Fentanyl is an opioid narcotic treatment approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe pain. Fentanyl can be used to treat vaso-occlusive crises in sickle cell disease. It is available as a tablet, injection, lozenge, film, and intranasal spray.

How does fentanyl work?

Sickle cell disease is a heritable condition caused by a mutation in the gene encoding for hemoglobin, the protein that carries oxygen in red blood cells. The mutation causes the red blood cells to “sickle”, a deformation that prevents them from passing through the smallest blood vessels. Those cells can aggregate or clot, which results in burst blood vessels and insufficient blood reaching organs and tissues, causing both chronic and acute pain, among other symptoms.

Fentanyl binds to protein receptors in the brain called opioid receptors, causing a decrease in nerve cell signaling and reducing the sensation of pain. In addition to reducing pain, fentanyl can also cause alterations in mood and may slow breathing.

Fentanyl in clinical trials

A randomized, double-blind, placebo-controlled, Phase 4 clinical trial (NCT01482091) evaluated whether intranasal fentanyl can decrease the pain of sickle cell disease patients who have vaso-occlusive crisis. Children with sickle cell disease ages 3-20 who were not taking daily opiates were eligible for the trial.

Participants were randomly given either a single dose of intranasal fentanyl (2 mg per kg of body weight) or an equivalent volume of intranasal saline. Pain scores were obtained using a modified Wong-Baker FACES pain scale prior to the administration of fentanyl and 10, 20, and 30 minutes afterward. A total of 49 patients completed the study (24 in the fentanyl group and 25 in the placebo group). The results, published in the journal Pediatric Blood and Cancer, showed that patients who received intranasal fentanyl had a greater decrease in their pain score at 20 minutes compared to those who received a placebo.

Another study examined whether intranasal fentanyl can decrease the time to analgesia in combination with other treatments. A total of 248 patients with sickle cell disease older than age 2 with vaso-occlusive crisis and moderate to severe pain were offered intranasal fentanyl. Patients then continued to the standard treatment for vaso-occlusive crisis. Pain scores were documented at frequent intervals by nursing staff, as well as the time between fentanyl treatment and the administration of other opioid treatments. These patients were compared to 48 patients who did not receive intranasal fentanyl and 231 historical controls who had not been offered intranasal fentanyl and whose records were available. The results of the study, published in the journal Blood, showed that the time from arrival to the hospital to first analgesia treatment decreased significantly in patients who received fentanyl compared to those who did not.

A Phase 4 study (NCT03682211) compared the effect of intranasal fentanyl versus intravenous (into the vein) morphine for pain from vaso-occlusive crisis. The study enrolled 31 participants between one and 21 years old. The protocol design for the study was published in 2012. The primary outcome was pain scores on the Face, Leg, Activity, Cry, Consolability (FLACC) scale and Manchester Pain Ruler after 20 minutes. The secondary outcome was the FLACC score at 0, 5, 15, 20, 30, 60, and 120 minutes. The study completed in November 2013 but no results have been published.

Other information

Like other opioid narcotics, fentanyl can be habit-forming. It can also cause side effects, including drowsiness, stomach pain, anxiety, and depression.


Last updated: Jan. 23, 2020


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