Cardiac Arrest in Special Circumstances: Anaphylaxis

Definition

Anaphylaxis is a severe, life-threatening, multi-organ hypersensitivity reaction, typically of rapid onset.

Context

• There are at least 20 deaths attributable to anaphylaxis in the UK each year (ref 1)
• The incidence of anaphylaxis is increasing (ref 1)
• The early recognition of anaphylaxis and its prompt treatment with adrenaline, is highly likely to prevent deterioration
• No randomised controlled trials regarding the critical management of anaphylaxis exist, or are likely to exist

So how might you identify which patients in cardiac arrest, or near cardiac arrest have anaphylaxis as the likely trigger?

Anaphylaxis is likely when:

• Your patient has been exposed to a known allergen, is he or she wearing a Medic-Alert bracelet?
• The onset of life-threatening airway or breathing or circulatory problems (more typically a combination) has been sudden, with rapid progression minutes, not hours
• Urticaria and/or angioedema are present

The original cardiac arrest rhythm is likely to be PEA, though there are of course many other causes of this rhythm.

In more detail:

The history

Typical triggers for anaphylaxis are drugs, foodstuffs and stings (venom).

Speed of onset

In a further large case series of UK patients with fatal anaphylaxis, the median time to cardiac arrest was within 5 minutes in cases receiving intravenous agents, 15 minutes for venom and 30 minutes for foodstuffs (ref 3)

• Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000;30(8):1144-50.

Symptoms and signs

Beware the pitfalls of misinterpreting the following symptoms and signs in the context of anaphylaxis:

Pitfall

WHEEZE = ASTHMA

Differentiating asthma and anaphylaxis might be difficult clinically. And made harder by the fact that in anaphylactic fatalities triggered by food, nearly all the cases had difficulty in breathing that led to respiratory arrest (ref 3). It is however unlikely that newly diagnosed asthma would present in such dramatic fashion; similarly, known asthmatics rarely deteriorate so abruptly. If in doubt give adrenaline (IM), the key agent in anaphylaxis and formerly a standard therapy in asthma.

Stridor = croup/epiglottitis

Stridor secondary to infection will have a slower onset and will usually be associated with fever.

ECG with ST depression = acute coronary syndrome

ST changes are recognized in anaphylactic patients with normal coronary arteries, with or without adrenaline; indeed, in the ischaemic heart disease population these changes might even be expected in severe anaphylaxis. Do not with hold adrenaline when you suspect anaphylaxis, even if ECG changes are present.

Bradycardia rules out anaphylaxis

Bradycardia can occur in anaphylaxis as a likely peri-arrest sign

Vomiting, abdominal pain and diarrhoea = not anaphylaxis

Not so, anaphylaxis is a multisystem insult that may well involve the gut.

Anxiety misdiagnosed as a panic attack

Be careful a sense of doom is well described in anaphylaxis. And patients whove previously experienced anaphylaxis might well panic when they suffer another episode. Weigh up the clinical situation in the resus room carefully.

Subtle rash only means not anaphylaxis

No rash is found in 20% of anaphylactic cases

Erythema is not compatible with anaphylaxis

Patchy or generalised erythema is recognized. Urticaria is not essential.

Pallor not compatible with anaphylaxis

Beware adrenaline-induced pallor via its vasopressor action.

Note too that mucosal rather than skin changes may exist ie angioedema. This most commonly presents as swelling of the eyelids and lips, sometimes the mouth and throat (with potential stridor in the latter).

Learning Bite

Skin and mucosal changes can be subtle or absent in up to 20% of anaphylactic cases.

Other conditions mimicking anaphylaxis include ACE inhibitor-induced angioedema ( which may indeed be more common than anaphylaxis), hereditary angioedema and scombroid poisoning.

ACE inhibitor induced-angioedema

• May occur years after starting the drug therapy
• Swollen tongue and oral mucosa typical
• Urticaria unlikely
• Hypotension unlikely

Hereditary angioedema

• Swollen tongue, lips, oropharynx and extremities
• Urticaria unlikely
• Episodes usually begin in childhood, becoming more frequent in adolescence
• C1 esterase inhibitor deficiency
• Abdominal symptoms common

Scombroid poisoning

• Flushing, occasional urticaria
• Follows ingestion of improperly preserved fish essentially causing ingestion of excessive histamine
• Hypotension quite possible

Angioedema

• Unresponsive to adrenaline
• Supportive therapy
• Stop the trigger drug

Hereditary angioedema

• Unresponsive to adrenaline
• Supportive therapy
• 2 units FFP
• 1000-1500 units of C1 esterase inhibitor

Scombroid poisoning

• Unresponsive to adrenaline
• Antihistamines
• Supportive therapy

Finally, beware overkill (call that trigger-happy if you will) skin and mucosal changes alone are insufficient for a diagnosis of anaphylaxis thats called allergy and adrenaline may cause more harm than benefit.

Learning Bite

• Beware conditions mimicking anaphylaxis
• Skin and mucosal changes alone represent allergy not anaphylaxis.

So how might you respond to severe anaphylaxis, so as to avoid cardiac arrest?

You’ve diagnosed anaphylaxis and your heart rate is beginning to match the patients you need a peri-arrest strategy.

Consider specific ABC issues:

A = adrenaline, not airway in this scenario

Adrenaline is the key life-saving drug

Alarmingly, in the largest UK case series of fatal anaphylaxis, a third received no adrenaline, and of the two thirds who did, only 14% were given adrenaline pre-arrest. (ref 3)

Not on your shift surely

0.5mg IM is the dose for those ages 12 years and above and hopefully the paramedics will have beaten you to it. In which case repeat if required.

Consider IV titrated adrenaline. 0.5ml (50mcg) increments of a 1mg in 10 ml pre-filled syringe (1 in 10,000) (image) is what the UK Resuscitation Council recommend for experienced practitioners. A titrated IV adrenaline infusion may be more suitable for less critical cases.

Airway

Is there any airway oedema, suggested by visible facial swelling, swollen tongue, stridor or if youre particularly unlucky, all three? In which case summon a senior anaesthetist. Consider intubation.

Circulation

• Are you titrating adrenaline yet?
• Weigh up whether your patient is best positioned sitting up (breathless) or flat with leg elevation (shocked).
• Crystalloid not colloid (as colloids are allergenic).
• Give 1000ml fluid challenges if the patient is hypotensive; half that in patients with known cardiac failure, listening carefully for lung crepitations in between boluses.
• 4-8l of crystalloid may be required in the peri-arrest or arrest case.
• Consider inserting an arterial line

In conjunction with addressing ABC issues, remove the trigger for anaphylaxis

• Stop the offending drug infusion or gelatin infusion
• Scrape away the sting
• Have any squirrels escorted from the resus room

Learning Bite

• Titrated adrenaline is the key treatment in anaphylaxis.
• 4-8l of crystalloid may be required peri-arrest.
• Stop or remove the anaphylactic trigger

So what modifications to the standard ALS protocol are required if your patient arrests, or is presented to you in cardiac arrest?

• Early intubation, particularly in the context of airway oedema, by the most experienced airway practitioner. As a competent RSI practitioner youll recognize the likelihood of a difficult airway. Ensure surgical airway equipment is readily available.
• IV adrenaline ensure 1 mg is given every 3-5 minutes, given that it is the key agent that might effect recovery.
• Large crystalloid challenges through large bore cannulae with pressure bags (image)
• Antihistamines and steroids? These have no role in cardiac arrest.
• Additional vasopressors in refractory cases? The evidence-base is weak case reports with potential flaws you might question (a) was enough adrenaline/fluid given? (b) was recovery truly attributable to the additional agent? In beta- blocked patients, consider a role for noradrenaline (50mcg boluses) or glucagon (1-2 mg every 5 minutes) in adrenaline-resistant cases.
• Smaller doses of adrenaline in patients on tricyclic antidepressants, or some antihypertensive agents? This is theoretical, and thankfully not supported by the Resuscitation Council.
• Be prepared for a prolonged resuscitation attempt typically patients are young and previously well.

Learning Bite

• Antihistamines and steroids have no role in cardiac arrest
• Alternative vasopressors have a theoretical role in cases refractory to repeated adrenaline

Post-arrest management

The preferred disposal for your patient with recovery of spontaneous circulation from anaphylaxis-induced cardiac arrest is intensive care.

In the meantime:

• Start a titrated adrenaline infusion follow local policy. 1 mg in 1000 ml saline at 1ml/min (60ml/hr) titratedto response is an example.
• Insert an arterial line to guide therapy.
• Give 200mg IV hydrocortisone and 10 mg chlorpheniramine (slowly) if these have not already been administered.
• Measure the serum tryptase level (in a standard U&Es bottle) labelling the time carefully. Arrange repeat measurement 1-2 hours later, in order to help confirm true anaphylaxis (ref 1)
• Consider targeted temperature management as per local guidelines in patients not regaining consciousness.
• Document the need for in-hospital teams to arrange the following for your patient Medic alert bracelet (image), auto- injector (image) and education in its use and administration, and referral to an immunologist.
• Remember that a biphasic reaction can recur many hours later.
• In cases of drug- induced anaphylaxis, report the incident to the Medicines and Healthcare products Regulatory Agency (MHRA) using the yellow card scheme (www.mhra.gov.uk). The BNF includes copies of the yellow card at the back of each edition.

Learning Bite

• Measure the serum tryptase level post-resuscitation and 1-2 hours later to help confirm true anaphylaxis.
• Survivors of peri-arrest anaphylaxis require a Medic alert bracelet, adrenaline auto-injector provision and education, and referral to an immunologist.

Finally, we the authors could find no evidence to reliably predict outcome from anaphylaxis induced cardiac arrest. We suggest that it is poor, particularly in cases refractory to prompt and correct application of the ALS protocol. Patients with recovery of spontaneous circulation may succumb to, or survive with hypoxic brain injury.

Interpret your team and the paramedics failed resuscitation effort in this context with appropriate feedback.

In which case your next task is informing the (typically young) family of their unexpected loss.

Case 1

A 31 year old man has both asthma and a nut allergy. He presents with breathlessness that started during lunch. He has self administered his salbutamol inhaler and 300mcg adrenaline auto-injector with reasonable response. You are both unsure as to whether his symptoms represent asthma or anaphylaxis.

Signs and symptoms supportive of asthma	Signs and symptoms supportive of either	Signs and symptoms supportive of anaphylaxis
	Wheeze Tachycardia Response to beta-2 agonist Response to IM adrenaline	Skin or mucosal changes Hypotension*

*hypotension in the context of asthma is suggestive of (critical) life-threatening asthma with possible tension pneumothorax

Are there any treatment strategies contraindicated in this case?

Not really.

• Intravenous fluids, if he needs them, benefit both asthma and anaphylaxis patients are generally dry in severe asthma; litres of crystalloid may be required in severe anaphylaxis.
• Steroids are indicated for both
• Antihistamines will have no impact on asthma
• Adrenaline, by whatever route is a recognized treatment for asthma and the key agent in anaphylaxis
• Beta-2 agonists are a reasonable option in the treatment of his asthma or anaphylaxis

Case 2

You have diagnosed severe lower leg cellulitis in an elderly, beta-blocked woman. Her observations are P 110, BP 90/42, RR 20, sats 100% on highflow O2. She has a lactate of 3 after 1500 ml of carefully titrated fluids. You have started an IV penicillin via infusion. You are anticipating initiating early goal directed therapy when you note a sudden deterioration: P 120 sinus tachycardia, BP 50/-. You are able to palpate a femoral pulse and a note a developing urticarial rash.

Five key management actions to perform in the next minute:

1. Summon team assistance
2. Stop the antibiotic infusion
3. Give 0.5mg IM adrenaline. If this truly is anaphylaxis (to an IV agent, in this case a penicillin) abrupt cardiovascular collapse is quite possible. If experienced and confident in its use, consider IV adrenaline.
4. Elevate the legs
5. Give 500 ml IV crystalloid STAT

Despite having performed the above actions (youve got the fluid challenge running quickly with the pressure bag) you note a clear deterioration. She is unresponsive and you cannot now feel a femoral pulse.

Two further key actions:

1. Start CPR as per the ALS protocol
2. Give 1 mg IV adrenaline and ensure that it is repeated every 3-5 minutes

Case 3

A 16 year old girl with a known food allergy presents having become breathless in a fast food restaurant. She has been given 0.5mg IM adrenaline by the paramedic crew. On arrival in ED she has P 105, BP 100/65, RR 30, sats 100% on high flow O2 and no wheeze. She has an urticarial rash on her upper chest.

The two main differential diagnoses:

• Allergic reaction
• Anaphylaxis

Anxiety may well be playing a part here, but doesn’t account for the urticarial rash.

How might you distinguish between these two?

• Examine the paramedic record, particularly the observations on crew arrival: did hypotension exist/on what basis was the IM adrenaline given?
• Observe her carefully in the resus room and see if her respiratory rate and heart rate settle

Remember skin or mucosal changes alone represent allergy, not anaphylaxis. You’ll have to carefully judge whether anxiety or anaphylaxis (+/- anxiety) accounts for her raised respiratory rate. A (venous) lactate might guide your decision making. Adrenaline is probably unwarranted in this case (at least at this stage) indeed it may cause more symptoms. In older patients unwarranted adrenaline may even cause harm.

How should she be managed?

• Close observation in the resus room (at least initially)
• Ensure that she is cannulated
• IV (or perhaps oral although absorption may be slowed by swelling of abdominal mucosa)) antihistamines and steroids
• Have 0.5 mg adrenaline drawn up

Key Learning Points

1. The early recognition of anaphylaxis and its prompt treatment with adrenaline, is highly likely to prevent cardiac arrest. Grade C, Level 4.
2. Beware conditions mimicking anaphylaxis. Grade D, Level 5.
3. Skin and mucosal changes can be subtle or absent in up to 20% of anaphylactic cases. Grade C, Level 4.
4. Skin and mucosal changes alone represent allergy not anaphylaxis. Grade D, Level 5.
5. Adrenaline is the key treatment in anaphylaxis. Grade C, Level 4.
6. 4-8l of crystalloid may be required peri-arrest. Grade D, Level 5.
7. Stop or remove the anaphylactic trigger. Grade D, Level 5.
8. Antihistamines and steroids have no role in cardiac arrest; alternative vasopressors have a theoretical role in cases refractory to repeated adrenaline. Grade C, Level 4.
9. Measure the serum tryptase level post-resuscitation and 1-2 hours later to help confirm true anaphylaxis. Grade D, Level 5.
10. Survivors of peri-arrest anaphylaxis require a Medic alert bracelet, adrenaline auto-injector provision and education, and referral to an immunologist. Grade D, Level 5.

1. Resuscitation Council (UK). Anaphylaxis. 2008
2. Pumphrey RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp 2004; 257: 116-28; discussion 128-32, 157-60, 276-85.
3. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy2000; 30(8): 1144-50.