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The Effect of Drug Concentration Expression on Epinephrine Dosing Errors: A Randomized Trial

Daniel W. Wheeler, PhD; Joseph J. Carter, MBChB; Louise J. Murray; Beverley A. Degnan, PhD; Colin P. Dunling, BSc; Raymond Salvador, PhD; David K. Menon, MD, PhD; and Arun K. Gupta, PhD
[+] Article, Author, and Disclosure Information

From the University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom, and Benito Menni—Centre Assistencial en Salut Mental Sant Boi de Llobregat, Barcelona, Spain.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement:Study protocol, statistical code, and data set: Available to approved individuals through written agreements.

Requests for Single Reprints: Daniel W. Wheeler, PhD, Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom; e-mail, dww21@cam.ac.uk.

Current Author Addresses: Drs. Wheeler, Carter, Degnan, Menon, and Gupta and Mr. Dunling: University Division of Anaesthesia and Department of Anaesthetics, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom.

Miss Murray: Simulation Centre, Addenbrooke's Hospital Postgraduate Centre, Box 111, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom.

Dr. Salvador: Benito Menni–Centre Assistencial en Salut Mental, Dr Pujadas 38, Sant Boi de Llobregat, 08830 Barcelona, Spain.

Author Contributions: Conception and design: D.W. Wheeler, B.A. Degnan.

Analysis and interpretation of data: D.W. Wheeler, B.A. Degnan, R. Salvador.

Drafting of the article: D.W. Wheeler.

Critical revision of the article for important intellectual content: D.W. Wheeler, J.J. Carter, L.J. Murray, B.A. Degnan, C.P. Dunling, R. Salvador, D.K. Menon, A.K. Gupta.

Final approval of the article: D.W. Wheeler, J.J. Carter, L.J. Murray, B.A. Degnan, C.P. Dunling, R. Salvador, D.K. Menon, A.K. Gupta.

Statistical expertise: R. Salvador, D.K. Menon

Obtaining of funding: D.W. Wheeler

Administrative, technical, or logistic support: J.J. Carter, L.J. Murray, B.A. Degnan, C.P. Dunling.

Collection and assembly of data: D.W. Wheeler, J.J. Carter, L.J. Murray, B.A. Degnan, C.P. Dunling.

Ann Intern Med. 2008;148(1):11-14. doi:10.7326/0003-4819-148-1-200801010-00003
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The study received institutional ethical approval. The scenario was enacted by using a pediatric mannequin in the hospital's high-fidelity patient simulator center (Human Patient Simulator, Medical Education Technologies, Sarasota, Florida), which was configured as a rural emergency room. Hospital-affiliated physicians in our institution without pediatric experience volunteered to participate without payment. The Appendix shows the volunteers' briefing.

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Appendix Figure.
Protocol for determining the dose of epinephrine.

IM = intramuscular; IV = intravenous.

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Dose and timing of epinephrine administration.

Top. Dose of epinephrine. Bars indicate median doses (122.5 µg [IQR, 120.0 to 125.0 µg] in the mass concentration group vs. 250.0 µg [IQR, 250.0 to 500.0 µg] in the ratio group; P = 0.003); 120 µg was the correct dose. The adjusted mean difference in dose made by the ratio group was 213 µg (95% CI, 76.4 to 350.1 µg) greater than the 120-µg target dose. Bottom. Time taken to give epinephrine. Bars indicate median times (35.5 seconds [IQR, 27.0 to 65.0 seconds] in the mass concentration group vs. 130.0 seconds [IQR, 112.0 to 171.0 seconds] in the ratio group; P < 0.001). The adjusted mean time was 91.0 seconds (CI, 61.0 to 122.1 seconds) greater in the ratio than in the mass concentration group.

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Submit a Comment/Letter
Optimal Pediatric Emergency Drug Dosing: Volume-Based Dosing
Posted on January 18, 2008
Young S. Choi
Womack Army Medical Center
Conflict of Interest: None Declared

TO THE EDITOR: Wheeler et al. (1) address the occurrence of medication errors during pediatric emergency treatment. In their simulated model, participants were required to calculate the correct dose of intramuscular epinephrine for a 5-year-old with peanut anaphylaxis. They concluded that patient safety might be improved by expressing epinephrine drug concentrations exclusively as mass concentration rather than ratio.

While the dose of emergency medications is standardized in adults, pediatric dosages are weight based. Once the milligram amount of a medication is determined, the correct volume must then be calculated. A volume-based protocol would eliminate the extra step of conversion and furthermore, might eliminate calculations altogether. The Broselow Pediatric Emergency Tape uses a child's length to estimate weight and automatically calculate not only the milligram amount but also the correct volume for two common intravascular resuscitative medications, epinephrine and atropine. For instance, a 13 kg child's dose of intravenous epinephrine (1:10,000 dilution) is 0.13 mg which is delivered as 1.3 mL. Unfortunately, the Broselow Pediatric Emergency Tape does not pre- calculate the volume for other medications.

A complete volume-based emergency protocol is the optimal method for delivery of resuscitative medications. Automated computerized "code" sheets can easily be developed for at risk patients. At Womack Army Medical Center, all pediatric patients have a weight based computerized "code" sheet posted at the bedside listing the specific volume for all the common emergency medications. No calculations are required.

For outpatients, a pediatric emergency protocol that does not require calculations remains optimal. The Color Coding Kids Hospital System is a commercially available example. While such a hospital-wide system may be a drastic change, it certainly is feasible to have some type of system in place for at least the most common emergencies (2). For example, for treatment of anaphylaxis, the recommended dose is 0.01 mg/kg of epinephrine (1:1,000 dilution or 1 mg/mL concentration) to a max of 0.3 mg intramuscularly or subcutaneously (3). Therefore, any child 30 kg or more would receive 0.3 mL. For those patients weighing less than 30 kg, a pre- calculated volume could be ascribed to various weights. Even if pre- calculated volume-based dosing is not used, the volume-based calculation can be posted to eliminate one additional calculation, i.e., the emergency dose would be 0.01 mL/kg rather than 0.01 mg/kg.


1. Wheeler DH, Carter JJ, Murray LJ, Degnan BA, Dunling CP, Salvador R, et al. The effect of drug concentration expression on epinephrine dosing errors. Ann Intern Med. 2008;148:11-14. [PMID: 18166759]

2. Shah AN, Frush K, Luo X, Wears RL. Effect of an intervention standardization system on pediatric dosing and equipment size determination: a crossover trial involving simulated resuscitation events. Arch Pediatr Adolesc Med. 2003;157:229-36. [PMID: 12622671]

3. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol 2005;115:S483-523. [PMID: 15753926]

Conflict of Interest:

The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense.

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Summary for Patients

The Effect of Drug Concentration Expression on Epinephrine Dosing Errors

The summary below is from the full report titled “The Effect of Drug Concentration Expression on Epinephrine Dosing Errors. A Randomized Trial.” It is in the 1 January 2008 issue of Annals of Internal Medicine (volume 148, pages 11-14). The authors are D.W. Wheeler, J.J. Carter, L.J. Murray, B.A. Degnan, C.P. Dunling, R. Salvador, D.K. Menon, and A.K. Gupta.


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