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Anaphylaxis



Debra O’Brien
  29/8/12
37 yr old man (PMHx Asthma)
30 minutes itchy red rash over his chest and abdomen
onset while eating dinner in restaurant
When is an allergic reaction
considered to be anaphylaxis?
When is an allergic reaction
             considered to be anaphylaxis?
                    National Institute of Allergy and Infectious Disease and the
                              Food Allergy and Anaphylaxis Network.

Anaphylaxis is highly likely when any 1 of the following 3 criteria are fulfilled:

1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or
     both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND at least 1 of the
     following:
      Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
      Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient
     (minutes 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 PEF, hypoxemia)
      Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence); persistent
          gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):
      Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP
      Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline
Anaphylaxis

        Acute onset multiple-organ hypersensitivity

 some degree of skin involvement appears to be nearly universal
                 (although often subtle, such as mild erythema)
                                     PLUS
respiratory (throat or chest tightness, breathlessness, wheeze, stridor, hypoxia)
         cardiovascular (hypotension, collapse, loss of consciousness)
           gastrointestinal (nausea, vomiting, abdominal pain)
What are the common triggers?
   Venomous stings and bites          30%

   Medication (antibiotics, NSAIDs)   22%

   Food (nuts, seafood)               18%

   Unidentified                       25%

   Other                              5%
What are the common triggers?
   Venomous stings and bites          30%

   Medication (antibiotics, NSAIDs)   22%

   Food (nuts, seafood)               18%
   Unidentified                       25%

   Other                              5%
When do you give Adrenaline?
• “The number one cause of death in anaphylaxis is the failure to
  administer adrenaline”
    Under-recognized and therefore under-treated

• Several case series have implicated the failure to administer
  adrenaline early in the course of treatment as a consistent finding
  in anaphylaxis deaths

• Not possible to predict
    –   severity
    –   rate of progress
    –   response to treatment
    –   risk of biphasic or protracted
• Consensus – even mild systemic reactions are best treated
  immediately with adrenaline → prevent progression to more
  severe symptoms more effectively than any other available
  therapies.

• There are NO absolute contraindications to adrenaline use in
  anaphylaxis
How much Adrenaline?
Adrenaline 0.01 mg/kg of 1:1000 (1 mg/mL)
to a maximum of 0.3-0.5 mg by INTRAMUSCULAR injection

every 3-5 minutes if life-threatening symptoms of hypotension,
  respiratory distress or stridor persist.

normal saline 10-20mL/kg boluses for persistent hypotension
Adrenaline Infusions
1 mg of adrenaline 1:10,000
inject into 1000mL bag of normal saline
start infusion at 1 mL/min (1 µg/min)
increase rate until resolution of severe anaphylaxis
Or
if you have a central line
6mg in 100 mL of 5% Glucose→ 60 µg/mL
Start infusion at 1 mL/hr (1 µg/min)
What is the role of antihistamines?
UpToDate and Cochrane Review
   No evidence to support the use of H1 antihistamines in
    anaphylaxis

Adjunctive to relieve itching and hives
   They DO NOT relieve the other symptoms of anaphylaxis
      and
   in standard doses do not inhibit mediator release

• 1st vs 2nd generation antihistamines
• H2 antihistamines
What is the role of steroids?
UpToDate and Cochrane Review
    No evidence to support the use of steroids in anaphylaxis

Adjunctive to prevent the biphasic or protracted reactions
    occur in up to 23 percent of adults with anaphylaxis, and up to 11 percent of
       children with anaphylaxis.

• Methylprednisolone of 1-2mg/kg
for 3 days without a taper
all biphasic reactions reported to date
have occurred within 72 hours
• Hydrocortisone 4 mg/kg IV or IM
then 2-4mg q6h
What is the role of bronchodilators?

Adjunctive treatment of bronchospasm not responsive to
  adrenaline
   do not prevent or relieve mucosal oedema in the upper airway
   or shock, for which the alpha-1 adrenergic effects of adrenaline are
      required
Should you do any investigations?
Lab tests are not usually required – clinical diagnosis

Helpful when diagnosis of anaphylaxis is unclear

• Total tryptase levels may be tested within 3 hours of
  symptom onset.
   – peak tryptase level correlated with severity of symptoms.
   – normal tryptase levels do not rule out a diagnosis of
     anaphylaxis, and are more likely with food-related anaphylaxis

• Histamine levels peak within 10 minutes of onset of
  anaphylaxis return to baseline within 60 minutes
Which patients need to be admitted?

Admission
• Severe anaphylaxis
• Mild to Moderate anaphylaxis that does not respond promptly
   to adrenaline
Vs
Observation
For patients with anaphylaxis which resolves promptly and
  completely with treatment → minimum observation period of
  4 hours, and prefer a period of 8 to 10 hours, if possible.
What is the risk of a biphasic
         reactions?
•   Occur about 5% of the time
•   May occur >24 hours after the initial episode
•   Usually less severe than the initial episode
•   Possible risk factors include:
    1. delayed administration of adrenaline
    2. slow response to adrenaline
    3. need for repeated doses of adrenaline
    4. need for IV fluids
Who needs an Epipen?
The mnemonic "SAFE" - four basic action steps suggested
  for patients with anaphylaxis who have been treated and
  are subsequently leaving the emergency department .

•   Seek support
•   Allergen identification and avoidance
•   Follow-up with specialty care
•   ‘Epinephrine’ for emergencies
Take Home Messages
• Early recognition

• Early treatment with
  adrenaline...know your doses!

• Risk of biphasic reactions

• “SAFE”

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Anaphylaxis

  • 2. 37 yr old man (PMHx Asthma) 30 minutes itchy red rash over his chest and abdomen onset while eating dinner in restaurant
  • 3. When is an allergic reaction considered to be anaphylaxis?
  • 4. When is an allergic reaction considered to be anaphylaxis? National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network. Anaphylaxis is highly likely when any 1 of the following 3 criteria are fulfilled: 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND at least 1 of the following: Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence) 2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes 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 PEF, hypoxemia) Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence); persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline
  • 5. Anaphylaxis Acute onset multiple-organ hypersensitivity some degree of skin involvement appears to be nearly universal (although often subtle, such as mild erythema) PLUS respiratory (throat or chest tightness, breathlessness, wheeze, stridor, hypoxia) cardiovascular (hypotension, collapse, loss of consciousness) gastrointestinal (nausea, vomiting, abdominal pain)
  • 6. What are the common triggers? Venomous stings and bites 30% Medication (antibiotics, NSAIDs) 22% Food (nuts, seafood) 18% Unidentified 25% Other 5%
  • 7. What are the common triggers? Venomous stings and bites 30% Medication (antibiotics, NSAIDs) 22% Food (nuts, seafood) 18% Unidentified 25% Other 5%
  • 8. When do you give Adrenaline? • “The number one cause of death in anaphylaxis is the failure to administer adrenaline” Under-recognized and therefore under-treated • Several case series have implicated the failure to administer adrenaline early in the course of treatment as a consistent finding in anaphylaxis deaths • Not possible to predict – severity – rate of progress – response to treatment – risk of biphasic or protracted
  • 9. • Consensus – even mild systemic reactions are best treated immediately with adrenaline → prevent progression to more severe symptoms more effectively than any other available therapies. • There are NO absolute contraindications to adrenaline use in anaphylaxis
  • 10. How much Adrenaline? Adrenaline 0.01 mg/kg of 1:1000 (1 mg/mL) to a maximum of 0.3-0.5 mg by INTRAMUSCULAR injection every 3-5 minutes if life-threatening symptoms of hypotension, respiratory distress or stridor persist. normal saline 10-20mL/kg boluses for persistent hypotension
  • 11. Adrenaline Infusions 1 mg of adrenaline 1:10,000 inject into 1000mL bag of normal saline start infusion at 1 mL/min (1 µg/min) increase rate until resolution of severe anaphylaxis Or if you have a central line 6mg in 100 mL of 5% Glucose→ 60 µg/mL Start infusion at 1 mL/hr (1 µg/min)
  • 12. What is the role of antihistamines? UpToDate and Cochrane Review No evidence to support the use of H1 antihistamines in anaphylaxis Adjunctive to relieve itching and hives They DO NOT relieve the other symptoms of anaphylaxis and in standard doses do not inhibit mediator release • 1st vs 2nd generation antihistamines • H2 antihistamines
  • 13. What is the role of steroids? UpToDate and Cochrane Review No evidence to support the use of steroids in anaphylaxis Adjunctive to prevent the biphasic or protracted reactions occur in up to 23 percent of adults with anaphylaxis, and up to 11 percent of children with anaphylaxis. • Methylprednisolone of 1-2mg/kg for 3 days without a taper all biphasic reactions reported to date have occurred within 72 hours • Hydrocortisone 4 mg/kg IV or IM then 2-4mg q6h
  • 14. What is the role of bronchodilators? Adjunctive treatment of bronchospasm not responsive to adrenaline do not prevent or relieve mucosal oedema in the upper airway or shock, for which the alpha-1 adrenergic effects of adrenaline are required
  • 15. Should you do any investigations? Lab tests are not usually required – clinical diagnosis Helpful when diagnosis of anaphylaxis is unclear • Total tryptase levels may be tested within 3 hours of symptom onset. – peak tryptase level correlated with severity of symptoms. – normal tryptase levels do not rule out a diagnosis of anaphylaxis, and are more likely with food-related anaphylaxis • Histamine levels peak within 10 minutes of onset of anaphylaxis return to baseline within 60 minutes
  • 16. Which patients need to be admitted? Admission • Severe anaphylaxis • Mild to Moderate anaphylaxis that does not respond promptly to adrenaline Vs Observation For patients with anaphylaxis which resolves promptly and completely with treatment → minimum observation period of 4 hours, and prefer a period of 8 to 10 hours, if possible.
  • 17. What is the risk of a biphasic reactions? • Occur about 5% of the time • May occur >24 hours after the initial episode • Usually less severe than the initial episode • Possible risk factors include: 1. delayed administration of adrenaline 2. slow response to adrenaline 3. need for repeated doses of adrenaline 4. need for IV fluids
  • 18. Who needs an Epipen? The mnemonic "SAFE" - four basic action steps suggested for patients with anaphylaxis who have been treated and are subsequently leaving the emergency department . • Seek support • Allergen identification and avoidance • Follow-up with specialty care • ‘Epinephrine’ for emergencies
  • 19. Take Home Messages • Early recognition • Early treatment with adrenaline...know your doses! • Risk of biphasic reactions • “SAFE”

Editor's Notes

  1. Only first-generation agents are available for parenteral treatment Oral second-generation H1 antihistamines (e.g. loratidine) similar onset of action (i.e. within 1 hour) without sedationH2 antihistamines - there is minimal evidence to support their use in conjunction with H1 antihistamines in the emergency treatment of anaphylaxis. Most guidelines do not include these medications.
  2. LABORATORY TESTS — The clinical diagnosis of anaphylaxis can sometimes be supported by documentation of elevated concentrations of serum or plasma total tryptase or plasma histamine [35,43-45]. It is critical to obtain blood samples for measurement of these mast cell and basophil mediators soon after the onset of symptoms, as elevations are transient. Instructions for proper collection of samples are provided in the table (table 6).Serum or plasma total tryptase - The test for measurement of total serum or plasma tryptase is widely available in clinical laboratories (normal range 1 to 11.4 ng/mL, Phadia AB, Uppsala, Sweden). Optimally, the blood sample for tryptase measurement needs to be obtained from 15 minutes to 3 hours of symptom onset. Tryptase elevations are more likely to be detected in anaphylaxis from stinging insect venoms or medications, and following reactions that involve hypotension [44,45].A tryptase level that is within normal limits cannot be used to refute the clinical diagnosis of anaphylaxis [35]. The history trumps the test results. As an example, in individuals with food-induced anaphylaxis, or in patients who are normotensive, tryptase levels are seldom elevated, even in optimally-timed blood samples obtained within 15 minutes to 3 hours of symptom onset [23].Serial measurements of total tryptase in serum or plasma over several hours may increase the sensitivity and the specificity of the tests. Comparison of a level obtained during the acute episode with a level obtained 24 hours after resolution of clinical symptoms and signs may be useful for confirming the clinical diagnosis [15]. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis" and "Anaphylaxis: Confirming the diagnosis and determining the trigger(s)".)If a tryptase level obtained 24 or more hours after resolution of clinical symptoms and signs is still elevated, the patient should be referred to an allergy/immunology specialist for evaluation of possible systemic mastocytosis or clonal mast cell disease. (See "Clinical manifestations, pathogenesis, and classification of mastocytosis (cutaneous and systemic)".)
  3. We also suggest that if patients are sent home after only a few hours, they should be trained to use an epinephrine autoinjector and should actually be supplied with one, rather than simply handed a prescription for one. As noted previously, up to 23 percent of adults may experience a biphasic reaction [31,32]. (See 'Biphasic anaphylaxis' above.)
  4. The mnemonic "SAFE" was developed to remind clinicians of the four basic action steps suggested for patients with anaphylaxis who have been treated and are subsequently leaving the emergency department or hospital [90]. The SAFE counseling is outlined below and has been incorporated into printable patient information materials. (See 'Information for patients' below.)Seek support — Advise the patient that:They have experienced anaphylaxis or "killer allergy," which is a life-threatening condition.Symptoms of the current episode may recur up to three days after the initial onset of symptoms.They should self-inject epinephrine, and call emergency medical services or get to the nearest emergency facility at the first sign of recurrence of symptoms.They are at risk for repeat episodes of anaphylaxis in the future.Refer the patient to resources. (See 'Information for patients' below.)Allergen identification and avoidance — Before the patient is discharged, an effort should be made to identify his or her anaphylaxis trigger using the history and in vitro testing (measurement of specific IgE to the allergen identified in the history). If the patient has received volume resuscitation, IgE levels might be falsely absent or undetectable due to the potential dilutional effects on circulating IgE, and it might be necessary to recheck the levels four to six weeks after the anaphylactic episode.Emphasize the importance of subsequent allergy skin testing to confirm the trigger, so that it can be successfully avoided in the future.Follow-up with specialty careAdvise the patient to follow-up with his or her primary care clinician and obtain a referral to an allergist or to seek consultation directly with an allergist for testing and ongoing management.Epinephrine for emergenciesProvide the patient with an epinephrine autoinjector or with a prescription for self-injectable epinephrine, as well as verbal plus DVD/written instructions for use.Explain the importance of carrying the epinephrine autoinjector at all times.Advise the patient to make sure that family and friends are aware of the risks of anaphylaxis, the triggers, and how to administer epinephrine. The correct injection technique is important to avoid unintentional injection into fingers, thumbs, or other body parts [91].