Effect of a patient-ventilator asynchrony (PVA) management protocol on treatment outcomes in ICU patients: a randomized controlled trial

Abstract

Background

Mechanical ventilation is a critical life support for ICU patients. However, this intervention can be associated with complications such as patient-ventilator asynchrony (PVA) and subsequent adverse events. This study aimed to investigate the impact of implementing a PVA management protocol on clinical outcomes in ICU patients.

Methods

In this single-blind randomized controlled trial conducted from January to August 2024, a total of 66 mechanically ventilated patients admitted to the ICU of a hospital affiliated with Ahvaz Jundishapur University of Medical Sciences (Ahvaz, Iran) were randomly allocated to either an intervention or control group using a permuted block randomization method. Patients in the intervention group were evaluated for patient–ventilator asynchrony (PVA) every two hours throughout their ICU stay, as long as they remained on mechanical ventilation. If PVA was detected, appropriate interventions were implemented in accordance with the protocol of PVA management. The control group received routine care without a specific PVA management protocol. Data were collected using a structured checklist and analyzed using SPSS version 22. This study registered in the Iranian Registry of Clinical Trials (IRCT20231001059572N1).

Results

There was a significant difference between the intervention and control groups in terms of duration of mechanical ventilation (p < 0.001), length of ICU stay (p < 0.001), and successful weaning from the ventilator (p < 0.001). In all three dimensions, the intervention group showed better outcomes. However, there was no significant difference between the two groups in terms of ICU mortality (p = 0.202) and self-extubation (p = 0.787). Being in the intervention group was the strongest predictive factor for length of ICU stay (β = −8.268, p < 0.001) and duration of mechanical ventilation (β = −3.906, p = 0.003). No major harms or unintended adverse effects were reported related to the intervention.

Conclusion

Implementation of a PVA management protocol was associated with improved clinical outcomes, including reduced duration of mechanical ventilation, shorter ICU stays, and higher rates of successful weaning. Given its simplicity, cost-effectiveness, and the favorable results observed, broader adoption of this protocol in ICU settings is recommended. Further studies are warranted to confirm these findings and examine their generalizability across different clinical contexts.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13104-025-07467-x.

Background

Mechanical ventilation using a ventilator is one of the most commonly used life support techniques in ICUs worldwide [1–3]. Approximately 20 million people globally require the use of ventilators daily for various reasons [4]. The primary goal of mechanical ventilation is not to treat lung diseases but to meet the patient’s ventilation and oxygenation needs by establishing mechanical ventilation and supporting the lungs until the underlying cause is resolved [5]. In fact, mechanical ventilation is a life-support system used to ensure blood gas exchange and to assist the respiratory muscles in ventilating the lung during the acute phase of lung disease or following surgery [6]. However, prolonged mechanical ventilation and intubation can be associated with numerous complications for patients [7]. Therefore, the ICU health care team always strives to wean patients off the ventilator as soon as the patient’s condition allows. However, some patients require the ventilator for several hours, some for several days, and some others for a longer period, even up to several months [8]. This makes the first 48 h after intubation particularly critical for monitoring and initiating extubation planning [4].

Some of the adverse effects of mechanical ventilation include decreased cardiac output, reduced blood flow to vital organs, increased intracranial pressure, gastric distension, tracheoesophageal fistula, increased airway resistance, ventilator-associated pneumonia (VAP), and extreme discomfort for the patient, to name only a few. These complications can increase the length of a patient’s stay, delay the recovery process, and increase the mortality rate in the ICU, and even cause complications after weaning from the ventilator and discharge from the ICU [7, 8]. These complications will be much more severe and frequent if the ventilator parameters are not properly and correctly adjusted according to the patient’s condition and if the treatment and care staff in the ICU do not carefully monitor the mechanical ventilation process [6]. Given their duties in this area and the constant presence at the bedside of patients, nurses play a very vital role in monitoring the proper functioning of the ventilator and preventing its complications [9].

One of the significant challenges that can exacerbate the complications of mechanical ventilation is patient-ventilator asynchrony (PVA). Result of De Haro et al. [10] study showed that 48% of patients had at least one PVA event per minute of ventilation. Also, the results of a systematic review and meta-analysis [11] showed that 30–50% of patients undergoing mechanical ventilation experience at least one type of PVA, and the most common types of PVA include; Ineffective Effort: ~40–60%, Double Triggering: ~15–25%, and Inadequate Flow: ~10–20% of cases. This asynchrony occurs when the patient’s respiratory efforts are not synchronized with the ventilator. This struggle against the machine is common during intubation and the initiation of mechanical ventilation, often stemming from the expected anxiety in such situations. However, asynchrony developing suddenly in a patient who was previously stable on the ventilator is considered a serious and potentially life-threatening event [12].

The interaction between the patient and the ventilator can be viewed as a relationship between two respiratory pumps: the patient’s respiratory system controlled by the neuromuscular system and the ventilator and its associated settings. If these two systems are synchronized, there will be no problem for the patient. Any factor that causes asynchrony between the two systems can lead to patient discomfort, restlessness, and increased work of breathing. This can result in inadequate ventilation, making mechanical ventilation poorly tolerated and causing serious complications [13].

Unfortunately, the incidence of patient-ventilator asynchrony in ICUs is high. For instance, a study by Saghaee et al. in February 2023 in the ICU of an Isfahan hospital revealed a high prevalence of PVA in ventilated patients, especially with volume-controlled modes, and this can prolong the duration of mechanical ventilation [14]. In addition, a study by Mirabella et al. [15] demonstrated a significant incidence of PVA in ICU patients, which can be associated with various complications such as diaphragm dysfunction, sleep disturbances, dyspnea, temporary or permanent neuropsychological changes, and difficult and prolonged weaning from the ventilator. Several factors can contribute to asynchrony, including patient characteristics (such as respiratory mechanics, respiratory effort, etc.), ventilator characteristics (mode settings, level of support, cycling criteria, etc.), and the interface used (invasive or non-invasive) [16].

Therefore, careful monitoring and assessment of the patient and ventilator during mechanical ventilation are essential to prevent and manage asynchrony [17]. In this regard, the results of several studies have shown that certain interventions can be effective in reducing the incidence of PVA. For example, the results of a study by Moghadasi showed that changing the ventilator mode from volume-controlled to pressure-controlled can be effective in reducing asynchrony between the patient and the ventilator [14].

However, some other studies have stated that using a more comprehensive and systematic protocol for monitoring asynchrony between the patient and the ventilator can yield better results. For instance, a study by Kay Choong See et al. in 2021 found that monitoring the status of patients and the interaction between them and the ventilator twice a day based on a specific protocol reduced mortality and complications related to patient-ventilator asynchrony [16]. Also, the results of Kyo et al. [11] showed PVA may be associated with longer mechanical ventilation duration, higher ICU mortality, and higher hospital mortality. Physicians may consider monitoring PVA and adjusting ventilator settings and sedatives to reduce PVA. The researchers stated in this study that further studies with adjustment for confounding factors are warranted to determine the impact of PVA on clinical outcomes [11].

However, currently, in the ICUs of the hospital where this research was conducted, there is no standardized protocol for the correct and timely management of patient-ventilator asynchrony, and the occurrence of this event is often diagnosed incidentally. Therefore, considering the importance of the correct and timely management of patient-ventilator asynchrony and the limited research conducted on this topic, this study aimed to investigate the impact of using a patient-ventilator asynchrony management protocol on treatment outcomes in ICU patients.

Hypothesis of the study

The implementation of a PVA management protocol reduces the duration of mechanical ventilation and improves ICU-related outcomes (e.g., length of ICU stay, weaning success and ICU mortality).

Methods

Design and setting

The present study is a clinical trial study with parallel design that was conducted to investigate the impact of using a patient-ventilator asynchrony management protocol on treatment outcomes in patients admitted to the Mega ICU of an affiliated Hospital to Ahvaz Jundishapur University of medical science (Golestan hospital), from January to August 2024. Due to the nature of the intervention and the patients’ clinical status (mechanically ventilated and often sedated), formal patient-level blinding was not feasible or applicable. However, outcome assessors and data analysts were kept blinded to group allocation to minimize bias. This study was conducted in a general Mega ICU that includes 20 beds and 32 nurses, with a nurse-to-bed ratio of approximately 1:4 in most shifts. An intensivist is typically present on-site during the morning shift. Most patients in this unit require Level 5 care, indicating the need for mechanical ventilation and intensive life-support measures.

The study followed the CONSORT (Consolidated Standards of Reporting Trials) guidelines for reporting clinical trials. Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of this trial. Also, no significant changes were made to the trial protocol after commencement.

Population

The sample size was determined based on previous studies [18] with the help of med calc statistical software with a power of 90% and an error of 10%, 60 cases (30 people in each group).

Due to the possibility of sample dropout, 10% was added to the above sample size (33 people in each group).

In this study, 66 patients were initially selected using a convenience sampling method based on the inclusion criteria, and they were then randomly assigned to two groups (intervention and control, n = 33 each) using a permuted block randomization method. This was done by selecting 11 blocks of 6 (with equal sizes, including 3 participants in the intervention group and 3 participants in the control group) and then assigning one of the 6 combinations (arranged alphabetically in English) of the two groups in each block. The allocation sequence was generated by a statistician and concealed in sequentially numbered, opaque, sealed envelopes. The allocation sequence was concealed from the researchers enrolling participants; only the independent statistician had access to the sequence until assignments were finalized.

Eligibility criteria for patients in this study were: informed consent from the legal guardian for the patient’s participation in the study, age range between 15 and 65 years, The patient be undergoing mechanical ventilation with assist- control mode, No more than one day has passed since the patient was admitted to the ICU, APACHE II score between 30 and 40, no history of lung disease, no history of smoking and absence of acid-base disturbance before the intervention begins. Exclusion criteria included: receiving neuromuscular blocking agents during the study and developing conditions that would cause the patient to be on controlled ventilator modes for a prolonged period (such as brain death).

Intervention

In the intervention group, the management of patient–ventilator asynchrony (PVA) was carried out based on a structured and standardized protocol for as long as the patient was under mechanical ventilation. Specifically, patients were systematically assessed for the presence of PVA every two hours by either the principal investigator or a trained assistant. All research assistants involved in the intervention were experienced ICU nurses (with at least two years of clinical experience) who received standardized training in identifying and managing patient–ventilator asynchrony based on the study protocol. To ensure consistency, the same structured training was provided to all assistants. Informed written consent was obtained from all assistants prior to their involvement in the study.

If PVA was identified, corrective actions were immediately implemented based on the stepwise procedures outlined in the protocol. Assessments were performed using clinical indicators as well as precise interpretation of pressure and flow waveforms on the ventilator. In cases where PVA was detected, the Asynchrony Index (AI) was calculated and recorded using the following formula [18].

As soon as PVA was detected, corrective measures were applied step-by-step by the researcher or trained assistant, in coordination with the ward nurses according to protocol. If pharmacological interventions or advanced ventilator setting adjustments were required, the opinion of the intensivist (who was also a member of the research team) was sought. It is worth noting that the protocol was designed in a way that allowed the trained nurse to carry out the initial interventions and make necessary decisions within the protocol framework—particularly in situations where the physician was not immediately available (e.g., during night shifts or holidays). This approach not only facilitated faster interventions but also reduced the clinical workload and improved team coordination.

In the control group, unlike the intervention group where a systematic and protocol-based approach was used for identifying and managing PVA, patients received routine care as provided in the ICU. In routine care, identification of PVA typically occurs sporadically and relies on incidental observations by nurses or physicians. In most cases, the response to PVA involves increasing the level of sedation without addressing the underlying cause, which may result in delayed diagnosis and suboptimal management of PVA. Nonetheless, both groups received standard ICU care (e.g., sedation, nutrition, etc.) according to hospital protocols.

The PVA management protocol used in this study was adapted from a study by See et al. [16]. This protocol was developed in December 2016 by a multidisciplinary team consisting of medical specialists in this field and a clinical nurse. The protocol’s development was informed by a comprehensive review of existing scientific evidence and a rigorous assessment of its practical feasibility in a clinical setting [18–20]. This protocol focused on detecting three common and clinically observable types of patient–ventilator asynchrony in the ICU; ineffective respiratory effort, double triggering, and inadequate flow. Ineffective respiratory effort was identified when the patient made a visible inspiratory effort—such as use of accessory muscles or chest movement—without triggering a ventilator breath, confirmed via the pressure–time waveform. Double triggering occurred when two or more breaths were delivered consecutively with minimal interval, often due to sustained patient effort or short inspiratory time. It was recognized by consecutive peaks in flow–time or pressure–time waveforms.

At each assessment (every 2 h), the patient was observed for at least 120 s to evaluate respiratory effort and ventilator patterns. Flow–time and pressure–time waveforms were carefully analyzed, and any identified asynchrony was documented by type. If PVA present, the AI was calculated accordingly.

The patient–ventilator asynchrony (PVA) management protocol consisted of six structured steps. First, patients were observed for 120 s and the presence of three common asynchrony types (ineffective efforts, double triggering, and inadequate flow) was assessed. If fewer than three asynchronous breaths were detected, monitoring continued. If three or more were observed, targeted interventions were implemented based on the asynchrony type. These included optimizing sedation levels, adjusting ventilator settings (e.g., flow trigger, tidal volume, inspiratory time), and applying appropriate PEEP or switching to proportional assist ventilation. After intervention, patients were reassessed using the same observational method. If asynchrony persisted, corrective steps were repeated. If asynchrony was controlled and the patient met weaning criteria, sedation was tapered and spontaneous breathing trials were initiated according to the extubation plan. Details of the PVA management protocol are presented in Table 1.

Table 1.

Patient ventilator asynchrony management protocol

Step diagnosis	Action
1. Observe patient for 120 s, counting the total number of the following types of asynchronous breaths:   Ineffective efforts  Double triggering  Inadequate flow	Document the following in the notes: date, time, presence of ineffective efforts Presence of double triggering, presence of inadequate flow breaths Document ventilator changes in the notes If total asynchronous breaths < 3: Go to Step 6 If total asynchronous breaths 3: Go to Steps 2–4
2. For ineffective efforts	Check and management airway obstruction Adjust sedation, aiming for RASS 0 to 2 Adjust flow trigger to 2 L/min. Measure intrinsic PEEP and apply appropriate external PEEP
3. For double triggering	Increase tidal volume to maximum of 8 ml/kg ideal body weight Increase respiratory rate to maximum of 30 breaths per minute Change to pressure assist-control and increase inspiratory time to achieve an inspiratory-to-expiratory ratio of no more than 1 If all fails, deepen sedation, aiming to eliminate the inspiratory drive (aim for RASS − 4 to 5) while underlying disease is being treated
4. For inadequate flow	Increase inspiratory flow to maximum of 80 L/min Change to pressure assist-control and adjust pressure to limit VT to maximum of 8 ml/kg ideal body weight Try proportional assist ventilation, adjusting support level to limit tidal volume to maximum of 8 ml/kg ideal body weight
5. Observe patient for 120 s, counting the total number of the following types of asynchronous breaths:   Ineffective efforts   Double triggering   Inadequate flow	Document the following in the notes: date, time, presence of ineffective efforts Presence of double triggering, presence of inadequate flow Document ventilator change in the notes If total asynchronous breaths < 3: Go to Step 6 If total asynchronous breaths 3: Go to Steps 2e4
6. Check extubation plan	If plan is not for extubation: do nothing. If plan is for extubation o Inform nurses to wean off sedation, aiming for RASS − 2 to 0 o Once RASS − 2 to 0 achieved, and if not already done, change to pressure support or proportional assist ventilation and commence weaning/spontaneous breathing trials

Data collection method and tools

Data were collected using a structured, two-part form. The first section included demographic and background information such as age, sex, clinical diagnosis, and APACHE II score, which were obtained through interviews with family members and nurses, medical record, and direct clinical examination of the patient. The second section recorded treatment outcomes, including ICU length of stay, duration of mechanical ventilation, ICU mortality, successful weaning from the ventilator, and self-extubation. Data were collected by trained research assistants who were blinded to group allocation. In the study period, each shift was staffed by either the principal investigator or a trained assistant to implement the intervention, and a separate assistant for outcome data collection. All data collectors were also experienced ICU nurses (≥ 2 years) and received standardized training to ensure consistency. It should be noted that during the study, all assistants involved in implementing the intervention and collecting data participated in regular coordination meetings to ensure adherence and consistency.

The primary outcome was duration of mechanical ventilation (measured in days from intubation to successful weaning, with analysis based on mean difference between groups). Secondary outcomes included ICU length of stay (days from admission to discharge) and successful weaning, ICU mortality, self-extubation, ICU mortality (binary outcomes). All outcomes were assessed until ICU discharge or death.

In this study, self-extubation refers to the unplanned removal of the endotracheal tube by the patient, either involuntarily or intentionally. Successful weaning from the ventilator also, refers to the process of discontinuing mechanical respiratory support, in which the patient is able to maintain effective and stable spontaneous breathing after separation from the ventilator, without requiring reintubation or mechanical ventilation within 48 h following extubation.

In this study, the APACHE II score was used to assess the severity of illness upon admission to the ICU. Developed by Knaus in 1985, APACHE II incorporates 12 physiologic variables to represent major physiological systems. According to the standard APACHE II table, mortality rates for patients with scores of 0–15, 16–19, 20–30, and greater than 30 are approximately 10%, 15%, 35%, and 75%, respectively [21]. APACHE II is a globally recognized standard tool widely used in studies in Iran [22] and worldwide [23–25] to determine the severity of illness in ICU patients, with established reliability and validity. In Rahmatinejad et al.’s study, the area under the receiver operating characteristic curve (AUC) was 0.775, indicating the tool’s high discriminative ability to identify patients at high risk of inhospital mortality [26].

Harms were defined as any adverse event related to the PVA management protocol (e.g., over-sedation, ventilator-induced lung injury). These were monitored systematically through daily clinical assessments by the ICU team and documented in the study records. No predefined thresholds for harm severity were set, but all events were reported descriptively.

Statistical analysis

In this study, descriptive and analytical statistical analysis methods were used in SPSS software (version 22, SPSS Inc., Chicago, IL, USA). Quantitative variables were reported as mean, standard deviation, and minimum and maximum, and qualitative variables were reported as frequency (percentage). The normality of quantitative variables was approved using the Shapiro–Wilk test. Independent t-test, independent samples t-test (To compare the mean of continuous variables in two group) and Chi-square test (To compare nonparametric variables in two group) were used to data analysis. The statistical significance level was considered to be 0.05. No missing data were encountered for the primary outcomes; all randomized participants were included in the analysis (intention-to-treat principle).

Results

A total of 66 patients were included in this study, and their data was subjected to statistical analysis (Fig. 1). The mean age of the participants in both groups was 48.42 ± 15.20 years, the mean GCS score upon admission was 6.92 ± 1.45, and the mean APACHE score was 33.84 ± 2.90. Of all participants, 25 (37.9%) were female and 41 (62.1%) were male. In terms of admission diagnosis, 35 patients (53%) were admitted to the ICU due to trauma and 31 (47%) due to medical conditions. There were no significant differences between the two groups in terms of demographic and baseline variables (Table 2). In general, 714 cases of PVA were identified and recorded for the intervention group. The average of AI calculated for these 714 identified asynchronies was 34%. The most common type of asynchrony was ineffective respiratory effort, accounting for 68.3% (488cases) of cases.

Fig. 1.

The consort flow diagram of patients participating in the study

Table 2.

Baseline patient characteristics

Variable	Group		Total	t/x2	DF	P value
	Intervention	Control
Age
Mean (SD)	43.18 (15.24)	47.78 (15.36)	42.48 (15.20)	0.370	64	*0.713
Initial GCS
Mean (SD)	6.87 (1.59)	6.96 (1.31)	6.92 (1.45)	− 0.253	64	*0.801
APACHE
Mean (SD)	33.60(2.86)	34.09(2.97)	33.84(2.90)	− 0.675	64	*0.502
Reason for admission to the ICU N (%)
Trauma	20 (30.3)	15 (22.7)	35(53.0)	1.52	1	**0.218
Internal problems	13 (19.7)	18 (27.3)	31 (47.0)
Gender N (%)
Male	21 (31.8)	20 (30.3)	41 (62.1)	0.064	1	**0.800
Female	12 (18.2)	13 (19.7)	25 (37.9)

*t-test, **Chi-square test

Chi-square test results showed no significant difference in ICU mortality between the control and intervention groups (p = 0.202). A total of 12 patients (18.18%) from both groups passed away in the ICU. Chi-square test results also showed no significant difference in the incidence of self-extubation between the control and intervention groups (p = 0.787), with a total of 19 patients (28.8%) experiencing self-extubation. However, results showed a significant difference between the intervention and control groups in terms of successful weaning from the ventilator (p < 0.001), with a higher rate in the intervention group (Table 3).

Table 3.

Comparative analysis of the intervention and control groups in terms of ICU mortality, incidence of Self-Extubation, weaning success, and duration of ICU stay and mechanical ventilation

Variable	Group		Total	t/x2	DF	P value
	Intervention	Control
Duration of ventilator connection
Mean (SD)	12.64 (6.12)	17.99 (4.23)	15.32(5.87)	− 4.13	64	*<0.001
Duration of ICU stay
Mean (SD)	14.33 (5.17)	22.57 (5.87)	18.45 (5.52)	− 6.05	64	*<0.001
Death in ICU N (%)
Yes	4 (6.1)	8 (12.1)	12 (18.2)	1.63	1	**0.202
No	29 (43.9)	25 (37.9)	54 (81.8)
Self extubation N (%)
Yes	9 (13.6)	10 (15.2)	19 (28.8)	0.074	1	**0.787
No	24 (36.4)	23 (34.8)	47 (71.2)
Successful weaning N (%)
Yes	24 (36.4)	7 (10.6)	31 (47.0)	17.58	1	**< 0.001
No	9 (13.6)	26 (39.4)	35 (53.0)

*t-test, **Chi-square test

Independent t-test results showed a significant difference between the intervention and control groups in terms of the number of days spent in the ICU (p < 0.001), with a mean of 22.57 ± 5.87 days in the control group and 14.33 ± 5.87 days in the intervention group. Furthermore, independent t-test results showed a significant difference between the two groups in terms of the duration of mechanical ventilation (p < 0.001), with a mean of 17.99 ± 4.23 days in the control group and 12.64 ± 6.12 days in the intervention group (Table 3).

Further, the multiple regression analysis showed that the model explained 46.4% of the variance in ICU stay duration (R² = 0.464, Adjusted R² = 0.366). According to this model, being in the intervention group was significantly associated with a shorter ICU stay (β = -8.268, p < 0.001), with an average reduction of about 8 days compared to the control group. Age was also positively associated with ICU stay (β = 0.130, p = 0.039). Other variables, including gender, type of PVA, self-extubation, successful weaning, reason for ICU admission, APACHE score, and initial GCS, were not significantly related to ICU stay duration (p > 0.05) (Table 4). Also, the results of the multiple regression analysis indicated that the model explained 39.3% of the variance in the duration of ventilator connection (R² = 0.393, Adjusted R² = 0.283). Being in the intervention group was significantly associated with a reduction in the duration of ventilator use (β = -3.906, p = 0.003). Additionally, successful weaning from the ventilator significantly reduced the duration of connection (β = -2.985, p = 0.034). Other variables, including gender, type PVA, self-extubation, reason for ICU admission, age, APACHE score, and initial GCS, were not significantly associated with ventilator duration (p > 0.05) (Table 4). No major harms or unintended adverse effects were reported related to the intervention.

Table 4.

Multiple regression analysis of factors associated with duration of ICU stay& ventilator connection

Variable	Parameter		B	Std. Error	t	Sig.	95% Confidence Interval
							Lower Bound	Upper Bound
Dependent Variable: Duration of ICU stay R Squared = 0.464 (Adjusted R Squared = 0.366)	Intercept		16.837	8.652	2.006	0.037	− 0.503	34.176
	Group	Intervention	− 8.268	1.648	− 5.016	0.000	− 11.571	− 4.964
		Control	0a	.	.	.	.	.
	Reason for admission to the ICU	Trauma	− 0.171	1.867	− 0.092	0.927	− 3.912	3.570
		Internal problems	0a	.	.	.	.	.
	Gender	Male	0.315	1.593	0.198	0.844	− 2.878	3.507
		Female	0a	.	.	.	.	.
	PVA-Type	Insufficient flow	2.029	1.915	1.060	0.294	− 1.808	5.866
		Double stimulation	0.522	2.842	0.184	0.855	− 5.173	6.217
		Ineffective respiratory effort	0a	.	.	.	.	.
	Self-extubation	Yes	− 0.913	1.636	− 0.558	0.579	− 4.192	2.367
		No	0a	.	.	.	.	.
	Successful weaning	Yes	− 0.585	1.771	− 0.331	0.742	− 4.134	2.963
		No	0a	.	.	.	.	.
	AGE		0.130	0.061	2.115	0.039	0.007	0.252
	APACHI		− 0.041	0.256	− 0.160	0.873	− 0.554	0.472
	INITIALGCS		0.088	0.504	0.175	0.862	− 0.922	1.098
Dependent Variable: Duration of ventilator connection R Squared = 0.393 (Adjusted R Squared = 0.283)	Intercept		22.679	6.714	3.378	0.001	9.224	36.134
	GROUP	Intervention	− 3.906	1.279	− 3.054	0.003	− 6.469	− 1.343
		Control	0a	.	.	.	.	.
	Reason for admission to the ICU	Truma	− 0.998	1.449	− 0.689	0.494	− 3.901	1.904
		Internal problems	0a	.	.	.	.	.
	GENDER	Male	− 0.235	1.236	− 0.190	0.850	− 2.712	2.242
		Female	0a	.	.	.	.	.
	PVATYPE	Insufficient flow	0.352	1.486	0.237	0.814	− 2.626	3.329
		Double stimulation	− 0.508	2.205	− 0.230	0.819	− 4.926	3.911
		Ineffective respiratory effort	0a	.	.	.	.	.
	Self-extubation	Yes	− 0.130	1.270	− 0.102	0.919	− 2.675	2.415
		No	0a	.	.	.	.	.
	Successful weaning	Yes	− 2.985	1.374	− 2.172	0.034	− 5.739	− 0.231
		No	0a	.	.	.	.	.
	AGE		− 0.032	0.048	− 0.679	0.500	− 0.128	0.063
	APACHI		− 0.007	0.199	− 0.036	0.972	− 0.405	0.391
	INITIALGCS		− 0.272	0.391	− 0.695	0.490	− 1.055	0.512

Discussion

The mean age of patients in this study was 42.48 years, which is expected given that most of the study participants were trauma patients. In a study by Zhou et al. [27], the mean age was reported as 64 years. In their study, age was identified as a risk factor for adverse clinical outcomes in mechanically ventilated patients. Similarly, in a study by Si et al. [16], the mean age of patients was reported as 61 years. However, what is consistent across these studies and the present study is that PVA management can be effective for all age groups.

The majority of participants (62.1%) in this study were male, which could be attributed to the fact that trauma patients comprised 53% of the sample, and the incidence of trauma is higher in males. In Zhou et al., the number of female and male patients was 292 and 384, respectively [27]. Si et al. observed a similar distribution of gender with 62% male and 38% female participants, and their results showed no significant association between gender and the incidence of PVA [15]. In Saghaee [14], male patients accounted for 57.1% of the participants, and their results showed that changing from volume-controlled ventilation to pressure-controlled ventilation was effective in reducing asynchrony for all patients, regardless of gender. Therefore, based on the results of these studies and those of the present study, it can be concluded that PVA management can be effective for both males and females.

In this study, the mean severity of illness score (APACHE II) was reported as 33.84 ± 2.90, and there was no significant difference between the two groups in this regard. In Si et al., the APACHE II score was reported as 27.1 ± 8.5 [15]. A higher APACHE II score is associated with an increased likelihood of PVA and adverse clinical outcomes such as prolonged mechanical ventilation [21]. Therefore, it can be argued that selecting a similar range of APACHE II scores for inclusion in the present study was appropriate for a more accurate evaluation of the intervention results.

This study showed that the most common cause of PVA was ineffective and inefficient respiratory efforts, accounting for an average of 69.7%, while the least common cause was double-triggering, with an average of 9.1%. Also, the average of asynchrony index was 34%, which indicates severe asynchrony and the urgent need for intervention to resolve it in most of the PVAs that identified in this study. In a study by De Haro et al. [10], the total average AI was between 30 and 40% and ineffective and inefficient respiratory efforts were also identified as the most common cause of PVA. Similarly, Blanche et al. [18] reported ineffective respiratory effort as the most common cause of patient-ventilator asynchrony. The average of asynchrony index in their study was 10.4%. Also, in a study by Zhou et al. [27], the total average AI was between 25.7% and ineffective triggering were identified as the most common cause of PVA. Based on these results, it can be concluded that efforts to eliminate ineffective respiratory efforts and increase respiratory muscle strength are key strategies for managing and eliminating PVA.

The results showed that there was no statistically significant difference between the two groups in terms of the incidence of self-extubation. Consistent with this result, De Haro [10] suggested that managing and preventing PVA does not have a direct impact on reducing self-extubation. Based on the results of the present study, it can be argued that in a study with a larger sample size, the effect of implementing a PVA protocol on the rate of self-extubation might become significant. However, it should be noted that many factors can affect the occurrence of self-extubation, such as agitation and restlessness, pain, and problems related to the endotracheal tube (e.g., cuff leak), which need to be addressed along with the elimination of patient-ventilator asynchrony to reduce the rate of self-extubation.

Results of the current study showed that there was no significant difference in mortality rates in ICU, between the two groups in the ICU, which is consistent with the results of Fang Zhou et al. who reported no significant association between the implementation of a PVA protocol and mortality rates in ICU patients [27]. However, contrary to these results, Si et al. [16] found that implementing a screening and management protocol for patient-ventilator asynchrony was associated with a significant 15% reduction in hospital mortality. Similarly, the results of a study by Megranz et al. [28] demonstrated a significant correlation between the occurrence of patient-ventilator asynchrony and increased mortality rates in ICU patients. The results of the study by Blanche et al. also showed that the mortality rate in the ICU and hospital was higher in patients who experienced PVA than in patients without PVA [18]. There could be several reasons for the discrepancy in the results of this study regarding the impact of the intervention on mortality rates in the ICU compared to the aforementioned studies. Factors such as sample size, different study methodologies (for example Si et al. [16] was a retrospective cohort study with a longer duration), as well as differences in patients’ clinical conditions, ICU environments, healthcare teams, diagnoses, etc., could contribute to these variations. However, given the positive results of the mentioned studies regarding the positive impact of implementing a PVA protocol, as well as the results of the present study regarding the positive impact of this protocol on length of stay, mechanical ventilation, and successful weaning, it can be argued that the implementation of a PVA management and diagnosis protocol is likely to have a positive impact on reducing mortality rates in patients. Since all of these factors can directly or indirectly affect mortality rates in ICU patients, it is necessary to conduct more comprehensive studies on this topic in the future.

The results of the present study showed a higher rate of successful weaning in the intervention group compared to the control group. However, in the multiple regression analysis, successful weaning did not independently predict ICU stay duration, although it was significantly associated with a shorter duration of mechanical ventilation. This suggests that while successful weaning is an important outcome, it may not by itself reduce ICU length of stay unless asynchrony is also resolved. These findings are consistent with the study by Kyo et al. [11], which found that protocol-based monitoring of PVA improved weaning outcomes, and with Si et al. [16], who reported that structured assessment of asynchrony increased successful ventilator separation. Similarly, Saghaee et al. [14] demonstrated that mode adjustment to reduce PVA facilitated more effective weaning.

The present study showed that the length of ICU stay was notably shorter in patients who received the intervention protocol compared to those in the control group. Multivariate analysis confirmed that the intervention itself was an independent predictor of reduced ICU stay, while age also played a contributory role in prolonging hospitalization. Other variables such as gender, baseline illness severity, and clinical outcomes like successful weaning or self-extubation did not show a significant association with ICU length of stay when controlling for other factors. These findings are consistent with those of Zhou et al. [27], who reported that inadequate management of patient–ventilator asynchrony can lead to prolonged ICU stays. Saghaee et al. [14] also observed a decrease in ICU stay duration following adjustments to ventilator settings aimed at improving synchrony. Similarly, Si et al. [16] found that implementing a structured PVA management protocol reduced the number of days patients remained in the ICU. In line with these results, Blanche et al. [18] demonstrated that patients experiencing frequent asynchrony events had significantly longer ICU stays than those without such events.

In this study, in line with previous outcomes, the duration of mechanical ventilation was significantly shorter in the intervention group. Regression analysis confirmed that being in the intervention group was an independent predictor of reduced ventilator time, and successful weaning also significantly contributed to shorter duration. These findings are consistent with those of Si et al. [16] and De Haro et al. [10], who both reported that unresolved PVA prolongs mechanical ventilation. Similarly, Saghaee et al. [14] found that switching to pressure-controlled ventilation decreased asynchrony and ventilation days. Moreover, Rodis Megranz et al. [28] showed that patients with more frequent double-triggering and asynchronous events had significantly longer durations of mechanical ventilation. Blanche et al. [18] also noted that patients with an asynchrony index greater than 10% remained on ventilators longer than those with minimal asynchrony.

Study limitations

In this study, despite efforts to reduce limitations, due to personnel and equipment conditions, there were the following limitations in the study implementation process:

• Only the patients were unaware of the grouping, but the ICU staff and researchers were aware of which group was the intervention or control. This may lead to performance bias.

• Although the two groups were homogeneous in terms of age, sex, and APACHE II score, other factors such as the level of experience of ICU personnel, individual differences in response to treatment, or differences in prescribed medications (e.g., type or dose of sedatives) were not controlled for.

• The results of this study showed that the assessment and management of PVA based on clinical symptoms and ventilator respiratory waves, without the use of computers and advanced methods, can also be associated with positive outcomes for patients admitted to the ICU. However, the diagnosis of asynchrony was based on observation of the ventilator waveform and the researcher’s assessment, which may have been influenced by subjective judgment. The use of computer algorithms (such as automated waveform analysis software) that were unavailable in this study could have been more objective.

Conclusion

The results of this study demonstrated that using a standardized protocol for managing patient-ventilator asynchrony can lead to positive outcomes such as a reduction in the duration of mechanical ventilation and length of stay in the ICU, and an increased chance of successful weaning from the ventilator for ICU patients. Therefore, based on the results obtained in this study, it can be suggested that this protocol (which is easy to implement, cost-effective, and has no specific side effects) be taught to all ICU nurses, and arrangements be made for its implementation. Further research is needed to solidify these findings and explore potential variations in implementation. So a multicenter trial with larger sample size is recommended.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

ICU

Intensive care unit

PVA

patient-ventilator asynchrony

APACHE

Acute physiology and chronic health evaluation

Author contributions

Study conception and design: “M A, M R, M S”- Data collection: “M A, MR” - Data analysis and interpretation: “MA, S GH”- Drafting of the manuscript: “All authors”- Critical revision of the manuscript: “M A, MR”.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and publication of this article: This work was supported by the Research Deputy of Ahvaz Jundishapur University of Medical Sciences (grant number U-02367).

Data availability

Data may be available by request submitted to the corresponding author.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences (IR.AJUMS.REC.1402.472) and registered in the Iranian Registry of Clinical Trials (IRCT20231001059572N1). Ethical procedures followed the Helsinki Declaration (1995, revised 2001). Informed consent was obtained from patients’ legal guardians, and participation was voluntary. Confidentiality and anonymity were maintained by assigning unique ID numbers, stored separately from identifying information.

Consent for publication

Not applicable.

Protocol access

The full trial protocol is available from the corresponding author upon reasonable request.

Competing interests

The authors declare no competing interests.