Outpatient Management of Sickle Cell Pain with Chronic Opioid Pharmacotherapy Lauren Shaiova, MD and David Wallenstein, MD New York, New York
We report our experience of providing chronic opioid pharmacotherapy on an outpatient basis to selected patients with frequent episodes of moderate-to-severe pain from sickle cell disease (SCD). Three cases illustrate our clinical experience in approximately 40 patients with sickle cell pain. Patients were seen at our sickle cell pain clinic at Beth Israel Hospital once each month for a three-hour visit. Visits included group music therapy and individual medical care, including comprehensive blood work and scheduling of medical tests when appropriate. Between visits, the pain and palliative care physicians followed patients on an asneeded basis. The SCD pain opioid pharmacotherapy protocol was modeled on a regimen used to treat malignant pain-typically a long-acting opioid in combination with a short-acting opioid, such as oral transmucosal fentanyl citrate (OTFCO; ActiqO) for breakthrough pain (BTP). Emergency department (ED) visits and hospital admissions were dramatically reduced in the three patients whose pain was managed by adapting the cancer pain model. During the year before their first visit to our pain clinic, the patients each had between six and 18 ED Visits, which resulted in six- to 13 hospital admissions amounfing to 32-182 inpatient days per patient. Each of the patients was prescribed a long-acting opioid (methadone, control-release oxycodone, or transdermal fentanyl) with a short-acting opioid for BTP from crises (oral transmucosal fentanyl citrate for two patients; short-acting oxycodone for one patient). Pain was well controlled. For each potient, hospital admissions were reduced to .1 visit per year. These reduced levels of ED visits and hospital admissions have remained constant for more than three years.
Key words: sickle cell disease * crsis U opioids-l chronic pain * breakthrough pain
© 2004. From the Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY. Send correspondence and reprint requests for J NatI Med Assoc. 2004;96:984-986 to: Lauren Shaiova, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003; phone: (212) 844-1466; fax: (212) 844-1464; e-mail:
[email protected]
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INTRODUCTION Pain is the most common and debilitating symptom experienced by patients with sickle cell disease (SCD). Not all patients, however, experience painful episodes with the same frequency or intensity. The frequency, intensity, and degree of disability associated with SCD crisis are highly variable. SCD also produces chronic pain. In SCD, increased pain has been shown to correlate directly with mortality.' Sickle cell pain crises typically result in emergency department (ED) visits and frequently lead to hospital admissions. Pain from SCD accounts for more than 90% of hospital admissions in adults with the disease.' One institution recently reported success with a dedicated outpatient facility for the treatment of uncomplicated painful crises, which reduced the time to pain relief, increased the number of patients discharged home, decreased the hospitalization rate, and reduced the use ofthe ED. Over the five years studied, savings amounted to more than $1.7 million as a result of fewer hospital admissions and shorter lengths of stay.2 Current strategies for managing SCD pain are typically based on principles of managing acute episodes of pain, i.e., as-needed opioids. This approach to pain management leads to inadequate pain relief for many patients and to a succession ofboth ED visits and hospital admissions. Although opioids are the mainstay of ED and inpatient treatment for SCD patients with moderate-to-severe pain, many clinicians are reluctant to prescribe opioids to SCD patients in the ambulatory setting. This reluctance is caused by a variety of factors, including fears of addiction and drug diversion, as well as lack of familiarity with the appropriate use of opioids. Although the prevalence of addiction in SCD patients is believed to be less than 1%,3 63% of nurses,34 53% of emergency department physicians,4 and 23% of hematologists4 surveyed believe that drug addiction is prevalent in SCD patients. When SCD pain recurs frequently, or when a continuous component of the pain develops, pain management might best follow the widely accepted principles for cancer pain management. In this model, a long-actVOL. 96, NO. 7, JULY 2004
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ing opioid for persistent pain is combined with a shortacting opioid for breakthrough pain (BTP), which can be described as a transitory exacerbation of pain that occurs on top of a background of otherwise-controlled persistent pain.10 In one cohort, managing SCD pain of this type with chronic opioid pharmacotherapy for persistent pain and BTP episodes was shown to result in a dramatic reduction in hospital admissions;4'5 the number of admissions for sickle cell pain decreased by 44%, total inpatient days by 57%, length of hospital stay by 23%, and the number of ED visits by 67%. In late 1997, we opened an outpatient pain program for selected patients with SCD. Our goal was to provide state-of-the-art pain management and psychosocial support in collaboration with primary care providers. Our hope was that the approach would reduce both ED visits and hospital admissions. Patients with recurring moderate-to-severe sickle cell pain were referred by their primary care providers or by word of mouth from other patients with SCD. All patients are seen in the clinic each month for a three-hour visit. Patients are welcome to bring any of their family or friends to visits. Each visit begins with a music therapy session that includes group support. Following music therapy, medical care is provided individually to each patient. Between visits, the pain and palliative physicians see patients on an as-needed basis. The pain management strategy for patients in the clinic is modeled on the approach used to treat pain in patients with cancer. Typically, persistent pain is managed with a long-acting opioid or methadone. The opioid for each patient is selected based upon the patient's prior history and current assessment. BTP is managed with a short-acting opioid, such as oral transmucosal fentanyl citrate (OTFCO; Actiq®). OTFCO, which was specifically designed to deliver rapid analgesia for the treatment of BTP, has been shown to produce analgesia within five- to 10 minutes.6 The efficacy and safety of Actiq® for the treatment of BTP have been firmly established in clinical trials in cancer patients,6-9 and we have had a very favorable experience with OTFCO in our patients with cancer. The initial dose of medication and the BTP medication is based on clinical judgment and may be titrated such that adequate efficacy is achieved with minimal side effects.
CASE REPORTS Currently, approximately 40 patients with SCD are managed in our clinic, and all except two currently are receiving a long-acting opioid in conjunction with a short-acting opioid for BTP. Three cases were selected to illustrate the experiences of patients from the sickle cell pain clinic.
Case #1 A
26-year-old single woman with SCD diagnosed
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at birth had frequent crises (>30/year) for 20 years. Among her complications of the disease is avascular necrosis (AVN) of the right hip. The patient lives at home with her mother, her siblings, and their children. During the year before her first visit to our clinic, she had 18 ED visits, 13 ofwhich resulted in admission to the hospital for a total of 97 inpatient days. The patient verbalized a high degree of mistrust of her healthcare providers. In the clinic, she was prescribed methadone 120 mg every six hours, which was equianalgesic to the meperidine that she had been receiving in the ED and in the hospital during previous admissions. We prescribed 1,600 mcg OTFC® as needed so that she could attain rapid relief from her BTP. ED visits and hospital admissions dramatically decreased. In 1998, the patient had no ED visits or hospital admissions. In 1999, the patient had one hospital admission of five days and, in 2000, the patient had one hospital admission for three days during a highly stressful period when the patient learned of an unplanned pregnancy. During the third trimester of her pregnancy, the patient was admitted to the hospital on three occasions for approximately one week per admission. The baby, who is free from SCD, was delivered in January 2002. There were no signs of physical dependency or withdrawal during the baby's postnatal period. Postpartum, the patient has not been admitted for crises. The patient currently receives 240 mg methadone every six hours and uses 1,600 mcg oral transmucosal fentanyl citrate for BTP from crises. She reports that her pain is generally well controlled.
Case #2 A 20-year-old single man had six hospital admissions through the ED, resulting in 32 inpatient days during the year prior to his first visit to our clinic. Based on his short-acting opioid requirement, we administered controlled-release oxycodone 160 mg twice a day with short-acting oxycodone 25 mg every three hours as needed for BTP from crises. We did not prescribe OTFC® for this patient, because the patient had previously attained adequate relief using short-acting oxycodone and preferred to continue using the same medication. There were no hospital admissions in 1998, one admission in 1999 for three days, one admission in 2000 for 12 days, and one admission in 2001 for eight days. The patient reports that his pain now is generally well controlled.
Case #3 A 39-year-old woman has had frequent crises since birth, has chronic osteomyelitis of the right femur, and has AVN of her hips bilaterally. She is wheelchairbound and lives with her mother. The patient suffers from two pain syndromes: chronic sickle cell pain VOL. 96, NO. 7, JULY 2004 985
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from AVN of the hips bilaterally caused by oxygen deprivation and infarction to the joints, and severe episodic pain of her right arm and intercostal muscles. The patient had eight hospital admissions amounting to 182 inpatient days in the year prior to her first clinic visit. She was prescribed 400 mcg/hour transdermal fentanyl with 1,600 mcg OTFC® for BTP Since presenting to our clinic in 1997, there were no hospital admissions in 1998, one admission in 1999 for 16 days, and one admission in 2000 for nine days.
DISCUSSION In general, there is enormous sympathy for patients with cancer pain, postoperative pain, or pain due to trauma. In contrast, many healthcare providers can be somewhat hesitant to prescribe opioids on an ongoing basis to patients without cancer, such as those with SCD. Clinicians may minimize or doubt their pain complaints. The pain of SCD crises, however, can be both excruciating and incapacitating and frequently leads to ED visits and hospital admissions. We found that a pain control program for patients with sickle cell pain modeled on the approach used to treat malignant pain notably improved pain control and reduced hospital use by adult patients with sickle cell pain. The patients were selected by referral, and they were patients that had very severe, refractory painful chronic pain due to SCD. These patients had already failed usual anti-inflammatory medications. A similar experience has been reported and suggests that chronic opioid pharmacotherapy for the treatment of sickle cell pain can be safely and effectively continued for long periods of time.'0 The use of a controlled-release opioid for chronic pain in combination with a short-acting opioid for BTP has been an effective strategy for our sickle cell patients. The choice of the opioid, its dose, and its route of administration should be individualized according to the patient's past history and experience. The decision whether to commence a sickle cell patient on a long-acting opioid preparation was based on the frequency ofadmissions per year. If the patient was admitted five times or more in one year, we then started the patient on chronic long-acting opioid pharmacotherapy as an outpatient. The choice of drug and route of administration was based on past experience and efficacy. The short-acting drug was usually given as needed. Based on our favorable clinical experience with OTFCO in patients with cancer, we commonly prescribe OTFCO for BTP in our sickle cell patients. Patients received an initial OTFC® dose between 600 mcg and 1,600 mcg as needed, based on the severity of their BTP and prior opioid exposure within our clinical experience. The usual dose of a breakthrough medication is 15% of the 24-hour long-acting opioid. The dose of OTFCI may be titrated, if necessary, to 986 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
achieve adequate efficacy with minimal side effects. The fear of addiction and tolerance to opioids generates enormous anxiety among healthcare providers, patients, and families despite the fact that studies in patients with SCD have reported low rates of addiction to opioid analgesics.1",2 Clinically significant tolerance to opioids did not complicate treatment in our patients receiving chronic opioid pharmacotherapy. The stability of the long-acting opioid dose over the years indicates that tolerance rarely becomes a clinically significant issue. No clinically significant adverse effects of opioid pharmacotherapy occurred in our patients despite several years of treatment-the side effect most prevalent in our patients was fatigue that was managed with rest, exercise, and occasionally a psychostimulant when indicated. Constipation was not a problem with our patients probably because good hydration was encouraged. And most of the patients we have treated in our clinic report that their pain is now well controlled. However, controlled clinical trials of long-term opioid therapy in patients with SCD pain are needed before conclusions about efficacy and safety can be drawn. Nevertheless, the lack of these trials should not exclude empirical treatnent when medical judgment supports it in these patients with intractable pain, for whom there are few alternatives.
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2. Ballas SK. (1998) Sickle Cell Pain. Progress in Pain Research and Management, vol. 11. IASP Press, Seattle, WA. 3. Portenoy RK, Hagen NA. Breakthrough pain: definition, prevalence, and characterstics. Pain. 1990;41:273-282. 4. Coluzzi PH, Schwartzberg L, Conroy JD, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFCI and morphine sulfate immediate release (MSIR®). Pain. 2001;91:123-130. 5. Brookoff D, Polomano R. Treating sickle cell pain like cancer pain. Ann Intem Med. 1992;1 16:364-368. 6. Christie JM, Simmonds M, Paff R, et al. Dose titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol. 1998;1 6:238-3245. 7. Shapiro BS, Benjamin LJ, Payne R, et al. Sickle-cell-related pain: perceptions of medical practitioners. J Pain Symptom Manage. 1997;14:168-174. 8. Lichtor JL, Sevarino FB, Joshi GP, et al. The relative potency of oral transmucosal fentanyl citrate (OTFCI compared with intravenous morphine in the treatment of moderate-to-severe postoperative pain. Anesth Anal. 1999;89:732-738. 9. Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFCI for the treatment of breakthrough pain in cancer patients: a controlled-dose titration study. Pain. 1999;79:303-312. 10. Martin J, Moore G. Pears, pitfalls, and updates for pain management. EmerMed Clin North Amer. 1997;15:399-415. 11. Pack-Mabien A, Labbe E, Herbert D, et al. Nurses' attitudes and practices in sickle cell pain management. AppI Nurs Res. 2001;14:187-192 and risk factors. N EnglJ Med. 2001;325:11-16. 12. Benjamin, L, Swinson G, Nagel R. Sickle cell anemia day hospital: an approach for management of uncomplicated painful crisis. Blood. 2000; 95:1130-1136.L
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