Succinylcholine: where to store it for emergency use?
Lynne G. Maxwell MD, Kyle J. Kramer DDS MS, and Myron Yaster MD
I so clearly remember my first experience with succinylcholine on day one of my anesthesia residency. My attending had me draw up succinylcholine and give it to my first (adult) patient. Within a few moments, the patient stopped breathing and my attending said “you better do something about this or the patient will die!” After intubating, ventilating, and oxygenating the patient, my attending said, “what makes succinylcholine so dangerous is that the effective dose IS the lethal dose. In fact, it so dangerous, it is manufactured and dispensed in square bottles to minimize the risk of error.” I don’t know why the square bottles disappeared but it was a lesson I never forgot. As a clinician and educator, I always drew up succinylcholine, atropine, and a rapidly acting hypnotic/general anesthetic for every case.
Today’s PAAD is a bit unusual and is in response to a reader’s question which required us to take a deeper dive into some older literature. The underlying question: Does succinylcholine require refrigeration and if it is not refrigerated will it lose potency” After all the package insert is very clear: “Store in refrigerator at 2° to 8°C (36° to 46°F). The multi-dose vials are stable for up to 14 days at room temperature without significant loss of potency.” Really? Myron Yaster MD
Original article
Merlin MA, Marques-Baptista A, Yang H, Ohman-Strickland P, Aquina C, Buckley B. Evaluating degradation with fragment formation of prehospital succinylcholine by mass spectrometry. Acad Emerg Med. 2010 Jun;17(6):631-7. doi: 10.1111/j.1553-2712.2010.00766.x. PMID: 20624143.
The back story:
Recently, an OR nurse who previously worked at many children’s hospitals contacted me (LGM) about her concern for the (in)accessibility of succinylcholine (sux) in a surgicenter where she now works.
The surgicenter does a mix of adult and pediatric cases, including occasional dental cases. However, the surgicenter did not store any sux in the operating or procedure center rooms (anesthesia cart) because of the package insert requirement for refrigeration between 2° to 8°C. After extubation, a pediatric patient had laryngospasm, and the anesthesiologist asked the nurse to get the sux. When she scanned the top of the anesthesia cart, she didn’t see a syringe or vial of succinylcholine. The anesthesiologist told her that the sux (vial) was stored in a refrigerator in the PACU, a substantial walk from the OR, and would have to be drawn up in a syringe before it could be administered STAT. By the time the nurse got back to the OR, having not yet drawn up the sux, the laryngospasm had been broken with positive pressure and the sux was no longer needed. Clearly a near miss. The nurse was uncomfortable with the inaccessibility of sux compared to what she had experienced working in children’s hospitals, where the sux was made readily available on the top of the anesthesia cart (frequently drawn up in a syringe with a needle on it) at the start of each OR day. Did this refrigeration policy make any sense?
What are the facts?
“It is estimated that 85% of succinylcholine is destroyed (by plasma cholinesterase) within the 30 seconds of injection into the blood, and only 5% remains present 2 minutes after injection. Studies have shown that succinylcholine is susceptible to a loss of potency with increases in temperature and light and decreases in pH.2–5 .”1 But how much is lost? In today’s PAAD, Merlin et al.1 measured degradation products of sux stored in ambulances in a light resistant environment at temperatures that ranged between 60° and 80°F. There was 10% degradation of succinylcholine at 3 months in ambulances kept indoors and at 2.4 months when stored in ambulances kept outdoors. For most drugs, manufacturers must guarantee a potency of 90% to 110%. The 10% degradation was regarded by the authors to not significantly impact efficacy and they recommended replacing the non-refrigerated sux every 3 months.
In most practices in which we have worked or have visited, succinylcholine is kept in the OR in the anesthesia cart or in non-refrigerated automated dispensing cabinets like Pyxis or Omnicell. The non refrigerated succinylcholine is replaced by pharmacy personnel at predefined intervals . Many pediatric anesthesiologists draw up a sux syringe for the day and discard it at the end of the day. When I (LGM) was in residency training, many of my pediatric attendings like Myron kept a sux syringe in the pocket of their scrubs, repeating the mantra, “always have it, never use it.” Others keep a syringe with a needle attached next to the unopened sux vial to facilitate rapid access without wasting the drug. What’s most important, especially for personnel (nurses, anesthesiologists) working in a facility new to them (so common these days with travel nursing and locum tenens jobs on the rise), is to be oriented as to location of emergency drugs and expectations for their role during OR emergencies prior to the first patient encounter in the OR.
There have been several other published studies addressing the question of unrefrigerated sux degradation. As this practice is common in out-of-hospital use (i.e., ambulances, EMT emergency kits, etc.), many of these studies are in the emergency medicine literature. De Winter et al.2 examined the stability (as assessed by high-performance liquid chromatography[HPLC]) of 5 emergency drugs when stored for 1 year at recommended refrigerated temperature, room temperature, or in an ambulance.2 The 10% degradation times for sux were 2.8 months at room temperature and 1.2 months in an ambulance, leading to the recommendation that the sux be stored at room temperature and replaced every 3 months.
Contrary to the finding of De Winter et al., Welter et al.3 more recently analyzed active drug concentrations by HPLC every 3 months for 12 months and found that sux stored in light resistant conditions in an actively used emergency car (temperature range 57° to 93°F) maintained an 89% concentration at 12 months. In other words, succinylcholine did not suffer pharmacologically relevant degradation from temperature variations. Finally, Adnet et al. studied the stability of sux solutions using nuclear magnetic resonance spectroscopy, finding a rate of degradation of 1.2%/month when stored at room temperature compared to 0.18%/month when stored at 4°C. They conclude that “if a 10% loss of potency is considered acceptable, then the 20 mg/mL solutions of sux can be safely stored in emergency resuscitation carts at room temperature for 8.3 months.”4
The nurse who asked the question came up with a creative solution which accommodated the facility’s desire to refrigerate sux and her desire to have it readily available in the OR. She obtained an insulated pouch with an ice block in which to store the sux in the room on the anesthesia cart next to a syringe with a needle for drawing up the drug along with a separate needle for possible IM injection. In light of the references provided, removing the vial from the refrigerator and keeping it at room temperature in the OR without such an insulated bag, should be acceptable. Regardless of the timing options selected for storing/replacing sux, we strongly feel that sux must be made readily available for all patients undergoing deep sedation or general anesthesia. Further, we would urge all of you, regardless of practice location, to develop a medication template to store your drugs to make them easily identifiable in an emergency.5
An OR clinical pharmacist, Katherine Klockau, contributed the following information about pharmacy policies with respect to room temperature storage of sux:
“The glass vial from manufacturers must be refrigerated during storage. When removed from the refrigerator and then stocked at room temp, they must be used or discarded within 14 days. Interestingly, the pharmacy used to be able to use primary literature to justify longer storage time at room temperature. Like other institutions, we would actually put 60 days on the vials after removal from refrigerator based on a published article that proved stability after 60 days. Then, as is so common with other evidence-based practice, the Joint Commission caught wind of hospitals using these published papers and put a stop to it, stating we could only use the manufacturer data (available at https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=succinylcholine&pagesize=20&page=1) Further, in contrast, a 503b compounding pharmacy (either local hospital or corporate supplier) can perform their own internal stability testing and market their products with longer dating. The succinylcholine syringes purchased from them are labeled with a 122 day beyond use date.”
What do you think? What is your (your facility’s) practice regarding sux availability for pediatric or really any cases? Send your comments to Myron who will post them in a Friday reader response.
References
1. Merlin MA, Marques-Baptista A, Yang H, Ohman-Strickland P, Aquina C, Buckley B. Evaluating degradation with fragment formation of prehospital succinylcholine by mass spectrometry. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 2010;17(6):631-7. (In eng). DOI: 10.1111/j.1553-2712.2010.00766.x.
2. De Winter S, Vanbrabant P, Vi NT, et al. Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting. Annals of emergency medicine 2013;62(4):380-387.e1. (In eng). DOI: 10.1016/j.annemergmed.2013.04.018.
3. Welter C, Roschel K, Schneider S, Marson C, Stammet P. Impact of Ambient Temperature on 5 Emergency Drugs Aboard an Emergency Medical Car Over a 1-Year Period. Annals of emergency medicine 2022;80(4):358-363. (In eng). DOI: 10.1016/j.annemergmed.2022.05.001.
4. Adnet F, Le Moyec L, Smith CE, Galinski M, Jabre P, Lapostolle F. Stability of succinylcholine solutions stored at room temperature studied by nuclear magnetic resonance spectroscopy. Emergency medicine journal : EMJ 2007;24(3):168-9. (In eng). DOI: 10.1136/emj.2006.041053.
5. Grigg EB, Martin LD, Ross FJ, et al. Assessing the Impact of the Anesthesia Medication Template on Medication Errors During Anesthesia: A Prospective Study. Anesthesia and analgesia 2017;124(5):1617-1625. (In eng). DOI: 10.1213/ane.0000000000001823.