The pathophysiology of sickle cell disease (SCD) manifestations, are complex with interactions of intracellular hemoglobin, membrane and endothelial activation but the hallmark remains recurrent and painful vaso-occlusive episodes (VOC). These painful episodes are thought to result from ischemia caused when small blood vessels are occluded by misshapen, inflexible erythrocytes. Painful episodes are the most common cause of hospitalization, morbidity, and impairment for SCD patients. There is no therapy that completely prevents or directly aborts painful events for all patients. Consequently, treatment for acute VOC is primarily supportive using hydration and medicinal pain control. Every pain medication has the potential to relieve pain but is associated with significant limitations and side effects.

The primary hypothesis to be tested in this double blind, randomized controlled trial is that Nalbuphine is equivalent to morphine for pain control and patients will suffer fewer episodes of acute chest syndrome. The investigators also expect subjects will report fewer side effects from respiratory depression, abdominal distention from reduced peristalsis, reduced histamine release causing pruritis and still be provided adequate pain control. Further hypotheses to be tested is ability to recruit patient participants while being treated in the Emergency Department and that continuous infusion of Nalbuphine with accompanying patient controlled analgesia (PCA) is safe and effective in controlling pain, requiring less total opiates consumption, while decreasing length of hospitalization.

Inclusion Criteria:

• Patients with sickle cell disease (SS, SC, SβThal) who are hospitalized for acute painful episodes
• 6 years old and < 19 years old
• Normal baseline chest radiograph
• Normal renal and hepatic function within the previous 12 months

Exclusion Criteria:

• Previous patient participation in this clinical trial

• Any patient on chronic transfusion Any patient with pulmonary infiltrate on chest radiograph on admission

• Any patient with DSM diagnosis, excluding those with Attention Deficit Disorder, on or off treatment

• Any patient with documented allergy to either study drug

• Any patient with known evidence of an underlying disease that would interfere with evaluation of a therapeutic response such as:

  • Hepatic dysfunction (3x ALT),
  • Renal dysfunction (Cr > 1 children/adolescents, Cr >2 adults),
  • Pulmonary Hypertension (TRJ >3.0),
  • Cardiac dysfunction.
  • Any patient with symptoms of an acute stroke.
  • Any patient known or suspected to be pregnant.
  • Any patient with priapism
  • The patient or guardian who will not give consent or assent to be randomized.