Oxygen Consumption (VO2), Effort, and Weaning in the Mechanically Ventilated Patient in the Intensive Care Unit (ICU) (EXTUBATE)

Oxygen Consumption (VO2), Effort, and Weaning in the Mechanically Ventilated Patient in the Intensive Care Unit (ICU): EXTUBATE Study

In patients who are mechanically ventilated for more than 72 hours weaning failure is a common issue. The Spontaneous breathing trial (SBT) is often done to assess if the patient can be extubated with a high chance of success. However, re-intubation rates are between 15 - 20 % after a successful SBT. The rapid shallow breathing index (RSBI) is an important parameter used in an SBT. Because the high incidence of extubation failure (re-intubation within 48 hours) a search for a better parameter than the RSBI is warranted. Using the measured end-tidal oxygen (etO2) of mechanically ventilated patients it is possible to calculate the VO2, which is a measure of patient effort. The VO2 is a parameter with the potential to predict weaning success or failure, together with other parameters of patient effort like the work of breathing (WOB), pressure time product (PTP) and esophageal pressure swings, reflecting muscle strength of the diaphragm. Therefore, the investigators want to investigate if these parameters are associated with an SBT success or failure.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Oxygen Consumption; Intensive Care Unit; Weaning Failure; Mechanical Ventilation; Spontaneous Breathing Trial
• Intervention / Treatment: Diagnostic test: Spontaneous Breathing Trial

Detailed Description

Weaning failure is a common problem in patients who are mechanically ventilated for more than 72 hours. Prediction of successful extubation is crucial for mechanically ventilated (MV) intensive care patients. Prolonged intubation leads to prolonged mechanical ventilation, which is known to have undesirable and detrimental effects. Premature extubation, on the other hand, is associated with clinical deterioration, a second episode of mechanical ventilation, and prolonged mechanical ventilation, resulting in multiple adverse outcomes.

In addition, up to 20% of all Intensive Care Unit (ICU) patients fail to wean from mechanical ventilation. Prolonged mechanical ventilation is associated with half of the total time spent on the ICU. Improving the prediction of successful weaning provides physicians with a mean to optimize extubation timing, while reducing the incidence of premature extubation.

The rapid shallow breathing index (RSBI) is a parameter commonly used to predict extubation success, next to some other clinical parameters such as consciousness level, the ability to cough and muscle strength. The most commonly used RSBI cut-off value for predicting save extubation incorrectly classifies 15% to 20% of patients. Which means that those patients require another period of mechanical ventilation with possible adverse consequences. It is therefore necessary to develop new parameters or indices aiding in the guidance of extubation timing.

Various other parameters, such as work of breathing (WOB), transpulmonary pressure swings (PS) and the pressure time product (PTP), which are manifestations of patient effort, have been investigated. Although a difference in transpulmonary pressure swings during a spontaneous breathing trial (SBT) has been linked to weaning failure, it has yet to be determined whether transpulmonary pressure swings predict extubation success or failure. For all these measures of effort the placement of an esophageal catheter is obligatory.

Oxygen consumption (VO2) is a direct manifestation of patient effort. It is defined as the difference between the amount of oxygen inhaled and exhaled over a predetermined time interval. Using end tidal oxygen (etO2) measurements and volumetric calculations, it is feasible to track VO2 variations breath-by-breath. A change in oxygen consumption during an SBT could be an early indicator of patient effort and failure.

The investigators hypothesize that VO2 measurement, together with indices of patient effort, could be valuable additional parameters when estimating weaning failure or success, and therefore, aid in the prediction of extubation success or failure.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Florence E Smits, MSc; Phone Number: +31 (0)71-5262164; Email: f.e.smits@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333ZA
    • Not yet recruiting
    • Leiden University Medical Center
    • Contact: Abraham Schoe, MD PhD; Email: a.schoe@lumc.nl
    • Contact: Florence E Smits, MSc; Email: f.e.smits@lumc.nl
  • Zuid - Holland
    • Leiden, Zuid - Holland, Netherlands, 2333 ZA
      • Recruiting
      • Leiden University Medical Centre
      • Contact: Abraham Schoe, MD, PhD; Phone Number: +32-715265018; Email: a.schoe@lumc.nl
      • Principal Investigator: Abraham Schoe, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The intended population consists of adults who are mechanically ventilated in the ICU and meet the criteria for a regular spontaneous breathing trial according to the ruling LUMC protocol.

Description

Inclusion Criteria:

• Age above 18 years
• > 24 hours mechanically ventilated
• Eligible for a spontaneous breathing trial according to the clinical team
• Regular SBT ("Regulier SBT") according to the Leiden University Medical Center (LUMC) protocol
• Hemodynamically stable
• Esophageal Catheter in situ

Exclusion Criteria:

• Severe chronic obstructive pulmonary disease (COPD) (Gold class IV) if it results in a non regular SBT according to the LUMC protocol.
• Heart failure (LVEF <30%) if it results in a non regular SBT according to the LUMC protocol
• Known pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Spontaneous Breathing Trial; Patients who will undergo a spontaneous breathing trial	Diagnostic test: Spontaneous Breathing Trial; Patients will undergo an SBT to determine whether they are ready for extubation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of weaning failure	weaning failure is defined as not meeting the criteria for a succesful spontaneous breathing trial (SBT) or extubation failure, defined as the need for re-intubation within 48 hours, after a succesful SBT and subsequent extubation.	48 hours after SBT
Differences of oxygen consumption during SBT	The values of oxygen consumption (in milliliter/minute) and the differences between start, during, and end of the SBT.	10 minutes before, through SBT (average of 30 minutes) and 10 minutes after SBT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of esophageal pressure swings measured with an esophageal catheter during SBT	The values of pressure swings (in cmH2O), measured with an esophageal catheter, and the differences between start, during, and end of the SBT.	10 minutes before, through SBT (average of 30 minutes) and 10 minutes after SBT
Differences of work of breathing measured with an esophageal catheter during SBT	The values of work of breathing (in Joules/liter), measured with an esophageal catheter, and the differences between start, during, and end of the SBT.	10 minutes before, through SBT (average of 30 minutes) and 10 minutes after SBT
Differences of pressure time product measured with an esophageal catheter during SBT	The values of pressure time product (in cmH2O/seconds), measured with an esophageal catheter, and the differences between start, during, and end of the SBT.	10 minutes before, through SBT (average of 30 minutes) and 10 minutes after SBT
Differences of rapid shallow breathing index during SBT	The values of rapid shallow breathing index (breaths/minute/liter) and the differences between start, during, and end of the SBT.	10 minutes before, through SBT (average of 30 minutes) and 10 minutes after SBT

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Abraham Schoe, MD PhD, Leiden University Medical Center

Publications and helpful links

General Publications

• Beduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Nicolas Terzi, Grange S, Barberet G, Guitard PG, Frat JP, Constan A, Chretien JM, Mancebo J, Mercat A, Richard JM, Brochard L; WIND (Weaning according to a New Definition) Study Group and the REVA (Reseau Europeen de Recherche en Ventilation Artificielle) Network double dagger. Epidemiology of Weaning Outcome according to a New Definition. The WIND Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):772-783. doi: 10.1164/rccm.201602-0320OC.
• Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest. 1997 Jul;112(1):186-92. doi: 10.1378/chest.112.1.186.
• Trudzinski FC, Neetz B, Bornitz F, Muller M, Weis A, Kronsteiner D, Herth FJF, Sturm N, Gassmann V, Frerk T, Neurohr C, Ghiani A, Joves B, Schneider A, Szecsenyi J, von Schumann S, Meis J. Risk Factors for Prolonged Mechanical Ventilation and Weaning Failure: A Systematic Review. Respiration. 2022;101(10):959-969. doi: 10.1159/000525604. Epub 2022 Aug 17.
• Li F, Nie J, Lu Y, Tong TK, Yi L, Yan H, Fu FH, Ma S. The impact of intermittent exercise in a hypoxic environment on redox status and cardiac troponin release in the serum of well-trained marathon runners. Eur J Appl Physiol. 2016 Oct;116(10):2045-51. doi: 10.1007/s00421-016-3460-5. Epub 2016 Aug 29.
• Pham T, Telias I, Beitler JR. Esophageal Manometry. Respir Care. 2020 Jun;65(6):772-792. doi: 10.4187/respcare.07425.
• Jubran A, Grant BJ, Laghi F, Parthasarathy S, Tobin MJ. Weaning prediction: esophageal pressure monitoring complements readiness testing. Am J Respir Crit Care Med. 2005 Jun 1;171(11):1252-9. doi: 10.1164/rccm.200503-356OC. Epub 2005 Mar 11.
• McClave SA, Kleber MJ, Lowen CC. Indirect calorimetry: can this technology impact patient outcome? Curr Opin Clin Nutr Metab Care. 1999 Jan;2(1):61-7. doi: 10.1097/00075197-199901000-00011.
• Takala J, Keinanen O, Vaisanen P, Kari A. Measurement of gas exchange in intensive care: laboratory and clinical validation of a new device. Crit Care Med. 1989 Oct;17(10):1041-7. doi: 10.1097/00003246-198910000-00015.
• Bellani G, Foti G, Spagnolli E, Milan M, Zanella A, Greco M, Patroniti N, Pesenti A. Increase of oxygen consumption during a progressive decrease of ventilatory support is lower in patients failing the trial in comparison with those who succeed. Anesthesiology. 2010 Aug;113(2):378-85. doi: 10.1097/ALN.0b013e3181e81050.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: P23.068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be shared upon request with researchers.

Drug and device information, study documents

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