Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06293976 |
| Other study ID # |
4506 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 12, 2024 |
| Est. completion date |
March 1, 2026 |
Study information
| Verified date |
May 2024 |
| Source |
Unity Health Toronto |
| Contact |
Antenor Rodrigues |
| Phone |
416-864-5686 |
| Email |
Antenor.Rodrigues[@]unityhealth.to |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: Reverse triggering (RT) is a frequent phenomenon observed in sedated patients
under a mechanical ventilation mode called assist-control ventilation. RT is when the
ventilator would trigger the patient's respiratory effort instead of the correct order of the
patient's respiratory effort triggering the ventilator. Reverse triggering can have negative
consequences (loss of protective lung ventilation, and causing double breaths - with the
ventilator giving two consecutive breaths and not allowing the patient to exhale) but also
offer some protective effects (avoid diaphragm disuse atrophy). The balance of its negative
vs positive effects depends on its frequency and magnitude of its associated respiratory
effort. Respiratory entrainment is the most often referred mechanism involving a change in
patient's rate of breathing effort from that of patient's intrinsic rate to the rate of
mechanical insufflation. The specific ventilatory settings associated with or responsible for
RT remains unknown.
Aims: To assess in mechanically ventilated critically ill patients the influence of the set
respiratory rate (RR) and tidal volume (Vt) on the presence/development of RT and to describe
the pattern of respiratory muscle activity during Reverse Triggering (RT).
Methods. 30 adult patients (15 in each group), sedated and under assist-controlled
ventilation will be included. Ventilator settings will be modified to modulate the frequency
and magnitude of reverse triggering. Initially, with the ventilator on a mode called volume
control, which means the ventilator controls the amount of air (tidal volume) and the number
of breaths the patients gets every minute (respiratory rate [RR]). The tidal volume will be
set at the current standard clinical practice setting (6 ml/kg of predicted body weight). The
presence of an intrinsic respiratory rate will be assessed with an end-expiratory occlusion
maneuver. Next, the number of breaths the ventilator gives per minute (RR) will be changed
from 6 breaths less to 6 breaths more, in steps of 2 breaths every minute. The protocol will
be repeated again changing the amount of air the patients gets (tidal volume) from 4, 5, 7
and 8 ml/kg. Continuous recordings of airway pressure, flow, esophageal pressure, electrical
activity of the diaphragm, main accessory muscles and frontal electroencephalography will be
obtained during the protocol and baseline clinical and physiological characteristics and
outcomes will be recorded. A validated software will be used to detect RT and measure the
intensity and timing of each muscle electrical activity and the magnitude of the inspiratory
effort during RT.
Description:
Participants. Critically ill patients (n: 30; aimed recruitment of equal numbers of men and
women) aged 18 years or older admitted to the St. Michael's Hospital, Unity Health Toronto,
Ontario, Canada.
Inclusion criteria:
- patients intubated for more than 12 hours
- exposed to sedation for at least 6 hours
- with a sedation-agitation score ≤ 4
- and corresponding to one of the following categories based on bedside inspection of
ventilator waveforms:
1. patients on assist-control ventilation having reverse triggering at clinical
settings (n: 15).
2. patients on assist-control ventilation without reverse triggering at the clinical
settings (n: 15).
Exclusion criteria:
- primary severe neurological disorders
- previous lung transplant
- contraindications for esophageal catheter insertion
- current use of continuous neuromuscular blocking agents at the time of the study
procedure
- severe metabolic acidosis (pH < 7.25) at the time of study procedure. Study design.
Briefly, first the ventilator Vt is set at 6 ml/kg of predicted body weight (PBW) (i.e.,
clinical practice recommendation) and either a up to 30sec-long (or two inspiratory
efforts) end-expiratory occlusion maneuver will be performed on the ventilator or the
patient will be switched to pressure support for 30 - 60 sec (based on discussion with
the clinical team) to assess the presence or absence of patient's intrinsic RR.
Secondly, the influence of the ventilator RR on both the occurrence of reverse triggering and
the level of effort associated with the reverse triggered breath will be assessed. In random
order the ventilator RR will be modified from 6 bpm below up to 6 bpm above the clinical RR
in steps of 2 bpm every 1 minute (Figure 1). A 1-minute stage at the patients clinical
settings of ventilation in-between each step will be performed to minimize changes in PaCO2.
Thirdly, the influence of the Vt set on the ventilator on both the occurrence of reverse
triggering and the level of effort associated with the reverse triggered breath will be
assessed. The ventilator Vt will be set to 5 ml/kg PBW, 7 and 8 ml/kg PBW in random order and
for each volume, repeat the sequence described in the paragraph above. A 1-minute clinical
settings ventilation will be performed in-between each step to minimize changes in PaCO2.
Next, the patient will be returned to their initial clinical settings. Another end-expiratory
occlusion of up to 30 seconds (or two inspiratory efforts) or switch the patient to pressure
support for 30 - 60 sec (based on discussion with the clinical team) will be performed to
search for an intrinsic RR (i.e., intrinsic respiratory drive). If an intrinsic respiratory
rate ≥8 breaths per minute is present and P/F ratio is ≥150, it will propose to the clinician
to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If
the patient tolerates well 5 minutes in pressure support, it be will propose to the clinician
to maintain the patient in pressure support ventilation.
The steps described above will be aborted at any point if SpO2 drops below 85% for at least
two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure >35 cmH2O.
Additionally, the ventilator waveforms and electroencephalography (EEG) will be recorded
continuously for the next 24 hours to investigate whether the presence of intrinsic RR was
associated with changes in the ventilation mode by the clinician and brain activity.
