WILDERNESS & ENVIRONMENTAL MEDICINE, 24, 67–74 (2013) REVIEW ARTICLE Cyanoacrylate Glues for Wilderness and Remote Travel Medical Care Kyle P. Davis, MD; Robert W. Derlet, MD From the Department of Emergency Medicine, UC Davis School of Medicine, Sacramento, CA (Drs Davis and Derlet). Cyanoacrylate (CA) glues are commonly used in medical and household repairs. Their chemical compositions have been refined over half a century, making some more suitable than others for creative applications. In remote settings where advanced medical care is not accessible, readily available CAs of differing chemical composition may possess an important therapeutic function. Within this paper we critically examine the published therapeutic risks and benefits of both pharmaceutical and hardware grade CAs when applied in acute care situations. Topics discussed include wound closure as well as the treatment of burns, abrasions, and blisters. Also considered are their chemical properties, toxicities, and potential off-label uses. Key words: cyanoacrylates, “super glue”, adhesives, Dermabond, lacerations, blisters Introduction tion (Indermil, TRUFILL, Histoacryl, and Histoacryl Blue). Given the barriers, including cost, availability, and the pre- From the hardened alpinist to the jungle explorer, most scription requirement for medical-grade adhesives, the use backcountry travelers have heard of or experimented of hardware store CAs in underdeveloped settings may be themselves with instant adhesive to mend wounds when an acceptable therapeutic alternative despite their rel- isolated from definitive medical care. Since their discovery ative toxicities and differing physical properties. In in 1947, cyanoacrylates (CAs) have been used in numerous this paper we describe these differences and explore applications deviating from their intended purpose as a clear 1,2 the therapeutic utility of commercial and medical- resin for gun sights. By 1959, the fast curing and strong grade CA glues in resource-poor and remote locations. adhesive properties had found their way into the medical field when Coover et al3 reported on their applicability to wound closure. Methyl 2-cyanoacrylate (MCA) and to a Methods greater extent, ethyl-2-cyanoacrylate (ECA), are commer- cially marketed today as hardware-grade instant adhesives.4 A comprehensive literature search of MEDLINE, The Early examination of these compounds revealed histotoxic Cochrane Database, Web of Science, Cinahl, CAB Ab- properties, and their use by many medical practitioners was stracts, Google Scholar, and BIOSIS through December subsequently discontinued. Nevertheless, these off-the-shelf 2011 was conducted with the oversight of our institu- adhesives continue to be used by some healthcare providers tion’s research librarian. Titles, abstracts, MeSH terms, for wound repair, hemostasis, and various surgical applica- and key words were searched for the following inclu- tions.5–7 Longer chain CAs with properties more conducive sions: super-glue, krazy-glue, cyanoacrylate(s), tissue to medical use have since been developed. Of these, there adhesive, methyl-cyanoacrylate, ethyl-cyanoacrylate, are currently only a few US Food and Drug Administra- butyl-cyanoacrylate, and octyl-cyanoacrylate. A single tion (FDA)-approved CAs: 2-octyl cyanoacrylate (OCA, reviewer evaluated all returned English-language ab- Dermabond) and various formulations of n-butyl-2-cya- stracts and full-text studies for relevance (ie, pertinence noacrylates (BCA), some with dye to visualize the applica- to CA properties, application to wound closure, applica- tion to skin problems, antimicrobial effects, adverse ef- Corresponding author: Kyle P. Davis, MD, Department of Emer- fects, and cost). The bibliographies of each of the se- gency Medicine, UC Davis School of Medicine, 2315 Stockton Bou- lected articles were then independently examined for levard, Sacramento, CA 95817. additional publications of pertinence. 68 Davis and Derlet spreads, there is more surface available for the nucleo- philic initiators to act and an accelerated polymeriza- tion results.10 On proteinaceous surfaces (eg, biologic tissues), higher n-alkl-␣-cyanoacrylate homologs (ie, a greater number of CH2 units in the main carbon chain) wet, spread, and polymerize faster. Methyl, ethyl, and propyl monomers do not spread and conse- quently take much longer to polymerize. On nonpro- teinaceous surfaces the reverse was found; lower ho- mologs wet, spread, and polymerize at faster rates.12 Although this is true of unadulterated CAs, manufac- turers have optimized polymerization speeds to better suit their intended purpose. It can be slowed by in- cluding a polymerization inhibitor, or sped up by Figure. Chemical structures of discussed cyanoacrylate glues. exposing it to an initiator as found in the foam appli- cator tip of a Dermabond ProPen (2-octylcyanoacry- Properties of Cyanoacrylate Glues late).13 Cyanoacrylates are synthesized by condensation of ● Stability cyano-acetate with formaldehyde in the presence of a 8 During extended travel, it is important that the CA catalyst. The resultant CA monomer is refined and aug- continues to function in extreme environments. Freez- mented with stabilizers, plasticizers, and other proprie- ing or heat exposure might render the glue useless, tary additives by manufacturers. It is then packaged and while a low flashpoint and high combustibility might distributed in liquid form. During application, the CA is allow it to serve as an improvised fire starter. A long exposed to anionic initiators (eg, hydroxyl groups or lone shelf life and the ability to use the glue more than once pairs of electrons on pendant NH2 groups) on the sur- 9,10 have many obvious benefits. Outlined in the Table are faces being glued, inducing polymerization. The some of the available, representative data on these polymer that forms has unique properties that better lend glues. Properties and recommendations will vary themselves to particular applications (Figure). The utility slightly depending on purity of the compounds, addi- of the various CAs in the backcountry is directly related tives, and the manufacturer. to their physical properties. Some of these characteristics include: Applications in Wound Closure ● Wetting, Spreading, and Polymerization Wetting and spreading are terms commonly used to The medicinal utility of CAs has been the subject of describe the interactions of CAs with their binding investigation for more than 50 years. Some of the earliest surface. They are indicative of the affinity and strength studies from the 1960s and 1970s claimed that the initial between the adhesive and substrate.11 When the CA tensile strength of wounds closed with MCA and BCA Table. Representative data on discussed cyanoacrylate glues Melting Packaging and Glue Storage considerations and shelf life point Flashpoint reusability Methyl-CA Shelf life 1 year. Store in original container, Ϫ40°C77 79°C77 Unsterile and upright in a cool, dry place76 reusable Ethyl-CA (eg, Krazy- Store in a cool, dark area and keep tightly ϽϪ20°C78 75°C77 Unsterile and Glue) sealed78 reusable n-Butyl-2-cyanoacrylate Expires after 1 year. Manufacturers Unlisted Ͼ80°C80 Sterile and intended (eg, Histoacryl) recommend refrigeration if being stored for single usea,79 for Ͼ28 days79 2-Octyl cyanoacrylate Expires after 2 years, no refrigeration Unlisted 65.6°–93.3°C82 Sterile and intended (eg, Dermabond) required81 for single use81 a Cultures from reused vials yielded no growth in one study.43 Cyanoacrylate Glues in Remote Medicine 69 surpassed that of conventional suture. Additional studies their histotoxicity. Nevertheless, there are a few examining challenged these conclusions.14,15 The 1994 examination various other CAs. by Noordzij et al16 of wound breaking strength using The first reports investigating blister treatment came Histoacryl (N-butyl-2-cyanoacrylate) and 5-0 polypro- out of the Letterman Army Institute of Research. They pylene (simple interrupted stitches) found the Histoacryl considered n-butyl, isobutyl, isoamyl (IACA), pentyl, closures to be one twelfth as strong as the percutaneous n-heptyl, and trifluoro-isopropyl CAs. After laboratory suture after 30 minutes. Breaking strength between the and field tests, they concluded that the CAs work best two equalized only after 7 days, when the suture was over a denuded and raw blister base. They further removed.16 A year later, a similar study removed the found IACA to be the most promising as it produced suture on day 7 and the Histoacryl was allowed to fall off the smallest halo of inflammation, relieved pain, in- on its own before strength testing on day 20. The re- hibited infection, allowed for the continuation of activ- searchers determined there were no significant differ- ity, and almost universally outperformed the control and ences at this time, when measuring displacement Neosporin with a bandage.27 Follow-up studies were (stretch) and energy absorption (wound strength).17 conducted on intact and abraded skin of rabbits. Use of Using Nexaband Liquid (OCA), the same conclusion, IACA was shown to be mildly irritating after its initial that suture is initially stronger than CA adhesives, was application. Nearly all IACA could be recovered after 2 demonstrated.18 Furthermore, OCA was proven to have a weeks, intimating that the irritation resulted from the three-dimensional breaking strength 4 times that of polymerization reaction and not from the release of toxic BCA.19,20 Singer et al21 went a step further, demonstrat- metabolites.28,29