Stability of Advanced Life Support Drugs in the Field

Mark A. Gill; Alice Z. Kislik; Lana Gore; Angela Chandna

Disclosures

Am J Health Syst Pharm. 2004;61(6) 

In This Article

Abstract and Introduction

Purpose: The effects of wide temperature variations on the stability of atropine, epinephrine, and lidocaine stored under field conditions in advanced life support (ALS) paramedic units were evaluated.
Methods: Vehicles from various ALS paramedic units were selected throughout Los Angeles County, California, including desert, marine, and helicopter-based divisions. A temperature-recording device was placed in the compartment where drugs are stored and used to record and store temperature data at 15-minute intervals. Three autoinjector-style syringes of atropine, epinephrine, and lidocaine were taken from stock for each ALS unit and placed in each vehicle, while three control syringes were stored in the laboratory under controlled conditions. Six samples of each drug were withdrawn at time 0 and on days 5, 10, 15, 30, and 45. Samples were analyzed using high-performance liquid chromatography. Stock solutions, created using analytical grade atropine, epinephrine, and lidocaine, were used to construct 5-point standard curves to determine the drug concentration of each sample.
Results: Seven sites exceeded 104 °F (40 °C) for as little as 30 minutes and as long as 795 minutes. Ten of the sites achieved a mean kinetic temperature (MKT) above 77 °F (25 °C), with the highest MKT calculated being 84.1 °F (28.9 °C) over a 45-day period. There was no evidence of drug degradation at any site, at any temperature, or at any time point.
Conclusion: Atropine, epinephrine, and lidocaine can be stored at temperatures of up to 84.1 °F (28.9 °C ) for up to 45 days and tolerate temperature spikes of up to 125 °F (51.7 °C) for a cumulative time of 795 minutes (13.25 hours) without undergoing degradation.

Pharmaceuticals approved for human use in the United States are required by the Food and Drug Administration (FDA) to maintain their purity for the labeled shelf life of the product. Drug manufacturers define the storage requirements for each product to maintain purity. Storage requirements tend to have a narrow temperature variance. The United States Pharmacopeial Convention (USP) establishes standards for the use of drugs, which FDA ultimately enforces. For example, drugs approved for storage at room temperature should be stored between 68 and 77 °F (20-25 °C), with allowed excursions between 59 and 86 °F (15-30 °C) as long as the calculated mean kinetic temperature (MKT) is no higher than 77 °F (25 °C).[1] USP defines MKT as "the single calculated temperature at which the total amount of degradation over a particular period is equal to the sum of the individual degradations that would occur at various temperatures." "Excessive heat" has been defined by USP as any temperature above 104 °F (40 °C). For drugs to be stored at room temperature, temperature excursions up to 104 °F (40 °C) are allowed as long as they do not exceed 24 hours and the MKT remains within the allowable range.[1] Yet, some of the most potent drugs are used in life-threatening situations and are exposed to temperatures far exceeding this narrow range. Advanced life support (ALS) units in Los Angeles County cannot control the temperature of the compartments holding their drugs. Other municipalities, such as Salt Lake City and Tucson, have recognized that ALS drugs are exposed to large temperature swings.

Atropine, epinephrine, and lidocaine are frequently used as part of the Advanced Cardiac Life Support algorithms. Epinephrine is the first-line agent for resuscitation of patients with pulseless electrical activity (PEA), asystole, ventricular fibrillation, and pulseless ventricular tachycardia. The adult dosage of epinephrine used for these indications is 1 mg given as an injection every three to five minutes until a response is achieved.[2] Epinephrine is also used as a second-line agent for patients with symptomatic bradycardia and for the maintenance of blood pressure in severely hypotensive patients. Atropine is used as the first-line agent for treatment of symptomatic bradycardia and a second-line agent for the treatment of PEA and asystole. The recommended dosage of atropine for adults is 1 mg given as an injection every three to five minutes until a response is achieved or a maximum total dosage of 0.04 mg/kg is reached. Lidocaine is used for treatment of ventricular tachycardias (with pulse).[2]

According to the manufacturer's requirements, atropine, epinephrine, and lidocaine injections should be stored below 104 °F (40 °C) at room temperature, between 59 and 86 °F (15-30 °C), preferably at 77 °F (25 °C).[3]

Valenzuela et al.[4] simulated a paramedic vehicle by placing 23 drugs in an outdoor metal shed equipped with an air probe for continuous temperature readings. The drugs were exposed to temperature variations from 77 to 100 °F (25-38 °C) for up to four weeks. Epinephrine showed a change in ionized state, and isoproterenol had 11% degradation. Johansen et al.[5] mimicked outdoor conditions by exposing several drugs to four-hour storage periods at -6 °F (-21 °C) or 150 °F (66 °C). The study did not show any degradation of atropine, lidocaine, epinephrine, or naloxone. However, longer exposure times may be required to degrade these agents.

The purpose of this study was to evaluate the effects of wide temperature variations on the stability of atropine, epinephrine, and lidocaine stored under field conditions in ALS paramedic units.

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