Pilot Study on Pairing Sedation Strategies and Weaning

Comparing Strategies of Pairing Sedation and Weaning Protocols on Outcomes of Mechanical Ventilation: A Pilot Study

A three-arm, randomized, pilot feasibility, study to assess the effect three validated sedation strategies on outcomes of patient on mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Drug: Sedation Protocol with Daily Interruption; Drug: Sedation Protocol Without Daily Interruption; Drug: Fentanyl Push First

Detailed Description

A three-arm, randomized, pilot feasibility, study to assess the effect three validated sedation strategies on outcomes of patient on mechanical ventilation.

A significant proportion of patients admitted to the intensive care unit (ICU) require mechanical ventilation (MV). To maintain comfort and facilitate quality care, large quantities of sedatives and analgesics are often administered either by continuous infusion, with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics. Three validated sedation strategies are currently available. A recently published study ( trial has shown that instituting protocol-directed sedation in patients requiring continuous infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial) evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a Danish study by Strom et al. investigated whether an analgesia-first approach to patient comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV sedation for short periods only when acute agitation was present, would be superior to a protocol similar to the ABC trial. While the three above mentioned approaches are accepted and currently implemented in the critical care community there is no comparative study or evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing weaning readiness with each of these strategies. It is possible that a SAT strategy, where sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a strategy in patients managed with a sedation protocol where intravenous sedative and analgesic therapy is regularly titrated to maintain patients in a lightly sedated state. Moreover, it remains unclear whether there are advantages of an analgesia-first sedation strategy over either an SAT or sedation protocol strategy in terms of the time it takes to wean patients from MV. However, it is noteworthy to mention that the analgesia-first strategy was associated with more delirium episodes, which were attributed to the ability to assess for it in a more awake patient. However, comparing delirium occurrence in studies with different sedation goals and methodologies may be inaccurate.

The investigators therefore propose a three-arm, randomized, pilot feasibility, study to assess the effect of these three (3) validated strategies for sedation and pain management

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥ 18 years of age
2. Mechanically ventilated with an expected duration of MV ≥ 48 hours
3. ICU team has initiated continuous sedative and/or /analgesic infusions

Exclusion criteria:

1. Admission after resuscitation from cardiac arrest
2. Admission with traumatic brain injury or another acute neurologic event (e,g. stroke, uncontrolled seizures).
3. History of severe dementia
4. Admission because of acute alcohol withdrawal or acute drug intoxication
5. Administration of more than 24 hours of continuous sedation
6. Allergy to fentanyl, midazolam, and/or propofol
7. Lack of informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sedation protocol with interruption; Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed.	Drug: Sedation Protocol with Daily Interruption; Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.; Other Names: midazolam; fentanyl
Active Comparator: Sedation protocol without Interruption; Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen.	Drug: Sedation Protocol Without Daily Interruption; Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.; Other Names: midazolam; fentanyl
Active Comparator: Fentanyl push first; This arm attempts to manage patient's pain and agitation with analgesia first. Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours.	Drug: Fentanyl Push First; Fentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs).; Other Names: propofol; fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Feasibility	Protocol/study feasibility based on protocol compliance.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of weaning	Time from initiation of weaning until successful extubation	Up to 180 days
ICU length of stay	The number of days from ICU admission to ICU discharge	Up to 180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical Ventilation Free Days	This is clinical outcome and represent the number of days where patients were breathing without assistance during the study period.	Up to 28 days
Duration of Weaning	Duration of weaning: Time from initiation of weaning until successful extubation	Up to 28 days

Collaborators and Investigators

• Sponsor: MemorialCare Health System
• Collaborators: Memorial Medical Center Foundation
• Investigators: Principal Investigator: Maged Tanios, MD, MPH, Long Beach Memorial Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimated): August 19, 2014

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: mechanical ventilation; ventilator weaning; sedation strategy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Propofol
• Other Study ID Numbers: 25613

Plan for Individual participant data (IPD)

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