Feasibility study on full closed-loop control ventilation (IntelliVent-ASV^™) in ICU patients with acute respiratory failure: a prospective observational comparative study

Mechanical ventilation is widely used in intensive care units (ICU) to support patients' respiratory failure. Ventilatory support must be adapted to each patient's metabolism to provide the oxygen required in the blood (oxygenation function) and to eliminate carbon dioxide (CO₂) (ventilation function). In conventional ventilation modes, physicians determine the oxygenation and ventilation settings manually. However, due to frequent changes in the physiological needs of ICU patients, these ventilation settings cannot be adjusted continuously, as this would require a continuous presence of caregivers at the bedside. To address this problem, ventilator management using an open-loop computerized decision support significantly reduces morbidity in patients with acute respiratory distress syndrome (ARDS) [1]. Closed-loop ventilation modes that automatically adjust some settings according to physiological input [2] represent a further advance. Closed-loop ventilation modes make it possible to select an individualized ventilation [3], to reduce workload [4], to improve patient-ventilator synchrony [5], and to reduce weaning duration in some settings [6‐8].

IntelliVent-ASV^™ is a further development of adaptive support ventilation (ASV) that automatically adjusts oxygenation and ventilation settings in passive (absence of spontaneous breathing activity) and active patients. Ventilation settings (minute volume (MV), tidal volume (V_T), and respiratory rate (RR)) are adjusted automatically to reach a target end-tidal CO₂ (PETCO₂) in passive patients and a target RR in active patients. Oxygenation settings (inspiratory fraction of oxygen (FiO₂) and positive end-expiratory pressure (PEEP)) are adjusted automatically to reach a target pulse oxymetry (SpO₂).

IntelliVent-ASV^™ has been studied during short periods of ventilation in passive and active ICU patients [9, 10], after cardiac surgery [11], and in pediatric care [12]. In all situations, IntelliVent-ASV^™ was safe and delivered lower V_T, peak inspiratory pressure (P_INSP) and FiO₂ in passive patients as compared to the controlled period in conventional ventilation. Up to now IntelliVent-ASV^™ has not been used for more than 24 hours in ventilated adult ICU patients. This prospective, observational feasibility study measured oxygenation and ventilation settings in ICU patients ventilated with IntelliVent-ASV^™ from inclusion to extubation or death. The primary objective was to compare ventilation delivered among three predefined lung conditions (normal lung, ARDS and chronic obstructive pulmonary disease (COPD)) in active and passive phases. The hypothesis was that IntelliVent-ASV^™ automatically selects different settings depending on the lung condition. The secondary objective was to assess the feasibility of IntelliVent-ASV^™ use defined as the number of safety events, the need to switch to conventional mode for any medical reason, or sensor failure.

This prospective, observational, comparative study was conducted from November 2010 to September 2011 in the 12-bed medical-surgical adult ICU of Font Pré Hospital in Toulon (France). The institutional review board approved the protocol, which was also declared at the Commission Nationale Informatique et Liberté (CNIL), and informed consent was obtained from each patient's next of kin.

During the study period, 789 patients were admitted in the ICU of which 103 patients were included in the study. Three patients were not analyzed (two for missing data and one was transferred for extracorporeal membrane oxygenation (ECMO) rapidly after inclusion). Thus, 100 patients were analyzed (Figure 1). Table 2 presents patient characteristics at inclusion, lung condition and outcomes. Seventy-seven patients were ventilated for longer than 24 hours.

In passive and active ventilation-days, MV, V_T/PBW, PEEP, FiO₂, P_INSP, and RR were statistically different based on lung condition (Table 3, Figure 2, 3, 4). In passive ventilation days, V_T/PBW was significantly different between normal lung, ARDS and COPD patients (8.1 (7.3 to 8.9) mL/kg; 7.5 (6.9 to 7.9) mL/kg; 9.9 (8.3 to 11.1) mL/kg, respectively; P <0.05) (Table 4 and Figure 2). In passive ARDS ventilation days, FiO₂ and PEEP were statistically higher than in passive normal lung patients (35 (33 to 47)% versus 30 (30 to 31)% and 11 (8 to 13) cmH₂O versus 5 (5 to 6) cmH₂O, respectively; P < 0.05) (Table 4 and Figure 3 and 4). In active ventilation days, V_T/PBW was significantly higher in COPD patients as compared to normal lung and ARDS patients (9.3 (8.6 to 11.6) mL/kg; 8.4 (7.8 to 9.1) mL/kg; 8.1 (7.5 to 9.3) mL/kg, respectively; P <0.05) (Table 5 and Figure 2). In active ARDS and COPD ventilation days, PEEP was significantly higher than in normal lung patients (8 (5 to 10) cmH₂O, 7 (5 to 10) cmH₂O, and 5 (5 to 5) cm H₂O, respectively; P <0.05) (Table 5 and Figure 4).

Regarding feasibility, all patients were ventilated using IntelliVent-ASV^™ from inclusion to extubation or death (392 days in total) and no safety issues occurred. There was never a medical need to switch to another ventilation mode. The fully automated ventilation was used for 95% of total ventilation time, and partial automated ventilation for 5% of ventilation time (ventilation controller alone: 4%; oxygenation controller alone: 1%). The ventilation controller was deactivated in two patients for one day because of an increased CO₂) gradient resulting in severe respiratory acidosis. PEEP and FiO₂ controllers were deactivated for one day in seven patients because of a poor SpO₂ quality measurement (five patients in shock, one patient with therapeutic hypothermia and one patient with severe chronic arterial disease). PEEP controller was deactivated in three patients; one COPD for manual adjustment according to intrinsic PEEP, one after a pneumothorax resulting from subclavicular catheter insertion and one ARDS patient for manual adjustment according to transpulmonary pressure. The FiO₂ controller was deactivated in one COPD patient because of hyperoxia.

This observational study measured ventilation and oxygenation parameters automatically determined by IntelliVent-ASV^™ in 100 unselected ventilated ICU patients. IntelliVent-ASV^™ automatically selected different ventilation and oxygenation parameters according to lung condition especially for passive breathing patients. It was feasible to use IntelliVent-ASV^™ with no resulting safety issues for patients and with very few sensor failures.

In passive patients, ventilation and oxygenation parameters determined by IntelliVent-ASV^™ were different according to lung condition. In normal lung patients, V_T/PBW was 8.1 (7.3 to 8.9) mL/kg with P_PLAT at 18 (17 to 20) cmH₂O and a PEEP at 5 (5 to 6) cmH₂O. Current recommendations regarding normal lung patients are to set V_T/PBW between 6 and 8 mL/kg in patients at risk of ARDS, and ≤10 mL/kg in patients without risk factors and to set PEEP between 5 and 12 cmH₂O [18, 19]. Thus, ventilation selected by IntelliVent-ASV^™ in patients with normal lungs at the onset of mechanical ventilation is in line with current recommendations to prevent ventilator-induced lung injuries (VILI). FiO₂ selected in passive normal lung patients was 30 (30 to 31)%. A recent retrospective database study found that hyperoxia is commonly seen in the ICU and in most cases does not lead to the adjustment of ventilator settings if FiO₂ is below or equal to 40% [20]. There have been studies in humans that report the physiological effects of hyperoxia including impaired myocardial blow flow [21], increased myocardial consumption [22], and reduced cerebral blood flow due to arterial vasoconstriction [23]. Thus, in normal lung patients, where hyperoxia is easily obtained, automatic adjustment of FiO₂ should minimize FiO₂ levels, prevent unnecessary hyperoxia and avoid potential systemic oxygen toxicity.

In passive ARDS patients, V_T/PBW was 7.5 (6.1 to 8.8) mL/kg with P_PLAT at 26 (23 to 29) cmH₂O and a PEEP at 11 (8 to 13) cmH₂O. These results are in line with current recommendations to use a protective ventilation strategy in order to prevent VILI. A meta-analysis of protective ventilation trials in ARDS patients found a favorable effect for V_T/PBW less than 7.7 mL/kg [24]. Even though P_PLAT and V_T/PBW are not good surrogates to assess lung stress and strain [25], these values are easily measured at the bedside and are widely used. A large international observational study showed that the current mechanical ventilation practice in ARDS patients is to set a median V_T/PBW between 6 and 8 mL/kg with a median PEEP at 5 to 12 cmH₂O [26]. A large multicenter observational study in Spain observed 255 ARDS patients and found a V_T/PBW at 7.2 ± 1.1 mL/kg, P_PLAT at 26 ± 5 cmH₂O, and PEEP at 9.3 ± 2.4 cmH₂O [27]. Thus, IntelliVent-ASV^™ selects V_T/PBW and PEEP that are in line with current recommendations and current practices. Despite the evidence showing that a reduced V_T strategy is associated with improved outcomes, physicians still routinely use higher V_T than recommended [28‐30]. The main reasons for physicians' underuse of low V_T ventilation are the use of actual body weight instead of PBW in the calculation of V_T, a general underrecognition of ARDS in clinical practice [31], physician concern about increasing RR with a potential risk of dynamic hyperinflation [32], and concern about permissive hypercapnia and acidosis [33]. IntelliVent-ASV^™ automatically computes the PBW based on height and gender, automatically recognizes short expiratory time constant (RC_EXP) and adjusts V_T and RR accordingly, prevents dynamic hyperinflation in passive patients by adjusting expiratory time according to RC_EXP, and allows a moderate permissive hypercapnia when P_INSP is above 25 cmH₂O. Overall, IntelliVent-ASV^™ is a useful way to help implement protective ventilation.

In ARDS patients, IntelliVent-ASV^™ selected oxygenation settings that combined a moderately high PEEP (11 (8 to 13) cmH₂O) with a low FiO₂ (35 (33 to 47)%). This combination follows the higher PEEP-FiO₂ table [34], which complies with the open lung concept [35] in order to prevent atelectrauma.

In passive COPD patients, V_T/PBW was 9.9 (8.3 to 11.1) mL/kg. There is no consensus as to the optimal V_T in passive COPD [36, 37]. However, because end-expiratory lung volume is increased in COPD, the lung strain associated with relatively high V_T remains limited [25].

In active patients, the difference in V_T/PBW between each lung condition was less than in passive patients. This is explained by the range of RC_EXP, which was narrower in the lung conditions in active compared to passive patients. As a consequence, there is not a significant difference between the target V_T/PBW determined by the ASV algorithm for the different lung conditions. In addition, V_T/PBW in active patients is very dependent on patient's drive, which may be increased as a result of elements such as metabolic acidosis, pain, discomfort, anxiety, and the sedation used. It should be noted that active ARDS patients are in the weaning phase after severe hypoxemia has been resolved.

In this study, assessment of feasibility was defined by the number of safety events, the need to switch to another mode and sensor failure. As in previous studies [9‐11], there was no safety issue according to the predefined safety criteria. None of the users were uncomfortable with IntelliVent-ASV^™ to the extent that it was necessary to switch to conventional ventilation. Overall, physicians had to deactivate one controller for only 5% of the total ventilation time. The main reasons were a large CO₂ gradient and SpO₂ signal of poor quality [38, 39]. Considering the large numbers of ventilation days and the relatively small number of problems, this study shows that the use of IntelliVent-ASV^™ is feasible on a daily basis in unselected ICU patients with different lung conditions. However, monitoring of patients is still required, especially for the CO₂ gradient in patients with large ventilation/perfusion ratio disturbances. Also, in case of sudden decrease of PETCO₂ due to a shock or pulmonary embolism, there is a risk of hypoventilation. The current software does not sound an alarm when PETCO₂ and MV change but does sound an alarm when the low PETCO₂ or MV threshold is reached.

The main limitation of this study is that it is observational, which does not allow comparison with conventional modes in terms of settings or outcome. In addition, numbers of severe ARDS patients were too small to draw definitive conclusions on safety. Studies in this subgroup population are required. Data were collected once a day and not continuously. Results would possibly be different if measured continuously or with a higher sampling rate. However, the times that were selected to collect the data were chosen specifically to be isolated from nursing care and medical procedures. Adaptation of IntelliVent-ASV^™ during nursing care and medical procedures deserves additional studies. Finally, this study was performed in a unit with a large experience of ASV use. Applicability of results may be different in other settings.

This observational study found that IntelliVent-ASV^™ seems safe for all ICU duration in ventilated unselected ICU patients with different lung conditions. More data is required for specific populations, in particular severe ARDS patients. Automatically selected oxygenation and ventilation settings were different according to the lung condition, especially in passive patients, and are in line with current recommendations. These results are a step forward in the implementation of closed-loop mode in daily practice in the ICU.

JMA designed the study, wrote the protocol, collected data, analyzed the results and drafted the manuscript. AG has made a substantial contribution to writing the protocol, collecting data, analyzing the results and drafting the manuscript. DD, LD, AB, SYD, and GC have made substantial contributions to collecting the data and revising the manuscript. DN, SJ and JDG have made substantial contributions to interpreting the results and revising the manuscript. All authors read and approved the final manuscript.