THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)

Inclusion Criteria:

• Sickle Cell Disease: Hemoglobin diagnosis of SS (two copies of the hemoglobin S gene),SC (one copy of the hemoglobin S gene and one copy of the hemoglobin C gene), SD (onecopy of the hemoglobin S gene and one copy of the hemoglobin D gene), or S-βthalassemia (β+ or β0)

• Male or female age ≥ 10 years.

• Typical vaso-occlusive pain that is not adequately controlled in an ambulatory oracute care setting and which is expected to require > 24 hours of hospital care.

• Pain Intensity Visual Analog (10 cm scale) score ≥ 4.5 cm, measured immediately afterobtaining informed consent.

• Adults willing and able to give informed consent; parents willing and able to givepermission for study participation by their children; minor subjects (ages 10-17)willing and able to provide assent.

• Ability to read/write English.

Exclusion Criteria:

• Medical Indication

• Presence of significant liver disease (ALT > 3 times institutional upper limit ofnormal, or direct bilirubin > 0.8 mg/dl within preceding 3 months)

• Presence of significant renal dysfunction (within preceding 3 months, creatinine ≥ 1.2 mg/dl for ages >18 yrs, or ages 10-18 yrs creatinine ≥ 1.0 mg/dl)

• Oxygen saturation by pulse oximetry ≤ 92% on room air at study entry

• Any other medical condition that renders the subject unable to or unlikely tocomplete the study or which would interfere with optimal participation in thestudy or which poses significant risk to the subject from study treatmentincluding but not limited to:

• Concurrent acute chest syndrome

• Right upper quadrant pain

• Symptomatic sleep apnea

• Brain injury or doses of opioids that preclude potential subjects' capacity togive informed consent.

• Known (documented) hypersensitivity/intolerance to morphine and/or hydromorphone.

• Clinically significant opioid tolerance in the opinion of the investigator thatprecludes safe and/or effective dosing or requires, under current management,receiving the following long-acting oral opioids:

• Methadone 40 mg/day

• Sustained/Extended release oral morphine 120 mg /day

• Oxycodone 80 mg/day

• Known pregnancy or currently breastfeeding.

• Poor venous access that in the investigator's judgment would preclude maintaining anIV throughout the admission.

• Currently participating in another research study.

• Previously randomized in the IMPROVE trial.

• Pain management in emergency department or Day Hospital ≥ 12 hours prior to decisionto admit for inpatient care.

• Subject or physician preference for treatment with opioids other than morphine orhydromorphone.