Subcutaneous versus intravenous route switch from oral to parenteral morphine in patients with cancer: randomised controlled trial

Background Subcutaneous (SC) administration is the preferred parenteral opioid route in palliative care, while intravenous infusion may allow faster titration. Comparative evidence remains limited. This study assessed whether intravenous or SC morphine, administered by continuous infusion with bolus doses, offered advantages in (1) time to stable infusion rate and (2) time to pain relief following a bolus dose. Methods In this double-blind, double-dummy randomised controlled trial, 60 hospitalised palliative care patients with cancer requiring opioid rotation to parenteral morphine were randomised to continuous SC or intravenous infusion with bolus doses over 48 hours. Results Mean time to final infusion rate was 20.4 hours (95% CI: 15.2 to 25.6) for SC and 16.3 hours (95% CI: 10.5 to 22.2) for intravenous (mean difference: 4.1 hours, 95% CI: –3.6 to 11.7; p=0.293). Median time to effect from bolus doses was 20 min (Q1, Q3: 15, 23) for SC and 15 min (10, 20) for intravenous (HR=1.08, 95% CI: 0.61 to 1.88; p=0.795), indicating no significant difference. NRS scores decreased from 3.9 to 2.1 (SC) and 3.3 to 2.3 (intravenous). Infusion rates increased from 2.4 to 3.3 mg/hour, bolus doses from 4.6 to 6.6 mg. Of 604 boluses, the proportion of effective doses was similar between groups. One intravenous patient developed catheter-related thrombosis and infection post-intervention. Conclusion No statistically significant or clinically meaningful differences in effectiveness or safety were observed between SC and intravenous morphine administration. Both routes allowed similar titration patterns, supporting the use of either route in palliative care without compromising analgesic efficacy or safety.