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Avoiding Admission for Afebrile Pediatric Sickle Cell Pain: Pain Management Methods
Christine Anne Dumaplin, BS, RN, MSN, ARNP J Pediatr Health Care. 2006;20(2):115-122.

Sickle cell disease is the most prevalent genetic hematologic disorder in the United States, according to the National Institutes for Health (NIH). Recent statistics indicate that 72,000 individuals, or 1 in 350 African American or 1 in 1000 to 1400 Hispanic newborn infants, are diagnosed with sickle cell anemia each year in the United States. (NIH, 2002). The Mayo Foundation for Medical Education and Research (2005) reports that almost 10% of African Americans have "sickle cell trait" or carry the sickle cell gene. From an international perspective, 25,000 babies are born with sickle cell disease in Uganda every year, and up to 80% of these infants do not live to be 2 years old (Sickle Cell Information Center [SCIC], 2005). In 1972, Congress passed the National Sickle Cell Disease Control Act, recognizing the need for improved care for individuals with sickle cell disease. Today, 44 states, the District of Columbia, Puerto Rico, and the Virgin Islands provide universal newborn sickle cell disease screening. It is available on request in the other 6 states (NIH, 2002). In addition, other pediatric-specific measures such as prophylactic penicillin regimens and the use of conjugated pneumococcal vaccine have been incorporated into the standards of health maintenance for children with sickle cell disease. The National Heart, Lung, and Blood Institute (NHLBI) is at the forefront of these efforts, committing more than $923 million for research for the National Sickle Cell Disease Program (Bonds, 2005). Recently, the New Sickle Cell Awareness postage stamp began dissimination by the U.S. Postal Service on September 29, 2004, during Sickle Cell Awareness Month. Efforts were focused to raise public consciousness of newborn health screenings for sickle cell disease and sickle cell carrier status (SCIC, 2005). From a public health perspective, the move toward providing counseling and educational programs for healthcare providers and the general public has flourished since 1972. Sickle cell pain has been classified as an acute, recurrent, unpredictable, and chronic problem that requires a variety of pain relief measures to alleviate and eliminate pain. Pain remains the most common and most troubling symptom experienced by children with sickle cell disease (Shapiro, 1989; Shapiro, 1992). Twenty percent of the population with sickle cell disease is thought to have most of the severe and frequent pain events requiring hospitalization (Vichinsky, Johnson & Lubin, 1982; Platt, 1991). Clinicians should support active client involvement in effective and practical methods to manage pain. In addition to the use of analgesics, the client's use of nonpharmacologic methods to control pain such as distraction (ie, playroom activities such as coloring and arts and crafts), relaxation techniques such as breathing methods, and massage should be supported. The object of pain management is to relieve and prevent suffering. Pain is a multidimensional phenomenon that varies with each individual and each experience. Thus clinicians need to learn how to successfully recognize and attend to these subjective characteristics. Culture also has a vital impact on illness beliefs and behaviors, healthcare practices, help-seeking activities, and receptivity to medical interventions. Effective pain management in a multicultural environment requires respect for the client's cultural needs and preferences, and an ability to adapt accepted Western healthcare practices to the client's cultural needs (Roger, 2001). Pain is a highly personal experience, influenced by cultural conditioning, the significance of the situation, and values unique to the individual. In pediatrics, the

concept of developmentally appropriate care is an essential one when approaching pain management strategies. Several qualitative studies have described children's perceptions of what helps when they have pain. Interestingly, the 2 most consistently reported pain-relieving strategies preferred by 5-to 17-year-olds were medication and parental presence, especially a mother's presence (National Institute of Nursing Research, 1994). The most common form of pediatric sickle cell disease pain occurs during vaso-occlusive episodes, which may start as early as age 6 months and often continue in an unpredictable manner throughout life. Vasoocclusive crisis is characterized as episodic micro-vessel blockage that induces debilitating pain from inflammation. Acutely, it can be classified as mild to severe, localized, or migratory and may last hours to weeks. Many patients use opioid medications during outpatient pain management. Sickle cell pain may become severe enough to warrant aggressive regimens that require hospitalization. In these situations, therapeutic doses of intravenous opioids such as morphine have historically been recommended as first-line therapy. Pediatric studies have demonstrated the efficacy of various analgesics and anesthetic agents for sickle cell pain. It is also important to consider developmentally appropriate and age-appropriate routes of medication administration that are often a disregarded aspect of pediatric care. Recent studies demonstrate synergistic effects of nonpharmacologic strategies used in conjunction with these agents (Bodhise, et al., 2004). Ironically, as evidence-based, pharmacologic, pediatric pain management methods have proliferated in professional literature, the under-treatment of sickle cell pain from a pharmacologic perspective has been sustained (Ballas, 2001). Currently accepted practices of sickle cell pain management are highly variable. This generalized inconsistency has been theorized to be reflective of a common lack of knowledge (Rupp & Delaney, 2004). Healthcare providers, patients, and parents may hesitate to use evidence-based pediatric practices on the basis of unjustifiable fears of opioid addiction and dependence. Avoidance of these practices, however, may result in suboptimal pain control and result in unnecessary suffering. A common manifestation of sickle cell disease in children is unpredictable, episodic pain that can be excruciating and incapacitating. Children with sickle cell anemia who experience frequent episodes of pain crisis are at risk for the development of problems with anxiety, depression, poor school performance, decreased participation in normal activities of daily living, and poor peer and family relationships (Jacob, 2001). Research on the long-term psychosocial implications for children with sickle cell disease provide evidence of how episodic pain can negatively affect a child's self-image. Low self-esteem can then affect their interaction with others and can subsequently lead them on a debilitating path to social isolation. During the most crucial years of human development, self-consciousness, intellectual growth, and creative individualization, it is ultimately an invisible, physical pain that can influence these children to self-limit their own dreams, their own goals, and the standards they set for themselves (Jacob, 2001). Emergency department (ED) visits for acute vaso-occlusive pain and inpatient hospitalizations are directly proportional to sickle cell disease severity and may correlate as risk factors for early death in patients with sickle cell disease. In a 2003 (Houston-Yu, et al.) case management study published in the American Journal of Hematology, mortality data was analyzed in 71 adult patients with sickle cell disease. The average hospitalization days of the patients in the group ranged from 40 to 116 days per year. Eleven of the 71 patients (15.5%) did not survive for 24 months and represented the higher hospitalization averages of the group before the study (Houston-Yu, et al., 2003). In an article published in the New England Journal of Medicine in 1991 (Platt, et al.), 3578 patients with sickle cell disease from diverse areas of the

United States and ranging in age from newborn to 66 years of age were clinically followed up. A total of 18,356 patient-years were observed, with 12,290 documented episodes of pain. These results suggest that the number of acute pain episodes that a patient with sickle cell disease has per year may be directly correlated to measure the same patient's severity of sickle cell disease and risk for premature death. This correlation was statistically significant for those over age 20 years. During episodes of severe pain, life-threatening, ominous complications may arise and accompany abrupt clinical changes. Severity, frequency, and duration of the pain can facilitate an increasing oxygen requirement, altered mental status, and decreasing hemoglobin levels or platelet counts (American Academy of Pediatrics [AAP], 2002). In 2003 (Manci, et al.), investigators of the Cooperative Study of Sickle Cell Disease in the Department of Pathology reported an autopsy study with 306 reports of deceased patients with sickle cell accrued from 1929 to 1996. Including, but not limited to, pediatric patients, this study concluded that 40.8% of the 306 deaths were unforeseen and unanticipated; 63.3% of the deaths were associated with an acute event, and a 28.4% mortality rate was reported to occur within 24 hours of presentation (Manci, et al., 2003). Thus, on presentation of a patient with sickle cell disease to the ED, healthcare providers must acknowledge that immediate attention, aggressive treatment and constant reassessment are paramount. It is during this critical 24-hour period that efforts may determine life or death. Fortunately, as of 2005, the childhood mortality rate in the United States is decreasing in patients with sickle cell disease, and sickle cell disease-related death is occurring at older ages. In a 2004 (Quinn, et al.) pediatric cohort study, 711 newborns screened positive for sickle cell disease were followed up for 18 years. At an average age of 5.6 years old, 25 of the 711 children had died of sickle cell disease-related deaths. Using survival analysis of children who survived during the study, Quinn, et al. (2004) reported that there was an 85.6% to 93.6% chance that a child with sickle cell disease would live to be 18 years old. With this said, it is inherent that pediatric healthcare providers of patients with sickle cell disease must be the first to put forth efforts early on to decrease and manage acute pain by empowering patients at home or in the ED and avoid hospitalization. In 1973, the average life span of a patient with sickle cell disease was 14 years (NIH, 2002). The efforts we have put forth have caused doubling of the life expectancy for patients with sickle cell disease, with patients now living on average into their mid-40s (Platt et al., 1994). Successful sickle cell pain management may significantly affect how many days these patients spend hospitalized. Little definitive information is available about the true frequency of pediatric sickle cell pain episodes and the multidimensional factors influencing this pain. Many events occur and are resolved in a child's home. The pathophysiological mechanism underlying the pain is microvascular vaso-occlusion. The "sickled" red blood cells are sticky and easily clump, thus blocking blood flow. Although the pathophysiology is relatively understood, objective measurements and qualitative descriptions defining precipitating events leading to pain crisis are few. In a 2003 article, Smith, et al. sought to identify causal relationships between environmental temperature and vasoocclusive pain: "weak or inconsistent confirmation of a relationship was found between daily ambient temperatures and ED visits or hospital admissions for sickle cell crises." Others have suggested that exposure to second-hand smoke may be an environmental risk factor (Schall et al., 2004). With little insight about specific events preceding the ultimate presentation of a child with severe pain crisis to the ED, pain episodes remain erratic and unpredictable. Once in the ED, it is important to anticipate asking what home medications were taken before arrival. Many hematologists and sickle cell

specialists provide patients with prescriptions for oral pain medications that are equianalgesic to the successful parenteral regimens of their past. Medications given for mild and moderate pain include acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil), and even opioids such as codeine. In a 2002 (Dampier, et al.) article, published in the Journal of Pediatric Hematology and Oncology, results delineate the importance of recognizing the demonstrated efficacy of multiple opioid medications, perhaps in combination, during pain episodes experienced at home. Nonetheless, if home management fails to control a child's sickle cell pain, parents are strongly encouraged to call their specialist or seek acute hospital-based care. The AAP and the World Health Organization have addressed ethics regarding sickle cell pain management. Despite position statements and national guidelines developed to address this issue, disparities within pain management strategies exist among all age, race, and gender demographics of sickle cell disease. In this day of advocating for patient rights, there should be no populations bearing witness to unethical undertreatment of any kind. Studies, published in the Annals of Emergency Medicine in 2004, identified unremitting inadequacies and inconsistencies of acute sickle cell pain management in EDs (Rupp & Delaney; Tamayo-Sarver, et al.). Given identical sickle cell patient crisis descriptions in an ED, providers and institutions have continued to remain unreliable regarding their discretion to treat sickle cell pain with opioid analgesics (TamayoSarver, et al., 2004). This inconsistency was also seen when asked to correctly identify addiction and drug-seeking behavior and to assess an individual's pain level. Judgmental behaviors held among providers oftentimes serve as the primary source for disparities in practice. Ironically, even the fundamental ideals of patient empowerment and involvement in one's own care can sometimes be perceived as a persuading component toward a negative stigma and foster the label of a "drug-seeker." Patients with sickle cell disease who were knowledgeable and vocalized the appropriate treatment they required were ultimately found as those least likely to receive it (TamayoSarver, et al., 2004). Consequently, to avoid providing suboptimal care, additional education on these topics would benefit those who must face these decisions and populations regularly in practice. As stated earlier, it is the ED setting where patients with sickle cell disease rely on pain management, many times parenteral therapy, after they have exhausted all medication options provided for home use. Ideally, pharmacologic therapy should be based on the patient's past analgesic history. The appropriate drug and dose of choice usually depends on how far along the increasing analgesic classes the patient's regimen has required. It should be noted, the concept of drug tolerance will not be discussed in further detail. This unique pharmacologic baseline information, however, is crucial to the ED clinician's knowledge base and can significantly aid them in individualizing treatment. The Georgia Pediatric Sickle Cell Program has designed a developmentally appropriate pediatric "passport" specifically for this purpose (Sicklecellkids.org, 2005). Children often welcome the responsibility of carrying their "important documents" and can have fun individualizing their passport by coloring or decorating it. While learning about their illness and informing others of valuable information regarding their care, this simple and effective tool can provide a way to empower pediatric patients with sickle cell disease to be actively involved in their own care (see Figure 1 for passport pictures).

Pediatric passport. Printed with permission from www.SickleCellKids.org. Nonetheless, for whatever reasons that can and do arise, providers, patients, and parents may not have access to previously mentioned information, and thus an empiric approach is necessary. According to a 2003 (Rees, et al.) article published in the British Journal of Haematology, analgesia for acute sickle cell pain should begin at least 30 minutes on ED arrival and controlled within 60 minutes of administration. Diamorphine (acetylated derivative of heroin) is unavailable for use in the United States but is widely used for severe pain for sickle cell disease in all ages in the United Kingdom (Rees, et al., 2003). In a small but compelling pediatric sickle cell disease pain management study published in 2004 (Moussavou, et al.), 66 children representing variable school levels, social backgrounds, and pain episode histories were treated with the World Health Organization's 3-step analgesic protocol. Of the patients' pain crises, 81.6% were treated in stage I within 2 to 16 hours, and the remaining 18.3% were effectively relieved in stage II. Thus stage III did not occur for any of the children. Diphenhydramine, promethazine, and hydroxyzine are examples of adjuvant medications that may be given to control nausea and itching, but their doses may need adjustment to prevent over sedation. Step 1: Mild pain Non-opioid /+ Adjuvant medication Step 2: Moderate pain Weak opioid (or low dose of a strong opioid) /+ non-opioid /+ Adjuvant medication Step 3: Severe pain Strong opioid /+ non-opioid /+ Adjuvant medication Please turn to for medication protocols used for pediatric sickle cell pain in the United States. Then note below the use of hydroxyurea in this same group of patients.
Accepted Medications for Pediatric Sickle Cell Pain in the U.S.

Hydroxyurea is a medication that has been shown to be effective in the prevention of pain and other complications of sickling. The NHLBI undertook a Multi-center Study of Hydroxyurea in Sickle Cell Disease (MSH) that showed that hydroxyurea treatment significantly reduced pain crises and pain-related hospitalization percentages by 50%. The study was concluded 4 months early because of its successful results (Charache, et al., 1995). In 1998, the Food and Drug Administration (FDA) approved hydroxyurea as the first agent for the prevention of pain crisis in adults with sickle cell disease. Another NHLBIsupported study assessed the safety and efficacy of hydroxyurea in patients ages 5 to 15 years. That study confirmed the efficacy of hydroxyurea in children, but it also demonstrated safety (Wang, et al.,

2002). Hydroxyurea showed no adverse effect on growth or development (Hoppe, et al., 2000). Further data analysis from MSH has shown that hydroxyurea reduces healthcare costs. Currently, investigators are monitoring volunteers from MSH to determine how long hydroxyurea will affect quality of life, morbidity, and death (Stuart & Nagel, 2004). The NHLBI is now evaluating whether hydroxyurea can benefit even younger patients. A placebo-controlled pilot study of hydroxyurea administered to children between ages 6 and 24 months demonstrated that the drug is well tolerated and stimulates fetal hemoglobin expression. Additional studies are underway, but until results are available, the drug is not recommended for this age group (Stuart & Nagel, 2004). Various nonpharmacologic strategies provide potentially beneficial sources of pain management; however, there is little empirical evidence for one specific strategy over another. The Society of Pediatric Psychology, the American Pain Society, the AAP, the World Health Organization, and the National Institute of Nursing Research Pain Consortium recommend a combination of medication and nonpharmacological interventions varying from physical to psychosocial interventions. Heating pads (which must be used with caution because of risk of burns associated with analgesic and sedative effects from concurrent opioid use), deep tissue/deep pressure massage therapy, neuromuscular trigger point and acupressure/acupuncture, and transcutaneous electrical nerve stimulation are some of the new nonpharmacological, physical interventions that have been providing successful outcomes in pain management when used in conjunction with medications. Psychological coping interventions are methods that use self-regulatory techniques (Chen, et al., 2004). Psychologists and other trained professionals teach self-management techniques to children with chronic pain not only for purposeful physical relaxation, but to help them manage negative emotions that can facilitate the pain cycle. There are many behavioral and cognitive-behavioral strategies classified as relaxation techniques; those currently used for pediatric pain are shown in .
Behavioral and Cognitive-behavioral Strategies Classified as Relaxation Techniques Currently Used for Pediatricpain

The Journal of Pediatric Psychology, among others, reported individual results about techniques such as those mentioned previously and in that result in fewer school absences and other detrimental impacts on daily childhood activities (Gil, et al., 2001). Rather than simply relying on pharmacologic relief, these tools may allow children to have an increased sense of control over their pain, allowing them to assume a more active role in managing and functioning with their pain.
Behavioral and Cognitive-behavioral Strategies Classified as Relaxation Techniques Currently Used for Pediatricpain

Day clinics are ideally designed as an alternative outpatient resource where patients with sickle cell disease can exclusively be seen by medical staff who are trained in sickle cell disease management. This allows patients to avoid the ED and has been shown, in some preliminary adult settings, to decrease admission rates for sickle cell pain. The use of patient-or nurse-controlled analgesia devices are often what define a day unit from conventional ED care, and evidence suggests improved narcotic delivery. In a 2004 (Wright, et al.) article, an adult sickle cell day center was not only safe but also cost-effective. The center decreased overall hospital admissions by 43% and had a 49% decrease in admission length of stay. In its third year of operation, 84% of patients with sickle cell disease were managed there without the need for admission. In March 2005, for the first time in American history, a sickle cell day facility received "Disease-Specific Certification" from The Joint Commission on Accreditation of Health-care Organizations (SCIC, 2005). Memorial Healthcare System's Sickle Cell Day Hospital opened in May 2003 and was the first sickle cell day facility in Florida. Accepting patients 16 years of age and older, this culturally-comprehensive program has a 24-hour, 7-days-a-week sickle cell information line (954) 985-6945 that accommodates 4 languagesEnglish, Spanish, Creole, and French (SCIC, 2005). The Georgia Comprehensive Sickle Cell Center at Grady Health System in Atlanta is another growing American resource that has reported similar successes in sickle cell disease management in adults. The interdisciplinary clinic is staffed with "four physician assistants, one nurse practitioner, four hematologists, a clinical nurse specialist in psychiatry, two social workers, six nurses, a newborn screening coordinator, clinic assistants, clerical and computer personnel" (Platt, et al., 2002). As "the only 24-hour acute care center in America, with the same staff providing both acute and routine health maintenance care" to their patients older than 15 years of age with sickle cell disease, this is continuity of care at its best. The facility also reports reduced admission rates and ED visits. In addition, their reports, reflecting data from 19912001, indicate that more than 80% of adult patients with sickle cell disease treated for acute pain were discharged home after 8 hours of aggressive pain management. Their management primarily includes parenteral nalbuphine (Nubain), an anti-emetic such as hydroxizine (Vistaril), and an NSAID such as ketorolac or ibuprofen. The American Pain Society, the American Academy of Pain Medicine, and the American Society of Addiction Medicine have endorsed this approach in select patients (Platt, et al., 2002). The Children's Hospital in Philadelphia (CHOP) initiated the Hematology Acute Care Unit (HACU) in 1996 as a "23-hour" virtual unit located on an inpatient floor where children with sickle cell disease were normally admitted. Any child admitted for longer than 23 hours is then transferred to the regular inpatient service. The HACU is staffed by pediatric nurse practitioners with hematology attending physician

supervision. Management is driven by written protocols, which allow for the administration of NSAIDs and up to 3 doses of parenteral or oral opioids. According to CHOP Sickle Cell Director Dr. Kwaku OheneFrempong (2005) "prior to the establishment of the HACU, the busy CHOP ED was the site where sickle cell patients in pain would be managed; 75% of children presenting to the ED in pain were admitted to the inpatient service. Now, most of that care is directly or indirectly managed in the HACU after initial ED evaluation, and less than 40% of those presenting with pain are admitted to the inpatient service." Nurse practitioners are well qualified to educate patients, their families, and other healthcare providers on subjects from preventive care to current treatment protocols. Interdisciplinary care is often needed for the patients with sickle cell disease; direct communication and collaboration between these specialties is essential. Coping strategies and disease management teaching must be initiated and elicited early in pediatric patients. The advanced practice nurses are most qualified to coordinate holistic approaches to care and can serve patients as supportive liaisons with other providers but also as educational resources for self-management. Nurse practitioners are well known to foster patient compliance through familiarity and trust among patients in the acutely ill and well settings and provide continuity of quality healthcare with consistent patient satisfaction. The increased successes of adult sickle cell day treatment clinics has spurred preliminary discussions about incorporating younger patient populations in these facilities and of developing models for pediatric facilities in the United States. Data from these facilities are eagerly awaited and hopefully will reflect similar outcomes in sickle cell pain management, admission rates, and ED care. As childhood mortality rates continue to steadily decline, pediatric providers must seek new ways to decrease childhood morbidity. Pediatric day clinics with interdisciplinary staff with current, evidence-based therapeutic regimens that are available for this population may be the answer to decreasing morbidity rate that patients with sickle cell disease experience in childhood. In doing so, perhaps we can eliminate sickle cell disease mortality rate in adulthood and change the prognosis for children with sickle cell disease. The print version of this article was originally certified for CE credit. For accreditation details, contact the publisher, Nina McElroy, Elsevier Science, The Curtis Center, Independence Square West, Philadelphia, PA 19106
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34. Vichinsky, E. P., Johnson, R., & Lubin, B. H. (1982). Multidisciplinary approach to pain management in sickle cell disease. American Journal of Pediatric Hematology and Oncology 4, 328-333. 35. Wang, W. C., Helms, R. W., Lynn, H. S., Redding-Lallinger, R., Gee, B. E., Ohene-Frempong, K., Smith-Whitley, K., Waclawiw, M. A., Vichinsky, E. P., Styles, L. A., Ware, R. E., & Kinney, T. R. (2002). Effect of hydroxyurea on growth in children with sickle cell anemia: results of the HUGKIDS Study. Journal of Pediatrics 140, 225-229. 36. Wright, J., Bareford, D., Wright, C., Augustine, G., Olley, K., Musamadi, L., Dhanda, C., & Knight, C. (2004). Day case management of sickle pain: 3 Years experience in a UK sickle cell unit. British Journal of Haematology 126, 878-880. Acknowledgments Special thanks to Dr. Lewis Hsu, Mr. Allan Platt, Ms. Cynthia Gentry, Mr. Josh Wright, Dr. Kwaku OheneFrempong, and Dr. Janet Deatrick for their professional expertise and essential guidance throughout the development of this manuscript. Reprint Address Christine Anne Dumaplin, BS, RN, MSN, ARNP, Department of Cardiovascular Surgery, Miami Children's Hospital, 3200 SW 60th Court, Suite 102, Miami, FL 33155-3009; christine@alumni.upenn.edu J Pediatr Health Care. 2006;20(2):115-122. 2006 Mosby, Inc.