Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: A phase III analgesic trial for hospitalized sickle cell patients with painful episodes

Abstract

Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

IMPROVE trial: A randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies

“…The magnitude of patient reported opioid-related withdrawal symptoms was assessed by scripted telephone interview at 3 and 14 days post hospital discharge based on a validated questionnaire. These results have been published elsewhere [30]. …”

“…Opioid usage in the 22 adult participants confirmed the feasibility of the two PCA dosing strategies, while the demand component of the PCA was not used optimally by the 12 pediatric participants [30]. In adults, the 25 mm drop in VAS scores occurred within a median of 2 days for both the HDLI and LDHI treatment groups, with 100% of adults achieving that threshold during the study (Table 2).…”

The Opioid System and Brain Development: Effects of Methadone on the Oligodendrocyte Lineage and the Early Stages of Myelination

“…It should also be considered that the possibility of interference with late myelination extends beyond opioid abuse and opioid detoxification treatments and could be particularly important in the case of patients within this age bracket subjected to frequent opioid treatments for pain relief. Such is the case of severe pain management in sickle cell disease in which patients are commonly prescribed opioid medications including morphine, methadone, and oxycodone [85]. …”

Hospital Readmissions in Patients With Inflammatory Bowel Disease

“…Several studies in the surgical literature (14,15) have demonstrated the potential for "fast-tracking" postoperative patients with some success. Additionally, in patients with sickle-cell disease, a lot of research in emergency rooms and outpatient and inpatient settings has been focused on developing the best collaborative approach to minimize resource utilization and improve pain control (16)(17)(18). Another significant issue in IBD patients is nutrition.…”