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A Long-Term Clinical Evaluation of AutoFlow During Assist-Controlled Ventilation: A Randomized Controlled Trial

Lasocki, Sigismond MD, PhD; Labat, Françoise MD; Plantefeve, Gaetan MD; Desmard, Mathieu MD; Mentec, Hervé MD

doi: 10.1213/ANE.0b013e3181f00015
Technology, Computing, and Simulation: Research Reports
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BACKGROUND: Many new mechanical ventilation modes are proposed without any clinical evaluation. “Dual-controlled” modes, such as AutoFlow™, are supposed to improve patient– ventilator interfacing and could lead to fewer alarms. We performed a long-term clinical evaluation of the efficacy and safety of AutoFlow during assist-controlled ventilation, focusing on ventilator alarms.

METHODS: Forty-two adult patients, receiving mechanical ventilation for more than 2 days with a Dräger Evita 4 ventilator were randomized to conventional (n = 21) or AutoFlow (n = 21) assist-controlled ventilation. Sedation was given using a nurse-driven protocol. Ventilator-generated alarms were exhaustively recorded from the ventilator logbook with a computer. Daily blood gases and ventilation outcome were recorded.

RESULTS: A total of 403 days of mechanical ventilation were studied and 45,022 alarms were recorded over a period of 8074 hours. The course of respiratory rate, minute ventilation, FIO2, positive end-expiratory pressure, PaO2/FIO2, PaCO2, and pH and doses and duration of sedation did not differ between the 2 groups. Outcome (duration of mechanical ventilation, ventilator-associated pneumonia, course of Sequential Organ Failure Assessment score, or death) was not different between the 2 groups. The number of alarms per hour was lower with AutoFlow assist-controlled ventilation: 3.3 [1.5 to 17] versus 9.1 [5 to 19], P < 0.0001 (median [quartile range]). In multivariate analysis, a low alarm rate was associated with activation of AutoFlow and a higher midazolam dose.

CONCLUSIONS: This first long-term clinical evaluation of the AutoFlow mode demonstrated its safety with regard to gas exchange and patient outcome. AutoFlow also allowed a very marked reduction in the number of ventilator alarms.

Published ahead of print August 12, 2010 Supplemental Digital Content is available in the text.

From the Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France.

Sigismond Lasocki, MD, PhD, is currently affiliated with Réanimation Chirurgicale, APHP, CHU Bichat Claude Bernard, Paris, France.

The Hospital Victor Dupouy, Argenteuil, France, supported this study. Drägger SA provided only technical assistance for the recording of a ventilator logbook, but had no access to the data and was not involved in the preparation of this manuscript.

Address correspondence to Sigismond Lasocki, MD, PhD, Réanimation Chirurgicale, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France. Address e-mail to sigismond@lasocki.com.

Accepted June 19, 2010

Published ahead of print August 12, 2010

“Dual-controlled” ventilation modes1,2 are reported to combine the advantages of both volume and pressure-controlled ventilation modes. The only studies comparing dual modes to conventional assist-controlled ventilation (ACV) focused on short-term effects (several hours). They report a reduction of inspiratory pressure.3,4 Dräger's AutoFlow™ (AF) is one of these dual-controlled ventilation modes that also allows spontaneous breathing throughout the respiratory cycle. Drager claims that AF is expected to improve patient–ventilator interfacing and could decrease the number of times patients fight the ventilator. AF could consequently reduce the number of ventilator alarms. Alarms are partly responsible for the high noise level in intensive care units (ICU),57 and a reduction of ventilator alarms would therefore be beneficial to both patients and ICU staff. ICU staff also fail to correctly identify many of these alarms.8 Reducing the number of alarms may therefore improve alarm efficiency.9 We hypothesize that activation of the AF would reduce the number of ventilation-generated alarms, without impairing the patient's ventilation. Because no clinical evaluation of this ventilation mode is available, this study was also designed to clinically evaluate AF activation.

The aim of this randomized controlled study was to clinically evaluate AF activation during ACV, with regard to ventilator-generated alarms (primary aim) and to gas exchange and patient outcome (secondary aims).

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METHODS

The study protocol was approved by the Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale (independent ethics committee) of Saint-Germain-en-Laye, France (ClinicalTrial.gov identifier: NCT0092774). Written informed consent was obtained from the patient or next of kin.

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Patients

Adult patients admitted to the ICU of Victor Dupouy Hospital, Argenteuil, France, were eligible when they required ACV with an Evita4 ventilator (Dräger Medical, Antony, France) for an expected duration of >2 days. Patients were not included in the case of coma, ventilation for >12 hours before inclusion, pregnancy, or inclusion in another study.

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AutoFlow

AF is a dual-control mechanical ventilation mode associated with ACV.1,10 All breaths are pressure-controlled, with a delivered level of pressure support that varies from breath to breath to deliver the set tidal volume (VT). AF uses a feedback loop that regulates inspiratory flow. Dynamic compliance is measured breath by breath, and the required δ pressure for the next breath is calculated by dividing the desired VT by dynamic compliance. Changes of inspiratory pressure from breath to breath are limited to 3 mbar. When inspiratory pressure reaches the upper pressure limit minus 5 mbar, inspiratory time is increased within the limits defined by the set respiratory rate.

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Mechanical Ventilation

Patients were randomly assigned to the control group (AF−) or the AF group (AF+) by opening a sealed envelope. Attending physicians chose all respiratory settings, without intervention by the study investigators. The upper limit of inspiratory pressure alarm was initially set at 50 cm H2O. Other alarm limits were set at the manufacturer's default values, which varied according to the patient's body weight. Attending physicians were allowed to change any alarm limit and ventilator mode when clinically indicated, except that AF was always used with ACV in the AF+ group, and AF was never used with ACV in the AF− group. Discontinuation of mechanical ventilation was performed according to our ICU standard protocol, by the gradual reduction of pressure support. Blood gases were obtained at least once daily during the first days. Morning values of ventilator settings, highest FIO2, highest positive end-expiratory pressure, highest PaCO2, lowest PaO2/FIO2 ratio, and lowest pH were recorded daily.

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Sedation

Patients were sedated by continuous infusions of midazolam and fentanyl according to a nurse-driven protocol (Fig. 1). The sedation goal was a Ramsay score11 of 2 or 3.

Figure 1

Figure 1

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Ventilator-Generated Alarms

Ventilators were periodically connected to a personal computer to download the number of alarms, changes in ventilator settings, alarm limit settings, and the number of times alarms were manually silenced (silence knob activation).

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Outcome

Organ failure was assessed daily using the Sequential Organ Failure Assessment (SOFA) score.12 Duration of mechanical ventilation, ICU and hospital survival, the incidence of pneumothorax, and the incidence of ventilator-associated pneumonia were recorded.

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Statistical Analysis

Results are expressed as median[Q1–Q3] or mean ± SD. Comparisons were performed with a Mann–Whitney test or Student's t test, a χ2 test with Yates' correction, or an analysis of variance (ANOVA) for repeated measures as appropriate. Analysis was performed by either intention to treat on the whole study period or per protocol (for the period during which patients were on ACV, with or without AF), depending on the variable considered. Thus we report the alarm rate for the different ventilation mode (ACV or non-ACV) in both groups. Obviously, in the AF+ group, AF was not activated during non-ACV ventilation (because it was not available).

To estimate the sample size of the study, we assumed that the total alarm rate in an ICU would be 36.5 alarms/hr,13 and that ventilator alarms would account for 38% of all alarms.14 The alarm rate during ACV was assumed to be 14 alarms/hr. A 50% reduction when AF was added to ACV was considered to be clinically relevant. Twenty-one patients in each group were needed to achieve a 90% power, with an α risk of 5%. To assess factors influencing the alarm rate, we divided patients into 2 groups—higher and lower than the median alarm rate—and we performed a logistic regression, including all the parameters that had a P value of <0.1 in the univariate analysis (i.e., indexed midazolam, indexed fentanyl and AF group, with indexed midazolam and indexed fentanyl being the total dose of midazolam or fentanyl indexed to the patient's body weight and the duration of drug infusion). Statistical analysis was performed with SPSS 15.0. P < 0.05 was considered statistically significant.

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RESULTS

Patients

Forty-two patients were included. No statistically significant differences in demographic data were observed between the 2 groups (Table 1). Indications for mechanical ventilation were not statistically different between groups (P = 0.31).

Table 1

Table 1

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Ventilation and Gas Exchange

Baseline ventilator settings and blood gases were not different between the 2 groups (Table 2). An ANOVA for repeated measures from day 1 to day 5 showed no significant difference between the 2 groups for either ventilator settings or blood gases (Fig. 2).

Table 2

Table 2

Figure 2

Figure 2

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Sedation

Sedation was not different between the 2 groups (Table 3). Total doses of midazolam (114 [0 to 163] vs. 150 [0 to 316] mg, P = 0.5) and fentanyl (6600 [0 to 55,480] vs. 8000 [0 to 21,500] μg, P = 0.8) were not different between the 2 groups (AF+ and AF− groups, respectively).

Table 3

Table 3

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Ventilator Alarms and Interventions

A total of 403 days (8074 hours) of mechanical ventilation were studied. ACV was used for 3997 hours. AF was used for 2133 hours. A total of 45,022 alarms were recorded; nearly 1 alarm every 10 minutes. During ACV, 7060 alarms were recorded in the AF+ group, and 16,817 alarms were recorded in the AF− group. Figure 3 shows that the ventilator alarm rate was lower when AF was used in conjunction with ACV (3.3 [1.5 to 17] alarms/hr with AF vs. 9.1 [5.2 to 19] without AF [P < 0.0001]). In the AF− group, the alarm rate was lower for ventilation modes other than ACV (mainly pressure support) than they were for ACV (without AF), but no difference was observed between these ventilation modes and ACV for the AF+ group (Fig. 3). The number of alarm setting modifications per hour was not different between groups (0.07 [0.02 to 0.23] vs. 0.09 [0.02 to 0.23] modifications per hour for AF+ and AF− patients, respectively; P = 0.85). Setting the high-pressure limit above 50 cmH2O was less frequent in the AF+ group (0 [0 to 2] vs. 2 [0 to 8] times per patient; P = 0.0007).

Figure 3

Figure 3

The type of alarm differed between the 2 groups. ACV plus AF generated fewer pressure alarms than did ACV alone (P < 0.0001) (Fig. 4). The silence knob activation rate was lower in the AF+ group during ACV (0.26 [0.1 to 1.1] vs. 0.72 [0.26 to 2] activation per hour; P = 0.0013).

Figure 4

Figure 4

The median alarm rate during ACV was 6.37 alarms/hr. Patients with alarm rates lower than 6.37 alarms/hr were more frequently randomized to the AF+ group (P = 0.0002) and had a higher dosage of sedative drugs (fentanyl, P = 0.02; midazolam, P = 0.07) (Table 4). In multivariate analysis, an alarm rate lower than 6.37 alarms/hr was associated with activation of AF (OR [95% CI], 90 [5 to 1570], P = 0.002) and a higher midazolam dosage (OR 1801 [3 to 1.1 106] per mg/d/kg, P = 0.02).

Table 4

Table 4

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Outcome

No patient suffered from pneumothorax in the AF+ group in comparison with 2 patients in the AF− group (P = 0.48). Four cases of ventilator-associated pneumonia were observed in the AF+ group in comparison with 8 in the AF− group (P = 0.16). The median duration of ventilation was 6 [2 to 25] versus 9 [2 to 36] days in AF+ and AF− groups, respectively (P = 0.33), and the median number of days free of mechanical ventilation at day 28 were 15 [0 to 26] and 13 [0 to 26], respectively (P = 0.55). An ANOVA for repeated measures from day 1 to day 5 showed no significant difference between the 2 groups for SOFA score (Fig. 2). Six patients in the AF+ group and 9 patients in the AF− group died in the ICU (P = 0.39), whereas 8 and 10 patients died in the hospital, respectively (P = 0.62).

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DISCUSSION

This study is the first long-term clinical evaluation of AF during ACV. Clinical outcome and blood gas variables were not different with and without AF. There were fewer ventilator alarms when AF was used.

AF is based on an attractive principle: to guarantee a set VT and minute ventilation while maintaining the advantages of pressure-controlled ventilation.1,2 Despite this potential advantage, clinical evaluations have not been performed. Even clinical efficiency in comparison with conventional ACV has not been formally demonstrated. This is the first report of around-the-clock observation and long-term bedside evaluation of this ventilation modality in the context of standard care. We found no differences with or without AF for gas exchange (P/F ratio or PaCO2) during ACV. No other studies are available for comparison. Previous studies have only reported the physiological advantages associated with pressure-regulated ACV in comparison with volume-controlled ventilation, such as lower inspiratory pressures3,4,15 and lower PaCO2.3,15

One concern regarding AF is that the level of support (i.e., the level of pressure delivered) could theoretically decrease as patient demand increases. Indeed, the work of breathing increases when pressure support decreases.16 This has been recently confirmed in a lung simulator.17 However, the absence of altered gas exchange in the AF+ group and the trend towards a shorter duration of ventilation do not support this hypothesis, in vivo. In fact, for a set VT, pressure-controlled ventilation reduces the work of breathing in comparison with volume-controlled ventilation.18 In the present study, 2133 hours of AF ACV were recorded, and no patient experienced any signs of respiratory distress. However, our study, with a sample size of 42 patients, is not powered to definitively assess these clinical aspects. Indeed, it was powered to compare the ventilation-related alarm rate with and without AF during ACV.

An original tool was used to record all ventilator-generated alarms. A higher alarm rate was observed than was previously reported by Chambrin et al. (0.6 alarm/hr in14). Gabor et al. found a higher rate of sound increase (37 ± 20 to 72 ± 13 times per hour of sleep),13 but they did not identify the source of each sound. The high alarm rate observed in the present study is certainly due to the method used, but could also be due to the target sedation level (Ramsay score of 2 to 3). A patient with less sedation may fight the ventilator. However, this low target is widely recommended and validated.1924 The lowest alarm rate was observed during ACV with AF, and the highest rate was observed during conventional ACV. It is not surprising that a pressure-controlled mode, such as AF, is associated with a reduction in pressure alarms. This is in accordance with studies demonstrating a reduction of peak inspiratory pressure during pressure-controlled ventilation.3,4,15 Multivariate analysis found only 2 factors associated with a lower alarm rate: midazolam doses and AF activation.

It may be beneficial to reduce the number of alarms in an ICU, because alarms are partly responsible for the high noise level in an ICU.57 The first consequence of alarm noise could be sleep disruption.25,26 In addition, an excess of false positive alarms may decrease alarm efficiency: Only 26.8% of ventilator-generated alarms lead to an action.14 Only one half of critical alarms are correctly identified by ICU staff.8 Reducing the total number of alarms should reduce noise in the ICU and improve alarm efficiency.9 We also showed that AF activation was associated with a reduction in a surrogate marker of care interruption, activation of the silence knob, which could help reduce cross-infections, because the ICU environment can be a reservoir for pathogens.27,28 Further studies will be needed to confirm the alarm reduction observed during AF ACV.

The major limitations of our study are the absence of fixed alarm limits and the unblinded design. The attending physician was allowed to modify alarm limits as usual, because no clear recommendations have been published.29 Physicians are unlikely to have set high alarm limits in view of the very high alarm rate observed in this study. Furthermore, no difference was observed for changes of alarm limits, apart from the upper-pressure alarm limit set above 50 cmH2O (more frequent in the AF− group), which should have reduced the alarms rate in that group. The trial could not be blinded because the ventilator screen displays ventilator settings. However, the end points (gas exchange, alarms, and outcome) were assessed objectively. Lastly, no modification of clinical outcome such as decreased duration of mechanical ventilation or mortality was observed. It is not surprising because no new mechanical ventilation mode has improved clinical outcome.10 In particular, a large-scale study comparing pressure-controlled ventilation with volume-controlled ventilation did not find any direct benefit.30 In the present study, sedation was controlled by a nurse-driven protocol, but it can be assumed that if physicians had prescribed sedation, they would have increased sedation during conventional ACV to decrease the alarm rate, which could have accentuated the trends observed in this study.

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CONCLUSIONS

ACV with AF appears to be safe in terms of gas exchange and clinical outcome in this first long-term around-the-clock clinical evaluation. AF was associated with a marked decrease in ventilator-generated alarms. The beneficial effect of such a reduction of alarm rate on the comfort of patients and ICU staff (quality of sleep and stress) deserves further evaluation.

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