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SIGH35 and end-expiratory occlusion test for assessing fluid responsiveness in critically ill patients undergoing pressure support ventilation

Critical Care volume 29, Article number: 176 (2025) Cite this article

Abstract

Background

Assessing fluid responsiveness is problematic for critically ill patients with spontaneous breathing activity, such as during Pressure Support Ventilation (PSV), since spontaneous breathing activity physiologically affects heart–lung interplay. We compared the reliability of two hemodynamic tests in predicting fluid responsiveness in this clinical setting: SIGH35, based on a ventilator-generated sigh applied at 35 cmH2O for 4 s and the end-expiratory occlusion test (EEOT).

Methods

Prospective study conducted in a general intensive care unit (ICU) and enrolling patients in PSV showing different inspiratory effort [assessed by airway occlusion pressure (P0.1)] and requiring volume expansion (VE). Hemodynamic variables were recorded by means of the MOSTCARE® system, patient received a VE using 4 ml/kg of crystalloids over 10 min and were considered responders if a cardiac output (CO) ≥ 10% was observed. The reliability of SIGH35 and EEOT in discriminating fluid responsiveness was assessed using receiver operating characteristic (ROC) curve approach and the area (AUC) under ROC curves was compared. For the EEOT, we considered the percent changes of CO between baseline the end of the test, while for the SIGH35, the percent changes of pulse pressure (PP) between baseline and the lowest value recorded after SIGH35 application.

Results

Sixty ICU patients were enrolled, and 56 patients analysed. The AUC of PP changes after SIGH35 was 0.93 (0.84–0.99) [sensitivity of 93.1% (78.0–98.7%); specificity of 91.6 (73.0–98.9%)]; best threshold − 25% PP from baseline (grey zone − 15%/35%)]; and greater than the AUC of CO changes after EEOT [0.67 (0.52–0.81); sensitivity of 72.4% (54.3–85.3%) specificity of 70.3% (73.0–98.9%)]; best threshold 4% of CO increase from baseline (grey zone − 1%/10%)]. In the subgroup having a P0.1 < 1.5 cmH2O, the AUC of SIGH35 [0.98 (0.94–0.99)] and of EEOT [0.89 (0.72–0.99] were comparable (p = 0.26).

Conclusions

In a selected ICU population undergoing PSV, SGH35 reliably predicted fluid responsiveness and performed better than the EEOT, which is, however, still reliable in the subgroup of ICU patients having a small extent of inspiratory efforts.

Background

Assessing preload dependence in mechanically ventilated critically ill patients retaining, to some extent, spontaneous breathing activity is a challenge for Intensive Care Unit (ICU) physicians [1,2,3].

Controlled mechanical ventilation (MV) affects both preload and afterload of the right ventricle (RV). During insufflation, the increase in intrathoracic pressure raises right atrial pressure, reducing the venous return and consequently decreasing right ventricular preload [4,5,6]. Simultaneously, the compression of pulmonary vessels elevates pulmonary vascular resistance, increasing right ventricular afterload [3, 4, 7, 8]. During expiration, venous return improves, restoring RV preload. The extent of these changes are affected by the compliance of the thoracic system [9], by the volemic status of the patient that determines the position of the right ventricle on the Frank-Starling curve [4, 8] and by RV function. The RV adaptive response to MV [10] affects–after some heartbeats–left ventricular (LV) preload and stroke volume (SV) and, finally, the arterial pulse pressure (PP) whose changes are, to some extent, proportional to SV changes [3, 11, 12]. In patients receiving assisted MV, inspiratory efforts significantly alter heart–lung interactions. Spontaneous efforts are unpredictable and can generate varying degrees of negative intrathoracic pressure, leading to random increases in RV preload [3, 4, 7, 8, 12]. Additionally, the resulting rise in transpulmonary pressure and pulmonary vessel distension may elevate RV afterload. Furthermore, a more negative pleural pressure can increase LV transmural pressure, thereby augmenting LV afterload [3, 4, 7, 8, 12].

There are several functional hemodynamic tests available at the bedside [2, 13]. However, spontaneous breathing activity physiologically affects those tests, needing fixed and static changes in heart–lung interplay. Among them, the end-expiratory occlusion test (EEOT), has been successfully used in many ICU settings [14, 15]. During positive pressure ventilation, insufflation raises intrathoracic pressure, increasing right atrial pressure and reducing RV preload. When ventilation stops at PEEP, venous return resumes, maximizing right preload. If EEO is prolonged, this preload increase is transferred to the left heart with a subsequent rise in SV, indicating biventricular preload responsiveness. When the MV is interrupted, as during the end-expiratory occlusion test (EEOT), the neural inspiratory triggers and consequent efforts are still present [14]. Accordingly, it has been reported a rate of EEOT failure of 22.5% consequent to ventilator’s trigger due to patients’ inspiratory efforts against the closed airway [16]. Finally, since the threshold of cardiac output (CO) change used to detect fluid responsiveness is only 5%, also spontaneous inspiratory efforts not triggering the ventilator may affect cardiac preload and, hence, the reliability of the EEOT.

To overcome these limitations, it has been proposed that increasing intrathoracic pressure during PSV by adding a brief sigh, augmenting the applied inspiratory pressure for a few seconds [17], should produce respiratory and hemodynamic effects and allow prediction of fluid responsiveness [5, 18, 19]. Moreover, by stretching the pulmonary mechanoreceptors, a sigh triggers the vagally mediated Hering–Breuer reflex which inhibits inspiratory neural triggers, prolongs the duration of expiration [20], and avoids the interference of inspiratory efforts during the manoeuvre. For instance, in the first proof-of-concept study, after the application of a sigh of 35 cmH2O for 4 s (SIGH35), a drop in PP of 35% from baseline predicted fluid responsiveness with a sensitivity of 75% and specificity of 92% [18].

The primary aim of this study is to compare the reliability of SIGH35 and EEOT in predicting fluid responsiveness in ICU patients undergoing PSV and, secondarily, in the subgroup of those having a small extent of inspiratory efforts.

Materials and methods

Setting

The study was conducted in the ICU of Humanitas Research Hospital (Rozzano, Milano). The protocol was designed in accordance with the principles outlined in the Declaration of Helsinki; the study was approved by the local ethical committee (Protocol Number 403/19; 04 June 2019], and prospectively registered (NCT04924920). Informed consent was obtained from all the participants. Data are presented according to CODEFIRE consensus on data reporting in ICU studies on fluid responsiveness [21].

Patients

Patients were included when they met the following criteria: (1) undergoing PSV with inspiratory support level (PS) between 8 and 15 cmH2O and positive end-expiratory pressure (PEEP) between 5 and 12 cmH2O; (2) indication to perform a volume expansion (VE) according to the attending physician’s decision, based on the presence of at least one sign of hemodynamic instability: systolic arterial pressure (SAP) ≤ 90 mmHg, or mean arterial pressure (MAP) ≤ 70 mmHg, or requiring vasopressors (any dose) to maintain SAP > 90 mmHg or MAP > 70 mmHg, or decline of SAP > 50 mmHg in known hypertensive patients, along with one or more of the following: urinary flow ≤ 0.5 mL/kg/min for ≥ 2 h; heart rate ≥ 100 beats per minute; presence of skin mottling or blood lactate concentration ≥ 4 mmol/L.

Exclusion criteria were: (1) known left ventricular ejection fraction < 30% or severe valvular dysfunction; (2) atrial fibrillation or sustained cardiac arrhythmias; (3) severe acute respiratory distress syndrome (ARDS) [22]; (4) abdominal compartment syndrome; (5) air leakage through chest drains; (6) artifacts in arterial waveform; (7) pathological respiratory patterns due to neurological diseases; signs of fatigue or respiratory distress.

Study protocol

In all patients, PSV was applied using the Maquet Servo-U ventilator (Maquet Critical Care, Solna, Sweden). The protocol was started during a period of stable ventilatory pattern, defined by a median variation of respiratory rate, tidal volume and minute ventilation < 15% in the hour preceeding patient enrolment as assessed by displaying trends on the ventilator screen [18]. The median Richmond Agitation Sedation Scale (RASS) was also collected at this step. Three consecutive measurements of the airway occlusion pressure (P0.1) displayed on the Maquet Servo-U ventilator have been recorded before performing EEOT or SIGH35, and the averaged values were considered as baseline (see further). At the same time, the patient was connected to the MOSTCARE® (Vygon, Padova, Italy) to obtain hemodynamic variables.

For clarity and as an example, since the sequence of tests was randomly computer-generated, the study protocol shown in Fig. 1 shows a sequence where the EEOT has been performed before SIGH35: (1) a first set of measurements was recorded (T0), and then the EEOT test was performed by using the “expiratory hold” function on the ventilator for 15 s and the ventilator trigger set at 2 L/min, as previously described [16]. The hemodynamic effect of EEOT was evaluated by considering the mean of CO values of the 10 beats before EEOT start (EEOT_baseline) and the highest CO value recorded at the end of the test (EEOT_zenith; Fig. 2) (T1); (2) three minutes after the end of the first test, a set of measurements was recorded (T2); (3) after 3 min or when all continuous variables had stabilized, the SIGH35 was performed, by setting the ventilator pressure controlled synchronized intermittent mandatory ventilation plus PSV [SIMV (PC) + PS mode], with SIMV rate set a 1/min inspiratory time of 4 s, as previously described [17]. The hemodynamic effect of SIGH35 was evaluated by considering the mean of PP values of the 10 beats before SIGH35 start (SIGH35_baseline) and nadir PP value recorded after SIGH3 application (SIGH35_nadir; Fig. 2 and Supplemental Fig. 1) (T3); (4) three minutes after the end of the first test, a set of measurements was recorded (T4) and subsequently the volume expansion (VE) consisting of 4 ml/kg of Ringer’s solution was performed in 10 min, (5) a final set of measurement was recorded at the end of the FC (T5).

Fig. 1
figure 1

Schematic illustration of study protocol. The sequence of tests was randomly computer-generated, and this figure shows a sequence where the EEOT has been performed before SIGH35. T0–5, timepoints of the study (see text for further explanations). The second test was applied after 3 min or when all continuous variables had stabilized. PSV, pressure support ventilation; SIGH35, sigh manoeuvre consisting of application of 35 cmH20 for 4 s; EEOT, end-expiratory occlusion test; VE, volume expansion. The acquisition software of the MOSTCARE® automatically records and averages all hemodynamic variables over 30-s periods, by default. Additionally, the device allows for the simultaneous recording of a second set of beat-to-beat measurements, which was initiated at T0 and stopped at T3, during the SIGH35 and EEOT (beat-to-beat dashed line). The 30-s recording file has been used for evaluating the response to VE administration (from T4 to T5) (30-s dashed line)

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Fig. 2
figure 2

The hemodynamic effect of EEOT was evaluated by considering the mean of cardiac output values of the 10 beats before EEOT start (EEOT_baseline; lower panel of the figure) and highest CO value recorded at the end of the test (CO_zenith). The hemodynamic effect of SIGH35 was evaluated by considering the mean of PP values of the 10 beats before SIGH35 start (SIGH35_baseline; upper panel of the figure) and the lowest value of PP recorded after SIGH3 application (PP_nadir); PSV, pressure support ventilation; SIGH35, sigh manoeuvre consisting of application of 35 cmH20 for 4 s; EEOT, end-expiratory occlusion test; VE, volume expansion; Paw, airway pressure

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Study measurements and data acquisition

All the hemodynamic measurements were acquired using the MOSTCARE® system, which works with a sampling rate of 1,000 points (P/t) per second, analysing both the systolic and diastolic parts of the arterial waveform signal. The SV is estimated as the ratio between the area under the systolic component of the curve and the systemic vascular impedance by analysing the profile of the ‘points of instability’ of the arterial waveform shape. These points are generated by the mechanical interaction between forward and backward pressure waves, and define the specific profile of each arterial waveform, which is analysed by MOSTCARE® for the calculation of the vascular impedance. Arterial pressures (SAP, diastolic, MAP, dicrotic) and pulse pressure variation are directly measured from arterial pressure waveform, while stroke volume variation is calculated by analysing the changes of SV over time. All the indexed values are calculated using the anthropometric measures of the patients. The least significant change (LSC) in SV estimation (i.e., the minimum percentage change between successive measurements that exceeds random error and represents a true change in SV [23]) has been reported to be as high as 4.5% [24].

The arterial pressure transducer was set at mid-chest level, zeroing procedure was performed before recording and, to detect the risk of under or over damping and the consequent inaccurate hemodynamic assessment, a square-wave test was performed in all patients before starting the study protocol [25].

The acquisition software of the MOSTCARE® automatically records and averages all hemodynamic variables over 30-s periods, by default. Additionally, the device allows for the simultaneous recording of a second set of beat-to-beat measurements, which was initiated at T0 and stopped at T3 (Fig. 1) during the SIGH35 and EEOT assessments to evaluate the Nadir and Zenith changes in PP and CO for each test, respectively (Fig. 2). The 30-s recording file has been used for evaluating the response to VE administration (from T4 to T5 in Fig. 1). The two hemodynamic files were separately imported into a dedicated EXCEL® (Microsoft, Redwood, MS, USA) spreadsheet for further analysis. One investigator manually marked on MOSTCARE® the start of SIGH35, EEOT and VE, while a second investigator operated on the ventilator to start the expiratory hold manoeuvre needed for the EEOT or to apply the SIGH35.

The occurrence of extrasystoles during the beat-to-beat evaluation of SIGH35 or ventilator triggering during EEOT were both criteria for excluding patients from the post-hoc analysis. Finally, the following variable have been recorded at T0 from the ventilator: (1) PS; PEEP; Tidal Volume; P0.1; respiratory rate; fraction of inspired oxygen.

Statistical analysis

Quantitative variables were summarized as mean and standard deviation (SD) or median and 25°–75° percentiles (interquartile range, IQR), whereas qualitative ones by absolute and relative (percentages) frequencies. Shapiro–Wilk test was used to assess normality. As appropriate, differences of quantitative variables were evaluated using Student t or Mann–Whitney tests. Pearson Chi-Square or Fischer exact tests were used for qualitative variables.

The sample size has been calculated by using the comparison of the area (AUC) under receiver operating characteristic (ROC) curves: assuming that the AUC of the SIGH35 should be of at least 0.85 to be clinically relevant as compared to an expected AUC for the EEOT in the whole population of 0.65, the calculated sample size was 50 patients (alpha error of 5% and a beta error of 10%). Considering the possibility of the occurrence of extrasystoles during the beat-to-beat evaluation of the EEOT and the SIGH35, the sample size has been increased by the 20% to account for the rate of loss of patients during the post-hoc data analysis. The final sample size was, hence, 60 patients.

The reliability of SIGH35 and EEOT in discriminating fluid responsiveness was assessed using ROC curve approach. For this purpose, patients were considered fluid-responsive if the CO increased by ≥ 10% after FC administration. Cut-off values were chosen to correspond to the best respective Youden index [26]. ROC curves were then compared using the Hanley-McNeil test [27].

ROC curves (CI95) were constructed (1) for the EEOT, considering the percent changes of CO between baseline and the CO zenith at the end of the test (as explained above and in the Fig. 2; T0 and T1, respectively in the Fig. 1); (2) for the SIGH35, considering the percent changes of PP between baseline and the PP nadir (as explained above and in the Fig. 2; T2 and T3, respectively in the Fig. 1). ROC curves were built for the overall population and for the subgroup of patients having a small extent of inspiratory efforts (i.e., baseline P0.1 ≤ 1.5 cmH2O [28, 29]).

The grey zones for all the statistically significant ROC curves were computed, with the low cut-off value, including 90% of negative FC responses, and the high cut-off value discriminating positive FC in 90% of cases [30, 31].

A p value < 0.05 was considered significant. Statistical analyses were conducted using GraphPad PRISM V6 (GraphPad Software Inc., San Diego, CA, USA) and Medcalc (Software 8.1.1.0; Mariakerke, Belgium).

Results

Sixty adult patients were enrolled over a 19-month period (from February 2022 to September 2022 and from January 2024 to November 2024; the MOSTCARE® has been temporarily not available in the ICU from October 2022 to December 2023); only 56 patients were analysed, since 3 were excluded from data analysis because of occurrence extrasystoles during the beat-to-beat evaluation SIGH35, and one because of ventilator triggering during EEOT.

Table 1 displays patients' characteristics at enrolment, while the hemodynamic measurements before and after VE administration are reported in Table 2. Overall, 27 patients (48.2%) responded to VE administration. At baseline, 5 patients (8.9%) (4 responders and 1 non-responder) did not receive any vasoactive drugs. The RASS score was − 2 [− 3/− 2], and did not differ between responders and non-responders (p = 0.72; Table 1) and only 2 patients (3.5%) did not receive any sedation.

Table 1 Patient characteristics at enrolment
Full size table
Table 2 Effects of fluid administration on hemodynamic parameters in fluid responders and non-responders
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ROC curves and AUC comparisons: overall population

The AUC of PP changes after SIGH35 was 0.93 (0.84–0.99; p < 0.001); with a sensitivity of 93.1% (78.0–98.7%) and a specificity of 91.6 (73.0–98.9%); the mean reduction of PP was significantly different between responders and non-responders [− 44.6% (9.5) vs. − 13.5% (10.3); p < 0.001)], and the PP best threshold value of the ROC curve was − 25% from baseline [grey zone–15%/35%] (Fig. 3). The SIGH35 correctly identified as responders or non-responders 51 of 56 patients (91.0%), while 5 patients (9.0%) (3 responders and 2 non-responders), have been wrongly classified.

Fig. 3
figure 3

The upper part of the Figure shows the ROC curves of the changes of PP after the SIGH35 [dark blue dots; AUC = 0.93 (0.84–0.99)] and after the EEOT [dark green dots; AUC = 0.67 (0.52–0.81)] in the overall population. The lower part of the Figure shows the ROC curves in the subgroup of patients having a small extent of inspiratory efforts (INSPe) of the changes of PP after the SIGH35 [light blue dots; AUC = 0.98 (0.94–0.99)] and after the EEOT [light green dots; AUC = 0.89 (0.72–0.99)]

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The AUC of CO changes after EEOT was 0.67 (0.52–0.81; p = 0.03), with a sensitivity of 72.4% (54.3–85.3%) and a specificity of 70.3% (73.0–98.9%)]; the CO increase was not significantly different between responders and non-responders [5.6% (− 2.2/11) vs. − 0.35% (− 5.2/4.3); p < 0.07)], and the CO best threshold value of the ROC curve was 4% from baseline [grey zone − 1%/10%]. The EEOT correctly identified as responders or non-responders 38 of 56 patients (67.9%), while 18 patients (32.1%) (10 responders and 8 non-responders) were wrongly classified.

The AUC of SIGH35 was significantly larger as compared to the AUC of the EEOT, in the overall population (p < 0.0008) (Fig. 3).

ROC curves and AUC comparisons: subgroup with low inspiratory effort

Twenty-four patients (42.8%) showed P0.1 ≤ 1.5 cmH2O at baseline. The AUC of PP changes after SIGH35 was 0.98 (0.94–0.99; p < 0.001), with a sensitivity of 92.8% (68.5–99.7%) and specificity of 100.0% (72.2–99.9%)], and the PP best threshold value of the ROC curve was − 28% from baseline (Fig. 3). The SIGH35 correctly identified as responders or non-responders 22 of 24 patients (91.5%), while 2 patients (8.5%) (1 responder and 1 non-responder) were wrongly classified.

The AUC of CO changes after EEOT was 0.89 (0.72–0.99; p = 0.001), with a sensitivity of 100.0% (78.4–100.0%) and of specificity 80.0% (49.0–96.4%), and the CO best threshold value of the ROC curve was 5% from baseline. The EEOT correctly identified as responders or non-responders 21 of 24 patients (87.5%), while 3 patients (12.5%) (1 responders and 2 non-responders), have been wrongly classified.

In this subgroup of patients, the AUCs of the two tests were comparable (p = 0.26) (Fig. 3).

Discussion

The main results of this study can be summarized as follows: (1) in a selected ICU population undergoing PSV, the percent changes of the PP (obtained from baseline to the nadir) after the application of one sigh at 35 cmH2O for 4 s reliably predicted fluid responsiveness; (2) in this setting, the SIGH35 performed better than the EEOT which showed a small AUC; (3) the EEOT is still reliable in the subgroup of ICU patients having a small extent of inspiratory efforts.

Titration of fluid balance after the resuscitation phase of ICU patients with hemodynamic instability is crucial for avoiding excessive fluid administration [8, 32, 33]. Most of these tests were first described in ICU patients undergoing controlled MV [34]. In the last two decades, several studies have proven the reliability of functional hemodynamic tests in this setting (e.g., passive leg raising [35], the EEOT [15], and, more recently, the “tidal volume challenge” [36, 37] and “mini-fluid challenge” [13].

However, sedation and ventilation practice have changed significantly over the last decades. Nowadays, a large proportion of ICU patients retain spontaneous breathing activity [38,39,40] which may affect the reliability of the dynamic indexes of fluid responsiveness by influencing tidal volume magnitude [41], increasing respiratory rate, and, therefore, reducing heart rate/respiratory rate ratio and causing asynchronies between the patient and the ventilator. Patients ventilated in assisted modes have spontaneous inspiratory efforts, decreasing pleural pressure, blunting the effect of ventilatory positive pressure. From a hemodynamic perspective, spontaneous inspiration counteracts the effect of mechanical ventilation, reducing the increase in pleural pressure and the effect on venous return and afterload of both the right and the left heart [3, 4, 8].

As confirmation, in patients undergoing MV with spontaneous breathing activity, the tidal volume challenge showed an AUC of 0.78 [42], as compared to the AUC of 0.98 in patients under controlled MV [36]. Moreover, a rate of EEO failure as high as 22.5% has been reported, consequently to visible patients’ effort against the occluded airway [16]. However, no studies have explored the impact of inspiratory effort intensity on the reliability of the EEOT. Our study highlights the critical role of P0.1 in this context.

We reasoned that assessing the performance of both the EEOT and SIGH35 in this specific setting could expand the range of available tests during weaning from controlled mechanical ventilation. This phase typically coincides with the stabilization period of critically ill patients, during which fluid responsiveness is observed in approximately 50% of ICU patients [43].

The application of a sigh to the PSV should, in principle, prevent the majority of artifacts and undesirable hemodynamic interactions between the patient, the ventilator and the cardiovascular system, by transiently increasing RV afterload and reducing RVSV through a beat-to-beat adaptive response [10] and, at the end, affecting left ventricle preload and SV (and surrogates, such as PP). Our study showed that a drop of PP ≤ 25% during SIGH35 reliably predicted fluid responsiveness with a sensitivity of 93.1% (78.0–98.7%) and a specificity of 91.6 (73.0%- 98.9%). This best cut-off is slightly lower as compared to the first (35% of PP reduction) found in the first study on SIGH35 [18]. However, the grey zone analysis confirmed that a PP drop of 35% is the threshold associated with the highest number of fluid responders, while a PP drop of 15% indicated fluid unresponsiveness. These results provide a valuable bedside instrument to test fluid responsiveness without continuous hemodynamic monitoring in ICU patients undergoing PSV.

The best thresholds of PP reduction identified in this study and in the previous one about SIGH35 are similar, but not identical [18]. In principle, during the sigh, it is not the intrathoracic pressure itself, but its percentage transmitted to the RV which is responsible for the hemodynamic effect. This variability is largely influenced by overall respiratory mechanics and individual patient factors, such as body weight [9]. Specifically, the reduction in PP is tied to the inconsistent hemodynamic effects of sigh application. Factors like lung and chest wall compliance (e.g., in cases of obesity) significantly affect the hemodynamic response to sigh, highlighting the need for further studies in specific subgroups of ICU patients.

As expected, the EEOT showed a small AUC in the overall population but, interestingly, it reliably predicted fluid responsiveness in the subgroup of patients with a low inspiratory effort. How inspiratory effort could influence functional hemodynamic assessment has been rarely considered. Recently, Chen et al. showed that the pulse pressure variation AUC was 0.91 (0.83–0.99) in ICU patients with spontaneous breathing activity and P0.1 < 1.5 cmH2O, as compared to 0.67 (0.55–0.78) in patients with P0.1 ≥ 1.5 cmH2O [44]. Our results confirm that, if the inspiratory effort is low (i.e., the smallest extent needed to trigger the ventilator), then the effects on the cardiovascular interplay with the ventilator are comparable to those obtained in patients under controlled MV.

Our study has some limitations that must be considered. First, our criteria for patient selection are quite strict, especially considering the concurrent presence of a stable ventilatory pattern associated with hemodynamic instability requiring VE administration. This leads, together with the single-centre design of the study, to a selection of ICU patents which limits the external validity of our results.

Second, we cannot exclude a carry-over haemodynamic effect of the first test on the second, potentially impacting the baseline hemodynamic status and, eventually, the results. However, this potential bias has been minimized because of the randomization of the sequence, and by increasing the time between the two tests up to 3 min or when all continuous variables stabilized (as previously described [45]).

In our “proof of concept” studies, we showed that the slope analysis of SAP variations after SIGH35 reliably predicted fluid responsiveness. However it was a post-hoc mathematical elaboration, not based on automatic computation of SAP changes, which is not currently available for routine use. Accordingly, we tested only the PP changes after SIGH35, which is, on the contrary, clinically applicable [18]. However, as shown in the Fig. 2, the baseline of a beat-to-beat analysis cannot be a single beat (too variable) but rather the mean of some beats before the application of the test. We therefore adopted the mean of 10 beats as baseline for this computation. However, the MOSTCARE® system does not commercially offer the option to set this baseline as the default mode. Additionally, the baseline calculation may be influenced by the number of beats considered, which depends on the patient's heart rate. Moreover, the EEOT has been previously mainly tested by using calibrated tools automatically averaging hemodynamic values [15], and not assessing beat-to-beat CO changes.

The reliability of uncalibrated hemodynamic monitoring, as the MOSTCARE® is still debated, especially if it is strictly dependent on the quality of the arterial pulse and on the ability of the operator to recognize artifacts of the signal [25]. However, the absolute CO values and their changes after fluid infusion or vasopressor titration recorded with this device have previously shown good agreement with transpulmonary thermodilution in ICU patients [46,47,48]. Moreover, in this study we only considered percent changes of the PP (which is a measurement derived from the arterial line, and not an estimation) and of the CO (which is not affected by the accuracy of the technique itself), as compared to baseline values.

SIGH35 application is affected by several factors, potentially impacting the reliability and applicability of the test. The occurrence of extrasystoles during the beat-to-beat evaluation makes the results useless, this still happened in a minority of patients (about 5% in our study). The sudden increase of airway pressure may lead to cough and subsequent respiratory distress. This could be reduced by manipulating the inspiratory rise time of the ventilator (i.e., the time taken to reach peak inspiratory flow or pressure at the start of each breath), which is normally increased during PSV from the default setting, to enhance patient comfort.

Conclusions

In a selected ICU population undergoing PSV, the percent changes of PP after the application of one sigh at 35 cmH2O for 4 s reliably predicted fluid responsiveness, with a best cut-off of − 25% from baseline. In this setting the SIGH35 performed better than the EEOT which is, however, still reliable in the subgroup of ICU patients having a small extent of inspiratory efforts.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge Dr. Emanuela Morenghi for her support in data analysis. This work was partially supported by “Ricerca Corrente” funding from Italian Ministry of Health to IRCCS Humanitas Research Hospital.

Funding

This work has not been funded by an external source.

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Authors and Affiliations

  1. IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Antonio Messina, Francesco Benedetto & Maurizio Cecconi

  2. Department of Biomedical Sciences, Humanitas University, Via Levi Montalcini 4,, Pieve Emanuele, Milan, Italy

    Antonio Messina, Francesco Benedetto & Maurizio Cecconi

  3. Department of Anesthesia and Intensive Care, University Bicocca, Milan, Italy

    Aurora Villa

  4. AP-HP, Service de Médecine Intensive-Réanimation, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS, Groupe de Recherche Clinique CARMAS, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France

    Xavier Monnet

  5. Faculté de Médecine Paris-Saclay, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France

    Jean-Louis Teboul

  6. Department of Intensive Care, Hôpital Universitaire (HUB), Brussels, Belgium

    Lorenzo Calabrò

  7. Humanitas University, Pieve Emanuele, Milan, Italy

    Guia Margherita Matronola & Andrea Brunati

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  1. Antonio Messina
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  2. Lorenzo Calabrò
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  3. Francesco Benedetto
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  4. Aurora Villa
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  5. Guia Margherita Matronola
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  7. Jean-Louis Teboul
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  8. Xavier Monnet
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  9. Maurizio Cecconi
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Contributions

AM conceived the idea for the manuscript and performed the data analysis. AM and MC drafted and wrote the final version of the manuscript. AM and MC had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. LC, FB, AV, GMM and AB and SR performed patient recruitment and data storing. JLT and XM were involved in data interpretation and made critical revisions of the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Antonio Messina.

Ethics declarations

Ethics approval and consent to participate

The study was performed after approval of the institutional ethics committee of the Humanitas Research Hospital, in accordance with the principles of the Declaration of Helsinki. Patient’s written consent was managed as indicated by the ethics committees.

Consent for publication

Not applicable.

Competing interests

Dr. Messina received travel expenses and registration for meetings, congresses, and courses and lecture fees from Vygon, Edwards, Philips and Getinge. Xavier Monnet is a member of the medical advisory board of Pulsion Medical Systems (Getinge) and has given lectures for Baxter. Prof. Cecconi is a consultant of Edwards Lifesciences (Directed Systems Consultancy).

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Messina, A., Calabrò, L., Benedetto, F. et al. SIGH35 and end-expiratory occlusion test for assessing fluid responsiveness in critically ill patients undergoing pressure support ventilation. Crit Care 29, 176 (2025). https://doi.org/10.1186/s13054-025-05398-4

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Keywords

Critical Care

ISSN: 1364-8535