Armenian Patil, Campagne Danielle, Stroh Geoff, Ives Tallman Crystal, Zeng William Z D, Lin Thomas, Gerona Roy R
Prehosp Emerg Care. 2017 May-Jun;21(3):378-385. doi: 10.1080/10903127.2016.1258098. Epub 2017 Jan 6.
National Park Service (NPS) Parkmedics provide medical care in austere environments. The objective of this study was to evaluate the stability of specific medications used by Parkmedics at extremes of temperatures likely to be faced in the field.
This is a bench research study conducted in the laboratory setting over a 4-week period. Parenteral medications were separated into 4 temperature exposure groups: A) 45°C (hot); B) -20°C (cold); C) hot then cold temperatures alternating weekly; and D) cold then hot temperatures alternating weekly. At study start and the end of each week, three aliquots from each group were sampled to determine the remaining drug concentration through liquid chromatography-quadrupole time-of-flight mass spectrometry (Agilent LC 1260- QTOF/MS 6550). Quantitative analysis was done using Agilent MassHunter Quantitative Analysis software. The mean drug concentration from triplicate aliquots was expressed as percentage of its baseline concentration to monitor the drug's stability during storage.
Eight medications were analyzed (atropine, diphenhydramine, fentanyl, hydromorphone, midazolam, morphine, naloxone, ondansetron). Hydromorphone, morphine, and ondansetron showed the greatest stability, at above 90% of original concentration in all study arms. Diphenhydramine, fentanyl and midazolam showed heat independent degradation, degrading the same way regardless of heat exposure. By the end of the study period, 51-56% midazolam remained in all groups. Atropine and naloxone showed heat dependent degradation, degrading more when exposed to heat. Atropine had the most degradation, being undetectable after 4 weeks of heat exposure.
We recommend that EMS providers replace atropine, naloxone, diphenhydramine, fentanyl, and midazolam frequently if they are practicing in low call volume or high-temperature environments. Further studies will be needed to determine if re-dosing midazolam, naloxone, and atropine is the appropriate clinical strategy in this setting if adequate clinical effect is not reached with a single dose.
国家公园管理局（NPS）的野外医疗急救员在艰苦环境中提供医疗护理。本研究的目的是评估野外医疗急救员使用的特定药物在野外可能面临的极端温度下的稳定性。
这是一项在实验室环境中进行的为期4周的实验研究。肠胃外用药被分为4个温度暴露组：A）45°C（高温）；B）-20°C（低温）；C）每周交替进行高温和低温暴露；D）每周交替进行低温和高温暴露。在研究开始时和每周结束时，从每组中抽取三份样本，通过液相色谱-四极杆飞行时间质谱法（安捷伦LC 1260-QTOF/MS 6550）测定剩余药物浓度。使用安捷伦MassHunter定量分析软件进行定量分析。将三份样本的平均药物浓度表示为其基线浓度的百分比，以监测储存期间药物的稳定性。
分析了8种药物（阿托品、苯海拉明、芬太尼、氢吗啡酮、咪达唑仑、吗啡、纳洛酮、昂丹司琼）。氢吗啡酮、吗啡和昂丹司琼表现出最大的稳定性，在所有研究组中均保持在原始浓度的90%以上。苯海拉明、芬太尼和咪达唑仑表现出与热无关的降解，无论受热情况如何，降解方式相同。在研究期结束时，所有组中咪达唑仑的剩余量为51%-56%。阿托品和纳洛酮表现出与热有关的降解，受热时降解更多。阿托品的降解最多，在受热4周后无法检测到。
我们建议，如果急救医疗服务人员在低出诊量或高温环境中工作，应频繁更换阿托品、纳洛酮、苯海拉明、芬太尼和咪达唑仑。如果单剂量达不到足够的临床效果，是否重新给药咪达唑仑、纳洛酮和阿托品是这种情况下合适的临床策略，还需要进一步研究来确定。
