Advertisement

Symjepi Epinephrine Injection Device Deconstruction and Residual Medication Retrieval in an Austere Environment

Published:December 21, 2022DOI:https://doi.org/10.1016/j.wem.2022.10.009
      Epinephrine is the primary therapy in the treatment of anaphylaxis. Epinephrine delivery devices are commonplace in out-of-hospital care of anaphylaxis because they administer a standardized dose of epinephrine, limit human error, and allow for ease of use by the operator. However, a major limitation of these devices is the single-use nature of the products. In an austere setting, the ability to obtain additional doses from an autoinjector may prevent further progression of anaphylaxis. Previous articles have demonstrated the deconstruction of spring-loaded epinephrine autoinjectors to extract additional medication doses. This article provides instruction and videography, outlining the process of deconstructing and obtaining additional doses of epinephrine from the Symjepi prefilled syringe.

      Keywords

      Introduction

      Anaphylaxis is defined as an acute allergic reaction evolving over minutes to hours that can lead to respiratory compromise, symptoms of end-organ damage, and potentially cardiovascular and hemodynamic collapse. This hypersensitivity reaction is an acute medical emergency, resulting from a systemic release of various mediators of allergic inflammation in response to an allergen.
      • Yu J.E.
      • Lin R.Y.
      The epidemiology of anaphylaxis.
      ,
      • Shaker M.S.
      • Wallace D.V.
      • Golden D.B.K.
      • Oppenheimer J.
      • Bernstein J.A.
      • Campbell R.L.
      • et al.
      Anaphylaxis-a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis.
      Epinephrine is the first-line pharmacotherapy and a critical intervention for both monophasic and biphasic anaphylaxis.
      • Shaker M.S.
      • Wallace D.V.
      • Golden D.B.K.
      • Oppenheimer J.
      • Bernstein J.A.
      • Campbell R.L.
      • et al.
      Anaphylaxis-a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis.
      Traditionally, epinephrine is administered intramuscularly with a syringe and needle after being drawn up from a vial or ampule. However, modern epinephrine delivery devices using either a spring under tension or a syringe and plunger system have been designed to administer a predetermined dose of the medication. These devices are carried by individuals who are at risk for anaphylaxis as a safe and effective means of treating this life-threatening condition. The American College of Allergy, Asthma, and Immunology recommends that people with a known anaphylactic reaction should carry 2 emergency doses of epinephrine.
      • Shaker M.S.
      • Wallace D.V.
      • Golden D.B.K.
      • Oppenheimer J.
      • Bernstein J.A.
      • Campbell R.L.
      • et al.
      Anaphylaxis-a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis.
      Although most of the epinephrine delivery systems are designed to deliver only a single dose of the medication, many of these products contain a residual amount of the medicine after initial deployment of the device. This discovery has led to the development of off-label protocols to identify ways to access the remaining epinephrine to administer additional doses. Previous articles specific to various spring-loaded or CO2-driven autoinjector devices have been published illustrating this process.
      • Granti A.
      • Pilkerton R.
      • Falsgraf E.
      • Vanwert E.
      • Brouwer N.
      • Beyer A.
      • et al.
      Retrieval of additional epinephrine from Adrenaclick-style epinephrine autoinjectors.
      • Hawkins S.C.
      • Weil C.
      • Baty F.
      • Fitzpatrick D.
      • Rowell B.
      Retrieval of additional epinephrine from auto-injectors.
      • Robinson P.E.
      • Lareau S.A.
      Novel technique for epinephrine removal in new generation autoinjectors.
      This type of product features a spring under tension housed in a plastic casing requiring pressure to the outer thigh to engage the mechanism and deploy a needle and syringe plunger to administer the predetermined amount of medication.
      The Symjepi injection device is an additional epinephrine delivery system on the market that is unique in that it does not use an automatic spring, but rather a physical plunger the user must manually deploy. According to the device package insert, Symjepi is available as 2 products, a 0.3 mg/0.3 mL syringe (typically prescribed for adults or pediatric patients weighing >30 kg) and a 0.15 mg/0.3 mL syringe (typically prescribed for pediatric patients weighing <30 kg). For each product, the syringe is set to deliver 0.3 mL or 1 full dose for the intended patient population, and the manufacturer endorses that there will be 0.5 mL of overfill remaining. As of May 2022, according to Lexicomp, the average wholesale price is $150 for both Symjepi prefilled syringe concentrations. In comparison, products that utilize autoinjector technology range from around $190 to $350. As a result, Symjepi devices may become more popular because of overall cost, and they may become much more prevalent in backcountry adventures. Here we outline and demonstrate, with photographic and video recordings, how to deconstruct the Symjepi epinephrine injection syringe. No medication dosing was performed, and no human subjects were involved. This demonstration of a disassembly method was approved for exemption from review by the Valleywise Health institutional review board.

      Implementation

      The following steps outline the protocol for product disassembly and are illustrated in the online supplementary video (see online Supplemental Video):
      Step 1: Remove the cap, exposing the needle. Insert the needle into the thigh and depress the plunger to administer the medication per package instructions (Figure 1).
      Figure 1
      Figure 1Prefilled syringe with cap removed from needle and depressed thumb rest of syringe after injected premeasured medication per package instructions.
      Step 2: Remove the instruction stickers on both sides of the plastic housing (Figures 2 and 3).
      Figure 2
      Figure 2Syringe with cap and instruction sticker peeled back exposing the plastic latch.
      Figure 3
      Figure 3Both instruction stickers peeled back exposing plastic latches.
      Step 3: Use a knife, or similar object, to depress the inside of the rectangle on both sides of the device, releasing the latches that hold the syringe in the housing (Figures 4 and 5). The latch is now released, indicated by the interior plastic that surrounds the plunger being displaced toward the thumb rest of the plunger (Figure 6).
      Figure 4
      Figure 4Knife depressing the plastic latch held in the rectangular cutout of the plastic housing.
      Figure 5
      Figure 5Repeated procedure detailed in Figure 4 and Step 3 on the other latch of the syringe.
      Figure 6
      Figure 6The interior syringe and attached plastic pieces are now displaced toward the thumb rest of the syringe, indicating successful release of the latch.
      Step 4: Slowly remove the syringe with a firm and steady hold (Figure 7).
      Figure 7
      Figure 7The interior syringe and attached plastic pieces are now displaced toward the thumb rest of the syringe, indicating successful release of the latch with an anterior view.
      Step 5: Separate and remove both the dark and light blue plastic pieces surrounding the plunger and thumb rest (Figure 8).
      Figure 8
      Figure 8External housing is now separated from the syringe and its accompanying plastic holds on the plunger.
      Step 6: Holding the device vertically with the needle pointing up, tap the barrel to bring the air toward the tip of the syringe and the epinephrine to displace toward the plunger’s rubber stopper. Carefully expel all the remaining air from the syringe until the medication meets the end of the syringe (Figure 9, Figure 10, Figure 11 through 12).
      Figure 9
      Figure 9Plastic pieces removed from plunger.
      Figure 10
      Figure 10Bevel held up displaying medication in contact with the rubber stopper and air toward the needle.
      Figure 11
      Figure 11Bevel held up displaying medication in contact with the rubber stopper and air toward the needle close up.
      Figure 12
      Figure 12Syringe after air is pressed out by pushing the plunger with the bevel up, but with effort to minimize medication loss.
      Step 7: If clinically indicated, administer the residual medication into the thigh by depressing the rubber tip all the way to the end of the barrel.

      Discussion

      This article demonstrates a method for obtaining an additional dose of epinephrine from a Symjepi epinephrine injection delivery system. The disassembly of this product is unique from the other traditional autoinjector style devices that have a self-contained spring-loaded syringe and medication delivery system because this system is an isolated syringe with a plunger that must be depressed manually to administer the medication. There is no automatic mechanism used, and the needle does not retract.
      Epinephrine delivery systems have simplified the administration of epinephrine in the emergency setting. These products are designed to deliver the appropriate dosage and reduce time to administration. They are also convenient to use in the austere setting because they are self-contained, do not require advanced medical knowledge to use, and are reliable.
      • Parish H.G.
      • Morton J.R.
      • Brown J.C.
      A systematic review of epinephrine stability and sterility with storage in a syringe.
      ,
      • Gaudio F.G.
      • Johnson D.E.
      • DiLorenzo K.
      • Anderson A.
      • Musi M.
      • Schimelpfenig T.
      • et al.
      Wilderness Medical Society clinical practice guidelines on anaphylaxis.
      However, there are nonmedical considerations, as outdoor recreationalists are often limited to the amount of space, weight of materials, and tools that they can carry with them. The addition of multiple devices may sometimes be seen as an inconvenience; therefore, many outdoor enthusiasts will forgo carrying an additional autoinjector, feeling that the risk-to-benefit ratio is low. Additionally, in many parts of the world, these devices are unavailable or not readily accessible, or the option to purchase multiple devices is cost prohibitive.
      • Parish H.G.
      • Morton J.R.
      • Brown J.C.
      A systematic review of epinephrine stability and sterility with storage in a syringe.
      Inadequate preparation and a lack of additional doses of epinephrine can be life-threatening for an individual experiencing an anaphylactic reaction. A recent meta-analysis shows that nearly 8% of individuals treated for anaphylaxis required >1 dose of epinephrine.
      • Patel N.
      • Chong K.W.
      • Yip A.Y.G.
      • Ierodiakonou D.
      • Bartra J.
      • Boyle R.J.
      • et al.
      Use of multiple epinephrine doses in anaphylaxis: a systematic review and meta-analysis.
      Patients with anaphylaxis in the austere setting may not have access to repeat doses of epinephrine after they have administered their initial dose from their epinephrine delivery system.
      It is widely recommended that urgent medical attention is obtained and early administration of epinephrine is provided in the treatment of anaphylaxis.
      • Gaudio F.G.
      • Johnson D.E.
      • DiLorenzo K.
      • Anderson A.
      • Musi M.
      • Schimelpfenig T.
      • et al.
      Wilderness Medical Society clinical practice guidelines on anaphylaxis.
      Outdoor enthusiasts with known allergic reactions are encouraged to carry sufficient medication with them on any type of outdoor expedition.
      • Gaudio F.G.
      • Johnson D.E.
      • DiLorenzo K.
      • Anderson A.
      • Musi M.
      • Schimelpfenig T.
      • et al.
      Wilderness Medical Society clinical practice guidelines on anaphylaxis.
      However, it is also important to be resourceful and improvise as a wilderness medicine provider. Understanding how to access and administer additional doses of medication may provide lifesaving medical treatment for a patient with anaphylaxis. This team encourages disassembly as a last resort, rather than a planned backup if multiple doses of epinephrine are required in an anaphylactic situation.
      Disassembly and use of overfill within the syringe are not condoned by the manufacturers of the various epinephrine delivery devices because there are risks of potential harm in the breakdown and error in administration of extra doses. Caution should be exercised when performing this intervention, and risks vs benefits analysis should be considered before the attempt is made. Furthermore, this practice must be performed only by an individual with specific training on how to appropriately identify and manage anaphylaxis and with additional training and an adequate skill set to determine how and when to manually administer additional doses of epinephrine.
      Disassembly of this prefilled syringe can be limited by tool availability and dexterity. In our disassembly attempts, we found that a knife was sufficient to assist the removal of the syringe from the external plastic housing. The points of most knives were small enough to compress the latches holding the syringe in the housing. We were unable to push in the latch with our fingers alone; however, using rocks or other hard objects could be attempted if they were small enough to fit into the rectangle and sturdy enough to compress the latch. Using the knife as the tool for disassembly was straightforward and relatively easy in our attempts. There is no cutting required, and pliers or other tools are not needed.
      In our experience of disassembling the autoinjector, we noted that the exposed needle and glass vial posed a threat of injury to the operator. Extreme care must be taken when disassembly is performed in the backcountry because working with an exposed needle used for patient care carries the risk of unintentional needle stick injury. In contrast to our research settings, high-intensity real-world settings with different or suboptimal tools can increase this risk.
      Furthermore, although rare, side effects of epinephrine must be considered when providing care in the backcountry. Conditions, including cardiac arrhythmias, stroke, and myocardial infarction, among others, after the administration of epinephrine, have been reported in the literature.
      • Gaudio F.G.
      • Johnson D.E.
      • DiLorenzo K.
      • Anderson A.
      • Musi M.
      • Schimelpfenig T.
      • et al.
      Wilderness Medical Society clinical practice guidelines on anaphylaxis.
      Although these are usually associated with elderly patients or those with preexisting medical conditions that put them at risk, the provider must be aware and ready to identify these emergencies. Administering multiple doses of the medication may increase this risk to the patient.
      An additional area for research is measuring and comparing the residual amount of epinephrine after initial use among all available epinephrine delivery devices. Although products of the same brand may have similar residual amounts of medication, there may be differences between the competing manufacturers. To prevent either overdosing or underdosing, next steps for possible investigation may include examining how the volume of residual medication may differ between brands of systems as well as differences in residual volumes between “adult” and “junior” products. Previous epinephrine delivery systems have had variations in dosing administration that have had major implications in the success of the product. According to multiple news outlets, including CNBC and Healthline, one autoinjector (AUVI-Q) was discontinued by the manufacturer for this reason in 2015 and returned in 2017 after concerns about dosing inaccuracy.
      The manufacturer endorses that 0.5 mL of overfill should be expected in the adult version of the Symjepi device. However, we measured a residual 0.4 mL of epinephrine in our disassembly process. Because the concentrations of epinephrine are different between adult and pediatric devices, we do not recommend interchanging these between patient populations. Additionally, extra caution should be taken when administering an additional dose from the overfill of a pediatric device because the remaining amount may not be within the acceptable dose range for a pediatric patient.

      Limitations

      Because Symjepi is a specific style of single-use epinephrine delivery device, this disassembly method will only work for this specific product. If other products are used or will be carried for medical expeditions or personal use, it is imperative that the provider review possible disassembly techniques discussed in other papers specific to that product. This authors’ team did not evaluate the residual amount of medication from the pediatric product. Therefore, the information provided here is limited to use with the adult product only. As well, we do not describe diagnostic criteria or adjunctive therapies for anaphylaxis but rather assume that the individuals reading and using the information here have obtained this medical knowledge prior to exploring the advanced topics and techniques discussed.
      This method was developed and described in a controlled fashion, and an individual working in the field may encounter other complications that would make the process of disassembly challenging. Inclement weather, suboptimal tools for the task, bulky gloves, or other possible dexterity limitations may all affect the time and ability for someone to perform this task. Potential errors that may occur also include accidental loss of epinephrine during disassembly from accidental compression of the plunger or inadvertent injection of air if it is not fully removed prior to repeat dosing.

      Conclusions

      Epinephrine delivery devices have become a mainstay therapy in the treatment of anaphylaxis in the out-of-hospital environment. The use of prescribed single-use epinephrine injectors has facilitated the safe dosing, administration, and treatment of anaphylaxis but is limited in providing additional doses of medication for refractory anaphylaxis. In the austere setting, the ability to obtain additional doses of epinephrine from these devices may provide lifesaving therapy for individuals suffering from refractory or biphasic anaphylactic reactions.
      Author Contributions: study concept and design (BT, LH, GC, AM); data acquisition (BT, LH); data analysis (BT, LH); drafting and critical revision of the manuscript (BT, LH, GC, AM); approval of final manuscript (BT, LH, GC, AM).
      Financial/Material Support: None
      Disclosures: LH reports support from the Residency for American College of Emergency Medicine Conference 2021 and Essentials of Emergency Medicine Conference 2021.

      Supplementary Data

      References

        • Yu J.E.
        • Lin R.Y.
        The epidemiology of anaphylaxis.
        Clin Rev Allergy Immunol. 2018; 54: 366-374
        • Shaker M.S.
        • Wallace D.V.
        • Golden D.B.K.
        • Oppenheimer J.
        • Bernstein J.A.
        • Campbell R.L.
        • et al.
        Anaphylaxis-a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis.
        J Allergy Clin Immunol. 2020; 145: 1082-1123
        • Granti A.
        • Pilkerton R.
        • Falsgraf E.
        • Vanwert E.
        • Brouwer N.
        • Beyer A.
        • et al.
        Retrieval of additional epinephrine from Adrenaclick-style epinephrine autoinjectors.
        Wilderness Environ Med. 2021; 32: 55-58
        • Hawkins S.C.
        • Weil C.
        • Baty F.
        • Fitzpatrick D.
        • Rowell B.
        Retrieval of additional epinephrine from auto-injectors.
        Wilderness Environ Med. 2013; 24: 434-444
        • Robinson P.E.
        • Lareau S.A.
        Novel technique for epinephrine removal in new generation autoinjectors.
        Wilderness Environ Med. 2016; 27: 252-255
        • Parish H.G.
        • Morton J.R.
        • Brown J.C.
        A systematic review of epinephrine stability and sterility with storage in a syringe.
        Allergy Asthma Clin Immunol. 2019; 15: 7
        • Gaudio F.G.
        • Johnson D.E.
        • DiLorenzo K.
        • Anderson A.
        • Musi M.
        • Schimelpfenig T.
        • et al.
        Wilderness Medical Society clinical practice guidelines on anaphylaxis.
        Wilderness Environ Med. 2022; 33: 75-91
        • Patel N.
        • Chong K.W.
        • Yip A.Y.G.
        • Ierodiakonou D.
        • Bartra J.
        • Boyle R.J.
        • et al.
        Use of multiple epinephrine doses in anaphylaxis: a systematic review and meta-analysis.
        J Allergy Clin Immunol. 2021; 148: 1307-1315