Remifentanil for Pain in ICU
Trial question
Is remifentanil noninferior to fentanyl in mechanically ventilated patients requiring pain relief in the ICU?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
23.0% female
77.0% male
N = 182
182 patients (41 female, 141 male).
Inclusion criteria: adult patients in the ICU requiring 6 hours to 10 days mechanical ventilation and pain relief.
Key exclusion criteria: severe damage to the CNS; neurological disease making pain/sedation assessment difficult; receipt of nalmefene within 1 week prior to study drug administration; requirement of local anesthetic, epidural, or intrathecal administration of analgesics, or nerve block.
Interventions
N=92 remifentanil (dose titration from an infusion rate of 1 mL/hr, remifentanil 0.025 mcg/kg/min, until the target level of analgesia was achieved by escalating the dose in 1 mL/hr).
N=90 fentanyl (dose titration from an infusion rate of 1 mL/hr, fentanyl 0.1 mcg/kg/hour, until the target level of analgesia was achieved by escalating the dose in 1 mL/hr).
Primary outcome
Proportion of patients who did not require rescue fentanyl
100%
97.8%
100.0 %
75.0 %
50.0 %
25.0 %
0.0 %
Remifentanil
Fentanyl
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in the proportion of patients who did not require rescue fentanyl (100% vs. 97.8%; AD 2.2%, 95% CI -0.8 to 5.3).
Secondary outcomes
No significant difference in duration from the start of dose reduction toward the ventilator weaning (1.89 hours vs. 1.45 hours; AD 0.44 hours, 95% CI -0.63 to 1.51).
No significant difference in the proportion of duration maintained RASS of -2 to 0 (89.66% vs. 83.86%; AD 5.8%, 95% CI -2 to 13.6).
No significant difference in the proportion of duration maintained Behavioral Pain Scale ≤ 5 or Numerical Rating Scale ≤ 3 (99.16% vs. 98.5%; AD 0.66%, 95% CI -0.24 to 1.55).
Safety outcomes
No significant difference in adverse events or adverse drug reactions.
Conclusion
In adult patients in the ICU requiring 6 hours to 10 days mechanical ventilation and pain relief, remifentanil was noninferior to fentanyl with respect to proportion of patients who did not require rescue fentanyl.
Reference
Matsuyuki Doi, Naoki Takahashi, Rumi Nojiri et al. Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study. J Intensive Care. 2023 Nov 13;11(1):51.
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