Editing Subcutaneous administration

{{Short description|Insertion of medication under the skin}}
{{Redirect|Subcut|the song|Aftermathematics}}
'''Subcutaneous administration''' is the insertion of medications beneath the skin either by injection or infusion.

A '''subcutaneous injection''' is administered as a [[bolus (medicine)|bolus]] into the [[subcutis]], the layer of skin directly below the [[dermis]] and [[Epidermis (skin)|epidermis]], collectively referred to as the [[Cutis (anatomy)|cutis]]. The instruments are usually a [[hypodermic needle]] and a [[syringe]]. Subcutaneous injections are highly effective in administering medications such as [[insulin]], [[morphine]], [[heroin|diacetylmorphine]] and [[goserelin]]. Subcutaneous administration may be [[List of medical abbreviations|abbreviated]] as '''SC''', '''SQ''', '''subcu''', '''sub-Q''', '''SubQ''',  or '''subcut'''. '''Subcut''' is the preferred abbreviation to reduce the risk of misunderstanding and potential errors.<ref name="abbrevs">{{cite web | url=http://www.ismp.org/tools/errorproneabbreviations.pdf | title=ISMP's List of Error-Prone Abbreviations, Symbols, and Dose Designations | author=<!--Staff writer(s); no by-line.--> |date=2013 |website=www.ismp.org | access-date=13 May 2013}}</ref>

Subcutaneous tissue has few blood vessels and so drugs injected into it are intended for slow, sustained rates of absorption, often with some amount of [[depot injection|depot]] effect. Compared with other [[route of administration|routes of administration]], it is slower than [[intramuscular injection]]s but still faster than [[intradermal injection]]s. '''Subcutaneous infusion''' (as opposed to subcutaneous injection) is similar but involves a continuous drip from a bag and line, as opposed to injection with a syringe.

==Medical uses==
[[Image:Insulin pump with infusion set.jpg|thumb|An [[insulin pump]] with a subcutaneous infusion site]]
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 | vauthors = 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===
Medications commonly administered via subcutaneous injection or infusion include [[insulin]], [[Attenuated vaccine|live vaccines]], [[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 | vauthors = Usach I, Martinez R, Festini T, Peris JE | title = Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site | journal = Advances in Therapy | volume = 36 | issue = 11 | pages = 2986–2996 | date = November 2019 | pmid = 31587143 | pmc = 6822791 | doi = 10.1007/s12325-019-01101-6 | name-list-style = 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" />

====Insulin====
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 | vauthors = Gedawy A, Martinez J, Al-Salami H, Dass CR | title = Oral insulin delivery: existing barriers and current counter-strategies | journal = The Journal of Pharmacy and Pharmacology | volume = 70 | issue = 2 | pages = 197–213 | date = February 2018 | pmid = 29193053 | doi = 10.1111/jphp.12852 | name-list-style = 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 }}</ref>

Insulin historically was injected from a vial using a syringe and needle, but may also be administered subcutaneously using devices such as [[injector pen]]s or [[insulin pump]]s. An insulin pump consists of a catheter which is inserted into the subcutaneous tissue, and then secured in place to allow insulin to be administered multiple times through the same injection site.<ref name=Taylor />{{rp|722}}

===Recreational drug use===
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 | vauthors = Lejmi H, Jen KY, Olson JL, James SH, Sam R | title = Characteristics of AA amyloidosis patients in San Francisco | journal = Nephrology | volume = 21 | issue = 4 | pages = 308–313 | date = April 2016 | pmid = 26370715 | doi = 10.1111/nep.12616 | name-list-style = vanc | s2cid = 31760853 | url = https://escholarship.org/uc/item/3h34t4b7 }}</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 | vauthors = Khan F, Mukhtar S, Anjum F, Tripathi B, Sriprasad S, Dickinson IK, Madaan S | title = Fournier's gangrene associated with intradermal injection of cocaine | journal = The Journal of Sexual Medicine | volume = 10 | issue = 4 | pages = 1184–1186 | date = April 2013 | pmid = 23347293 | doi = 10.1111/jsm.12055 | name-list-style = vanc }}</ref> [[mephedrone]],<ref>{{cite journal | vauthors = Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, Rampe D | title = Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat | journal = Toxicology Letters | volume = 208 | issue = 1 | pages = 62–68 | date = January 2012 | pmid = 22037396 | doi = 10.1016/j.toxlet.2011.10.010 | name-list-style = vanc }}</ref> and [[amphetamine]] derivatives such as [[para-Methoxy-N-methylamphetamine|PMMA]].<ref>{{cite journal | vauthors = Steele TD, Katz JL, Ricaurte GA | title = Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) | journal = Brain Research | volume = 589 | issue = 2 | pages = 349–352 | date = September 1992 | pmid = 1382813 | doi = 10.1016/0006-8993(92)91298-s | s2cid = 232653 | doi-access =  }}</ref>

==Contraindications==
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 | vauthors = Mathaes R, Koulov A, Joerg S, Mahler HC | title = Subcutaneous Injection Volume of Biopharmaceuticals-Pushing the Boundaries | journal = Journal of Pharmaceutical Sciences | volume = 105 | issue = 8 | pages = 2255–2259 | date = August 2016 | pmid = 27378678 | doi = 10.1016/j.xphs.2016.05.029 | name-list-style = 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 | vauthors = Prettyman J | title = Subcutaneous or intramuscular? Confronting a parenteral administration dilemma | journal = Medsurg Nursing | volume = 14 | issue = 2 | pages = 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 | vauthors = Ballweg R, Brown DL, Vetrosky DT |title=Physician assistant : a guide to clinical practice |date=2013 |publisher=Elsevier/Saunders |location=Philadelphia, PA |isbn=9781455723102 |edition=5th}}</ref>{{rp|144}}

==Risks and complications==
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 reaction]]s". 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 | vauthors = Thomaidou E, Ramot Y | title = Injection site reactions with the use of biological agents | journal = Dermatologic Therapy | volume = 32 | issue = 2 | pages = e12817 | date = March 2019 | pmid = 30637967 | doi = 10.1111/dth.12817 | s2cid = 58544258 | doi-access = free }}</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.

===Medication-specific===
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 | vauthors = Guo X, Wang W | title = Challenges and recent advances in the subcutaneous delivery of insulin | journal = Expert Opinion on Drug Delivery | volume = 14 | issue = 6 | pages = 727–734 | date = June 2017 | pmid = 27626885 | doi = 10.1080/17425247.2016.1232247 | name-list-style = 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>{{cite journal | vauthors = Mohammady M, Radmehr M, Janani L | title = Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 6 | pages = CD008077 | date = June 2021 | pmid = 34101161 | pmc = 8186522 | doi = 10.1002/14651858.CD008077.pub6 }}</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 | vauthors = Bilen O, Teruya J | title = Complications of anticoagulation | journal = Disease-a-Month | volume = 58 | issue = 8 | pages = 440–447 | date = August 2012 | pmid = 22818558 | doi = 10.1016/j.disamonth.2012.04.002 | name-list-style = 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 | vauthors = Müller T | title = An evaluation of subcutaneous apomorphine for the treatment of Parkinson's disease | journal = Expert Opinion on Pharmacotherapy | volume = 21 | issue = 14 | pages = 1659–1665 | date = October 2020 | pmid = 32640853 | doi = 10.1080/14656566.2020.1787379 | name-list-style = 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 | vauthors = DeLorenzi C | title = Complications of injectable fillers, part I | journal = Aesthetic Surgery Journal | volume = 33 | issue = 4 | pages = 561–575 | date = May 2013 | pmid = 23636629 | doi = 10.1177/1090820X13484492 | name-list-style = vanc | doi-access =  }}</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 | vauthors = Erlichson K, Waight J | title = Therapeutic applications for subcutaneous triptans in the acute treatment of migraine | journal = Current Medical Research and Opinion | volume = 28 | issue = 7 | pages = 1231–1238 | date = July 2012 | pmid = 22401601 | doi = 10.1185/03007995.2012.674501 | name-list-style = vanc | s2cid = 10487801 }}</ref> [[medroxyprogesterone acetate]] for contraception,<ref name="Contra2016">{{cite journal | vauthors = Dragoman MV, Gaffield ME | title = The safety of subcutaneously administered depot medroxyprogesterone acetate (104mg/0.65mL): A systematic review | journal = Contraception | volume = 94 | issue = 3 | pages = 202–215 | date = September 2016 | pmid = 26874275 | doi = 10.1016/j.contraception.2016.02.003 | name-list-style = 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 | vauthors = Grange JM | title = Complications of bacille Calmette-Guérin (BCG) vaccination and immunotherapy and their management | journal = Communicable Disease and Public Health | volume = 1 | issue = 2 | pages = 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 | vauthors = Ma SJ, Li X, Xiong YQ, Yao AL, Chen Q | title = Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety | journal = Medicine | volume = 94 | issue = 44 | pages = e1721 | date = November 2015 | pmid = 26554769 | pmc = 4915870 | doi = 10.1097/MD.0000000000001721 | name-list-style = vanc }}</ref>

==Technique==
[[File:Needle-insertion-angles-1.png|thumb|right|Comparison of angle of subcutaneous injection of a needle with other injection types.]]
Subcutaneous injections are performed by cleaning the area to be injected followed by an injection, usually at a 45-degree angle to the skin when using a syringe and needle, or at a 90-degree angle (perpendicular) if using an injector pen. The appropriate injection angle is based on the length of needle used, and the depth of the subcutaneous fat in the skin of the specific person. A 90-degree angle is always used for medications such as [[heparin]]. If administered at an angle, the skin and underlying tissue may be pinched upwards prior to injection. The injection is administered slowly, lasting about 10 seconds per milliliter of fluid injected, and the needle may be left in place for 10 seconds following injection to ensure the medicine is fully injected.<ref name=Taylor/>{{rp|724}}

===Equipment===
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 3.5&nbsp;mm (commonly 3.5&nbsp;mm to 5&nbsp;mm).<ref name="MD2019">{{cite journal | vauthors = Leonardi L, Viganò M, Nicolucci A | title = Penetration force and cannula sliding profiles of different pen needles: the PICASSO study | journal = Medical Devices: Evidence and Research | volume = 12 | pages = 311–317 | date = 28 August 2019 | pmid = 31695523 | pmc = 6717876 | doi = 10.2147/MDER.S218983 | 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}}

===Locations===
[[File:Subcutaneous-injection-sites-274x300.png|thumb|Subcutaneous injection sites]]
Commonly used injection sites include:<ref name=Taylor />{{rp|723}}
* The outer area of the [[upper arm]].
* The abdomen, avoiding a 2-inch circle around the navel.
* The front of the [[thigh]], between 4&nbsp;inches from the top of the thigh and 4&nbsp;inches above the knee.
* The upper back.
* The upper area of the [[buttock]], just behind the [[human pelvis|hip bone]].

The choice of specific injection site is based on the medication being administered, with [[heparin]] almost always being administered in the abdomen, as well as preference. Injections administered frequently or repeatedly should be administered in a different location each time, either within the same general site or a different site, but at least one inch away from recent injections.<ref name=Taylor />{{rp|724}}

===Self-administration===
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 | vauthors = Frid AH, Kreugel G, Grassi G, Halimi S, Hicks D, Hirsch LJ, Smith MJ, Wellhoener R, Bode BW, Hirsch IB, Kalra S, Ji L, Strauss KW | display-authors = 6 | title = New Insulin Delivery Recommendations | journal = Mayo Clinic Proceedings | volume = 91 | issue = 9 | pages = 1231–1255 | date = September 2016 | pmid = 27594187 | doi = 10.1016/j.mayocp.2016.06.010 | name-list-style = vanc | doi-access = free }}</ref>

===Infusion===
'''Subcutaneous infusion''', also known as '''interstitial infusion''' or '''hypodermoclysis''', is a form of subcutaneous (under the skin) administration of fluids to the body, often [[saline (medicine)|saline]] or glucose solutions.<ref>[http://www.merriam-webster.com/medical/hypodermoclyses "hypodermoclysis"], ''Merriam-Webster's medical dictionary online''. Retrieved July 19, 2009.</ref> It is the infusion counterpart of [[subcutaneous injection]] with a syringe.

Subcutaneous infusion can be used where a slow rate of fluid uptake is required compared to [[intravenous infusion]].  Typically, it is limited to 1 mL per minute, although it is possible to increase this by using two sites simultaneously.  The chief advantages of subcutaneous infusion over intravenous infusion is that it is cheap and can be administered by non-medical personnel with minimal supervision.  It is therefore particularly suitable for home care.  The enzyme [[hyaluronidase]] can be added to the fluid to improve absorption during the infusion.<ref>Menahem Sasson, Pesach Shvartzman, [http://www.aafp.org/afp/20011101/1575.html "Hypodermoclysis: an alternative infusion technique"], ''American Family Physician'', vol. 64, no. 9, pp. 1575-1579 (November 1, 2001).</ref>

Subcutaneous infusion can be speeded up by applying it to multiple sites simultaneously.  The technique was pioneered by [[Evan O'Neill Kane]] in 1900.  Kane was looking for a technique that was as fast as intravenous infusion but not so risky to use on trauma patients in unhygienic conditions in the field.<ref>Edwin M. Hasbrouck, [https://jamanetwork.com/journals/jama/article-abstract/477272 "An improved device for rapid hypodermoclysis"], ''Journal of the American Medical Association'', '''34''', p.&nbsp;1273, 1900.</ref>

== See also ==
{{Wiktionary|hypodermoclysis}}
* [[Intramuscular injection]]
* [[Intravenous injection]]
* [[Intradermal injection]]

== References ==
{{Reflist}}

{{Dosage forms|state=expanded}}

{{DEFAULTSORT:Subcutaneous Injection}}
[[Category:Dosage forms]]
[[Category:Routes of administration]]
[[Category:Injection (medicine)]]