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Adrenaline (Epinephrine) & Its use in Anaphylaxis

Vincent St Aubyn Crump

Adrenaline is a hormone naturally secreted by the medulla (inner portion) of the adrenal gland, which are situated just above the kidneys. This hormone is secreted along with noradrenaline (norepinephrine) to bring about the "flight or fight" response in times of stress, exercise, and response to low blood sugar. It prepares the body for strenuous activity or life-threatening situations. Increased secretion caused by fear or anger results in increased heart rate, and glycogen in the liver is broken down to glucose. The hormone was first extracted from the adrenal gland of animals in 1901, and first synthesized in 1904.

In medicine adrenaline is used to treat:

Anaphylaxis
Cardiac arrest – stimulates the heart
Asthma — acts as a bronchodilator (opens up the airways)
Glaucoma — when applied topically to the eyes it decreases intra-ocular pressure
Dental analgesia — added to local anaesthetic to reduce bleeding

Actions of Adrenaline

Increased metabolism
Cardiac stimulant & Increased heart rate
Increased blood pressure
Increased mental activity
Increased blood flow to muscles
Constriction of blood vessels (vasoconstriction)

Side Effects of Adrenaline

Anxiety (transient), Fear & Tremor
Cold fingers and toes and dry mouth (due to vasoconstriction)
Headaches
Pallor ("white as a sheet") — also due to vasoconstriction
Cardiac arrhythmias, Angina, and excessive rise in blood pressure
Intracerebral bleeding leading to strokes
Hyperventilation

Contraindications

Adrenaline may be administered in life-threatening anaphylactic reactions, even when the following relative contraindications are present:

Coronary artery disease
Uncontrolled hypertension
Serious ventricular arrhythmias (life-threatening abnormal heart rhythm)
Second stage of labour

Interactions

Sympathomimetics like ventolin & isoprenaline cause additive effects
Beta-blockers antagonize therapeutic effects of adrenaline
Digitalis potentiates the proarrhythmic effects of adrenaline
Phenothiazine causes a paradoxical decrease in blood pressure
Monoamine oxidase inhibitors (MOAIs) potentiate the cardiovascular effects of adrenaline

Use of Adrenaline in Pregnancy

Classified as Pregnancy Category A: Adrenaline has been given to a large number of pregnant women and women of child-bearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.

Precautions

Use with caution in elderly and patients that have:

Hyperthyroidism
Diabetes
Hypertension
Cardiovascular disease (angina, arrhythmias)
Stroke
Prostatic enlargement

Rapid intravenous infusion can cause death from cerebrovascular hemorrhage or cardiac arrhythmias.

Dosage & Administration in Anaphylaxis

Adult

Adrenaline 1:1000, 0.3 to 0.5 mL (0.3-0.5mg), administered slowly. The dose may be repeated every 10 minutes if necessary. In severe reactions the dose can be increased to 1mL. The intramuscular route is better than the subcutaneous route. Adrenaline 1:1000 should never be injected intravenously.

Children up to 12 years of age

Adrenaline 1:1000, 0.01ml / Kg (minimum 0.1ml 1:1000).

How is adrenaline supplied (in New Zealand)

Ampoules

Injection: 1/1000, 1ml (Baxter)
Adrenaline Injection is available in a single use ampoule containing 1mg adrenaline acid tartrate in 1mL (1:1,000). It is supplied in packs of 5 or 50.

Injection: 1/10000 (Baxter)
Adrenaline Injection 1/10,000 is available in single use ampoules containing 1mg adrenaline acid tartrate in 10 mL (1:10,000). It is presented in packs of 5 or 50.

This preparation is more suitable for intravenous use, preferably with cardiac monitoring.

A study done by Dr Estelle Simons in Winnipeg, Canada showed that adrenaline for out-of-hospital (first-aid) treatment of anaphylaxis in infants, the ampoules/syringe/needle method is not practical. Most parents were unable to draw up an infant adrenaline dose rapidly or accurately. (J Allergy Clin Immunol 2001; 108:1040-4)

Pre-filled syringe

Injection: 1/1000 Min-I-jet (CSL)
Adrenaline Injection is available in a single use prefilled MIN-I-JET syringe containing 1 mg adrenaline hydrochloride in 1 mL (1:1,000).

Auto-injectors

EpipenŽ & EpipenŽ junior (only form available in NZ).

The EpiPenŽ auto-injector is disposable drug delivery system featuring spring activation and a concealed needle. It is designed for self-administration of adrenaline in acute allergic emergencies (anaphylaxis)

The EpipenŽ and EpipenŽ Jr auto-injectors contain 2mls of adrenaline for emergency intramuscular use. Each EpiPen auto-injector delivers a single dose of 0.3mg adrenaline from adrenaline injection UPS, 1:1000 (0.3ml) in a sterile solution.

The EpiPenŽ Jr auto-injector delivers 0.15mg adrenaline injection UPS, 1:2000 (0.30ml) in a sterile solution. EpiPen contains sodium metabisulfite as preservative, but contains no latex.

They should be stored in a dark place at room temperature. Should not be refrigerated.

EpiPen and EpiPen Jr should only be injected in the outer thigh (antero-lateral portion). (Never in the buttocks)

When should adrenaline be given in (suspected) Anaphylaxis?

The ASCIA Anaphylaxis Action Plan (NZ version)

Mild to Moderate Allergic Reaction

Swelling of lips, face, eyes
Hives or welts
Abdominal pain, vomiting

ACTION

Stay with child and call for help
Give medications if prescribed (eg. Antihistamines)
Locate EpiPenŽ or EpiPenŽ Jr
Contact parent / carer

WATCH FOR SIGNS OF ANAPHYLAXIS (severe allergic reaction)

Difficulty / noisy breathing
Swelling of tongue
Swelling / tightness in throat
Difficulty talking and / or hoarse voice
Wheeze or persistent cough
Loss of consciousness and / or collapse
Pale and floppy (young children)

ACTION

Give EpiPenŽ or EpiPenŽ Jr
Call Ambulance. Telephone 111
Contact parent / carer

IF IN DOUBT GIVE EPIPENŽ OR EPIPENŽ Jr

EpiPenŽ Dosing

Adrenaline dosing is based on body weight. Normal adult dose of adrenaline in anaphylaxis is 0.30mg (0.30ml of 1:1000 adrenaline).

The paediatric dose is 0.01ml / Kg (minimum 0.1ml 1:1000). The EpiPenŽ Jr has 0.15mg adrenaline, which is the dose for a child weighing 15Kg. This might be too much for a 5Kg child, but not enough for a 25Kg child. For children weighing 15Kg to 30 Kg it is advisable to give EpiPenŽ instead of EpiPenŽ Jr, but one should bear in mind that this dose will have more side effects (tremor, palpitations, headaches and nausea).

Can Adrenaline Inhalations be substituted for adrenaline injection in children at risk for systemic anaphylaxis?

This question was answered by a study done by Dr Estelle Simons, et al, Winnipeg, Canada. (Paediatrics Vol. 106 No. 5 November 2000, pp 1040 —1044)

The study concluded: " Despite expert coaching, because of the number of adrenaline inhalation required and the bad taste of the inhalations, most children were unable to inhale sufficient adrenaline to increase their plasma adrenaline concentrations promptly and significantly...


 

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