Acute painful events in children with sickle cell disease

By Amanda Brandow, DO, MS

Introduction and epidemiology

Sickle cell disease is the most common inherited blood disorder in the United States, affecting about 72,000 Americans and 1 in 400 African-Americans. Sickle cell disease is caused by inheritance of the sickle beta globin gene, either in homozygous form (HgbSS) or in combination with hemoglobin C (HgbSC), B-thalassemia (HgbSâ-thal) or several less common hemoglobin genotypes. This disorder of hemoglobin structure manifests as a chronic, debilitating disease characterized by episodic and chronic pain, hemolytic anemia, severe infections, stroke and pulmonary complications beginning in early childhood and lasting throughout life. The hallmark of sickle cell disease is the vaso-occlusive painful event, which is the leading cause of emergency department visits and hospitalizations for children with sickle cell disease. In 2003, there were more than 20,000 hospitalizations for children with sickle cell disease and more than 16,000 of these were for vaso-occlusive painful events – resulting in more than 65,000 hospital days per year. It has been estimated that 5.2 percent of patients with 3 to 10 pain episodes per year make up 33 percent of all hospitalizations, and the pain rate also correlates with early death in adults with sickle cell disease. Sickle cell pain may involve any part of the body, the onset often is unpredictable and the severity, location and duration of the pain vary among patients and longitudinally in the same individual. In addition, objective signs of pain on physical examination usually are absent. In a subset of patients with sickle cell disease, acute pain can be superimposed on chronic pain; however, the focus of this article will be on the assessment and management of acute pain. 

Initial assessment and management of acute pain

It has been shown that the majority of acute painful events initially are managed at home, and children seek medical treatment only when oral medications have not adequately alleviated their pain or another sickle cell-related complication is suspected by the child and/or family. The severity of pain in sickle cell disease can vary enormously and objective physical findings often are lacking. Thus, each child should be treated as an individual with reliance on the child's report of pain. In addition, patients with sickle cell disease often are tolerant to opioids, thus may require significantly higher doses of narcotics than other children with equivalent age and weight. Initial management should be aimed at providing rapid pain control with intravenous opioid-based narcotics such as morphine or dilaudid using weight of the patient as a starting point. In addition, adjuvant pain control with a non-steroidal anti-inflammatory agent often is used. Once adequate acute pain relief is achieved, the decision to admit the child and continue parental analgesics or discharge the child with oral analgesics should be made collectively between the treating physician, child and caregivers. If the child is admitted, Table 1 outlines suggested treatment as per a protocol developed by the sickle cell team at Children's Hospital of Wisconsin. Pain relief in appropriate-aged children (usually 5 years or older) is best managed with patient-controlled analgesia (PCA) pumps. A basal infusion in addition to bolus dosing is most often used, usually provides adequate pain relief and gives the child some control over managing his or her own pain. If a child is too young to use a PCA, intravenous pain medication should be ordered on a scheduled basis (not as needed) to ensure that the child maintains adequate continued pain relief, minimizing the peaks and valleys of pain. Continual reassessment by the provider with continued input by the child and caregiver will allow the provider to titrate intravenous pain medication and transition to oral pain medication when appropriate in preparation for discharge. Upon discharge, outpatient pain management is best achieved by scheduled pain medications for 2 to 3 days post-discharge, consisting of an opioid-based drug such as oxycodone, roxicet or immediate release morphine combined with a NSAID such as ibuprofen.

Initial medical assessment of a child with sickle cell disease presenting in acute pain also should include evaluation for life-threatening medical complications found in sickle cell disease that are outlined in Table 2. Any complication of sickle cell disease can occur in the setting of acute pain, thus prompt evaluation with a CBC, reticulocyte count and thorough physical examination with further symptom-specific evaluation is absolutely warranted while simultaneously providing adequate pain relief.

What happens after a child is discharged from the hospital after admission for pain?

The average length of stay for children admitted for an acute painful event is 4.4 days, though this varies by age, with older children having increased length of stay and more hospitalizations for pain. However, the morbidity of a painful event that brings a child to medical attention does not end once the child is discharged. A study completed by our sickle cell center at Children's Hospital of Wisconsin found 47 percent of children reported three or more days of pain and 54 percent of children had two or more days of school absenteeism post-discharge from the inpatient unit or emergency department. (See Figure 1.) The impact of vaso-occlusive painful events at the school level is not trivial since children with sickle cell disease are at risk of poor academic attainment. In our study, on average, children were hospitalized for three days resulting in school absenteeism with an additional two days of school absenteeism post-discharge. Therefore, a single painful event can result in five missed school days. We also found vaso-occlusive painful events affect the caregiver's ability to work or attend school, with 24 percent of caregivers missing two or more days of work/school post-discharge. (See Figure 1.) This can, in turn, impact the socioeconomic status of the family. This is extremely important for children with sickle cell disease because they are more likely to live in poverty. In addition, many caregivers of these children are single parents who are the sole provider for the entire family and work outside the home in jobs that don't give them the benefit of paid sick leave. In summary, a single painful event has significant impact on the whole family, thus our ultimate goal should be prevention of these events.

Prevention of painful events

Currently, there are only three commonly used treatments to prevent vaso-occlusive painful events. These include bone marrow transplantation (BMT), chronic blood transfusions and hydroxyurea. BMT is curative, however, it is limited by the need to have an HLA-matched sibling donor and significant treatment-related toxicity. A current study is looking at the role of unrelated BMT or alternative donors for children with sickle cell disease. Chronic blood transfusions are effective, however, in order to achieve maximum effect in preventing vaso-occlusive painful events, they are required long-term, which leads to problems with iron overload and potential infection. Hydroxyurea decreases vaso-occlusive painful events, is safe and should be considered for every child who has three or more significant painful episodes in one year.

Summary

Vaso-occlusive painful events are the most common reason children with sickle cell disease seek medical attention. These painful episodes also can be associated with life-threatening complications of sickle cell disease. Frequent pain causes significant issues for children with sickle cell disease and their caregivers, and those with more frequent painful events have a higher mortality rate. Prompt assessment and rapid initiation of analgesic medications titrated to patient comfort is the most important intervention to improve the severe, debilitating pain experienced by children who suffer from sickle cell disease. In addition, preventive measures such as hydroxyurea should be utilized in children presenting with frequent pain.

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Amanda Brandow, DO, MS, is a pediatric hematologist/oncologist at Children's Hospital of Wisconsin, an assistant professor of Pediatrics (Hematology/Oncology) at The Medical College of Wisconsin and a member of Children's Specialty Group.

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