Sickle cell disease affects an estimated 100,000 patients in the United States.1 By the time just one of these patients reaches the age of 45, his or her health care costs will reach nearly $1 million.2
Pain is the primary reason patients seek treatment for this disorder. Individuals with sickle cell disease have pain that is characterized as chronic with intermittent episodes of acute pain crises. The pain during a crisis is related to the ischemia the sickle-shaped red blood cells cause as they aggregate, resulting in decreased blood flow to distal tissues. (For more on other factors that can influence sickle cell pain, see “The role of age and depression in sickle cell crises”3 below.)
THE ROLE OF AGE AND DEPRESSION IN SICKLE CELL CRISES
Sickle cell pain is primarily due to ischemia; however, there are other factors that may play a role. The PiSCES project was an epidemiologic longitudinal cohort of adults with sickle cell pain designed to address the relationship between sickle cell pain and the individual response to pain.3 Researchers enrolled 260 patients and compared the genotype of sickle cell, sex of patient, presence of depression, and age with location of pain, number of associated painful crises, and overall health care utilization for pain management. Researchers found that the areas of the body associated with the most painful episodes were the lower back, knee/shin area, and hips. Interestingly, more pain sites were reported by those with depression (3.8 vs 3.1 for those with no depression; P=.0011) and by those who were 45 years and older (2.7 pain sites [<25 years old]; 3.3 pain sites [25-44 years old]; 4.0 pain sites [≥45 years old]; P=0.0120 for overall test for older patients vs those <45 years).3
Key Point Patients ≥45 years and those suffering from depression had more pain sites than younger patients and those with no depression.
In the review that follows, I’ll describe the mainstays of pharmacologic treatment to address this pain and provide strategies to help minimize patients’ time in the hospital and maximize their quality of life. But first, a brief review of what occurs during a sickle cell crisis.
What you’ll see during a crisis
Dehydration, infection, stress, and changes in body temperature are common triggers of a sickle cell crisis.4 Once set into motion, a crisis unfolds in 4 distinct phases:
Prodromal. During this phase, patients typically become lethargic and experience mild pain in a single localized area, such as the lower back, hips, or legs. There are no hematologic changes at this point and the pain can be managed using oral analgesics.
Initial infarctive. At this point, the pain increases from mild to moderate intensity. This phase is marked by a decrease in hemoglobin and alterations in mood, such as increased anxiety or irritability. The laboratory findings often occur much later than the patient’s report of symptoms. Prompt attention by the physician when the patient begins to experience the symptoms is key to initial management.
Post-infarctive/inflammatory. The peak of severe pain occurs during this phase. The pain is intense enough to cause patients to seek emergency services or hospitalization for pain relief. Laboratory changes include an increase in reticulocyte count, lactate dehydrogenase, and C-reactive protein. CRP levels, for instance, will rise to 70 mg/L during a crisis. Patients with sickle cell disease normally average 32.2 mg/L; non-sickle cell patients average 10 mg/L.5
Resolving. After adequate fluid hydration and intravenous analgesics, the pain of a crisis will return to a moderate intensity.
Pain management centers on opioids
Opioids form the foundation of sickle cell pain management, both in acute crisis management and for the chronic pain that patients experience as the disease progresses. (See “Case study: Helping Annie stay out of the hospital” below.) Opioids like codeine and tramadol are typically used to treat moderate pain, whereas drugs such as morphine, oxycodone, hydrocodone, and hydromorphone have a more prominent role in severe and breakthrough pain management.
CASE STUDY: Helping Annie stay out of the hospital
Annie is a 29-year-old African American woman with sickle cell disease. She arrives at the local emergency department (ED) and tells the staff that she’s there because of her “usual sickle cell pain.” She has pain (9/10) in her lower back, hips, and lower extremities. She says the pain is sharp, constant, and localized—with no radiation to other areas. She has no chest pain or shortness of breath.
A review of systems is negative, except for what was documented in the history of her present illness. Annie’s home medications include oxycodone extended release 40 mg twice daily, oxycodone immediate release 5 to 10 mg every 4 hours as needed for pain, and ibuprofen 600 mg as needed.
Before coming into the ED, Annie says she took her morning oxycodone extended release dose and oxycodone 40 mg immediate release over the past 24 hours with little relief. Her vital signs in the ED are blood pressure, 150/85 mm Hg; heart rate, 95 beats per minute; respiratory rate, 14 breaths per minute; temperature 99.2°F.
The patient has scleral icterus and bilateral mild lower extremity swelling. Her lab work reveals a serum creatinine concentration of 1.4 mg/dL and lactate dehydrogenase level of 256 IU/L.
During her 8-hour stay in the ED, Annie receives hydromorphone 2 mg IV every 30 minutes for 3 doses, 3 liters of IV rehydration, and 25 mg oral diphenhydramine for itching with the third dose of hydromorphone. She is discharged to home after rating her pain as 5/10, which she finds tolerable. Discharge instructions indicate that she should follow up with her primary care provider.
One week later, Annie goes to see her family physician. Because she’s been taking her oxycodone prescriptions as directed and has still ended up in the ED twice in the past 3 weeks, her physician talks to her about increasing her oxycodone extended release to 80 mg twice a day and the immediate release to 10 to 15 mg every 4 hours as needed.
During their conversation, Annie mentions that as her use of oxycodone has gone up, the number of bowel movements has gone down. So her physician prescribes a stimulant laxative (senna with docusate) twice a day. The physician also talks to Annie about restarting her hydroxyurea, which she hasn’t been taking for the past few months. Before Annie leaves, her physician reminds her to stay hydrated, pointing out that it will not only prevent dehydration, but it will aid with bowel regulation.