Opioid vs. Benzodiazepine-based Sedation for Mechanically Ventilated Patients in the Internal Medicine Ward

Opioid-based sedation as a first line in mechanically ventilated patients has been considered the "gold standard" in intensive care unit patients around the world for several decades. Advantages of opiate-based sedation, compared to benzodiazepine-based sedation, which has been used in the past, include a reduction in delirium scores, better pain control, decreasing the time between cessation of sedation and patient awakening, and decreasing the time between cessation of sedation and extubation, with decreased ICU admission times.

In most Western European countries, as well as in the United States, there are almost no mechanically ventilated patients hospitalized outside the intensive care unit. In a few countries, including Japan and Israel, mechanically ventilated patients are also hospitalized outside of intensive care units, as part of internal or surgical wards. Contrary to the vast knowledge accumulated regarding different sedation methods in ventilated patients in intensive care units, there are almost no studies that have evaluated different sedation methods in ventilated patients hospitalized in non-intensive care wards. Thus, while there is consensus on the benefits of opioid-based sedation in intensive care units, there is insufficient information to recommend the preferred sedation method in non-ICU wards.

For various reasons, in a large number of the internal medicine wards of hospitals in Israel, the common sedation practice for ventilated patients is still benzodiazepine-based sedation. In the past year, a pilot program was initiated in Internal Medicine Department A at Meir Hospital in Kfar Saba, in which a new protocol for opioid-based sedation in ventilated patients was implemented.

The protocol is based on the continuous intravenous infusion of fentanyl as the first line of treatment for sedation in ventilated patients only. If the sedation-agitation level (as measured by the RASS score) did not match the target RASS score set by the attending physician, a dose up to a maximum limit could be increased according to the protocol. Second-line sedation drugs were addition of continuous intravenous infusion of midazolam (in addition to fentanyl) in hemodynamically stable patients, or addition of continuous intravenous infusion of ketamine in unstable patients. In stable patients who did not reach the desired RASS level under continuous infusion of fentanyl and midazolam, ketamine could be added as a third line drug, in addition to fentanyl and midazolam.

Study Overview

• Status: Completed
• Conditions: Mechanically Ventilated Patients
• Intervention / Treatment: Drug: fentanyl-based sedation; Drug: midazolam-based sedation

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Kfar Saba, Israel
    • Meir medical center Kfar Saba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Patients aged 18-99 who were admitted to Internal Medicine Department A at Meir Hospital in Kfar Saba from January 2020 to January 2021 (inclusive), and required mechanical ventilation.

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Exclusion Criteria: Patients who were sedated and ventilated for palliative care only without any fututre plan for weaning them of ventilation, or patients in whom there was a deviation from the treatment protocol

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fentanyl-based sedation group	Drug: fentanyl-based sedation; fentanyl-based sedation instead of midazolam-based sedation in ventilated patients
Active Comparator: midazolam-based sedation group	Drug: midazolam-based sedation; midazolam-based sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RASS score	comparison of delirium score between the groups	1 year

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Principal Investigator: Sara Dichtwald, Dr, Meir Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: July 25, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: opioid-based sedation, delirium
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Midazolam; Fentanyl
• Other Study ID Numbers: 0114-21-MMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No