• 
• 

Three Part Question

For [children with severe allergies] the which [dose of adrenaline autoinjector] is most suitable to achieve [appropriate plasma adrenaline levels]?

Clinical Scenario

You care for a 8 year old patient in paediatric A&E who is recovering from an anaphylactic reaction after a bee-sting. In accordance with NICE guidelines he should be discharged with an adrenaline autoinjector (AAI). The correct dose for adrenaline is 0.1mg per kg although only two strengths of AAI are available - 0.15mg and 0.3mg He weighs 23kg. You wonder which is the most appropriate one to prescribe?

Search Strategy

Medline 1946 to June Week 1 2013
EMBASE 1980 to 2013 Week 26

“((exp hypersensitivity/) OR (exp anaphylaxis/) OR (anaphyla$.mp) OR (allerg$.mp) OR (acute ADJ allergic ADJ reaction)) AND ((exp epinephrine/) OR (exp self, administration/) OR (exp injections, intramuscular/) OR (adrenalin$.mp) OR (autoinjector.mp) OR (auto-injector.mp) OR (epipen.mp) OR (auvi-q.mp) OR (JEXT.mp) OR (IM.mp) OR (intramuscular$.mp)) AND ((exp drug dose/) OR (exp recommended drug dose/) OR (exp optimal drug dose/) OR (“Epinephrine”/ad[administration & dosage]) OR (dose$.mp)) Limits – English Language, Humans, Children 0-18 years.

Search Outcome

442 papers were found, only one was relevant to the question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Simons, FER et al 2002 Canada	10 Children with a history of severe allergy whom carry an AAI between the ages of 4 and 8 years and between 15 to 30kg. Children randomly allocated either 0.3mg or 0.15mg adrenaline injection.	Randomised, double-blinded, parallel group pilot study	Mean adrenaline concentrations before, during and up to 180 minutes after IM adrenaline injection into midpoint of vastus lateralis of the thigh	Mean plasma adrenaline concentration from 0.3mg vs 0.15mg was not significantly different (2037±541pg/ml vs. 2289±405pg/ml)	Small sample size 0.15mg group were significantly smaller than the 0.3mg group, p<0.05
			Time taken to achieve mean plasma adrenaline concentrations	The time taken to achieve mean plasma adrenaline concentrations was not significantly different between the 0.3mg and 0.15mg groups. (16±3minutes vs. 15±3 minutes)
			Blood pressure and heart rate changes before, during and after injection	At 30 minutes after injection the mean systolic blood pressure was significantly higher in 0.3mg compared to the 0.15mg group.
			Adverse effects	In both groups all children experienced pallor. However in the 0.3mg group this lasted longer and was accompanied with tremor and anxiety. Some children also experienced palpitations, headache and nausea

Comment(s)

Simons et al specifically considered children between the weights of 15kg and 30kg, the study demonstrated there was no difference in terms of plasma adrenaline levels or time to achieve this between the groups. This study suggests appropriate adrenaline levels will be achieved regardless of the dose used. Unfortunately the significant (p<0.05) weight difference between the groups has reduced the validity.

Clinical Bottom Line

Ideally more dose options for children between the weights of 15 and 30kg would be beneficial but weight should be combined with other factors such as severity of previous reactions and ready accessibility to emergency services to determine the most appropriate dose of AAI to prescribe.

References

1. Simons FER, Gu X, Silver NA, Simons KJ. EpiPen Jr versus EpiPen in young children weighing 15 to 30 kg at risk for anaphylaxis Journal of Allergy and Clinical Immunology. 2002;109(1):171-5.