Steroid Treatment for Sickle Cell Pain Crisis
Steroid Treatment for Sickle Cell Pain Crisis
The painful episode is the most common problem experienced by children with sickle cell
 disease. Although various treatments are available during painful episodes, the medication
 most commonly given for pain is a pain medication such as morphine. Fluids are also used.
 Even with these treatments, many children still have severe pain that is difficult to
 control. In addition to pain medications, there are other medications that may be useful.
 Methylprednisolone (solumedrol) and prednisone are a group of medications called steroids
 that may be helpful for painful episodes. These medications are known to lower the amount of
 inflammation (this means swelling, tenderness, and soreness) in the body. Because this
 medication may help with your pain, you are being asked to be a part of this study. These
 types of medications are used in other illnesses such as asthma, especially during times when
 the illness has gotten worse.

 The main purpose of this study is to see if the methylprednisolone and prednisone will lower
 the amount of pain and the length of hospital stay.

 In addition to the pain medication you will normally receive, you will be assigned to one of
 2 groups: 1) the experimental group with the active form of the medicine, or 2) a comparison
 group without the active form of the medicine. In either group, you will still receive all of
 the treatments you would normally receive for a painful episode, including pain medicines and
 fluids. You and your doctors will not know what group you will be assigned.

 If you decide to be a part of the study the following will happen:

 For the first 5 days, you will be asked to: 1) describe your current pain (0=no pain to 10=a
 lot of pain), worst pain (0=no pain to 10=a lot of pain), least pain (0=no pain to 10=a lot
 of pain), and the amount of pain relief (0=no relief to 10=complete relief); 2) describe any
 signs or symptoms you feel, including filling out a pain scale form each day; 3) and take the
 medicines for 5 days, either at home or when in the hospital. Thirty days after the study, a
 study researcher will call and will ask questions about your pain, any painful episodes, and
 any medications you had. If you are discharged home sooner than 5 days after the start of the
 study, research staff will call you to ask you these questions, remind you to fill out your
 pain forms, and remind you to take your medicine. If you are discharged home, you will be
 given pain scales to fill out each day at home.
In the United States, 9% of African Americans have sickle cell trait and 1 in 600 has sickle
 cell disease. Vaso- occlusive crises in sickle cell disease remain a frequent cause of severe
 pain, leading to emergency room visits, hospitalizations, and dependence upon narcotics for
 analgesia. Current treatments for vaso-occlusive crises includes IV analgesia with narcotics,
 NSAIDS, and hydration. Admissions can be frequent, prolonged, and can significantly diminish
 quality of life.

 Understanding the pathophysiology of vaso-occlusive crises helps to find possible treatments.
 The etiology of vaso- occlusive crises includes HbS polymerization; sickle erythrocyte
 polymerization; endothelial damage; and inflammation, reperfusion injury, and oxidant radical
 production (Steinberg et al, Hematology, 2004). For example, hydroxyurea works by increasing
 the amount of fetal hemoglobin (HbF) and thus inhibiting polymerization, and reduces the
 incidence of pain by nearly 50%. Glucocorticoids would be expected to exert effects on the
 endothelium and inflammation.

 Vaso-occlusive crises share similar features with other inflammatory processes, including
 clinical symptoms of swelling, erythema, and warmth; and laboratory findings of leukocytosis
 and elevated ESR. It has previously been theorized that glucocorticoids, which are used in
 many other inflammatory disorders, could decrease the duration or severity of vaso-occlusive
 crises. Methylprednisolone is a corticosteroid which decreases inflammation by suppression of
 migration of polymorphonuclear leukocytes and reversal of increased capillary permeability
 (Takemoto, et al 2004). A randomized, placebo-controlled study of 2 doses of intravenous
 methylprednisolone for vaso-occlusive crisis showed that the duration of severe pain and the
 need for inpatient analgesia was decreased in patients who received methylprednisolone;
 however the intervention patients had more rebound attacks than those who received placebo.
 (Griffin et al, NEJM, 1994)

 Previous studies have examined long-term administration of steroid hormones including
 testosterone, progesterone, and medroxyprogesterone to patients with sickle cell disease. In
 placebo-controlled crossover trials, patients who received steroids had fewer vaso-occlusive
 episodes than placebo-treated patients (Isaacs et al, Lancet,1972; DeCeulaer et al, Lancet,
 1982). Initial reports of glucocorticoids for vaso-occlusive crisis include an uncontrolled
 report of hydrocortisone as adjunctive therapy for VOC (Araujo et al, Blood, 1990). A case
 report showed efficacy of dexamethasone for vaso-occlusive crisis in children (Robinson et
 al, Lancet, 1979). The mechanism of steroids effect is uncertain.

 In acute chest syndrome, which shares many clinical features with vaso-occlusive crises,
 intravenous therapy with dexamethasone has been shown to reduce the length of hospital stay,
 prevent clinical deterioration, and reduce the need for blood transfusion (Bernini et al,
 Blood, 1998).

 In a placebo-controlled trial of high-does methylprednisolone for VOC, patients with severe
 pain requiring hospital admission were randomized to receive methylprednisolone or placebo
 (15 mg/kg to maximum 1 gram) at admission and again 24 hours later. The duration of inpatient
 analgesia was significantly shorter in patients who received methylprednisolone. However,
 patients who received methylprednisolone were much more likely to be readmitted shortly after
 finishing therapy. In addition, the study was criticized because patients did not rate their
 pain, and very few patients received patient-controlled analgesia while hospitalized.

 Since this trial was published, there have been other advances in the standard management of
 VOC. Ketorolac, a non-steroidal analgesic, is now a standard adjunctive therapy, and most
 patients are quickly placed on patient-controlled analgesia. In addition, more patients now
 receive chronic, preventative therapies such as hydroxyurea and chronic transfusions.

 We are therefore interested in repeating and expanding upon the results obtained several
 years ago and in evaluating the role of steroids if given over a slightly longer period of
 time.

 The primary objective of this study is to determine whether the use of high-dose
 methylprednisolone followed by steroid taper decreases the duration of hospitalization and
 severity of pain in VOC of sickle cell disease.

 Primary Hypothesis: The experimental group treated with high-dose methylprednisolone and
 steroid taper plus conventional therapy will have an improvement in pain scores using a
 10-point scale.

 In addition, the secondary objectives were:

 1. duration of inpatient admissions

 2. to examine the number and type of complications and side effects (infection,
 hypertension, and GI bleeding)

 3. to determine rate of recurrent episodes of pain within one month of treatment.

 4. to determine whether the amount of analgesic used will decrease during the
 hospitalization, as measured by the # of days in which IV opioids were given.
Inclusion Criteria:

 Sickle cell and acute pain Age 8 and up English or Spanish-speaking

 Exclusion Criteria:

 Fever greater than 101 Acute chest syndrome or pneumonia Other SS complications
 (sequestration, aplastic crisis) Other explanation for pain (chronic, AVN, surgical)
 History of GI bleeding, HTN, or hyperglycemia/DM