Assessment of Respiratory Drive and Inspiratory Effort Across Pressure Support Levels in Patients After Major Abdominal Surgery
Phase: NA
Conditions: Inspiratory Effort, Mechanical Ventilation, Major Abdominal Surgeries
Sponsor: Mahidol University

 
Official Title: 
Assessment of Inspiratory Effort and Diaphragmatic 
Function Across Pressure Support Levels in Surgical ICU 
Patients: A Prospective Physiological Study 
ClinicalTrials.gov Identifier (NCT Number): 
NCTXXXXXXXX  
Document Date: 
17th September 2025 
 
 
 
 
 
 
 
 
 
 
 
 

Title Assessment of Respiratory Drive and Inspiratory Effort Across Pressure 
Support Levels in Patients After Major Abdominal Surgery: A Physiological 
Observational Study 
 
Background 
Pressure support ventilation (PSV) is one of the most used modes of partial ventilatory 
assistance in critically ill patients, such as those recovering from acute respiratory 
failure, major surgery, or during weaning from mechanical ventilation (1,2). In PSV, tidal 
volume (Vt) is the result of a dynamic interaction between patient-generated inspiratory 
effort and ventilator-delivered pressure. While this mode aims to unload respiratory 
muscles and preserve spontaneous breathing, inappropriate levels of support—
whether too low or too high—may contribute to patient harm(3). 
Patients undergoing major abdominal surgery(4) often experience significant 
physiological changes that impair respiratory function, including reduced 
diaphragmatic excursion, decreased lung compliance, and impaired cough and 
secretion clearance due to postoperative pain, abdominal splinting, and the effects of 
anesthesia. These changes can persist for days, increasing the risk of atelectasis, 
ventilator-associated complications, and delayed weaning(5,6). In this context, carefully 
titrated PSV is essential to provide sufficient support while avoiding over-assistance 
that may promote diaphragm disuse (3,7,8) or under-assistance that may lead to 
excessive respiratory effort and patient self-inflicted lung injury (P-SILI).(3,9,10) 
Traditional parameters such as Vt and respiratory rate alone are insufficient to evaluate 
the patient’s contribution to breathing effort. The gold standard for measuring 
inspiratory effort remains esophageal pressure (Pes) monitoring, which allows 
estimation of the work of breathing and transpulmonary pressure (1,11,12). Alternatively, 
the electrical activity of the crural diaphragm (EAdi) has been proposed as a surrogate 
for respiratory drive and effort (13). However, both methods are limited by their 
invasiveness, cost, and technical complexity, which limits their feasibility in routine 
practice. 
Given these limitations, several simpler bedside tools have emerged, including 
occlusion pressure at 0.1 seconds (P0.1), maximum negative occlusion pressure 
(Pocc), and the pressure muscle index (PMI). P0.1 (airway occlusion pressure 
measured during the first 100 milliseconds of inspiration) is a useful screening tool for 
assessing respiratory drive, whereas Pocc (the maximum negative pressure during an 
inspiratory occlusion) and PMI (a derived measure estimating inspiratory effort) may 
better reflect inspiratory effort (1,3,14,15). Low PMI or a lack of inspiratory pressure plateau 
may indicate over-assistance, while high Pocc values suggest excessive effort and 
under-assistance(1,3,14).  

Importantly, no prior studies have specifically investigated how respiratory parameters 
change in response to pressure support level adjustments in the postoperative setting 
following major abdominal surgery. To date, only two relevant studies exist: Docci et al. 
(2023)(7) conducted a physiological study in patients recovering from acute respiratory 
failure, examining the impact of PSV level changes on PMI, Vt, and related variables. 
Another earlier study by Umbrello et al. (2015) (16) included a broader population of post-
major elective surgery patients (10 of whom had undergone abdominal surgery), 
evaluating the correlation between diaphragm ultrasound and traditional effort indices 
during varying PSV levels. Neither study focused exclusively on the unique 
postoperative physiology of major abdominal surgery patients requiring prolonged 
mechanical ventilation, leaving an important knowledge gap. 
Despite these developments, no consensus exists on the optimal PSV level that 
ensures sufficient ventilatory support while preserving respiratory muscle activity. 
Docci et al. (7) introduced a conceptual model suggesting a patient-specific “adequate 
PSV window,” wherein patients modulate their effort to maintain a target Vt across a 
range of support levels. However, data supporting precise bedside criteria or cutoff 
values for over- or under-assistance remain limited 
This study has two primary objectives. First, to evaluate changes in respiratory drive 
and inspiratory effort—measured by Pocc, PMI, and P0.1—and corresponding Vt across 
varying levels of pressure support in surgical ICU patients after major abdominal 
surgery who require prolonged mechanical ventilation (>48 hours)(17). Second, we aim to 
determine the incidence of inadequate assistance (active, quasipassive)(7) in patients 
receiving PSV and explore its association with relevant clinical outcomes. 
Study Design 
This is a prospective, single-center, observational physiological study conducted in the 
surgical intensive care unit (ICU). A repeated-measures design is employed to 
systematically evaluate the effects of pressure support (PS) level adjustments on 
respiratory effort, drive, and diaphragmatic function in mechanically ventilated 
patients.
 
Study Population 
Inclusion Criteria 
• Adult patients (age ≥18 years) admitted to the surgical ICU. 
• Recent major abdominal surgery requiring postoperative ICU care 
• Receiving invasive mechanical ventilation for more than 48 hours 
• Clinically stable, with no plan for extubation within 6 hours of study enrollment. 

• Able to tolerate short-term adjustments in pressure support (PS) level as per 
protocol. 
Exclusion Criteria 
• Known neuromuscular diseases affecting respiratory muscle function. 
• Hemodynamic instability requiring escalation of vasopressor support. 
• Severe hypoxemic respiratory failure requiring PEEP >10 cmH₂O or FiO₂ >60%. 
• Deep sedation (Richmond Agitation-Sedation Scale [RASS] score < –3) or 
ongoing neuromuscular blockade. 
• History of chronic obstructive pulmonary disease (COPD) or other obstructive 
lung diseases. 
 
Intervention / Protocol 
After confirming eligibility and obtaining informed consent (from patients or legally 
authorized representative), enrolled patients will undergo a standardized stepwise 
adjustment of pressure support (PS) levels while remaining in pressure support 
ventilation mode. During the protocol, Automatic Tube Compensation (ATC) will be 
turned off to avoid interference with respiratory measurements. This protocol was 
adapted from Docci et al. (7). Measurements will be performed once daily for up to three 
consecutive days or until the patient is extubated—whichever occurs first. 
 
Pressure Support Steps 
Patients will be studied at six PS levels in the following sequence: 
• Baseline PS (clinically set level) 
• Baseline −6 cmH₂O 
• Baseline −3 cmH₂O 
• Return to baseline PS 
• Baseline +3 cmH₂O 
• Baseline +6 cmH₂O 
 
The order of the four non-baseline steps will be randomized for each patient using 
sealed envelopes, while the baseline PS step will be performed first and repeated last to 
assess measurement reproducibility. 
At each pressure support (PS) level, a 2-minute stabilization period will be followed by 
three consecutive measurements of the following parameters: tidal volume (Vt), 
respiratory rate, P0.1, Pocc, pressure muscle index (PMI), static compliance of the 

respiratory system (Crs), and peripheral oxygen saturation (SpO₂). Vt, RR, P0.1, Pocc, 
PMI, and Crs will be obtained from the ventilator, while SpO₂ will be recorded from the 
ICU monitor. PMI will be calculated as PMI = Pplat − (PEEP + PS), and Crs as Crs = Vt / 
(Pplat − PEEP). All values will be averaged across the three readings. Figure 1. Study 
Protocol Flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening and Eligibility  
Informed Consent Obtained  
Turn off Automatic Tube Compensation (ATC)  
PS Baseline (Pbase1) for 2 min  
Baseline –6 cmH₂O (P-6) for 2 min  
Baseline –3 cmH₂O (P-3) for 2 min  
Baseline +3 cmH₂O (P+3) for 2 min  
PS Baseline (Pbase2) for 2 min  
Baseline +6 cmH₂O (P+6) for 2 min  
Each step measure the 
following parameters ×3 
•
Vt  
•
RR, HR, BP 
•
SpO2  
•
EtCO2 
•
P0.1  
•
Pocc  
•
PMI  
•
Crs  
 
*Orders of non-baseline 
steps will be randomized  

 
Measurements and Outcomes 
Primary Outcome 
• To evaluate changes in respiratory drive and inspiratory effort—quantified using 
P0.1, maximum negative occlusion pressure (Pocc), and pressure muscle index 
(PMI)—across varying levels of pressure support in adult surgical ICU patients 
after major abdominal surgery. 
Secondary Outcomes 
• To quantify the incidence of quasi-passive and active response patterns during 
pressure support ventilation, based on physiological criteria derived from 
patient responses. 
• To assess the relationship between these ventilatory response patterns and 
clinical outcomes, including duration of mechanical ventilation, ICU length of 
stay, reintubation or non-invasive ventilation use, and ICU/hospital discharge 
disposition. 
Definition of ventilatory response patterns: 
• An active pattern is characterized by relatively stable Vt and plateau pressure 
despite reductions in pressure support, accompanied by a compensatory increase 
in PMI—indicating greater patient-driven effort. In contrast, a quasi-passive 
pattern is marked by a progressive decline in Vt and plateau pressure with little or 
no change in PMI, suggesting limited patient contribution to ventilation. (7) 
• As no standardized thresholds currently exist, these classifications will be 
determined post hoc based on individual response trends observed in the study 
dataset. 
 
Data Collection 
All data will be prospectively collected during each predefined pressure support (PS) 
level (baseline, ±3 cmH₂O, ±6 cmH₂O), following a 2-minute stabilization period at each 
step. The following variables will be recorded: 
 
1. Demographics and Baseline Clinical Data 
- Age, sex, height, weight, BMI 
- Primary diagnosis and operation 
- APACHE II or SOFA score at ICU admission 
- Time from intubation to enrollment (hours) 
- Baseline ventilator settings (PEEP, FiO₂, baseline PS) 
- Baseline arterial blood gas (ABG): pH, PaCO₂, PaO₂, HCO₃⁻, SaO₂ 

 
2. Ventilatory and Physiological Parameters (at each PS level) 
- Tidal volume (Vt) – measured from ventilator display 
- Respiratory rate– measured from ventilator 
- Minute ventilation (MV) – calculated 
- P0.1 – occlusion pressure at 0.1 seconds 
- Pocc – airway pressure drop during inspiratory hold 
- PMI – pressure muscle index calculated as Pplat − (PEEP + PS) 
- Pplat – plateau pressure (via inspiratory hold) 
- Ppeak – peak inspiratory pressure 
- Crs – static compliance: Vt / (Pplat − PEEP) 
- SpO₂ – peripheral oxygen saturation (pulse oximetry) 
- EtCO₂ – end-tidal CO₂ if available 
- HR and MAP – heart rate and mean arterial pressure (non-invasive or arterial line) 
- Use of accessory muscles – observational note 
- Signs of distress or dyssynchrony – e.g., paradoxical breathing, anxiety, diaphoresis 
 
 
4. Post-Protocol Clinical Follow-up 
- Duration of mechanical ventilation after study (in hours) 
- Need for reintubation or non-invasive ventilation within 48 h 
- Total ICU length of stay (LOS) 
- ICU and hospital discharge status 
- Complications: VAP, barotrauma, unexpected weaning failure 
 
 
Safety and Tolerability 
The protocol allows immediate cessation of PS level changes and return to baseline 
settings if any of the following occur: 
• 
Respiratory rate >35 breaths/min 
• 
SpO2 < 90% 
• 
HR > 140 bpm or >30% change from baseline 
• 
Signs of distress: diaphoresis, agitation, anxiety 
• 
Hemodynamic instability 
 
Sample Size 
This is an exploratory physiological study using a repeated-measures design. Based on 
prior literature (Docci et al., 2023; Umbrello et al., 2015), a within-subject difference in 

the pressure muscle index (PMI) of approximately 2.0 cmH₂O (standard deviation ~2.5) 
between pressure support (PS) levels is considered clinically meaningful. 
 
Using a two-sided paired t-test with the following assumptions: 
 
• Alpha (α) = 0.05 
• Power (1 − β) = 0.90 
• Effect size = 0.8 
 
The calculated minimum required sample size is 20 patients. To improve the precision 
of subgroup analyses, enhance generalizability, and account for possible dropouts or 
incomplete data, we plan to enroll a total of 40 patients.
 
Statistical Analysis 
Descriptive statistics will be used to summarize baseline characteristics. Continuous 
variables will be presented as mean ± standard deviation or median (IQR), depending 
on distribution. Categorical variables will be summarized as counts and percentages. 
 
Primary analysis: 
 
• Repeated-measures ANOVA or Friedman test (non-parametric) will be used to 
assess changes in PMI, Pocc, and P0.1 across PS levels. 
• Post-hoc pairwise comparisons will be performed with Bonferroni correction. 
 
Secondary analysis: 
 
• Pearson or Spearman correlation will be used to evaluate relationships between 
effort indices (PMI, Pocc, P0.1). 
• Linear mixed models will explore associations between PS levels and effort 
parameters, accounting for intra-patient variability. 
• The incidence of under- and over-assistance will be described, and logistic 
regression may be used to assess their associations with clinical outcomes 
(e.g., prolonged ventilation). 
 
A p-value <0.05 will be considered statistically significant. Statistical analyses will be 
performed using R. 
 
Ethical Considerations 
• 
Study protocol to be approved by institutional ethics board. 
• 
Written informed consent obtained from patient or surrogate. 
• 
Minimal risk as PS level adjustments are brief and within clinically accepted 
ranges. 

 
 
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