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Procedural sedation
Intravenous fentanyl is often used for anesthesia and analgesia. It is also administered in combination with a benzodiazepine, such as midazolam, to produce sedation for procedures such as endoscopy, cardiac catheterization, and oral surgery, or in emergency rooms. During anesthesia in surgery, it is often used along with a hypnotic agent like propofol.

Obstetrics
Fentanyl is sometimes given intrathecally as part of spinal anesthesia or epidurally for epidural anaesthesia and 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. However, it's widely used in obstetrical anesthesia because of its short time to action peak (about 5 min), the rapid termination of its effect after a single dose, and the occurrence of relative cardiovascular stability. In obstetrics, the dose must be closely regulated in order to prevent large amounts of transfer from mother to fetus. At high doses, the drug may act on the fetus to cause postnatal respiratory distress.

Emergency and pediatrics
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, and 200 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 out-of-hospital patients.

In children, intranasal fentanyl is useful for the treatment of moderate and severe pain and is well tolerated.

Combat medical use
USAF Pararescue combat medics in Afghanistan use fentanyl lozenges in the form of lollipops on combat casualties from IED blasts and other trauma. The stick is taped to a finger and the lozenge put in the cheek of the person. When enough fentanyl has been absorbed, the (sedated) person generally let the lollipop fall from the mouth, indicating sufficient analgesia and somewhat reducing the likelihood of overdose and associated risks.

Chronic pain management
It is also used in the management of chronic pain including cancer pain. Often, transdermal patches are used. The patches work by slowly releasing fentanyl through the skin into the bloodstream over 48 to 72 hours, allowing for long-lasting pain management. Dosage is based on the size of the patch, since, in general, the transdermal absorption rate is constant at a constant skin temperature. 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. Under normal circumstances, the patch will reach its full effect within 12 to 24 hours; thus, fentanyl patches are often prescribed with a fast-acting opioid (such as morphine or oxycodone) to handle breakthrough pain. Yet, it is unclear if fentanyl gives long-term pain relief to people with neuropathic pain.

Breakthrough pain
Sublingual fentanyl solves quickly and is absorbed through the sublingual mucosa to provide rapid analgesia. Fentanyl is a highly lipophilic compound, which is well absorbed sublingually and generally well tolerated. Such forms are particularly useful for breakthrough cancer pain episodes, which are often rapid in onset, short in duration and severe in intensity.

Palliative care
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 kidney failure.
 * troublesome side effects of oral morphine, hydromorphone, or oxycodone.

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 of too much medications and cause potentially deadly complications.

Storage and disposal
The fentanyl patch is one of a few medications that may be especially harmful, and in some cases fatal, with just one dose, if used by someone other than the person for whom the medication was prescribed. Unused fentanyl patches should be kept in a secure location out of children's sight and reach, such as a locked cabinet.

In British Columbia, Canada where there are environmental concerns about toilet flushing or garbage disposal, pharmacists recommend that unused patches be sealed in a child-proof container which is then returned to a pharmacy. In the United States where patches cannot always be returned through a medication take-back program, flushing is recommended for fentanyl patches because it is the fastest and surest way to remove them from the home to prevent them from ingestion by children, pets or others not intended to use them.

Other
Some routes of administration such as nasal sprays and inhalers generally result in 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 as equally effective as IV morphine and superior to intramuscular morphine for management of acute hospital pain.

A fentanyl patient-controlled transdermal system (PCTS) is under development, which aims to allow people to control administration of fentanyl through the skin to treat postoperative pain.