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Research Letter
April 2017

Accuracy of Prefilled “Code Cart” Epinephrine Syringes for Direct Administration of Small Doses

Author Affiliations
  • 1Department of Emergency Medicine, Oregon Heath & Science University, Portland
  • 2Department of Pediatrics, Oregon Health & Science University, Portland
  • 3Department of Pharmacy Services, Oregon Health & Science University, Portland
  • 4Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
  • 5Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon
JAMA Pediatr. 2017;171(4):393-394. doi:10.1001/jamapediatrics.2016.4167

Prefilled syringes offer a convenient way to administer epinephrine to patients experiencing cardiac arrest. Epinephrine is a critical drug that can improve survival in children experiencing cardiac arrest, although very high doses (0.1 mg/kg) of the drug can worsen outcomes.1,2 One practice for administering epinephrine during pediatric resuscitation is direct administration of a partial volume from commercially available prefilled syringes. We conducted a study examining the accuracy of direct injection of an infant dose (0.05 mg or 0.5 mL) of epinephrine from prefilled epinephrine syringes using the graduated lines on the syringe. We used the recommended dose in the Pediatric Advanced Life Support algorithm (0.01 mg/kg), although the Neonatal Resuscitation Program includes a range of 0.01 mg/kg to 0.03 mg/kg. We hypothesized that direct injection may yield inaccurate doses.

Methods

We evaluated the accuracy of the 2 types of epinephrine 1:10 000, 1 mg per 10 mL prefilled syringes available for purchase in the United States: LifeShield ABBOJECT (Hospira) and Luer-Jet Luer-Lock (International Medication Systems Ltd).

To determine the actual volume expelled when the plunger was depressed to the 0.5-mL mark of the prefilled syringe, we connected the prefilled syringes to a 1-mL syringe via a flushed 3-way stopcock and depressed the plunger on the epinephrine syringes to the 0.5-mL mark. This simulates direct injection from the syringe into an intravenous port followed by a flush, where 100% of the medication enters the patient and none is lost in tubing or intravenous ports. We recorded the volume delivered to the 1-mL syringe, attaching a new 1-mL syringe if volume exceeded 1 mL. We then measured the total volume in the prefilled syringe by expelling the remaining contents. For each test, at least 2 investigators were present (M.H., N.M., and C.E.) to provide dual verification of volumes.

We conducted 2 additional validation tests. First, we tested the volume when the plunger was depressed to the 0.5-mL mark, expelling the medication into a graduated cylinder. Second, we tested the volume using the weight and density of the medication using an Ohaus EX224N precision scale (Ohaus Corporation). We weighed 1 mL of epinephrine 1:10 000 (1.010 g) and 1 mL of water (1.000 g) using the same syringe. We subsequently weighed each dose of epinephrine expelled by the prefilled syringe when the plunger was depressed to the 0.5-mL mark and then calculated the volume using the density. The Oregon Health & Science University institutional review board reviewed the study and found it was not human subjects research.

Results

We analyzed 56 prefilled syringes. Table 1 shows the number of syringes tested, the mean volume expelled, standard deviation, and 95% confidence interval by year of expiration. The mean quantity expelled by the syringe when the stopper was pushed to the 0.5-mL mark was 0.90 mL (95% CI, 0.85-0.96 mL), with a range of 0.50 mL to 1.30 mL. Only 3 of 56 the syringes (5%) tested delivered volumes within 20% of 0.5 mL, and 17 of 56 (30%) delivered greater than 200% of the intended volume. Thirteen of the analyzed syringes were manufactured by LifeShield and 43 by Luer-Jet. The mean volume expelled from LifeShield syringes was 0.98 mL and the mean volume from the Luer-Jet syringes was 0.88 mL, with a difference of 0.099 mL (95% CI, –0.028 mL to 0.23 mL). Table 2 shows a comparison of the volumes measured using the graduated cylinder and weight/density–based validation methods.

Table 1.  
Measured Volume of Epinephrine Expelled From Prefilled Epinephrine Syringe With Intended Volume Delivery of 0.5 mL by Year of Syringe Manufacture
Measured Volume of Epinephrine Expelled From Prefilled Epinephrine Syringe With Intended Volume Delivery of 0.5 mL by Year of Syringe Manufacture
Table 2.  
Results of Measurement Validation
Results of Measurement Validation
Discussion

Administering a small volume of epinephrine directly from prefilled syringes risks delivering more than the intended dose. Owing to limited accuracy, clinicians should transfer epinephrine to a smaller syringe for infant dosing.3 Manufacturers could also make devices to better meet the needs of pediatric patients.

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Article Information

Corresponding Author: Matt Hansen, MD, MCR, Oregon Health & Science University, Emergency Medicine, CR114, 3181 SW Sam Jackson Park Rd, Portland, OR 97239 (hansemat@ohsu.edu).

Published Online: February 27, 2017. doi:10.1001/jamapediatrics.2016.4167

Author Contributions: Dr Hansen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hansen, Guise.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Hansen, Meckler.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hansen, Eriksson, Meckler.

Obtained funding: Guise.

Administrative, technical, or material support: All authors.

Supervision: Guise.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work is supported by the National Heart Lung and Blood Institute grant 5K12HL108974-03. This work is also supported by the epidemiology of preventable safety events in prehospital EMS of children grant 1R01HD062478-04 from the National Institute of Child Health and Human Development.

Role of the Funder/Sponsor: The funding sources did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institute of Child Health and Human Development, or the National Institutes of Health.

References
1.
Andersen  LW, Berg  KM, Saindon  BZ,  et al; American Heart Association Get With the Guidelines–Resuscitation Investigators.  Time to epinephrine and survival after pediatric in-hospital cardiac arrest.  JAMA. 2015;314(8):802-810. doi:10.1001/jama.2015.9678PubMedGoogle ScholarCrossref
2.
Perondi  MBM, Reis  AG, Paiva  EF, Nadkarni  VM, Berg  RA.  A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest.  N Engl J Med. 2004;350(17):1722-1730. doi:10.1056/NEJMoa032440PubMedGoogle ScholarCrossref
3.
NRP Instructor DVD: An Interactive Tool for Facilitation of Simulation-based Learning. Elk Grove Village, IL: American Academy of Pediatrics; 2010.
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