Comparing Patient-Controlled Analgesia Versus Non-PCA Hydromorphone Titration for Severe Cancer Pain: A Randomized Phase III Trial

Abstract

Background: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]). Patients and Methods: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4–6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals). Results: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25–0.50) and 0.79 hours (0.50–1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23–2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25–0.75) and 1.00 hours (0.50–2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32–2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88–2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15–3.22) than in the non-PCA group (3.00; 2.47–3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001). Conclusions: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.

Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial

“…26,27 Autonomy and immediacy of PCA administration are also important. 3,8,9 Only bolus intravenous hydromorphone PRN was associated with a short interval from pain recognition to pain resolution. Importantly, we educated patients to administer analgesic concurrent with prodromal symptoms of pain to further mitigate pain intensity.…”

“…[5][6][7][8][9][10] Better pain control also brings greater PSS. 3,28 Notably, 1 patient declined to switch to oral morphine on ATC dosing because the patient achieved good pain control via IPCA titration.…”

“…org), 2,3 and 0.5 mg hydromorphone for opioid-naïve patients. 3 All patients were trained and tested to score pain according to NRS criteria and to use the PCA pump. Lockout time was set to 10 minutes; patients were educated to self-press the PCA pump button every 10 minutes if NRS $4.…”

“…The pump setting was not changed within the 24-hour period. 3 Patients who were successfully titrated began the treatment to which they were randomly assigned: (A1) bolusonly arm: IPCA hydromorphone with bolus-only (dosage was 10%-20% of the TEOP24H) PRN; (A2) continuous infusion plus bolus arm: IPCA hydromorphone with continuous infusion (dosage per hour was the TEOP24H divided by 24) for background pain plus bolus (dosage was 10%-20% of TEOP24H) PRN for BTcP; or (B) oral ER plus NR arm: oral ER morphine (TEOP24H/2 3 75%, every 12 h/d) ATC for background pain and NR morphine (10%-20% of the TEOP24H) PRN (minimal 60-minute interval 1 ) for BTcP. Pain was evaluated and dosages adjusted once every 24 hours from day 1 to day 6.…”

“…1,2 Intravenous opioid titration with patient-controlled analgesia (PCA) provides earlier analgesia and higher patient satisfaction for pain control than conventional titration administrated by medical staff, as reported in our previous study. 3 After successful opioid titration, it is appropriate to maintain analgesia with regularly scheduled medication plus supplemental doses for breakthrough cancer pain (BTcP). 1,2 Compared with regularly scheduled doses, continuous infusion using a PCA pump can confer a more stable effective plasma concentration to control background pain.…”