Editing Fentanyl (section)

== Medical uses ==

=== Anesthesia ===
Intravenous fentanyl is often used for [[anesthesia]] and as an [[analgesic]].<ref>{{cite book |vauthors = Brunton LL, Hilal-Dandan R, Knollmann BC |date=5 December 2017 |title=Goodman & Gilman's: The pharmacological basis of therapeutics |isbn=978-1-259-58473-2 |edition=13th |location=New York | publisher = McGraw-Hill Education |oclc=993810322}}</ref> To induce anesthesia, it is given with a [[sedative-hypnotic]], like [[propofol]] or [[thiopental]].<ref name="Gropper_2019">{{cite book |vauthors = Gropper MA, Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Cohen LH, Leslie K |date=7 October 2019 |title=Miller's Anesthesia |edition=9th |location=Philadelphia| publisher = Elsevier |isbn=978-0-323-61264-7 |oclc=1124935549}}</ref> To maintain anesthesia, inhaled anesthetics and additional fentanyl may be used.<ref name="Gropper_2019" /> These are often given in 15–30{{nbsp}}minute intervals throughout procedures such as [[endoscopy]] and [[surgeries]] and in emergency rooms.<ref>{{cite journal | vauthors = Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FM | title = Clinical policy: procedural sedation and analgesia in the emergency department | journal = Annals of Emergency Medicine | volume = 63 | issue = 2 | pages = 247–58.e18 | date = February 2014 | pmid = 24438649 | doi = 10.1016/j.annemergmed.2013.10.015 }}</ref><ref>{{cite journal | vauthors = Smith HS, Colson J, Sehgal N | title = An update of evaluation of intravenous sedation on diagnostic spinal injection procedures | journal = Pain Physician | volume = 16 | issue = 2 Suppl | pages = SE217–SE228 | date = April 2013 | pmid = 23615892 | doi = 10.36076/ppj.2013/16/SE217 | url = http://www.painphysicianjournal.com/current/pdf?article=MTg4MQ%3D%3D&journal=74 | url-status = live | access-date = 1 May 2017 | archive-url = https://web.archive.org/web/20151019192759/http://www.painphysicianjournal.com/current/pdf?article=MTg4MQ%3D%3D&journal=74 | archive-date = 19 October 2015 | doi-access = free | title-link = doi }}</ref>

For pain relief after surgery, use can decrease the amount of inhalational anesthetic needed for emergence from anesthesia.<ref name="Gropper_2019"/> Balancing this medication and titrating the drug based on expected stimuli and the person's responses can result in stable blood pressure and heart rate throughout a procedure and a faster emergence from anesthesia with minimal pain.<ref name="Gropper_2019"/>

=== Regional anesthesia ===
Fentanyl is the most commonly used [[Intrathecal administration|intrathecal]] opioid because its lipophilic profile allows a quick onset of action (5–10 min) and intermediate duration of action (60–120 min).<ref>{{cite book |vauthors=Gudin MA, López R, Estrada J, Ortigosa E |chapter=Neuraxial Blockade: Subarachnoid Anesthesia |date=28 November 2011 |title=Essentials of Regional Anesthesia |pages=261–291 |place=New York |publisher=Springer |doi=10.1007/978-1-4614-1013-3_11 |isbn=978-1-4614-1012-6 |chapter-url=http://dx.doi.org/10.1007/978-1-4614-1013-3_11 |access-date=4 July 2021 |archive-date=8 February 2023 |archive-url=https://web.archive.org/web/20230208191557/https://link.springer.com/chapter/10.1007/978-1-4614-1013-3_11 |url-status=live }}</ref> Spinal administration of hyperbaric [[bupivacaine]] with fentanyl may be the optimal combination. The almost immediate onset of fentanyl reduces visceral discomfort and even nausea during the procedure.<ref>{{cite journal |vauthors=Buggy D |date=1 July 2008 |type=book review |title=Anesthesiology: Longnecker DE, Brown DL, Newman MF, Zapol WM, Editors, McGraw Hill, New York (2007) {{text|ISBN}}: 978-0-07-145984-6, 2278 pp, hardcover, $249{{nbsp}}... |journal=Regional Anesthesia and Pain Medicine |volume=33 |issue=4 |page=380 |publisher=BMJ Journals |doi=10.1016/j.rapm.2008.03.003 |issn=1098-7339 |url=https://rapm.bmj.com/content/33/4/380 |access-date=18 July 2021 |archive-date=18 July 2021 |archive-url=https://web.archive.org/web/20210718162807/https://rapm.bmj.com/content/33/4/380 |url-status=live }}</ref>

=== Obstetrics ===
Fentanyl is sometimes given intrathecally as part of [[spinal anaesthesia|spinal anesthesia]] or epidurally for [[epidural anaesthesia]] and [[epidural analgesia|analgesia]]. Because of fentanyl's high lipid solubility, its effects are more localized than morphine, and some clinicians prefer to use morphine to get a wider spread of analgesia.<ref>{{cite journal | vauthors = Bujedo BM | title = Current evidence for spinal opioid selection in postoperative pain | journal = The Korean Journal of Pain | volume = 27 | issue = 3 | pages = 200–209 | date = July 2014 | pmid = 25031805 | pmc = 4099232 | doi = 10.3344/kjp.2014.27.3.200 }}</ref> It is widely used in [[Obstetrics|obstetrical]] anesthesia because of its short time to action peak (about 5 minutes), the rapid termination of its effect after a single dose, and the occurrence of relative cardiovascular stability.<ref name="Moisés_2005">{{cite journal | vauthors = Moisés EC, de Barros Duarte L, de Carvalho Cavalli R, Lanchote VL, Duarte G, da Cunha SP | title = Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women | journal = European Journal of Clinical Pharmacology | volume = 61 | issue = 7 | pages = 517–522 | date = August 2005 | pmid = 16021436 | doi = 10.1007/s00228-005-0967-9 | s2cid = 26065578 }}</ref> In obstetrics, the dose must be closely regulated to prevent large amounts of transfer from mother to fetus. At high doses, the drug may act on the fetus to cause [[neonatal withdrawal]].<ref name="Moisés_2005" /> For this reason, shorter-acting agents such as [[alfentanyl]] or [[remifentanil]] may be more suitable in the context of inducing general anaesthesia.<ref>{{cite journal | vauthors = White LD, Hodsdon A, An GH, Thang C, Melhuish TM, Vlok R | title = Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials | journal = International Journal of Obstetric Anesthesia | volume = 40 | pages = 4–13 | date = November 2019 | pmid = 31230994 | doi = 10.1016/j.ijoa.2019.04.007 | hdl = 10072/416502 | s2cid = 181816438 | url = https://researchonline.nd.edu.au/cgi/viewcontent.cgi?article=2384&context=med_article | hdl-access = free | access-date = 23 May 2022 | archive-date = 22 May 2022 | archive-url = https://web.archive.org/web/20220522185407/https://researchonline.nd.edu.au/cgi/viewcontent.cgi?article=2384&context=med_article | url-status = live }}</ref>

=== Pain management ===
[[File:PecFent 100mcg.jpg|thumb|A fentanyl nasal spray with a strength of 100{{nbsp}}[[Microgram|μg]] per use]]
The bioavailability of intranasal fentanyl is about 70–90% but with some imprecision due to clotted nostrils, pharyngeal swallow, and incorrect administration. For both emergency and palliative use, intranasal fentanyl is available in doses of 50, 100, 200, 400(PecFent){{nbsp}}μg. In emergency medicine, safe administration of intranasal fentanyl with a low rate of side effects and a promising pain-reducing effect was demonstrated in a prospective observational study in about 900{{nbsp}}out-of-hospital patients.<ref>{{cite journal | vauthors = Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS | title = Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study | journal = Annals of Emergency Medicine | volume = 63 | issue = 6 | pages = 699–703 | date = June 2014 | pmid = 24268523 | doi = 10.1016/j.annemergmed.2013.10.025 }}</ref>

In children, intranasal fentanyl is useful for the treatment of moderate and severe pain and is well tolerated.<ref name="ReferenceA">{{cite journal | vauthors = Murphy A, O'Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J, McCoy SC, Hom J, Kandamany N | title = Intranasal fentanyl for the management of acute pain in children | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | page = CD009942 | date = October 2014 | pmid = 25300594 | pmc = 6544782 | doi = 10.1002/14651858.CD009942.pub2 }}</ref> Furthermore, a 2017 study suggested the efficacy of fentanyl lozenges in children as young as five, weighing as little as 13{{nbsp}}kg. Lozenges are more inclined to be used as the child is in control of sufficient dosage, in contrast to buccal tablets.<ref>{{cite journal | vauthors = Coombes L, Burke K, Anderson AK | title = The use of rapid onset fentanyl in children and young people for breakthrough cancer pain | journal = Scandinavian Journal of Pain | volume = 17 | issue = 1 | pages = 256–259 | date = October 2017 | pmid = 29229211 | doi = 10.1016/j.sjpain.2017.07.010 | s2cid = 8577873 }}</ref>

==== Chronic pain ====
It is also used in the [[Pain management|management]] of [[chronic pain]].<ref>{{cite journal | vauthors = Plante GE, VanItallie TB | title = Opioids for cancer pain: the challenge of optimizing treatment | journal = Metabolism | volume = 59 | issue = Suppl 1 | pages = S47–S52 | date = October 2010 | pmid = 20837194 | doi = 10.1016/j.metabol.2010.07.010 }}</ref> Often, [[transdermal patch]]es are used.<ref name="www.dea.gov">{{cite web |title=Fentanyl |type=factsheet |publisher=[[Drug Enforcement Administration]] |url=https://www.dea.gov/factsheets/fentanyl |access-date=4 December 2018 |archive-date=4 December 2018 |archive-url=https://web.archive.org/web/20181204053826/https://www.dea.gov/factsheets/fentanyl |url-status=live }}</ref> The patches work by slowly releasing fentanyl through the skin into the bloodstream over 48 to 72{{nbsp}}hours, allowing for long-lasting pain management.<ref name="AC-Durogesic2">{{cite book | veditors = Jasek W |year=2007 |title=Austria-Codex |edition=62nd |publisher=Österreichischer Apothekerverlag |isbn=978-3-85200-181-4 |location=Vienna |pages=2621{{nbsp}}ff |language=de}}</ref> Dosage is based on the size of the patch, since, in general, the transdermal absorption rate is constant at a constant skin temperature.<ref name="AC-Durogesic2" /> Each patch should be changed every 72{{nbsp}}hours.<ref>{{cite web |title=Fentanyl patches (Durogesic) for chronic pain |website=NPS Medicinewise |date=August 2006 |url=https://www.nps.org.au/radar/articles/fentanyl-patches-durogesic-for-chronic-pain#:~:text=The%20patch%20should%20be%20changed,and%20100%20micrograms%20per%20hour. |access-date=7 December 2021 |archive-date=7 December 2021 |archive-url=https://web.archive.org/web/20211207205934/https://www.nps.org.au/radar/articles/fentanyl-patches-durogesic-for-chronic-pain#:~:text=The%20patch%20should%20be%20changed,and%20100%20micrograms%20per%20hour. |url-status=live }}</ref> Rate of absorption is dependent on a number of factors. Body temperature, skin type, amount of body fat, and placement of the patch can have major effects. The different delivery systems used by different makers will also affect individual rates of absorption, and route of administration. Under normal circumstances, the patch will reach its full effect within 12 to 24{{nbsp}}hours; thus, fentanyl patches are often prescribed with a fast-acting opioid (such as morphine or oxycodone) to handle breakthrough pain.<ref name="AC-Durogesic2" /> It is unclear if fentanyl gives long-term pain relief to people with [[neuropathic pain]].<ref>{{cite journal | vauthors = Derry S, Stannard C, Cole P, Wiffen PJ, Knaggs R, Aldington D, Moore RA | title = Fentanyl for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 5 | page = CD011605 | date = October 2016 | pmid = 27727431 | pmc = 6457928 | doi = 10.1002/14651858.CD011605.pub2 }}</ref>

==== Breakthrough pain ====
Sublingual fentanyl dissolves quickly and is absorbed through the [[sublingual]] mucosa to provide rapid analgesia.<ref name="trib">{{cite web |title=Abstral sublingual tablets |date=May 2016 |publisher=UK Electronic Medicines Compendium |url=http://www.medicines.org.uk/emc/medicine/21371/SPC/Abstral+Sublingual+Tablets/ |url-status=live |access-date=1 May 2017 |archive-url=https://web.archive.org/web/20170323181204/http://www.medicines.org.uk/emc/medicine/21371/SPC/Abstral+Sublingual+Tablets/ |archive-date=23 March 2017 }}</ref> Fentanyl is a highly lipophilic compound,<ref name="trib" /><ref>{{cite journal | vauthors = | title = Abstral (Fentanyl Sublingual Tablets for Breakthrough Cancer Pain) | journal = P & T | volume = 36 | issue = 2 | pages = 2–28 | date = February 2011 | pmid = 21560267 | pmc = 3086091 }}</ref> which is well absorbed sublingually and generally well tolerated.<ref name="trib" /> Such forms are particularly useful for breakthrough cancer pain episodes, which are often rapid in onset, short in duration, and severe in intensity.<ref>{{cite journal | vauthors = Ward J, Laird B, Fallon M |year=2011 |title=The UK breakthrough cancer pain registry: Origin, methods and preliminary data |journal=BMJ Supportive & Palliative Care |volume=1 |page=A24 |doi=10.1136/bmjspcare-2011-000020.71 |s2cid=73185220}}</ref>

==== Palliative care ====
[[File:A generic fentanyl transdermal patch, with a release rate of 12mcg per hour, applied to the skin (cropped).jpg|thumb|A fentanyl transdermal patch with a release rate of 12 micrograms per hour, on a person's arm]]
In [[palliative care]], transdermal fentanyl patches have a definitive, but limited role for:
* people already stabilized on other opioids who have persistent swallowing problems and cannot tolerate other parenteral routes such as subcutaneous administration.
* people with moderate to severe [[Renal failure|kidney failure]].<ref>{{cite journal | vauthors = Roy PJ, Weltman M, Dember LM, Liebschutz J, Jhamb M | title = Pain management in patients with chronic kidney disease and end-stage kidney disease | journal = Current Opinion in Nephrology and Hypertension | volume = 29 | issue = 6 | pages = 671–680 | date = November 2020 | pmid = 32941189 | pmc = 7753951 | doi = 10.1097/MNH.0000000000000646 }}</ref>
* troublesome side effects of oral morphine, [[hydromorphone]], or [[oxycodone]].<ref>{{cite journal | vauthors = Aurilio C, Pace MC, Pota V, Sansone P, Barbarisi M, Grella E, Passavanti MB | title = Opioids switching with transdermal systems in chronic cancer pain | journal = Journal of Experimental & Clinical Cancer Research | volume = 28 | page = 61 | date = May 2009 | issue = 1 | pmid = 19422676 | pmc = 2684533 | doi = 10.1186/1756-9966-28-61 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Minami S, Kijima T, Nakatani T, Yamamoto S, Ogata Y, Hirata H, Shiroyama T, Koba T, Komuta K | title = Opioid switch from low dose of oral oxycodone to transdermal fentanyl matrix patch for patients with stable thoracic malignancy-related pain | journal = BMC Palliative Care | volume = 13 | issue = 1 | page = 46 | date = 8 October 2014 | pmid = 25313295 | pmc = 4195703 | doi = 10.1186/1472-684X-13-46 | doi-access = free | title-link = doi }}</ref>

When using the transdermal patch, patients must be careful to minimize or avoid external heat sources (direct sunlight, heating pads, etc.), which can trigger the release and absorption of too much medication and cause potentially deadly complications.<ref>{{cite web |title=Fentanyl (Transdermal Route) Precautions |url=https://www.mayoclinic.org/drugs-supplements/fentanyl-transdermal-route/precautions/drg-20068152 |website=Mayo Clinic |access-date=19 January 2023 |archive-date=19 January 2023 |archive-url=https://web.archive.org/web/20230119051903/https://www.mayoclinic.org/drugs-supplements/fentanyl-transdermal-route/precautions/drg-20068152 |url-status=live }}</ref>

==== Combat medicine ====
[[File:Fentanylové lízatko.jpg|thumb|Fentanyl lollipos Actiq 200 mcg]]

[[Usaf|USAF]] [[United States Air Force Pararescue|Pararescue]] [[combat medic]]s in Afghanistan used fentanyl lozenges in the form of lollipops on combat casualties from [[Improvised explosive device|IED]] blasts and other trauma.<ref name="Shachtman_2009">{{cite magazine| vauthors = Shachtman N |date=10 September 2009|title=Airborne EMTs Shave Seconds to Save Lives in Afghanistan|url=https://www.wired.com/2009/09/airborne-emts-in-astan/|url-status=live|department=Danger Room|magazine=[[Wired (magazine)|Wired]]|archive-url=https://web.archive.org/web/20100706140612/http://www.wired.com/dangerroom/2009/09/airborne_emts_in_astan|archive-date=6 July 2010|access-date=1 July 2010 }}</ref> The stick is taped to a finger and the lozenge put in the [[Buccal administration|cheek]] of the person. When enough fentanyl has been absorbed, the (sedated) person generally lets the lollipop fall from the mouth, indicating sufficient analgesia and somewhat reducing the likelihood of overdose and associated risks.<ref name="Shachtman_2009" />

==== Breathing difficulties ====
Fentanyl is used to help relieve shortness of breath ([[dyspnea]]) when patients cannot tolerate morphine, or whose breathlessness is refractory to morphine. Fentanyl is useful for such treatment in [[palliative care]] settings where pain and shortness of breath are severe and need to be treated with strong opioids. [[Nebulizer|Nebulized]] fentanyl citrate is used to relieve end-of-life dyspnea in [[hospice]] settings.<ref>{{cite journal | vauthors = van Dijk M, Mooren KJ, van den Berg JK, van Beurden-Moeskops WJ, Heller-Baan R, de Hosson SM, Lam-Wong WY, Peters L, Pool K, Kerstjens HA | title = Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD) | journal = BMC Pulmonary Medicine | volume = 21 | issue = 1 | page = 289 | date = September 2021 | pmid = 34507574 | pmc = 8431258 | doi = 10.1186/s12890-021-01647-8 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Simon ST, Köskeroglu P, Gaertner J, Voltz R | title = Fentanyl for the relief of refractory breathlessness: a systematic review | journal = Journal of Pain and Symptom Management | volume = 46 | issue = 6 | pages = 874–886 | date = December 2013 | pmid = 23742735 | doi = 10.1016/j.jpainsymman.2013.02.019 | doi-access = free | title-link = doi }}</ref>

=== Other ===
Some [[Route of administration|routes of administration]] such as nasal sprays and inhalers generally result in a faster onset of high blood levels, which can provide more immediate analgesia but also more severe side effects, especially in overdose. The much higher cost of some of these appliances may not be justified by marginal benefit compared with buccal or oral options. Intranasal fentanyl appears to be equally effective as IV morphine and superior to intramuscular morphine for the management of acute hospital pain.<ref name="ReferenceA" />

A fentanyl patient-controlled transdermal system (PCTS) is under development, which aims to allow patients to control the administration of fentanyl through the skin to treat postoperative pain.<ref name="pmid15914877">{{cite journal | vauthors = Koo PJ | title = Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl | journal = American Journal of Health-System Pharmacy | volume = 62 | issue = 11 | pages = 1171–1176 | date = June 2005 | pmid = 15914877 | doi = 10.1093/ajhp/62.11.1171 | url = http://www.medscape.com/viewarticle/505784_2 | url-status = live | access-date = 28 March 2016 | archive-url = https://web.archive.org/web/20180806203216/https://www.medscape.com/viewarticle/505784_2 | archive-date = 6 August 2018 | doi-access = free | title-link = doi }}</ref> The technology consists of a "preprogrammed, self-contained drug-delivery system" that uses [[iontophoresis|electrotransport]] technology to administer on-demand doses of 40{{nbsp}}μg of fentanyl hydrochloride over ten minutes. In a 2004 experiment including 189 patients with moderate to severe postoperative pain up to 24{{nbsp}}hours after major surgery, 25% of patients withdrew due to inadequate analgesia. However, the PCTS method proved superior to the placebo, showing lower mean [[Visual analogue scale|VAS]] pain scores and having no significant respiratory depression effects.<ref>{{cite journal | vauthors = Chelly JE, Grass J, Houseman TW, Minkowitz H, Pue A | title = The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial | journal = Anesthesia and Analgesia | volume = 98 | issue = 2 | pages = 427–433 | date = February 2004 | pmid = 14742382 | doi = 10.1213/01.ANE.0000093314.13848.7E | s2cid = 24551941 | doi-access = free | title-link = doi }}</ref>