In EMS systems in which benzodiazepines are in-protocol, there is often a discussion about whether lorazepam is worth having on the ambulance, especially since it requires secure, refrigerated storage. In comparison, diazepam and midazolam, which are other commonly carried benzodiazepines, do not require refrigeration. An argument for lorazepam’s place on the ambulance can be made by a couple unique features.

While midazolam can also be administered by this route, it is more short-acting that lorazepam, and thus is less suitable for the treatment of seizures (which may recur when the drug wears off). While diazepam has been considered for intranasal use, the bioavailability and tolerance of the IV formulation appear to be poor by this route (although there appears to be some interest in modifying the vehicle for delivery in order to make it a viable route) [1, 2, 3].

Consequently, lorazepam may be a more safe and predictable medication when administered to patients with poor liver function [4 ]. Examples of these types of patients may include cirrhotic alcoholics who are experiencing withdrawal seizures, as well as the general elderly population. Despite this difference in metabolism, admittedly there does not appear to be an abundance of evidence to suggest that this theoretical advantage is clinically significant. 

When considering the investment in human and physical capital required to amend or extend a narcotics-control program to include secure refrigeration, the advantage of lorazepam may be even further disregarded. Thus, it must be questioned as to whether lorazepam truly does need refrigeration.

To summarize, it was found that lorazepam does undergo a heat-dependent degradation, which is greatest at temperatures over 30C (86F). At refrigerated temperatures, degradation is negligible. However, it is the area between these extremes of temperature that is most interesting.

In one study, the reduction in lorazepam concentration over a 210-day period was 0% when refrigerated, 10% at ambient temperature, and 75% at 37C (98.6F). In this system, lorazepam retained 90% of its original concentration for 150 days of on-ambulance storage. For lorazepam, the probability of a greater than 10% decline in concentration after 150 days of storage under ambient conditions (77-86F) was .02; after 180 days, the probability increased to .34. From this information, one might infer that the degradation was non-linear, and that retention of the drug for up to 180 days at temperatures below 86F would likely result in a drug with greater than 90% of its original potency.

This information was corroborated by a second study, which found that lorazepam did experience some degradation, with greater degradation correlating with increased mean kinetic temperature. While it is believed that lorazepam maintained clinically acceptable concentrations of active drug after 60 days of EMS deployment, the study failed to determine whether the degradation was clinically significant.

Finally, the third study compared stability of lorazepam in an emergency physician transport vehicle versus an ambulance and found that the lorazepam became unstable within four weeks in light-resistant, room temperature storage aboard an operational ambulance.

Variance in the results between these studies may reflect differences between the EMS systems used in the studies, including whether the ambulances were housed in a climate-controlled facility, as well as differences in ambient temperature of study locations. To account for some of these differences and minimize their influence on the data, one of the studies ensured to analyze samples from fourteen different cities.

In cooler regions where ambient temperatures are predictably below 86F, or when ambulances are stored in climate-controlled facilities, it may be possible to store lorazepam in an unrefrigerated area, and to rotate the drugs every ~150 days (or less, if one were more conservative about it).

While cost-effectiveness of this practice is beyond the scope of this discussion, it is likely that this would depend upon the turnover rate of the drug in the system of interest. In high-volume systems, especially those in which the paramedics have become comfortable with the use of lorazepam, the practice of storing lorazepam in a non-refrigerated area may be completely viable. Suffice it to say, the evidence endorses the possibility, but not ubiquity, of this practice.