Hydroxyurea may reduce pain-related complications of sickle cell anemia

Issue: December 10, 2010

Patients who responded to hydroxyurea as a treatment for sickle cell anemia spent about 2 fewer days in the hospital than placebo recipients for pain-related issues, according to recent study results.

Researchers from several sites in the US gathered data on this aspect of sickle cell anemia from the Multicenter Study of Hydroxyurea. The final analysis involved 299 patients from 21 sites in North America.

The primary objective of the current analysis was to determine the effects of hydroxyurea on the duration of hospital stay. A concurrent objective was to summarize the type and amount of opioids and other analgesics during hospitalization, outpatient acute care contacts and at home. The third objective was to compare the length of hospital stay and opioid use between treatment and placebo groups, and between responders and nonresponders within the treatment group.

Results

Responders to hydroxyurea spent about 5.9 days in the hospital vs. 7.7 days among nonresponders and 7.8 days among placebo recipients (P<.022). Regarding dosing levels, patients receiving hydroxyurea had lower doses of parenteral opioids during acute care crises than patients in other groups (P=.015).

Daily diary results indicated that at-home analgesics were used on 39.9% of entries (range 0%-99% of all days) and 80% of 16,818 biweekly follow-up visits. Oral opioids were used in 59.5% of those follow-up visits.

Oxycodone was used in 23% of 2-week follow-ups, and codeine was reported in 18% of those visits. These two drugs combined accounted for 61.7% of all analgesic use and were used three times more frequently than meperidine and hydromorphone, which were the next most frequently used analgesics.

Responders to hydroxyurea used analgesics on 22.6% of days, which was (P=.005) fewer than nonresponders (42.2%) or placebo patients (42%), according to diary reports. During biweekly follow-up, hydroxyurea patients used analgesics less frequently than nonresponders (40.8% vs. 63.3%) or placebo patients (40.8% vs. 59.7%), both of which were statistically significant differences (P=.006).

Among 2,249 acute care contacts that did not lead to inpatient hospitalization but were defined as painful crises, parenteral opioids were used in 95.5% of cases and oral opioids in 10.9% of cases. Meperidine was the most frequently used parenteral opioid used in these instances, at 69.3%, and oxycodone was the most frequently used oral opioid, at 3.9%.

Study protocols

The researchers evaluated types and dosages of opioids used at home, in acute care facilities and in other hospital settings. The findings were gathered from patient diaries, follow-up visit forms and medical contact forms.

Information gathered from patient diaries focused on frequency of analgesic use rather than specific drugs and doses. The follow-up form contained more specific physician-guided information dosing and frequency of both transdermal opioid at-home analgesic use.

The medical contact forms indicated dosing and frequency data on use of oral or transdermal opioids such as meperidine, oxycodone, morphine, hydromorphone, codeine and the fentanyl patch; parenteral opioids such as meperidine, morphine and hydromorphone; and NSAIDs such as ketorolac. Hydrocodone and methadone were write-in oral opioids that were not on the form, and nalbuphine and butorphanol received coding as write-in parenteral opioids.

The analysis involved painful crises, which were defined as visits to a medical facility that lasted more than 4 hours for acute sickling-related pain that were treated with a parenterally administered opioid. The two types of crises were those involving inpatient hospitalization and those involving acute care facilities.

Hydroxyurea responders were defined as patients whose baseline percentage of fetal hemoglobin was less than 15% at baseline but at least 15% at follow-up.

For more information:

Ballas SK. J Pain Sym Man. 2010;doi:10.1016/j.jpainsymman.2010.03.020.