Fentanyl Versus Hydromorphone as First Line Strategy in Patients on Mechanical Ventilation, a Pilot Pragmatic Randomized Superiority Clinical Trial: the FenHydro Trial
Beth Israel Deaconess Medical Center
Summary
Patients with respiratory failure who require mechanical ventilation are not only at risk of death, but also of complications of prolonged ICU stay. Patients may have significant functional decline, impact in quality of life, develop psychiatric disorders and at long-term can lead to significant cost to society. Although sedation and analgesia are considered only supportive therapy, several studies have shown that in patients on mechanical ventilation, different approaches can have significant impact on patient centered outcomes. However, to date, randomized clinical trials on critically ill patients have mostly evaluated the sedative agent but not the analgesic agent. Although morphine and its derivates are the most common used opioid analgesic agents in the critical care setting, only some retrospective studies and some prospective studies compared them head-to-head (ramifentanyl versus morphine and fentanyl versus morphine). Current guidelines recommend choosing the analgesic agent based on pharmacokinectics, physician experience and side-effects profile. To evaluate the differences of two standard-of-care analgosedation agents, the FenHydro trial will be a cluster randomized, pragmatic, pilot and feasibility superiority clinical trial in mechanically ventilated patients in the ICU. The main question the study hopes to answer is whether there is any difference in morphine milligram equivalents administered during mechanical ventilation.
Description
Fentanyl is a synthetic derivate of morphine that is 100 times more potent than morphine, has a great lipid solubility leading to fast onset (one to two minutes), has a short half-life (up to three hours) and limited histamine release. It is metabolized by the liver and its excretion is not affected by the kidneys. Those characteristics allow fentanyl to be versatile and be used in many different scenarios in the ICU. Despite those advantages, concerns have been raised regarding adipose tissue accumulation, tachyphylaxis, CYP3A4 interaction and chest wall rigidity, particularly when on high do…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Admitted to either MICU A, B, C or FICU at Beth Israel Deaconess Medical Center * Requiring mechanical ventilation * Felt by primary team to require opioid infusion for analgosedation Exclusion Criteria: * Age \< 18 years old * Do not intubate orders prior to enrollment * Comfort measures only * Contraindication to fentanyl or hydromorphone
Interventions
- Drugfentanyl
Suggested initial continuous infusion * Route: Intravenous * Dose: 0-200 mcg/hr (max 1,440 MME/day) * Initial dose: 50mcg/hr * Concentration: 50 mcg/mL * Bolus: 50-200mcg up to every 5 minutes as needed * Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 25 mcg/hr every 60 minutes Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.
- DrugHydromorphone
Suggested initial continuous infusion * Route: Intravenous * Dose: 0-3 mg/hr (max 1,440 MME/day) * Initial dose: 0.5mg/hr * Concentration: 0.2 mg/mL * Bolus: 0.5-2mg up to every 5 minutes as needed * Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 0.25 mg/hr every 60 minutes Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.
Location
- Beth Israel Deaconess Medical CenterBoston, Massachusetts