Modified Deep vs. Standard Awake Extubation

(mDE Trial)

Overseen By naveed siddiqui, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Must not be taking: Remifentanil, Chronic opioids

Disqualifiers: Difficult airway, Pregnancy, BMI>30, others

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

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is to compare a modified DE technique, which is regularly used for low-risk patients by staff anesthesiologists at our institution, to a standard awake extubation. This modified deep extubation (mDE) occurs while the patient is still anaesthetized but at a lower dose of anaesthetic gas than previously described, and balanced with long acting opioids to attenuate the airway reaction. As previously stated, the literature shows that the risks of DE are equivalent to those of regular AE practice. Our hypothesis is that mDE will shorten the time from the end of the surgery (completion of last stitch) to the moment the patient is ready to leave the OR by at least 5 minutes when compared to standard AE practice.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you use opioids for chronic pain, you cannot participate in the trial.

What data supports the idea that Modified Deep vs. Standard Awake Extubation is an effective treatment?

The available research does not provide any data on Modified Deep vs. Standard Awake Extubation. The studies focus on treatments for multiple myeloma, rheumatoid arthritis, and COPD, but none of them mention or evaluate the effectiveness of Modified Deep vs. Standard Awake Extubation. ^{1 2 3 4 5}

What safety data exists for Modified Deep vs. Standard Awake Extubation?

The provided research does not contain specific safety data for Modified Deep vs. Standard Awake Extubation or any of its variations. The studies focus on adverse drug events and generic product substitutions, not on extubation techniques. ^{6 7 8 9 10}

Is Modified Deep Extubation a promising treatment?

Yes, Modified Deep Extubation is promising because it can help patients breathe better after being on a ventilator. It uses techniques like mechanical insufflation-exsufflation and noninvasive ventilation to improve breathing and reduce the need for re-intubation, which means patients can recover faster and spend less time in the ICU. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for patients with physical status classifications ASA I-III who are undergoing laparoscopic surgery under general anesthesia. It's not specified who can't join, but typically those with higher risks or conditions that could interfere with the study might be excluded.

Inclusion Criteria

ASA I-III

I am having surgery with small incisions under general anesthesia.

Exclusion Criteria

Pregnant women

Patients with full stomach

Patients using opioids in chronic pain management

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Preoperative Assessment

Patients undergo assessment in the Pre-Admission Unit (PAU) and are introduced to the study

1 day

1 visit (in-person or phone)

Randomization and Extubation Procedure

Patients are randomized to either the AE or mDE group and undergo the extubation procedure

Day of surgery

1 visit (in-person)

Post-Anesthesia Care Unit (PACU) Monitoring

Patients are monitored in the PACU for recovery and interviewed about their experience

Until discharge from PACU

1 visit (in-person)

Follow-up

Participants are monitored for any complications or adverse events post-extubation

1 day

Treatment Details

Interventions

• Modified Deep Extubation
• Standard Awake Extubation

Trial Overview The study compares two ways of removing a breathing tube after surgery: standard awake extubation (AE) and modified deep extubation (mDE). mDE involves reducing anesthetic gas and using long-acting opioids to lessen airway reactions. The goal is to see if mDE speeds up recovery time in the operating room by at least 5 minutes.

Participant Groups

Group I: standard awake extubation Experimental Treatment 1 Intervention

awake extubation (AE) is still considered the standard practice.

Group II: modified deep extubation Experimental Treatment 1 Intervention

This modified deep extubation (mDE) occurs while the patient is still anaesthetized but at a lower dose of anaesthetic gas than previously described, and balanced with long acting opioids to attenuate the airway reaction.

Who Is Running the Clinical Trial?

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Lead Sponsor

Trials

132

Recruited

11,400+

Findings from Research

The phase 3 FIRST trial demonstrated that continuous treatment with lenalidomide plus low-dose dexamethasone (Rd continuous) significantly prolonged progression-free survival and overall survival in transplant-ineligible patients with newly diagnosed multiple myeloma compared to standard treatment with melphalan, prednisone, and thalidomide (MPT).

In patients achieving complete response (CR) or very good partial response (VGPR), Rd continuous reduced the risk of progression or death by up to 67% compared to MPT, and showed similar survival rates to Rd for 18 cycles, indicating its effectiveness across various levels of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial. Bahlis, NJ., Corso, A., Mugge, LO., et al.[2018]

In a study of 1107 rheumatoid arthritis patients, DMARD (disease-modifying antirheumatic drug) intensification was primarily influenced by patient-reported outcomes (PROs), accounting for 61% of the decisions, compared to 42% from doctor-reported outcomes (DROs).

Despite having high disease activity (DAS28 >3.2), only 15% of patients received DMARD intensification, highlighting a gap in treatment adjustments based on inflammation levels versus patient symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative importance of doctor-reported outcomes vs patient-reported outcomes in DMARD intensification for rheumatoid arthritis: the DUO study. Dougados, M., Nataf, H., Steinberg, G., et al.[2015]

In a study of 140 patients with relapsed or refractory multiple myeloma, those treated with low-dose dexamethasone (Rd) alongside lenalidomide showed a median overall survival of 41 months, compared to 20 months for those on intermediate doses (RD).

While both treatment regimens resulted in similar partial response rates (62% for RD and 73% for Rd), the low-dose regimen (Rd) was associated with fewer severe side effects, such as grade 3 and 4 neutropenia and fatigue, indicating it may be a safer option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide with low- or intermediate-dose dexamethasone in patients with relapsed or refractory myeloma. Zagouri, F., Roussou, M., Kastritis, E., et al.[2019]

In a study of 389 newly diagnosed multiple myeloma patients, those treated with carfilzomib, lenalidomide, and dexamethasone (KRd) showed significantly better progression-free survival (PFS) and event-free survival (EFS) compared to those treated with bortezomib, lenalidomide, and dexamethasone (VRd), particularly in high-risk patients.

The 5-year PFS was 67% for KRd versus 56% for VRd, and the 5-year overall survival (OS) was 90% for KRd compared to 80% for VRd, indicating that KRd may offer better long-term outcomes for patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, Lenalidomide and Dexamethasone (VRd) vs Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Therapy in Newly Diagnosed Multiple Myeloma. Tan, CR., Derkach, A., Nemirovsky, D., et al.[2023]

In a study of 110 COPD patients, those with a history of moderate to severe acute exacerbations and specific blood eosinophil counts showed significant clinical deterioration, indicating that triple therapy (ICS/LABA/LAMA) may be more effective for these patients.

Key predictors for clinical deterioration included low baseline lung function (FEV1 ≤ 42%), high symptom scores (CAT score ≥ 18), and frequent exacerbations, suggesting that these factors should guide treatment intensification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When to Use Initial Triple Therapy in COPD: Adding a LAMA to ICS/LABA by Clinically Important Deterioration Assessment. Cheng, WC., Wu, BR., Liao, WC., et al.[2021]

Out of 423 reports on adverse events related to generic substitution, 232 (55%) were of sufficient quality to detect signals, indicating that many reports were useful for analysis.

The study found that the substitution of the original drug Norvasc with the generic Amlodipin Ratiopharm did not present significant safety issues, with only two serious adverse events reported and common symptoms like dizziness and muscle pain identified as potential signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse events related to substitution of generic products in Norway 2005]. Reppe, LA., Stenberg-Nilsen, H., Harg, P., et al.[2013]

In a study analyzing 1,567,659 hospital discharges in Spain from 2005-2007, 96,607 adverse drug events (ADEs) were identified, representing 5.55% of all discharges, with a significant portion (82.86%) deemed not preventable.

The study found that adverse drug reactions (ADRs) were more common in women and led to longer hospital stays, highlighting the importance of monitoring and reporting ADEs for improving patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse drug events in patients hospitalized in internal medicine]. Zapatero Gaviria, A., Barba, R., Ruiz Giardin, JM., et al.[2013]

A study analyzed 381 adverse events (AEs) from 148 case reports of generic medications, including tamsulosin, levothyroxine, and amphetamine/dextroamphetamine, revealing that a significant majority (75%-76%) of AEs were related to physical health issues.

The findings highlight that while most AEs were physical, a smaller percentage (9%-18%) were linked to mental health, indicating that patient-reported outcomes for generics should consider both physical and mental health domains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-relevant outcomes associated with generic tamsulosin, levothyroxine and amphetamine in the FDA Adverse Event Reporting System: a pilot study. Marimuthu, SP., Iyer, G., Segal, JB., et al.[2022]

In a study of 26,176 hospitalized patients, 10 life-threatening or fatal adverse drug events (ADEs) were identified, indicating a prevalence of 0.04%, with most related to hemorrhages and respiratory issues.

None of these serious ADEs were reported in the national incident reporting system during the 3-month study period, highlighting a significant gap in the detection and reporting of critical patient safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-Threatening and Fatal Adverse Drug Events in a Danish University Hospital. Tchijevitch, OA., Nielsen, LP., Lisby, M.[2023]

From 2006 to 2014, serious adverse drug events (ADEs) reported to the FDA increased two-fold, totaling 902,323 serious outcomes, including 244,408 deaths, indicating a growing concern for drug safety in real-world settings.

The majority of serious ADE reports came from health professionals (47.3%), with a significant number of reports among older adults (72.6% for ages 45 and above), highlighting the need for targeted monitoring and safety measures for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006-2014 Database. Sonawane, KB., Cheng, N., Hansen, RA.[2023]

In a study of 98 intubated patients with respiratory muscle failure, 97 were successfully extubated to continuous noninvasive ventilatory support (CNVS) using mechanical insufflation-exsufflation (MIE), demonstrating the efficacy of MIE in facilitating extubation for patients who could not meet traditional weaning criteria.

The use of MIE not only normalized oxygen saturation but also significantly increased vital capacity (VC) by 270% within three weeks post-extubation, indicating its potential to improve respiratory function in patients previously dependent on ventilatory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of mechanical insufflation-exsufflation in extubating unweanable subjects with restrictive pulmonary disorders. Bach, JR., Sinquee, DM., Saporito, LR., et al.[2022]

A study involving 1623 patients with progressive neuromuscular disorders (NMDs) showed that many can successfully use continuous noninvasive ventilation (CNVS) as an alternative to tracheostomy mechanical ventilation (TMV), with 47% of users becoming CNVS dependent for an average of 5.4 years in Duchenne muscular dystrophy (DMD) and 1.2 years in amyotrophic lateral sclerosis (ALS).

While CNVS allows for extended respiratory support without hospitalization, it is not a permanent solution for all patients, particularly those with advanced upper motor neuron diseases, indicating a need for careful management of respiratory care in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous noninvasive ventilatory support outcomes for patients with neuromuscular disease: a multicenter data collaboration. Gonçalves, MR., Bach, JR., Ishikawa, Y., et al.[2021]

In a study of 48 postoperative patients on ventilatory support, conventional respiratory mechanics for determining extubation had a high false-negative rate of 48%, potentially delaying necessary extubation.

In contrast, using gas exchange values for extubation criteria accurately predicted successful outcomes in 94% of patients, suggesting that gas exchange metrics are more reliable for guiding extubation decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of two different extubation criteria: attributes contributing to success. DeHaven, CB., Hurst, JM., Branson, RD.[2019]

Intermittent Mechanical Ventilation (IMV) combines spontaneous and mechanical breathing, which can improve gas distribution and reduce respiratory alkalemia compared to conventional mechanical ventilation.

IMV helps maintain normal cardiopulmonary function by lowering mean airway pressure and pulmonary vascular resistance, allowing for better oxygen therapy and minimizing the work of breathing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiopulmonary effects of intermittent mandatory ventilation. Douglas, ME., Downs, JB.[2019]

In a study of 75 patients who had been on mechanical ventilation for over 48 hours, the use of mechanical insufflation-exsufflation (MI-E) as part of the extubation protocol significantly reduced reintubation rates from 48% in the control group to 17% in the MI-E group.

Patients in the MI-E group also experienced a shorter ICU length of stay after extubation, averaging 3.1 days compared to 9.8 days in the control group, indicating that MI-E enhances the effectiveness of noninvasive ventilation (NIV) in preventing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of mechanical insufflation-exsufflation in preventing respiratory failure after extubation: a randomized controlled trial. Gonçalves, MR., Honrado, T., Winck, JC., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Relative importance of doctor-reported outcomes vs patient-reported outcomes in DMARD intensification for rheumatoid arthritis: the DUO study. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide with low- or intermediate-dose dexamethasone in patients with relapsed or refractory myeloma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Bortezomib, Lenalidomide and Dexamethasone (VRd) vs Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Therapy in Newly Diagnosed Multiple Myeloma. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

When to Use Initial Triple Therapy in COPD: Adding a LAMA to ICS/LABA by Clinically Important Deterioration Assessment. [2021]

6. Norway pubmed.ncbi.nlm.nih.gov

[Adverse events related to substitution of generic products in Norway 2005]. [2013]

7. Spain pubmed.ncbi.nlm.nih.gov

[Adverse drug events in patients hospitalized in internal medicine]. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Patient-relevant outcomes associated with generic tamsulosin, levothyroxine and amphetamine in the FDA Adverse Event Reporting System: a pilot study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Life-Threatening and Fatal Adverse Drug Events in a Danish University Hospital. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006-2014 Database. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Efficacy of mechanical insufflation-exsufflation in extubating unweanable subjects with restrictive pulmonary disorders. [2022]

12. Spain pubmed.ncbi.nlm.nih.gov

Continuous noninvasive ventilatory support outcomes for patients with neuromuscular disease: a multicenter data collaboration. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Evaluation of two different extubation criteria: attributes contributing to success. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Cardiopulmonary effects of intermittent mandatory ventilation. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Effects of mechanical insufflation-exsufflation in preventing respiratory failure after extubation: a randomized controlled trial. [2022]