressive effects of epinephrine, along with its effects in preventing and relieving laryngeal edema and bronchoconstriction, may be life saving 29 Sampson HA, et al. N Engl J Med . 1992;327:380-384.

IM EPINEPHRINE DOSING:

IM EPINEPHRINE DOSING Epinephrine dosing: IM epinephrine (to lateral aspect of thigh) from 1:1,000 dilution (1 mg/mL) injected as 0.2 to 0.5 mL (0.01 mg/kg in children, maximum dose 0.3 mg) 30 Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480.

ACTION OF EPINEPHRINE:

31 Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol . 2010;10:354-361. ACTION OF EPINEPHRINE  Vasoconstriction  Peripheral vascular resistance  Heart rate  Mucosal edema  Insulin release  Inotropy  Chronotropy  Bronchodilation  V asodilation  Glycogenolysis  M ediator release  1 -adrenergic receptor  2 -adrenergic receptor  1 -adrenergic receptor  2 -adrenergic receptor Epinephrine

ABSORPTION OF EPINEPHRINE FASTER WITH IM VS SC INJECTION:

ABSORPTION OF EPINEPHRINE FASTER WITH IM VS SC INJECTION 32 Adapted from Simons FER, et al. J Allergy Clin Immunol. 2004;113:837-844 . Time to C max After Injection (minutes) P <.05 Minutes 0 5 10 15 20 25 30 35 40 45 50 SC epinephrine IM epinephrine 8 ± 2 min 34 ± 14 min SC, subcutaneous.

ANCILLARY TREATMENTS: SECOND LINE TO EPINEPHRINE:

ANCILLARY TREATMENTS: SECOND LINE TO EPINEPHRINE Ranitidine: 50 mg in adults and 12.5 to 50 mg (1 mg/kg) in children diluted in 5% dextrose to a total volume of 20 mL and injected IV over 5 minutes Nebulized albuterol: 2.5 to 5 mg in 3 mL normal saline Methylprednisolone: 1 to 2 mg/kg per 24 hours 33 Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480.

ANCILLARY TREATMENTS: FOR REFRACTORY HYPOTENSION:

ANCILLARY TREATMENTS: FOR REFRACTORY HYPOTENSION Dopamine: 400 mg in 500 mL normal saline IV 2 to 20 μ g/kg/min Glucagon: 1 to 5 mg (20-30 μ g/kg, max 1 mg in children), IV over 5 minutes followed with continuous IV infusion 5 to 15 μ g /min 34

IV EPINEPHRINE:

IV EPINEPHRINE If repeated IM doses are needed, patient may benefit from IV dosing Ensure patient is monitored: Continuous ECG and pulse oximetry and blood pressure Children: IM adrenaline is the preferred route for children IV route is recommended only in specialist settings by those familiar with use ONLY if patient is monitored and IV access is already available No evidence on which to base a dose recommendation 35 ECG , electrocardiogram.

IV EPINEPHRINE DOSING IN ADULTS:

IV EPINEPHRINE DOSING IN ADULTS Adrenaline IV bolus dose Titrate IV adrenaline using 50 mcg boluses according to response The prefilled 10-mL syringe of 1:10,000 adrenaline contains 100 mcg/mL A dose of 50 mcg is 0.5 mL, which is the smallest dose that can be given accurately Do not give the undiluted 1:1,000 adrenaline concentration IV 36

WHY NOT AN ANTIHISTAMINE?:

37 WHY NOT AN ANTIHISTAMINE? Anaphylaxis is not mediated by histamine alone* Antihistamines antagonize only histamine and have slower onset of action than epinephrine Guidelines state that antihistamines are second line to and should not be administered in lieu of epinephrine Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480. *Other mediators include leukotrienes , prostaglandins, kinins , platelet-activating factor, interleukins, and tumor necrosis factor.

Oral Diphenhydramine Takes 80 Minutes for 50% Suppression:

Time to 50% Suppression of Histamine-Induced Flare 51.7 79.2 T 50 Minutes Oral Diphenhydramine Takes 80 Minutes for 50% Suppression 38 PO, by mouth. Jones DH, et al. Ann Allergy Asthma Immunol . 2008;100:452-456. (capsules)

PRACTICE PARAMETER GUIDELINES: CORTICOSTEROIDS:

PRACTICE PARAMETER GUIDELINES: CORTICOSTEROIDS Corticosteroids should never be used in place of or prior to epinephrine and are not helpful acutely However, they theoretically have the potential to prevent recurrent or protracted anaphylaxis although there is no conclusive evidence that the administration of corticosteroids prevents a biphasic response Corticosteroids have a slower onset of action 39 Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480.

PATIENTS AT RISK FOR ANAPHYLAXIS UNIVERSAL RECOMMENDATIONS :

Across available guidelines: Epinephrine auto-injector (2 doses) Auto-injector training Education on avoidance of allergen Follow-up with primary care physician Referral to allergist if first presentation or cause is unknown Monitor auto-injector expiration dates Block auto-injector substitution at pharmacy Emergency action plan PATIENTS AT RISK FOR ANAPHYLAXIS UNIVERSAL RECOMMENDATIONS 40 Burks AW, et al. J Allergy Clin Immunol . 2012;129:906-920. Simons FER, et al. WAO Journal . 2011;4:13-37. Boyce JA, et al. J Allergy Clin Immunol . 2010;126:S1-S58. Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480. Soar J, et al. Resuscitation . 2008;77:157-169.

Additional Considerations: ED and Hospital-based Management:

Additional Considerations: ED and Hospital-based Management 41

DISCUSSION QUESTIONS:

DISCUSSION QUESTIONS Are other diagnostic tests warranted in the ED or hospital setting? 42

Plasma Histamine and Tryptase Levels Following Bee Sting Challenge:

Plasma Histamine and Tryptase Levels Following Bee Sting Challenge 43 0 2 4 80 40 0 Schwartz LB, et al. J Clin Invest . 1989;83:1551-1555. Time After Sting (hours) 60 30 0 Histamine (ng/mL) Tryptase (ng/mL)

Tryptase and Histamine Dynamics:

Tryptase and Histamine Dynamics Tryptase levels provide a more precise measure of involvement of mast cells than clinical presentation 1 Total serum tryptase may remain elevated acutely for 6+ hours 2 Peaks at 1 hour: obtain blood sample within 3 hours Normal serum tryptase value is <10 ng/mL; the higher the value, the higher the sensitivity 3 Positive predictive value of serum tryptase can be 92.6% 3 Negative predictive value is only 52% Plasma histamine begins to rise within 5 minutes but remains elevated for 30 to 60 minutes 4 Because of longer half-life, serum tryptase is preferred 44 Schwartz LB, et al. Immunol Clin North Am . 2006;26:451-463. 2. Lieberman P, et al. J Allergy Clin Immunol . 2010;126:477-480. 3. Tanus T, et al.   Ann Emerg Med.  1994; 24:104-107. 4. Laroche D, et al.  Anesthesiology.  1991;75:945-949.

SUMMARY:

SUMMARY Anaphylaxis is a life-threatening systemic reaction with rapid onset Anaphylaxis is increasing in the US In children, foods are the most common cause anaphylaxis Early recognition is essential to optimal anaphylaxis management IM epinephrine is the treatment of choice for anaphylaxis Epinephrine should be administered immediately at the onset of likely anaphylaxis Some reactions may be protracted or biphasic and warrant additional consideration and monitoring Emergency action plans should be developed for all patients at risk for anaphylaxis Education on anaphylaxis and allergen avoidance is critical for patients and their caregivers 49

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