Fentanyl Versus Hydromorphone in Patients on Mechanical Ventilation

Purpose

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.

Conditions

  • Mechanical Ventilation
  • Sedation and Analgesia
  • Critical Care, Intensive Care

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Randomization will occur at the level of the ICU, rather than for each individual patient. Cluster I (MICU A, B, C) and cluster II (FICU) will be randomized to start from a period with fentanyl or hydromorphone and after 3 months will be crossed over to the other group. The process will be repeated during the study period. Cluster cross-over are planned to be 3 months to avoid seasonal variability. The investigators plan to start the enrollment in the middle of a season, so that the clusters have 1.5 months of each season. No washout period is planned.
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Fentanyl as first line agent 		Patients in an ICU on a three-month period randomized to Fentanyl will have Fentanyl used as suggested first-line therapy for analgosedation, when clinically warranted.
  • Drug: fentanyl
    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.
Experimental
Hydromorphone as first line agent 		Patients in an ICU on a three-month period randomized to Hydromorphone will have Hydromorphone used as suggested first-line therapy for analgosedation, when clinically warranted.
  • Drug: Hydromorphone
    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.
    Other names:
    • Dilaudid

Recruiting Locations

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Contact:
Elias Baedorf Kassis, MD

More Details

Status
Recruiting
Sponsor
Beth Israel Deaconess Medical Center

Study Contact

Valerie Goodspeed, MPH
6176328055
vgoodspe@bidmc.harvard.edu

Detailed 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 doses. Hydromorphone is an alternative analgesic agent. It is a semisynthetic morphine derivate that can be five to ten times more potent than morphine. It also has a fast onset (up to 10 minutes), a short half-life (up to three hours) and is less renally excreted than morphine. Some concerns have been raised regarding the accumulation of hydromorphone metabolites including hydromorphone-3-glucuronide, which can lead to neuroexcitatory effects and delirium. A few retrospective studies compared fentanyl and hydromorphone in the critical care setting. Due to the retrospective nature, small size of the studies and several imbalances in the groups, no significant conclusion can be drawn regarding the benefits and risks of fentanyl versus hydromorphone. However, the largest and most recent retrospective study, showed no difference in 28-day mechanical ventilation free days and death during mechanical ventilation. Opioids currently used for analgosedation in mechanically ventilated ICU patients include morphine, fentanyl and hydromorphone. The selection of a specific agent as standard-of-care is determined by primary ICU team preference, logistics, patient characteristics and experience. Although small differences may affect the decision of one over the other, dosage reduction and close monitoring are used rather than switching to an alternative in most cases. Whether or not either of these agents afford additional meaningful clinical benefits, advantages or contribute to meaningful clinical outcomes has not been fully established in available literature and represents the basis for performing this clinical pilot study. Therefore, the investigators propose to study the use of fentanyl and hydromorphone in the critically ill population on mechanical ventilation due to the paucity of data comparing both medications head-to-head and their widespread use. Between November 2025 and April 2026, all patients on mechanical ventilation admitted to the medical intensive care units (MICU) and Finard intensive care unit (FICU - medical and surgical ICU) at Beth Israel Deaconess Medical Center who are 18 years or older will be enrolled. The study will be pragmatic and randomization will be in two clusters. The MICU and the FICU will be randomized to an initial opioid (fentanyl or hydromorphone) in three-months blocks. The assigned opioid will be used as the first line agent of choice for analgosedation. The assigned opioid will be switched at the end of the three-months block. Since the study has a 6 months duration, each ICU will have 3 months with each opioid as first line for analgosedation. The investigators anticipate that 300 patients will be required for sample size.