Anaphylaxis

1. Anaphylaxis Approach and Management Prepared by Shane Barclay MD

2. Goals and Objectives • Review the causes and clinical presentation of anaphylaxis. • Review the management of acute anaphylaxis.

3. Definition of Anaphylaxis - an acute, potentially life-threatening hypersensitivity reaction, involving the release of mediators from mast cells, basophils and recruited inflammatory cells. Anaphylaxis is defined by a number of signs and symptoms, alone or in combination, which occur within minutes, or up to a few hours, after exposure to a provoking agent. It can be mild, moderate to severe, or severe. Most cases are mild but any anaphylaxis has the potential to become life-threatening, often within minutes.

4. Causes of Fatal Anaphylaxis • Medications (most common trigger in adults) - beta lactam antibiotics - the most common cause - radiocontrast agents - allergy immunotherapy 2. Foods (most common trigger in children) - In order of frequency : peanuts, tree nuts, cow's milk and seafood 3. Insect stings (second most common trigger in adults) - yellow jacket, honey bee, wasp, hornet, and fire ants

5. Fatal Anaphylaxis Analysis of fatal anaphylaxis show that in most cases of death, less the 60 minutes elapsed from allergen exposure to time of death. With medications, symptoms appeared after an average of 5 – 10 minutes. With insect stings, symptoms appeared after an average of 10 -15 minutes. With foods, symptoms appeared after and average of 25 – 35 minutes. The most common cause of death is cardiovascular and/or respiratory arrest.

6. Pathophysiology of Anaphylaxis A number of mediators including histamine, nitric oxide, calcitonin gene-related peptide, platelet-activating factor and others all contribute to the cardiovascular and pulmonary features of anaphylaxis. The end result however is a syndrome like hypovolemic shock (not necessarily the traditional view that anaphylaxis was distributive shock like in sepsis). There is massive fluid extravasation causing reduced venous return and depressed myocardial function. Up to 35 % of the intravascular volume can shift to the extravascular space within 10 minutes during anaphylaxis. This can result in what is known as ‘empty ventricle syndrome’.

7. Pathophysiology of Anaphylaxis Anaphylaxis can also be associated with cardiac ischemia and conduction abnormalities. Most patients will present with tachycardia, but some will be bradycardic after this initial phase. Patients are often then hypotensive and bradycardic. If cardiac arrest occurs, the most common rhythm is PEA.

8. Differentiating allergic versus anaphylaxic reaction This can be difficult and is probably the most common error in treating anaphylaxis – ie failure to realize the patient is having an anaphylactic reaction and NOT just an allergic reaction. In fatal anaphylaxis, median times to cardiorespiratory arrest are 5 minutes in iatrogenic anaphylaxis, 15 minutes in stinging insect venom-induced anaphylaxis, and 30 minutes in food-induced anaphylaxis.

9. Differentiating allergic versus anaphylaxic reaction Although not universally accepted, some authors suggest that an anaphylactic reaction versus allergic reaction is defined by: More than 2 body systems being involved. ie skin (urticaria) and respiratory or GI and respiratory etc. When any patient presents with TWO system involvement, they should definitely be treated as anaphylactiod.

10. Differentiating allergic versus anaphylaxic reaction Several studies of fatal anaphylaxis have shown that the most common mistake is not giving epinephrine early enough or not at all!

11. Clinical Presentation of Anaphylaxis 1. Respiratory compromise. Wheezing, dyspnea, stridor. 2. Hypotension – Systolic < 90 mmHg. • Skin/mucosal involvement – hives, itch, flushing, swollen lips /tongue/uvula, pilar erection • Persistent gastrointestinal symptoms – cramps, abdominal pain, vomiting. • Anxiety, apprehension, sense of impending doom. • Seizures, headache. • Uterine cramping and/or bleeding.

12. Biphasic Reaction Biphasic reaction is the recurrence of symptoms that develop after the apparent resolution of the initial anaphylactic reaction without additional exposure. Can occur in up to 20% of patients Usually occur within 10 hours of initial reaction, but have been reported to occur up to 72 hours later.

13. Concurrent Medications Patient who are taking: Beta blockers ACEI alpha-adrenergic blockers (eg trazadone, antipsychotics, mirtazapine) All increase the chance of fatal anaphylaxis and can block or interfere with treatment response (epinephrine)

14. Management • Epinephrine • Benadryl • H-2 Blocker • Steroids • Fluid Volume

15. Management Epinephrine 0.3 mg IM (anterolateral thigh) Is the most important treatment. There are NO absolute contraindications to epinephrine use.Approximately 20% of patients require a second IM injection. If no response to IM epinephrine start IV infusion. Epinephrine infusion: start 1 mcg/min then titrate. Worth mixing up push dose epinephrine if infusion is going to take time to mix. Use 9 cc N/S in 10 cc syringe. Add 1 cc of 1:10,000 cardiac ampule. Makes 10 mcg/ml. Give 5 – 10 mcg IV (0.5 – 1 cc IV)

16. Management Epinephrine infusion: (rule of 1’s) • Take 1 mg of epinephrine • Mix in 1 liter of fluid • Start at 1 ml per minute • If no response after 1 minute, increase to 2 ml per minute

17. Management So what if you are in a public area, a child develops anaphylaxis and some adult has an adult Epipen. Do you give that to the child? Yes. The risk of anaphylaxis is greater than the risk of over treating with IM epinephrine.

18. Management What about overdoses with epinephrine? The vast majority of epinephrine overdoses are via IV injections(ie using 1:1000 epinephrine IV)

19. Management Stop or remove inciting agent - eg. stop IV infusion of drug. Place patient in supine position with legs elevated. Give supplemental oxygen. Use 100% via non rebreather. Give salbutamol via nebulizer continuously. IV fluid volume resuscitation. May need 1 -2 liter bolus N/S.

20. Management If patient on beta blockers give Glucagon. Helps reverse the bronchoconstriction effect of beta blockers. Glucagon: 1- 5 mg IV over 5 minutes (If given too fast can cause vomiting) Then start infusion at 0.05 – 0.15 mg/kg/h

21. Management Airway: Use high flow oxygen with nebulized salbutamol Intubate if any indication of impending airway obstruction or angioedema. Remember with angioedema these may be difficult intubations. Be prepared for Cricothyrotomy. If normotensive can use standard RSI protocol. If hypotensive use ‘shock intubation’ protocol.

22. Management H1 Antagonists – antihistamines (Benadryl) 25 mg Benadryl as effective as 50 mg IM These help itch and hives but do not treat upper airway bronchoconstriction. Caution: if given IV can worsen hypotension. H2 Antagonists (Ranitidine) Help with itch but otherwise have no benefit in treating anaphylaxis. If used give Ranitidine 50 mg IV

23. Management Corticosteroids - There are no clinical trials showing benefit in treatment of acute anaphylaxis. - Take several hours to be of any benefit. - Rationale for using is to prevent the biphasic response in anaphylaxis - If used give Methylprednisolone 1-2 mg/kg daily PO or 100 mg IV. (no advantage of IV over PO as benefit is slow regardless)

24. Clinical Scenario 1 27 year old male with known peanut allergy inadvertently ate a sauce that had peanut oil. Within 1 minutes he developed hives, generalized flushing, feeling unwell and sweaty. He presents to the ER looking ill, flushed and hives on his face and neck. BP 110/75, HR 140, Sats 98% RR 28/min

25. Clinical Scenario 1 What are you going to do?

26. Clinical Scenario 2 A 45 year old woman was started on Pen V by her dentist earlier this morning. After the first pill she noticed some mild flushing, feeling warm and mild rash on her trunk. No itch. After taking the second pill 30 minutes ago she again noticed flushing, an itchy rash on her trunk and arms.

27. Clinical Scenario 2 Past history: Hypertension Medications: HCTZ 12.5 mg od, Ramipril 5 mg od On presentation: she looks anxious but no respiratory distress. She has hives on her face, neck and arms. BP 130/65 HR 145, RR 26, O2 sats 90%

28. Clinical Scenario 2 What are you going to do?

29. Clinical Scenario 3 68 year old male was just admitted to hospital with cellulitis and is being started on IV antibiotics. Past history: CAD with 2 stents Asthma Chronic renal insufficiency Gout

30. Clinical Scenario 3 Allergies: none known Medications: Ramipril 5 mg od Metoprolol 12.5 bid ASA 81 mg od Atorvastatin 40 mg od Symbicort 200 bid Salbutamol bid prn

31. Clinical Scenario 3 The nurse calls you to see him as he is appearing unwell. When you come in the room he is diaphoretic, rash over his face and upper trunk. Lips appear slightly swollen. He looks at you ‘with fear in his eyes’. You can hear audible wheezing as he breathes. His IV is running (with the antibiotics). Vitals: BP 110/40 HR 145, RR 40, O2 Sats 92%

32. Clinical Scenario 3 What are you going to do?