What to use—and when—during a crisis
In order to manage acute painful episodes, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adequate hydration are standard. Parenteral NSAIDs are beneficial because of their opioid-sparing effects; they can also lead to a more efficient transition to oral analgesics.
A Cochrane review of the medical management of pain associated with a sickle cell crisis6 acknowledges the opioid-sparing effects of parenteral NSAIDs in the initial phases of a crisis. This review also suggests that:
The use of parenteral opioids with their fast onset in a pain crisis should be transitioned to oral sustained-release opioids once the patient is able to tolerate oral medications.
Short-acting oral opioids are appropriate for intermittent (breakthrough) pain during a crisis, while sustained-release opioids are useful for persistent (baseline) pain.
Parenteral corticosteroids may be of some benefit during the crisis phases, but data related to their efficacy are lacking after the first 48 hours of the crisis.
PCA can make a big difference to patients
Many opioids such as morphine, fentanyl, and hydromorphone are available for delivery via patient-controlled analgesia (PCA). This allows the patient to give him- or herself a dose of opioid when the pain intensity is greater than baseline. During the inflammatory phase of a crisis, the PCA opioids are preferred by many patients because of their convenient dosing and the ease of self-titration to adequate analgesia. Once the resolving phase begins, the patient can decrease his or her breakthrough PCA opioid use and return to the pre-crisis amount of opioids.
Hydroxyurea can help with crisis prevention
The use of hydroxyurea in the maintenance of sickle cell disease and the prevention of crises has been documented in the literature.7 Hydroxyurea increases the circulating amounts of fetal hemoglobin, which has been shown to inhibit the sickling of mature red blood cells. In one study, patients on hydroxyurea had fewer crises (5.1 per year vs 7.9 with placebo) and their risk of death was reduced by approximately 40% during a 6- to 8-year observation period.8
Long-term data are lacking and other novel approaches to outpatient maintenance and prevention of sickle cell crises are still being discovered. Relative contraindications to hydroxyurea therapy include bone marrow suppression, impaired renal or hepatic function, and pregnancy.9
Key Point In one study, patients on hydroxyurea had fewer crises and their risk of death was reduced by about 40%. |
Pharmacologic management of chronic pain
Patients with sickle cell disease are typically managed using opioids and other pharmacologic agents, such as NSAIDs and acetaminophen, along with nonpharmacologic strategies. The goal of sickle cell management is to enable the patient to resume activities of daily living.
Some patients have a very high tolerance to opioids and are subsequently on large doses of long-acting and short-acting opioids. Patients who are on long-term opiates should have an opioid agreement in place to monitor adherence to therapy and potential diversion, as well as to document potentially risky patient behaviors, such as a pattern of early refills in the absence of clinical change or prescription “problems,” such as lost or stolen medications.10
Opioid agreements generally have language that indicates the patient will receive opioids from only one provider, utilize one pharmacy to fill prescriptions for opioids, and inform the clinic if he or she receives care from another provider who is also prescribing opioids. These agreements can also include specific language related to urine drug screening practices, medication counts, and consequences of breaking the treatment agreement. It is good practice to institute opioid agreements for all patients on long-term opiates in order to ensure consistency within the clinic.
Addressing the pain from many angles
Management of the chronic underlying pain requires a multifaceted approach to ensure patient adherence to treatment and adequate management of symptoms. Chronic pain involves modulation of the afferent nociceptive pathways in the spinal cord (such as the spinothalamic tract), which are responsible for transmission of pain from the periphery to the brain for processing. Medications that can alter the perception of pain in the spinothalamic tract include opioids, serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants. The SNRIs duloxetine and milnacipran have indications for chronic pain—although not for sickle cell pain. No tricyclics are FDA approved for chronic pain, though they are routinely used for this purpose as an adjunct to nonpharmacologic therapy for chronic neuropathic pain.
Nonpharmacologic management strategies include minimizing caffeine intake, avoiding or minimizing intake of alcohol, and adequate rest. Also, because dehydration can lead to a crisis, it’s important to avoid—whenever possible—the use of diuretics in these patients.