Analgesia-First Sedation for Respiratory Failure

Overseen By Hyunsoon Park, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MemorialCare Health System

Must be taking: Sedatives, Analgesics

Must not be taking: Neuromuscular blockers

Disqualifiers: Cardiac arrest, Neurological deficit, Alcohol dependence, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to manage pain and sedation for trauma patients who require mechanical ventilation. It compares two methods: one prioritizes pain medication and uses sedatives only as needed (Analgesia First Sedation Strategy for Mechanically Ventilated Trauma Subjects), while the other involves regular sedation with daily breaks. The study seeks patients who have been on a ventilator for at least 48 hours and are candidates for weaning off the machine. As an unphased trial, it offers patients the chance to contribute to important research that could enhance care for future trauma patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are receiving neuromuscular blocking agents or have allergies to certain sedatives, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that starting with pain relief, using medications like fentanyl before sedatives, may be safer. When administered in small amounts and infrequently, fentanyl is usually well-tolerated. However, monitoring for side effects like low blood pressure or breathing problems is important.

Studies have found that sedation directed by a specific plan can help achieve sedation goals and might reduce the time patients need a breathing machine. Propofol, a common sedative used in this method, is generally safe but can cause low blood pressure or a slower heartbeat.

Both methods require careful monitoring by medical staff to ensure safety and manage any side effects. Researchers are studying these strategies to find the safest and most effective way to assist trauma patients who need a breathing machine. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two different sedation strategies for mechanically ventilated trauma patients. The "Analgesia First Sedation" approach is unique because it prioritizes pain relief using intermittent doses of fentanyl before sedation, potentially reducing the need for continuous sedative infusions, which can lead to fewer side effects and shorter ventilation times. On the other hand, "Protocol Directed Sedation and Daily Sedation Interruption" methodically adjusts sedation levels to optimize patient comfort and respiratory function, possibly enhancing recovery times. Unlike typical sedation protocols that may rely heavily on continuous sedation, this trial aims to find a balance that could improve patient outcomes and reduce time on mechanical ventilation.

What evidence suggests that this trial's treatments could be effective for respiratory failure?

This trial compares two sedation strategies for patients on breathing machines. One arm uses the Analgesia First Sedation strategy, focusing on managing pain first with medications like fentanyl and using calming drugs only if needed. Research has shown that starting with pain relief can effectively stabilize brain function and potentially reduce risks associated with constant sedation. The other arm employs Protocol Directed Sedation and Daily Sedation Interruption, involving a structured sedation approach and regular assessment. Although more research is needed, early findings suggest that the Analgesia First Sedation strategy might help patients recover faster and spend less time on the ventilator, potentially improving outcomes for trauma patients on ventilators. ^{1 2 3 4 6}

Who Is on the Research Team?

Maged Tanios, MD, MPH

Principal Investigator

Long Beach Memorial Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are on mechanical ventilation due to trauma, expected to need it for at least 48 hours, and can potentially be weaned off. It's not suitable for those with chronic neurological issues, allergies to certain sedatives, a history of substance abuse, prior continuous sedation from another hospital or those on muscle relaxants.

Inclusion Criteria

You are currently using a breathing machine and are expected to continue using it for at least 48 hours.

I am considered for weaning off mechanical ventilation.

I am receiving continuous pain or sedation medication from the ICU team.

Exclusion Criteria

I have a long-term neurological condition that affects my daily activities.

You are allergic to midazolam, lorazepam, or propofol.

I was admitted to the hospital after being revived from a cardiac arrest.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either protocol-directed sedation with daily sedation interruption or analgesia-first sedation while on mechanical ventilation

28 days

Daily assessments in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events related to mechanical ventilation

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Analgesia First Sedation Strategy for Mechanically Ventilated (MV) Trauma Subjects
• Protocol Directed Sedation and Daily Sedation Interruption

Trial Overview The study compares two methods of managing pain and sedation in mechanically ventilated trauma patients: the usual method with daily wake-up checks versus an 'analgesia-first' strategy that prioritizes pain management and minimizes sedative use.

How Is the Trial Designed?

Group I: Analgesia First Sedation Experimental Treatment 1 Intervention

Subjects will be randomized to receive analgesia-first sedation by intermittent doses of Fentanyl (25 mcg), instead of continuous IV infusions. If the intermittent IVP x4 fails to achieve the target pain score, an infusion starts at 50 mcg/hr and titration by 25 mcg q15 minutes. If sedation score is not achieved, propofol infusion starts at 5 mcg/kg/min to achieve goal RASS of 0 to -2. Subjects will be assessed for a ventilator weaning trial daily.

Group II: Protocol Directed Sedation and Daily Sedation Interruption Active Control 1 Intervention

Pain management will be initiated with intravenous fentanyl at 50 mcg/hr. If the goal pain score is not achieved, use bolus doses and increase the rate by 25 mcg/hr every 15 minutes until the goal pain score is achieved. If the goal pain score is surpassed, lower the rate by 25 mcg/hr every 15 minutes. If at goal pain score, continue the current dose. If RASS scores less than the goal and Propofol is already off - decrease Fentanyl infusion. Agitation management will be initiated with intravenous propofol starting at 5 mcg/kg/min. Bolus doses will be used, and the rate will be increased by 5 mcg/kg/min every 15 minutes until goal RASS is achieved. If goal RASS is surpassed, lower the rate by 5 mcg/kg/min every 15 minutes until goal RASS is achieved. Bolus dose: 25 mg IVP every 5 minutes up to 2 doses PRN agitation before increasing infusion rate. Midazolam or dexmedetomidine substitutions for propofol are allowed according to the institutional protocol.

Who Is Running the Clinical Trial?

MemorialCare Health System

Lead Sponsor

Trials

21

Recruited

2,600+

Published Research Related to This Trial

In a study of 105 critically ill patients, remifentanil-based sedation significantly reduced the duration of mechanical ventilation by over 2 days and improved the weaning process, leading to faster extubation compared to conventional midazolam-based sedation.

Remifentanil was well tolerated and allowed for a lower total dose of midazolam, with no evidence of drug accumulation or tolerance, indicating its safety and efficacy for prolonged sedation in ICU patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial [ISRCTN47583497]. Breen, D., Karabinis, A., Malbrain, M., et al.[2018]

The implementation of an analgesia/sedation protocol (ASP) in a surgical ICU significantly reduced the use of fentanyl and midazolam, leading to a decrease in cumulative dosages of these medications (P < 0.001 for fentanyl and P = 0.001 for midazolam).

Patients managed under the ASP achieved sedation goals more effectively (86.8% vs. 74.4%, P < 0.001) and experienced fewer days on mechanical ventilation (3.8 days vs. 5.9 days, P = 0.033), indicating improved management of sedation and pain in critically ill surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre- and post-intervention study to assess the impact of a sedation protocol in critically ill surgical patients. Porhomayon, J., Nader, ND., El-Solh, AA., et al.[2015]

Individualized sedation management, which includes using assessment tools and protocols, can significantly improve patient outcomes in mechanically ventilated adults in the ICU.

Despite the availability of effective strategies and guidelines for sedation and analgesia, their implementation in clinical practice remains slow, highlighting the need for better education and research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current sedation practices: lessons learned from international surveys. Mehta, S., McCullagh, I., Burry, L.[2022]

A sedation strategy that focuses on minimizing changes in consciousness while ensuring comfort and adaptation to mechanical ventilation is feasible for critically ill patients, even though high doses of sedatives may be needed for those with severe conditions like ARDS or ICH.

Using a structured sedation algorithm can significantly reduce the duration of mechanical ventilation by up to 50%, highlighting the importance of a multidisciplinary approach in managing sedation effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of the sedated patient]. De Jonghe, B., Appéré-De-Vecchi, C., Outin, H.[2020]

The implementation of an Analgesia-Delirium-Sedation (ADS) protocol in critically ill trauma patients significantly reduced the median duration of mechanical ventilation from 3.2 days to 1.2 days, indicating improved respiratory outcomes.

Patients under the ADS protocol also experienced a shorter hospital stay, averaging 12 days compared to 18 days in the control group, while also requiring less sedative medication, demonstrating both efficacy and potential safety benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay. Robinson, BR., Mueller, EW., Henson, K., et al.[2022]

The implementation of a sedation and analgesia protocol in a pediatric intensive care unit led to a significant reduction in the continuous infusion of opioids and benzodiazepines in patients requiring mechanical ventilation for more than 72 hours, with opioid use decreasing from 7.6 to 6 days and benzodiazepine use from 7.6 to 3.3 days.

This study involved 191 patients (99 pre-intervention and 92 post-intervention) and highlights the effectiveness of structured protocols in managing sedation and analgesia, although no significant changes were observed in overall mechanical ventilation days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the implementation of a sedation and analgesia protocol in a pediatric intensive care unit. Taffarel, P., Widmer, J., Fiore, Á., et al.[2023]

Standardized pain assessment using tools like the Behavioral Pain Scale (BPS) and Critical-Care Pain Observation Tool (CPOT) is crucial for providing effective pain management in mechanically ventilated patients, yet assessment rates in ICUs remain low.

Implementing an analgesia-first sedation approach and maintaining patients in lighter sedation states can lead to better clinical outcomes, highlighting the importance of individualized and patient-centered care strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Progress of pain assessment and analgesia strategy for mechanical ventilation patients]. Li, Q., Wan, X.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7653978/

Analgesia and sedation in patients with ARDS - PMC First, patients have an additional risk, i.e., the displacement/malfunction ... Sevoflurane for sedation in acute respiratory distress syndrome. a ...

2. uptodate.com uptodate.com/contents/sedative-analgesia-in-ventilated-adults-management-strategies-agent-selection-monitoring-and-withdrawal/print

Sedative-analgesia in ventilated adults: Management ... ... respiratory distress ... Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019.

3. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/cc6151

Strategies to optimize analgesia and sedation - Critical Care Long-term consequences of recovery from respiratory failure include ... mechanically ventilated patients at risk for coronary artery disease.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05751863?term=AREA%5BConditionSearch%5D(%22Respiratory%20Failure%22)%20AND%20AREA%5BInterventionSearch%5D(%22Propofol%22)&rank=10

NCT05751863 | Analgesia-First Sedation in Trauma Patients ... sedation only if the analgesia-first approach failed. The intervention arm had ... Mechanical Ventilation Respiratory Failure. Mechanical Ventilation ...

5. atsjournals.org atsjournals.org/doi/10.1164/rccm.201102-0273CI

Sedation and Analgesia in the Mechanically Ventilated ... It is safe to use in moderate renal insufficiency but has not been studied yet in liver failure. Further study is necessary to determine whether ...

6. withpower.com withpower.com/trial/analgesia-first-sedation-for-respiratory-failure-37cbb

Analgesia-First Sedation for Respiratory Failure ... efficacy for patients with Peroneal Nerve Injury, Anosognosia, Respiratory Impairment, Mechanical Ventilation and Breathing Failure. See if you qualify today!