Epinephrine dosing

In this review, we will describe the pharmacologic activity of epinephrine in anaphylaxis, the evidence base for its use, epinephrine dosing and routes of administration, epinephrine autoinjector use in first-aid treatment, reasons for failure to inject epinephrine promptly, reasons for occasional apparent lack of response, and future directions in epinephrine research. 

Epinephrine is administered by a variety of different routes in anaphylaxis, except for the oral route, which is not feasible because of rapid inactivation of epinephrine in the gastrointestinal tract by catechol-O-methyltransferase and monoamine oxidase [9]. The initial intramuscular epinephrine doses of 0.3-0.5 mg currently recommended for adults with anaphylaxis are low compared with the doses required for resuscitation following cardiac arrest [1, 2,4,18]. 

Optimal use of epinephrine autoinjectors for first-aid treatment of anaphylaxis in community settings is hampered by several issues. In most countries, these include the availability of only two pre-measured epinephrine doses and only a few different needle lengths, and the need to replace outdated autoinjectors at 12- to 18-month intervals due to degradation of the epinephrine solution they contain. 

Physicians face a dilemma with regard to prescribing an optimal epinephrine dose in an autoinjector for first-aid treatment of people at risk for anaphylaxis in a community setting, because only two pre-measured epinephrine doses, 0.15 and 0.3 mg, are... 

Currently, many physicians advise their patients at risk for anaphylaxis in the community to carry two epinephrine doses with them at all times [30]. In school settings, it has been proposed that one epinephrine autoinjector should be available for each child at risk, along with several extra autoinjectors available as back-up for all children at risk [31]. 

Although a 5- to 15-min interval between epinephrine injections is often recommended, this interval has not been established in randomized controlled trials, and consequently remains somewhat controversial in reality, the optimal time interval depends mainly on the clinical response to the initial epinephrine dose [1,2]. 

Epinephrine is an inherently unstable chemical in aqueous solution, even at a low pH and in the presence of an antioxidant such as sodium metabisulfite, up to 1 mg/ ml. With the passage of time, the epinephrine dose gradually decreases due to degradation into inactive compounds. If the expiry date has passed, the epinephrine dose correlates inversely with the number of months or years past that date, and will likely be lower than the dose stated on the label even if the solution appears clear and colorless. Nevertheless, if this is the only source of epinephrine available for injection, it should be used in preference to not administering epinephrine at all [32]. 

Although epinephrine autoinjectors are widely dispensed for first-aid treatment of anaphylaxis in some countries, they are neither available nor affordable in many others [33]. In these situations, physicians sometimes equip patients at risk for anaphylaxis in the community with an epinephrine ampule and a disposable 1-ml syringe. Some physicians also recommend this approach for infants, for whom, as noted previously, no appropriate epinephrine dose is available in an autoinjector formulation. 

Rarely, anaphylaxis progresses so rapidly that the initial first-aid dose of epinephrine which, as noted previously, is low relative to the initial epinephrine dose of 1 mg used in resuscitation, is ineffective even if given promptly. More commonly, anaphylaxis progresses because epinephrine is given too late, or administered in a suboptimal dose for the patient s body mass (weight), or through a suboptimal route [5]. 

The effect of drug concentration expression on epinephrine dosing errors a randomized trial. Ann 37 Intern Med 2008 148 11-14. 

Simons PER, Lieberman PL, Read EJ Jr. Edwards ES Hazards of unintentional injection of epinephrine from auto-injectors a systematic review. Ann Allergy Clin Immunol 2009 102 267-272. Rawas-Qalaji MM, Simons PER, Simons KJ Sublingual epinephrine tablets versus intramuscular injection of epinephrine dose equivalence for potential treatment of anaphylaxis. J Allergy Clin Immunol 2006 117 398-403. 

Report 957-77, E.I. du Pont de Nemours and Co., Newark, DE. Test species/Strain/Sex/Number male beagle dogs (1-2 per exposure group) Exposure route/Concentrations/Durations Inhalation 2,600, 5,200, 10,000, and 21,600 ppm for 10 min (the cardiac sensitization test is a 10-min test) epinephrine dose at 8 g/kg. The cardiac sensitization test is based on the observation that some halocarbons make the mammalian heart abnormally sensitive to epinephrine, resulting in ectopic beats and/or ventricular fibrillation, which may result in death. 

Reduce epinephrine dose if bronchial irritation, nervousness, restlessness, or... 

Overdosage or inadvertent IV injection Overdosage or inadvertent IV injection of conventional subcutaneous epinephrine doses may cause severe or fatal hypertension or cerebrovascular hemorrhage resulting from the sharp rise in blood pressure. Fatalities may also occur from pulmonary edema resulting from peripheral constriction and cardiac stimulation. 

Author Design Epinephrine Dosing SDE vs HDE N Initial Resuscitation SDE vs HDE Hospital Discharge SDE vs HDE Discharge Neurologic Status SDE vs HDE... 

The primary pharmacologic agents used in the treatment of asystole are epinephrine and atropine. The recommended epinephrine dose is identical to that used for the treatment of VF/PVT. 

Behringer W, Kittler H, SterzF, et al. Cumulative epinephrine dose during 75. 

Carroll TG, Dimas VV, Raymond TT. Vasopressin rescue for in-pediatric intensive care unit cardiopulmonary arrest refractory to initial epinephrine dosing a prospective feasibility pilot trial. Pediatr Crit Care Med 2012 13(3) 265-72. Epub 2011/09/20. 

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