| Relevant studies | Comments | |
| Patient/caregiver/clinician | ||
| Rapid anaphylaxis progression | Case reports, autopsy reports | In 10% of anaphylaxis episodes, epinephrine does not work, even if given promptly |
| Epinephrine given too late | Case reports, autopsy reports | Cause-and-effect hard to prove |
| Individuals do not know how to use epinephrine autoinjectors | Cross-sectional surveys, demonstrations | Frequently reported |
| Epinephrine-related | ||
| Dose too low | Few dose response studies | Optimal dose unknown; based on tradition, 0.3 mg is used for adults in many countries, 0.5 mg in some countries |
| Lack of availability of fixed doses 0.05, 0.1, 0.2, 0.25 mg in autoinjectors | Impossible to give an appropriate dose to infants and to some young children | |
| Route/site not optimal | Intramuscular versus subcutaneous* | Intramuscular, thigh preferred to subcutaneous, arm |
| Ampule and syringe* | Nonmedical personnel lack speed and accuracy | |
| Pressurized metered-dose inhaler (MDI)¶ | For systemic effects, adults need 20 to 30 puffs (children 10 to 20; has been phased out in most countries) | |
| Past expiration date | Bioavailability measured in animal models; content measured in vitroΔ | Epinephrine content inversely related to number of months past expiration date |
| Other | ||
| Individual not supine | Autopsy reports | If the individual is standing, venous return is decreased, the ventricles are empty, and death may occur despite timely epinephrine-induced reversal of vasodilation and shock |
| Individual taking medications (beta-blocker or alpha-blocker, angiotensin-converting enzyme inhibitor) that prevent optimal epinephrine effect | Case reports | There is more information about lack of effect in asthma than in anaphylaxis |
| Adverse effects of sodium metabisulfite (antioxidant in epinephrine) | Case reports | Additional studies needed, because sulfite-sensitive asthmatics tolerate epinephrine |
