Subcutaneous administration: Difference between revisions

A subcutaneous injection is administered into the fatty tissue of the [[subcutaneous tissue]], located below the [[dermis]] and [[Epidermis (skin)|epidermis]].<ref>{{DorlandsDict|four/000053802|subcutaneous injection}}</ref> They are commonly used to administer medications, especially those which cannot be administered by mouth as they would not be absorbed from the [[gastrointestinal tract]]. A subcutaneous injection is absorbed slower than a substance injected [[intravenous therapy|intravenously]] or [[intramuscular injection|into a muscle]], but faster than a medication administered by mouth.<ref name=Taylor>{{cite book |last1=Taylor |first1=Carolvauthors |name-list-style=vanc Taylor C |title=Fundamentals of nursing : the art and science of nursing care |date=2011 |publisher=Wolters Kluwer Health and Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0781793834 |edition=7th}}</ref>{{rp|721}}

Medications commonly administered via subcutaneous injection or infusion include [[insulin]], [[monoclonal antibodies]], and [[heparin]]. These medications cannot be administered orally as the molecules are too large to be absorbed in the intestines.<ref name="Adv2019">{{cite journal |last1 vauthors = Usach |first1=IrisI, |last2=Martinez |first2=RafaelR, |last3=Festini |first3=TeodoraT, |last4=Peris |first4=José-EstebanJE |name-list-style=vanc |title = Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site | journal = Advances in Therapy |date=November 2019volume |volume= 36 | issue = 11 | pages = 2986–2996 | date = November 2019 | pmid = 31587143 | pmc = 6822791 | doi = 10.1007/s12325-019-01101-6|pmid=31587143 |pmc name-list-style =6822791 vanc }}</ref> Subcutaneous injections can also be used when the increased bioavailability and more rapid effects over oral administration are preferred. They are also the easiest form of [[parenteral administration]] of medication to perform by lay people, and are associated with less adverse effects such as pain or infection than other forms of injection.<ref name="Adv2019" />

Perhaps the most common medication administered subcutaneously is insulin. While attempts have been made since the 1920s to administer insulin orally, the large size of the molecule has made it difficult to create a formulation with absorption and predictability that comes close to subcutaneous injections of insulin.<ref name="insulin2018">{{cite journal |last1 vauthors = Gedawy |first1=AhmedA, |last2=Martinez |first2=JorgeJ, |last3=Al-Salami |first3=HaniH, |last4=Dass |first4=Crispin R.CR |name-list-style=vanc |title = Oral insulin delivery: existing barriers and current counter-strategies | journal = The Journal of Pharmacy and Pharmacology |date=February 2018 |volume = 70 | issue = 2 | pages = 197–213 | date = February 2018 | pmid = 29193053 | doi = 10.1111/jphp.12852 |pmid name-list-style =29193053 vanc | s2cid = 12848146 | doi-access = free }}</ref> People with [[type 1 diabetes]] almost all require insulin as part of their treatment regimens, and a smaller proportion of people with [[type 2 diabetes]] do as well - with tens of millions of prescriptions per year in the United States alone.<ref>{{cite web |title=Insulin Human - Drug Usage Statistics, | work = ClinCalc DrugStats Database |url=https://clincalc.com/DrugStats/Drugs/InsulinHuman |website=clincalc.com}}</ref>

Subcutaneous injection may also be used by people to (self-) administer [[Recreational drug use|recreational drugs]]. This can be referred to as [[skin popping]].<ref name="neph2016">{{cite journal |last1 vauthors = Lejmi |first1=HibaH, |last2=Jen |first2=Kuang-YuKY, |last3=Olson |first3=JeanJL, L. |last4=James |first4=SH, Sam H.R |last5=Sam |first5=Ramintitle |name-list-style=vanc |title=Characteristics of AA amyloidosis patients in San Francisco: AA| amyloidosisjournal |journal= Nephrology |date=April 2016volume |volume= 21 | issue = 4 | pages = 308–313 | date = April 2016 | pmid = 26370715 | doi = 10.1111/nep.12616 |pmid name-list-style =26370715 vanc | s2cid = 31760853 }}</ref> In some cases, the administration of illicit drugs in this way is associated with unsafe practices leading to infections and other adverse effects. In rare cases, this results in serious side effects such as [[AA amyloidosis]].<ref name="neph2016" /> Recreational drugs reported to be administered subcutaneously have included [[cocaine]],<ref>{{cite journal |last1 vauthors = Khan |first1=FahdF, |last2=Mukhtar |first2=SaheelS, |last3=Anjum |first3=FaqarF, |last4=Tripathi |first4=BharatiB, |last5=Sriprasad |first5=SeshadriS, |last6=Dickinson |first6=IanIK, K. |last7=Madaan |first7=SanjeevS |name-list-style=vanc |display-authorstitle =6 |title=Fournier's Gangrenegangrene Associatedassociated with Intradermalintradermal Injectioninjection of Cocainecocaine | journal = The Journal of Sexual Medicine |date=April 2013volume |volume= 10 | issue = 4 | pages = 1184–1186 | date = April 2013 | pmid = 23347293 | doi = 10.1111/jsm.12055 |pmid name-list-style =23347293 vanc }}</ref> [[mephedrone]],<ref>{{cite journal |last1 vauthors = Meng |first1=H, |last2=Cao |first2=J, |last3=Kang |first3=J, |last4=Ying |first4=X, |last5=Ji |first5=J, |last6=Reynolds |first6=W, |last7=Rampe |first7=D |name-list-style=vanc |display-authors=6 |title = Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. | journal = Toxicology Letters |date=5 Januaryvolume 2012= |volume=208 | issue = 1 | pages =62–8 62–68 | date = January 2012 | pmid = 22037396 | doi = 10.1016/j.toxlet.2011.10.010 |pmid name-list-style =22037396 vanc }}</ref> and [[amphetamine]] derivatives such as [[para-Methoxy-N-methylamphetamine|PMMA]].<ref>{{cite journal |last1 vauthors = Steele |first1=TD, |last2=Katz |first2=JL, |last3=Ricaurte |first3=GA | title = Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA). | journal = Brain Research |date=4 Septembervolume 1992 |volume= 589 | issue = 2 | pages =349–52 349–352 | date = September 1992 | pmid = 1382813 | doi = 10.1016/0006-8993(92)91298-s |pmid=1382813| s2cid = 232653 }}</ref>

Contraindications to subcutaneous injections primarily depend on the specific medication being administered. Doses which would require more than 2 mL to be injected at once are not administered subcutaneously.<ref>{{cite journal |last1 vauthors = Mathaes |first1=RomanR, |last2=Koulov |first2=AtanasA, |last3=Joerg |first3=SusanneS, |last4=Mahler |first4=Hanns-ChristianHC |name-list-style=vanc |title = Subcutaneous Injection Volume of Biopharmaceuticals—PushingBiopharmaceuticals-Pushing the Boundaries | journal = Journal of Pharmaceutical Sciences |date=August 2016 |volume = 105 | issue = 8 | pages = 2255–2259 | date = August 2016 | pmid = 27378678 | doi = 10.1016/j.xphs.2016.05.029 |pmid name-list-style =27378678 vanc }}</ref> Medications which may cause necrosis or otherwise be damaging or irritating to tissues should also not be administered subcutaneously.<ref name="Prettyman">{{cite journal |last1 vauthors = Prettyman |first1=J |name-list-style=vanc |title = Subcutaneous or intramuscular? Confronting a parenteral administration dilemma. | journal = Medsurg Nursing |date=April 2005volume |volume= 14 | issue = 2 | pages =93–98 93–8; quiz 99 | date = April 2005 | pmid = 15916264 | name-list-style = vanc }}</ref> An injection should not be given at a specific site if there is inflammation or skin damage in the area.<ref>{{cite book |last1 vauthors = Ballweg |first1=RuthR, |last2=Brown |first2=DarwinDL, L. |last3=Vetrosky |first3=Daniel T. |name-list-style=vancDT |title=Physician assistant : a guide to clinical practice |date=2013 |publisher=Elsevier/Saunders |location=Philadelphia, PA |isbn=9781455723102 |edition=5th}}</ref>{{rp|144}}

With normal doses of medicine (less than 2 mL in volume), complications or adverse effects are very rare. The most common adverse reactions after subcutaneous injections are administered are termed "injection site reactions". This term encompasses any combination of redness, swelling, itching, bruising, or other irritation that does not spread beyond the immediate vicinity of the injection.<ref name="Derm2019">{{cite journal |last1 vauthors = Thomaidou |first1=ElenaE, |last2=Ramot |first2=YuvalY | title = Injection site reactions with the use of biological agents | journal = Dermatologic Therapy |date=2019 |volume = 32 | issue = 2 | pages = e12817 | date = March 2019 | pmid = 30637967 | doi = 10.1111/dth.12817 |pmid=30637967 |s2cid = 58544258 }}</ref> Injection site reactions may be minimized if repeated injections are necessary by moving the injection site at least one inch from previous injections, or using a different injection location altogether.<ref name="Derm2019" /> There may also be specific complications associated with the specific medication being administered.

Due to the frequency of injections required for the administration of insulin products via subcutaneous injection, insulin is associated with the development of [[lipohypertrophy]] and [[lipoatrophy]]. This can lead to slower or incomplete absorption from the injection site. Rotating the injection site is the primary method of preventing changes in tissue structure from insulin administration.<ref>{{cite journal |last1 vauthors = Guo |first1=XiaohuiX, |last2=Wang |first2=WeiW |name-list-style=vanc |title = Challenges and recent advances in the subcutaneous delivery of insulin | journal = Expert Opinion on Drug Delivery |date=3 June 2017 |volume = 14 | issue = 6 | pages = 727–734 | date = June 2017 | pmid = 27626885 | doi = 10.1080/17425247.2016.1232247 |pmid name-list-style =27626885 vanc | s2cid = 19820269 }}</ref> Heparin-based anticoagulants injected subcutaneously may cause [[hematoma]] and bruising around the injection site due to their anticoagulant effect. This includes [[heparin]] and [[low molecular weight heparin]] products such as enoxaparin. There is some low certainty evidence that administering the injection more slowly may decrease the pain from heparin injections, but not the risk of or extent of bruising.<ref>{{Citecite journal |last1 vauthors = Mohammady|first1=Mina|last2= M, Radmehr|first2=Maryam|last3= M, Janani L |first3=Leila|date=2021-06-08| title = Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity | journal = The Cochrane Database of Systematic Reviews | volume =2021 6 | issue = 6 | pages = CD008077 | date = June 2021 | pmid = 34101161 | pmc = 8186522 | doi = 10.1002/14651858.CD008077.pub6|issn=1469-493X|pmc=8186522|pmid=34101161 }}</ref> Subcutaneous heparin-based anticoagulation may also lead to necrosis of the surrounding skin or lesions, most commonly when injected in the abdomen.<ref>{{cite journal |last1 vauthors = Bilen |first1=OzlemO, |last2=Teruya |first2=JunJ |name-list-style=vanc |title = Complications of Anticoagulationanticoagulation | journal = Disease-a-Month |date=1 August 2012volume |volume= 58 | issue = 8 | pages = 440–447 | date = August 2012 | pmid = 22818558 | doi = 10.1016/j.disamonth.2012.04.002 |pmid name-list-style =22818558 vanc }}</ref>

Many medications have the potential to cause local lesions or swelling due to the irritating effect the medications have on the skin and subcutaneous tissues. This includes medications such as [[apomorphine]]<ref>{{cite journal |last1 vauthors = Müller |first1=ThomasT |name-list-style=vanc |title = An evaluation of subcutaneous apomorphine for the treatment of Parkinson's disease | journal = Expert Opinion on Pharmacotherapy |date=21 Septembervolume 2020= |volume=21 | issue = 14 | pages = 1659–1665 | date = October 2020 | pmid = 32640853 | doi = 10.1080/14656566.2020.1787379 |pmid name-list-style =32640853 vanc | s2cid = 220435665 }}</ref> and [[hyaluronic acid]] injected as a filler, which may cause the area to appear bruised. Hyaluronic acid "bruising" may be treated using injections of [[hyaluronidase]] enzyme around the location.<ref>{{cite journal |last1 vauthors = DeLorenzi |first1=ClaudioC |name-list-style=vanc |title = Complications of Injectableinjectable Fillersfillers, Partpart I | journal = Aesthetic Surgery Journal |date=1 May 2013 |volume = 33 | issue = 4 | pages = 561–575 | date = May 2013 | pmid = 23636629 | doi = 10.1177/1090820X13484492 |pmid name-list-style =23636629 vanc | doi-access = free }}</ref>

Other common medication-specific side effects include pain, burning or stinging, warmth, rash, flushing, or multiple of these reactions at the injection site, collectively termed "injection site reactions". This is seen with the subcutaneous injection of [[triptan]]s for migraine headache,<ref>{{cite journal |last1 vauthors = Erlichson |first1=KathyK, |last2=Waight |first2=JulieJ |name-list-style=vanc |title = Therapeutic applications for subcutaneous triptans in the acute treatment of migraine | journal = Current Medical Research and Opinion |date=1 July 2012 |volume = 28 | issue = 7 | pages = 1231–1238 | date = July 2012 | pmid = 22401601 | doi = 10.1185/03007995.2012.674501 |pmid name-list-style =22401601 vanc | s2cid = 10487801 }}</ref> [[medroxyprogesterone acetate]] for contraception,<ref name="Contra2016">{{cite journal |last1 vauthors = Dragoman |first1=MonicaMV, V. |last2=Gaffield |first2=Mary E.ME |name-list-style=vanc |title = The safety of subcutaneously administered depot medroxyprogesterone acetate (104 mg104mg/0.65 mL65mL): A systematic review | journal=Contraception |date=September 2016Contraception | volume = 94 | issue = 3 | pages = 202–215 | date = September 2016 | pmid = 26874275 | doi = 10.1016/j.contraception.2016.02.003 |pmid name-list-style =26874275 vanc | doi-access = free }}</ref> as well as many monoclonal antibodies. In most cases, injection site reactions are self-limiting and resolve on their own after a short time without treatment, and do not require the medication to be discontinued.<ref name="Contra2016" />

The administration of vaccines subcutaneously is also associated with injection site reactions. This includes the [[BCG vaccine]] which is associated with a specific scar appearance which can be used as evidence of prior vaccination.<ref>{{cite journal |last1 vauthors = Grange |first1=JM | title = Complications of bacille Calmette-Guérin (BCG) vaccination and immunotherapy and their management. | journal = Communicable Disease and Public Health |date=June 1998 |volume = 1 | issue = 2 | pages =84–8 84–88 | date = June 1998 | pmid = 9644119 }}</ref> Other subcutaneous vaccines, many of which are live vaccines including the [[MMR vaccine]] and the [[varicella vaccine]], which may cause [[fever]] and rash, as well as a feeling of general [[malaise]] for a day or two following the vaccination.<ref>{{cite journal |last1 vauthors = Ma |first1=SJ, |last2=Li |first2=X, |last3=Xiong |first3=YQ, |last4=Yao |first4=AL, |last5=Chen |first5=Q |name-list-style=vanc |title = Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety. | journal=Medicine |date=November 2015Medicine | volume = 94 | issue = 44 | pages = e1721 | date = November 2015 | pmid = 26554769 | pmc = 4915870 | doi = 10.1097/MD.0000000000001721 |pmid name-list-style =26554769|pmc=4915870 vanc }}</ref>

The [[Birmingham gauge#Sizes of hypodermic needles|gauge]] of the needle used can range from 25 gauge to 27 gauge, while the length can vary between {{frac|1|2}}-inch to {{frac|5|8}}-inch for injections using a syringe and needle.<ref name=Taylor/>{{rp|722}} For subcutaneous injections delivered using devices such as [[injector pen]]s, the needle used may be as thin as 34 gauge (commonly 30-32 gauge), and as short as 3.5mm (commonly 3.5mm to 5mm).<ref name="MD2019">{{cite journal |last1 vauthors = Leonardi |first1=LucaL, |last2=Viganò |first2=MaraM, |last3=Nicolucci |first3=AntonioA | title = Penetration force and cannula sliding profiles of different pen needles: the PICASSO study | journal = Medical Devices: Evidence| andvolume Research= 12 | pages = 311–317 | date = 28 August 2019 |volume pmid =12 31695523 |pages pmc =311–317 6717876 | doi = 10.2147/MDER.S218983 |pmid=31695523 |pmc=6717876 |doi-access = free }}</ref> Subcutaneous injections can also be delivered via a pump system which uses a cannula inserted under the skin. The specific needle size/length, as well as appropriateness of a device such as a pen or pump, is based on the characteristics of a person's skin layers.<ref name=Taylor />{{rp|722–724}}

As opposed to intramuscular or intravenous injections, subcutaneous injections can be easily performed by people with minor skill and training required. The injection sites for self-injection of medication are the same as for injection by a healthcare professional, and the skill can be taught to patients using pictures, videos, or models of the subcutaneous tissue for practice. People who are to self-inject medicine subcutaneously should be trained how to evaluate and rotate the injection site if complications or contraindications arise. Self-administration by subcutaneous injection generally does not require disinfection of the skin outside of a hospital setting as the risk of infection is extremely low, but instead it is recommended to ensure that the site and person's hands are simply clean prior to administration.<ref name="Mayo2016">{{cite journal |last1 vauthors = Frid |first1=AH, |last2=Kreugel |first2=G, |last3=Grassi |first3=G, |last4=Halimi |first4=S, |last5=Hicks |first5=D, |last6=Hirsch |first6=LJ, |last7=Smith |first7=MJ, |last8=Wellhoener |first8=R, |last9=Bode |first9=BW, |last10=Hirsch |first10=IB, |last11=Kalra |first11=S, |last12=Ji |first12=L, |last13=Strauss |first13=KW |name-list-style=vanc |display-authors = 6 | title = New Insulin Delivery Recommendations. | journal = Mayo Clinic Proceedings |date=September 2016volume |volume= 91 | issue = 9 | pages =1231–55 1231–1255 | date = September 2016 | pmid = 27594187 | doi = 10.1016/j.mayocp.2016.06.010 |pmid name-list-style =27594187 vanc | doi-access = free }}</ref>

== See also ==

== References ==