Morphine is an opioid narcotic available in various formulations — pill, tablet, injection, and suppository — to treat chronic and acute pain.  Morphine can be used to manage moderate to severe pain in sickle cell disease.

About sickle cell disease

Sickle cell disease is a heritable disease caused by mutations in the gene encoding for the hemoglobin protein, which is responsible for carrying oxygen in red blood cells. Mutations in this gene cause the red blood cells to deform or “sickle.” Sickled cells cannot easily travel through small blood vessels and are sticky because of damage to the cell’s membrane, and often block blood flow in these vessels. Such blockage leads to pain episodes known as vaso-occlusive crises (VOC).

How does morphine work?

Morphine is a narcotic that interacts predominantly with a protein receptor in the brain called the mu-opioid receptor. Morphine acts primarily in the brain, spinal cord, stomach, and intestines, causing sedation and reducing pain.

Like other opioids, morphine can be addictive, and long-term use can lower its effectiveness so that larger doses are necessary to maintain an adequate reduction in pain.

There is also some risk that morphine may exacerbate the symptoms of sickle cell disease, though the mechanisms by which this might occur are not clear.

Morphine in clinical trials

A study published in the journal Hospital Pediatrics in 2013 examined reports of a link between morphine use and the development of acute chest syndrome in children with sickle cell disease. Acute chest syndrome is marked by the blocking of blood vessels in the lungs and can progress quickly without proper care.  It is the leading cause of death and hospitalization in children with sickle cell disease; about 40 percent of all acute chest syndrome episodes are reported to occur in children hospitalized for acute pain linked to a vaso-occlusive crisis.

For the study, researchers examined the hospital records of 38 children, ages 2 to 18, hospitalized for acute pain who went on to develop acute chest syndrome. They compared these data — including survival data — with that of 45 sickle cell children also hospitalized for pain but who did not develop the syndrome and were randomly selected as controls. They found that morphine use — especially with increases in cumulative dose — could be associated with an increased risk of acute chest syndrome. The scientists recommended close monitoring of children with sickle cell disease being treated with morphine.

A Phase 3 clinical trial (NCT02222246) investigated the effectiveness of a patient-specific pain treatment plan versus a standardized weight-based pain management protocol. In the study, 106 adult patients were enrolled with 52 of them returning one or more times to the emergency department for VOC pain. Between the 52 patients, they totaled 126 emergency department visits during the study period. The 52 patients were split in half with one group receiving weight-based pain management and the other receiving initial doses that took into account current home opioid usage and previously used hospital opioid dosage. Patients received either morphine sulfate or hydromorphone depending on which had been more useful in pain treatment in the past for the patient.

The results of the study were published in the American Journal of Hematology. The study found that the initial doses of pain treatment tended to be higher in the patient-specific group than the weight-based group and that the patient-specific group had a statistically significant improvement in change-in-pain score from arrival to discharge compared to the weight-based group. The study mentioned that the open-label nature of the study might have led to some placebo effects in the change in pain scale and in the number of adverse events reported.

To address the placebo effect and the small number of study sites (two sites) of the previous study, the same group is currently recruiting for a new double-blind Phase 3 study (NCT03933397) called COMPARE-VOE. The study aims to recruit 460 participants from six different hospital sites in the US. As in the previous study, participants will be randomized to receive either a weight-based or patient-specific initial dose of pain treatment, either morphine or hydromorphone depending on which has been more helpful in the past for that patient. The patients will receive re-dosing every 20 to 30 minutes for up to 6 hours with one increase in dosage, up to 25%, allowable. The study aims to be completed in January 2022.

Other information

Common side effects of morphine include drowsiness, nausea, stomach pain, confusion, and respiratory depression.


Last updated: Feb. 24, 2020.


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