Ketamine is a medication approved by the U.S. Food and Drug Administration for anesthesia, generally for surgery or other medical procedures. Ketamine can also be used to treat acute pain in sickle cell anemia patients.

How ketamine works

Sickle cell anemia is a disease caused by a mutation in the gene that provides instructions to make hemoglobin, the protein in red blood cells that carries oxygen. The mutation causes red blood cells to form “sickle” shapes that stick to each other and the sides of small blood vessels.

This makes it difficult for these cells to pass through the smallest blood vessels, and may block them. These blockages  cause pain, inflammation, and vaso-occlusive crisis.

The precise mechanism of action of ketamine is not known, but scientists know that it binds to protein receptors in the brain, including the N-methyl-D-aspartate (NMDA) receptors and opioid receptors. The NMDA receptors are normally involved in the transmission of nerve signals, learning, and memory.

Ketamine is thought to cause anesthesia (a treatment that prevents patients from feeling pain) primarily through the blockage of the NMDA receptors, but this process is not well understood.

The binding of ketamine to opioid receptors, the receptors by which narcotic anesthetics such as morphine work, is not as strong as the binding to NMDA receptors. So it is not clear how much this binding explains the anesthetic effect of ketamine.

Ketamine in clinical trials

A retrospective study published in the journal Blood examined the records of 30 patients with sickle cell anemia who had received a low dose of ketamine to treat episodes of acute pain. The aim was to determine whether ketamine could reduce the need to use opioid narcotics to manage pain. The results showed that the use of low-dose ketamine significantly reduced the need for opioids.

The results of a clinical trial published in the Scandinavian Journal of Pain examined whether low-dose ketamine is as effective as morphine in treating acute pain in children, ages 7 to 18. A total of 240 patients were randomly assigned to receive either morphine or ketamine infused into the bloodstream.

After the infusion, pain was assessed at intervals to determine the time to maximum effect. The authors found that low-dose ketamine was as effective as morphine in treating acute pain in sickle cell anemia patients.

A Phase 2 clinical trial (NCT02573714) is currently recruiting children with sickle cell anemia in Cameroon and Tanzania. The aim of this trial is to determine whether intranasal ketamine is safe and effective in reducing vaso-occlusive crises.

The treatment group will receive intranasal ketamine in addition to the normal pain intervention. The placebo group will receive an intranasal salt solution. Pain will be assessed at intervals following treatment by the faces pain scale-revised (FPS-R).

Another Phase 2 clinical trial (NCT03296345) is currently recruiting 90 patients with sickle cell anemia, ages 10-25, in California. The aim is to investigate the safety and tolerability of ketamine for the treatment of vaso-occlusive crises in emergency care facilities.

The trial will also assess the effectiveness of the treatment in controlling pain and reducing hospitalization rates. Patients will receive low-dose ketamine infused into the bloodstream in addition to their normal pain-relieving medication and will be monitored for safety and side effects following treatment.

Another clinical trial (NCT03431285) is currently recruiting 264 adult patients with sickle cell anemia in Saudi Arabia. Investigators hypothesized that the administration of ketamine early on will lead to a more rapid improvement in pain score and a reduced need for narcotics.

Patients will be randomly assigned to receive either morphine or ketamine infused into the bloodstream. Pain will be assessed for six hours following treatment.

Finally, a Phase 3 clinical trial (NCT03502421) aims to enroll 60 patients with sickle cell anemia in Florida.  One group of patients will receive a continuous infusion of ketamine into the bloodstream in addition to Dilaudid, an opioid narcotic similar to morphine.

The patients in the control group will receive Dilaudid only. Pain will be assessed by the visual analog scale for three hours following the start of treatment, as well as the total amount of Dilaudid required to manage patients’ pain in either group.

Other information

Ketamine can cause some side effects such as confusion, nausea, blurred vision, dizziness, and coughing.

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