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Original Research: Critical Care |

A Randomized Controlled Trial Comparing the Ventilation Duration Between Adaptive Support Ventilation and Pressure Assist/Control Ventilation in Medical Patients in the ICUAdaptive Support Ventilation in the ICU FREE TO VIEW

Cenk Kirakli, MD; Ilknur Naz, PT, MS; Ozlem Ediboglu, MD; Dursun Tatar, MD; Ahmet Budak, MD; Emel Tellioglu, MD
Author and Funding Information

From Izmir Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Intensive Care Unit, Izmir, Turkey.

CORRESPONDENCE TO: Cenk Kirakli, MD, Pulmonary and Critical Care Medicine, 9 Eylul Mah. 35. Sokak Sitesi F10, Ulukent, Menemen, Izmir, Turkey; e-mail: ckirakli@hotmail.com


This study was presented in abstract form at the 27th Annual Congress of the European Society of Intensive Care Medicine, September 27-30, 2014, Barcelona, Spain.

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):1503-1509. doi:10.1378/chest.14-2599
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Published online

BACKGROUND:  Adaptive support ventilation (ASV) is a closed loop mode of mechanical ventilation (MV) that provides a target minute ventilation by automatically adapting inspiratory pressure and respiratory rate with the minimum work of breathing on the part of the patient. The aim of this study was to determine the effect of ASV on total MV duration when compared with pressure assist/control ventilation.

METHODS:  Adult medical patients intubated and mechanically ventilated for > 24 h in a medical ICU were randomized to either ASV or pressure assist/control ventilation. Sedation and medical treatment were standardized for each group. Primary outcome was the total MV duration. Secondary outcomes were the weaning duration, number of manual settings of the ventilator, and weaning success rates.

RESULTS:  Two hundred twenty-nine patients were included. Median MV duration until weaning, weaning duration, and total MV duration were significantly shorter in the ASV group (67 [43-94] h vs 92 [61-165] h, P = .003; 2 [2-2] h vs 2 [2-80] h, P = .001; and 4 [2-6] days vs 4 [3-9] days, P = .016, respectively). Patients in the ASV group required fewer total number of manual settings on the ventilator to reach the desired pH and Paco2 levels (2 [1-2] vs 3 [2-5], P < .001). The number of patients extubated successfully on the first attempt was significantly higher in the ASV group (P = .001). Weaning success and mortality at day 28 were comparable between the two groups.

CONCLUSIONS:  In medical patients in the ICU, ASV may shorten the duration of weaning and total MV duration with a fewer number of manual ventilator settings.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01472302; URL: www.clinicaltrials.gov

Figures in this Article

Closed-loop modes such as adaptive support ventilation (ASV) may improve the adaptation of the ventilator to the patient’s ventilatory needs and facilitate early recognition of the ability to breathe spontaneously.1 Some studies have reported shorter weaning times, fewer alarms, and fewer manipulations with ASV as compared with conventional modes, especially in the weaning period.25

ASV uses an algorithm to select the optimal respiratory rate (RR)/tidal volume (Vt) combination associated with the least work of breathing based on to the Otis equation.6 ASV is an adaptive pressure controlled ventilation in passive patients and switches to an adaptive pressure support ventilation (PSV) in spontaneously breathing patients. ASV was able to reduce the weaning duration of patients with COPD, compared with PSV.5 In most studies, it was used only in the weaning phase, and patients were ventilated with conventional modes until weaning. Because ASV can be used from intubation to extubation, it may also offer some advantages before the weaning phase.

Therefore, we conducted a randomized controlled study to test the hypothesis that ASV may shorten the total mechanical ventilation (MV) duration when compared with conventional ventilation. The secondary objective was to evaluate the impact of ASV on weaning duration, total number of manual settings of the ventilator, and weaning success rates.

This study was performed in a 29-bed medical ICU of a hospital specializing in pulmonary diseases and thoracic surgery; therefore, most of the patients were pulmonary patients (especially COPD). The study was approved by the institutional review board (approval number 298). Written informed consent was obtained from each patient’s relatives.

Patients

Adult patients who were admitted to the ICU between December 2011 and December 2013, intubated, and mechanically ventilated for > 24 h were included in the study. Patients with COPD underwent a noninvasive ventilation (NIV) trial first and if they failed NIV, they were intubated and included in the study population. Patients who were ventilated for < 24 h, patients who were intubated and mechanically ventilated for > 24 h in another center prior to ICU admission, and patients with a tracheotomy or who were treated with home MV were not included in the study. Patients with ARDS were not included because of its specific ventilation procedures. Patients who fulfilled the inclusion criteria were randomized into ASV or pressure assist/control ventilation (P-ACV) according to a computer-generated randomization procedure. For each individual patient, the randomization sequence was reported to the respiratory therapist and physician in charge in a sealed envelope. Sedation protocols and treatments for the underlying disease were standardized equally for each group. Midazolam boluses were used at a dosage of 0.05 mg/kg at certain intervals to achieve a Ramsay sedation score of 2 to 3.7 Fentanyl boluses were used at a dosage of 0.5 μg/kg for pain management. All patients with COPD in both groups had the same medical therapy (short-acting β2 agonists, anticholinergics, systemic corticosteroids, and antibiotics when signs of bacterial infection occurred). Sedation and fluid management, antibiotic strategy, glucose control, and enteral nutrition were also standardized between the two groups according to the ICU protocols.

Study Design and Protocols

All patients were ventilated with a microprocessor-controlled ventilator that also had a closed-loop ventilation capability (Galileo GOLD; Hamilton Medical). The ventilation protocol for each mode is described later.

ASV Group:

In this ventilation mode, minute volume (MinVol) was expressed as a percentage (MinVol %) of physiologic MinVol, 100% MinVol being equal to 0.1 L/kg predicted body weight per minute. The setting was started at 100% and was adjusted according to the Paco2 levels for passive patients or patient’s RR for spontaneously breathing patients. A positive end-expiratory pressure (PEEP) of around 3 to 5 cm H2O was applied to all patients with an Fio2 gradually decreased from 100% to 40% according to the arterial oxygen saturation. Inspiratory trigger sensitivity was set to 2 L/min and was titrated to achieve the minimum level without autotriggering. Expiratory trigger sensitivity was set to 40% of the maximal inspiratory flow.

P-ACV Group:

P-ACV was used as a conventional mode because of its similarity to ASV except for the cycling criteria. Pressure control levels were started at 30 cm H2O and were titrated to obtain a Vt of 6 to 8 mL/kg according to the unit protocol. A PEEP of around 3 to 5 cm H2O was applied to all patients with an Fio2 gradually decreased from 100% to 40% according to the arterial oxygen saturation. RR was set to 12 to 15 breaths/min, and inspiratory time was set to 1.5 s. The inspiratory to expiratory ratio was adjusted by either changing the inspiratory time or RR or both. Inspiratory trigger sensitivity was set to 2 L/min and was titrated to achieve the minimal level without autotriggering.

Weaning Period:

Weaning was performed in both groups according to the European Respiratory Society Weaning Task Force recommendations.8 Readiness to wean was assessed every morning by the respiratory therapist and physician in charge, who were not involved in the study. When the patients were able to trigger the ventilator and met the readiness to wean criteria (adequate cough, absence of excessive tracheobronchial secretions, in a stable cardiovascular status with a systolic BP between 90 and 160 mm Hg with no or minimal vasopressors, stable metabolic status, Pao2/Fio2 ≥ 150 with an Fio2 ≤ 40% and RR ≤ 35 breaths/min, no sedation or adequate mentation on sedation), they underwent a spontaneous breathing trial (SBT) with a T-tube for 2 h.9,10 At the end of the SBT, patients were evaluated again and extubated. If signs of intolerance occurred, the trial was stopped and they were connected to the ventilator again with the previous mode and settings. The T-tube trial was performed for 3 consecutive days (one trial for each day). If patients failed all three SBTs with the T-tube, those in the P-ACV group were switched to PSV and weaning was continued with gradual reductions in pressure support (PS) levels (at least bid with 2-4 cm H2O intervals) to 7 cm H2O (12 cm H2O if an heat and moisture exchanger was used in the circuit); and in the ASV group, MinVol % was gradually decreased to 30% (at least bid by steps of 10%) until a PS level of 7 cm H2O (12 cm H2O if an heat and moisture exchanger was used in the circuit) was tolerated for 2 h. For patients who failed to be weaned from the ventilator after 10 days, a percutaneous dilatational tracheotomy was performed and weaning was continued by disconnecting the patients daily from the ventilator if tolerated. An NIV trial with the same ICU ventilator was performed in patients who developed respiratory failure after extubation if there was no contraindication.

Measurements, Definitions, and Outcomes:

Patients in whom SBT could not be performed because of the clinical status were defined as nonweaned patients. Simple, difficult, and prolonged weaning were defined according to the European Respiratory Society weaning task force definitions.8 Weaning success was defined as independence from MV (invasive or noninvasive) at least 48 h after extubation.

Weaning duration was defined as the time beginning from the first SBT until the last successful extubation. Total MV duration was defined as the time from intubation until the last successful extubation.

The number of manual settings was defined as the total number of settings in the inspiratory pressure, RR, and inspiratory time for the P-ACV group and the number of manual adjustments in MinVol% and expiratory trigger sensitivity for the ASV group to achieve the desired Vt and Paco2 levels. Settings made in the Fio2 and PEEP levels were not taken into account. Intubation-free days were defined as the number of days under NIV or spontaneous breathing from extubation until day 28.

Statistical Analysis

Sample size calculation was made according to the total MV duration of our center, which was 9 ± 8 days according to the hospital database at the time of study design. The sample size of a minimum of 112 in each group was chosen to give a power of 0.80 to detect a 3-day reduction in mean total ventilation duration, assuming an SD of 8 days with a two-sided test at the 0.05 level. Continuous data are expressed as mean ± SD or median (interquartile range) and were compared with the Student t test or Mann-Whitney U test where appropriate. Categorical data are expressed in numbers and percentages and were compared with the Fisher exact test. Time to event data were analyzed using Kaplan-Meier survival analysis. Time comparisons between groups were done with a log-rank test. A two-sided P value < .05 was considered significant.

The flow of 229 study patients throughout the study is shown in Figure 1. Demographic, clinical, and laboratory characteristics were comparable at the time of randomization (Table 1). The ASV group had more patients with COPD (64% vs 51%, P = .06).

Figure Jump LinkFigure 1 –  Flow of patients throughout the study. ASV = adaptive support ventilation; MV = mechanical ventilation; P-ACV = pressure assist/control ventilation.Grahic Jump Location
Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of the Two Groups at the Time of Inclusion

Data are presented as median (interquartile range), No. (%), or No. Respiratory function tests are for the patients with obstructive and restrictive lung disease only. Arterial blood gas results are the ones just before intubation. APACHE = Acute Physiologic and Chronic Health Evaluation; ASV = adaptive support ventilation; MV = mechanical ventilation; P-ACV = pressure assist/control ventilation.

MV duration until weaning, weaning duration, and total MV duration were significantly shorter in the ASV group (Figs 2, 3, Table 2). Patients in the ASV group also required a fewer number of manual settings on the ventilator to reach the desired pH and Paco2 levels (P < .001) (Table 2).

Figure Jump LinkFigure 2 –  Total MV duration expressed as a Kaplan-Meier curve in the ASV and conventional ventilation groups. (Patients who were self-extubated or died before planned extubation are censored.) See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 –  Weaning duration expressed as a Kaplan-Meier curve in the ASV and conventional ventilation groups. (Patients who were self-extubated or died before planned extubation are censored.) See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Table Graphic Jump Location
TABLE 2 ]  Comparison of ASV and Conventional Ventilation Groups

Data are presented as No. (%) or median (IQR). Mean ± SD is also presented for some variables because of the skewed distribution of the data. LOS = length of stay; VAP = ventilator-associated pneumonia. See Table 1 legend for expansion of other abbreviations.

The number of patients extubated successfully without difficulty and on the first attempt was significantly higher in the ASV group (Table 3). Self-extubation, ventilator-associated pneumonia, tracheostomy, and 28-day mortality rates were comparable between the two groups (Table 2).

Table Graphic Jump Location
TABLE 3 ]  Weaning Status of the Two Groups

Data are presented as No. (%). See Table 1 legend for expansion of abbreviations.

a 

n = 114.

b 

n = 115.

c 

n = 78.

d 

n = 79.

e 

Simple group when compared with difficult and prolonged group.

The main finding of this study was that ASV was able to reduce total MV and weaning duration with fewer manual ventilator adjustments when compared with P-ACV. Moreover, the shortening of MV duration was not only a result of the shorter weaning period, but also the shorter ventilation time from intubation to the beginning of the weaning period.

Several studies have evaluated the impact of automated modes on weaning duration. Most of these studies using ASV were performed on patients who had had cardiac surgery. These studies reported reductions in the controlled and assisted phases of ventilation, duration until weaning, and total MV duration or no difference but with fewer manual settings of the ventilator with ASV.24 In a previous study, we used ASV only in the weaning period of patients with COPD and found a reduction in the weaning duration.5 The use of ASV from intubation to extubation during the entire ventilation period in the current study may have been the cause of the additional reduction in the duration of MV until weaning. The automatic decrease of PS when patient effort increases in ASV allows early detection of patients ready to be weaned.

Regarding the use of ASV in different patient groups, one randomized controlled study performed in patients with ARDS reported a median 1-day reduction in the duration of MV when compared with volume controlled ventilation, but this difference did not reach statistical significance because of the small sample size.11 In mixed medical patients in the ICU, the number of patients achieving extubation readiness within 1 day was significantly higher in the ASV group when compared with those receiving conventional ventilation,12 consistent with our results.

To our knowledge, this is the first randomized controlled study that used ASV from intubation until extubation. An interesting finding was the reduction in the time from intubation to weaning period that was initiated with the first T-tube trial. ASV automatically switches to PSV when spontaneous activity is detected. This automatic selection of ventilation may have some additional advantages. Physicians are unable to make the right changes at the right moment because lung mechanics are prone to change very rapidly in patients who are mechanically ventilated in the ICU. ASV provides an automatic selection of the Vt-RR combination in passive patients and afterwards it can adjust the level of PS according to patient needs in spontaneously breathing patients, probably leading to a better patient ventilator interaction and earlier recognition of extubation readiness when compared with P-ACV.2,12,13

The choice of optimal ventilatory mode to facilitate weaning and shorten the duration of intubation is still controversial, but some studies suggest that specific approaches may influence the duration of MV. Esteban et al14 reported that daily trials of spontaneous breathing with a T-tube were superior to synchronized intermittent mandatory ventilation and PSV. Strategies such as mandatory daily SBTs can detect extubation readiness, but these kinds of algorithms are often underused depending on factors such as the nurse to patient ratio, staffing, training, patient population, and workload of the unit. In the center in which the current study was conducted, weaning and extubation procedures were made according to physician decisions regardless of a standard protocol, and the mean duration of ventilation was around 8 days before the study period. During the study period, patients who were in the assisted phase of ventilation were assessed with a daily SBT with a T-tube in both groups. Daily screening of the respiratory functions, followed by a trial of spontaneous breathing in appropriate patients, may have led to shorter ventilation duration in both groups, as reported in a study by Ely et al.15 Protocols similar to those in the control group that were used in different studies also reported similar outcomes of a ventilation duration of 4 to 6 days, consistent with the outcome of the control group in this study.1517 Another explanation for the shorter duration of MV in both groups may be the population selected. Most of the patients had acute exacerbations of COPD, the requirements of sedation were minimal, and patients with ARDS were excluded. Therefore, the reproducibility of these results in a nonselected population of medical patients in the ICU is questionable.

One interesting finding of this study was the significantly higher number of patients extubated successfully in the first SBT attempt (simple weaning) in the ASV group. The treatment of the control group in these types of studies is always a complicated issue. The choice of P-ACV until the patients reach “readiness to wean” may be debatable. Some centers switch to PSV as the patients recover some respiratory activity to improve patient-ventilator interaction (as done automatically in ASV) and to prevent diaphragm deconditioning. This may be an explanation for the larger number of T-tube failures in the P-ACV group.

This study has some limitations. First, it was conducted in a single center that has experience with ASV. This makes difficult the generalizability of the results to other centers and patient groups. Second, although the staff in charge of the patients were blind to the aim of the study, it was impossible to blind both groups, as with most studies on MV. Third, the sample size calculation was done according to the ventilation duration of all patients in our ICU (including ARDS, and so forth). Last, because of technical difficulties, we did not have the chance to record physiologic data such as inspiratory pressure, Vt, RR, inspiratory and expiratory times, static lung compliance, inspiratory resistance, esophageal pressure, and auto-PEEP. The effect of these parameters on outcomes such as ventilator-induced lung injury, patient ventilator interaction, complications, and ventilation duration also deserves further evaluation.

ASV may have a positive impact on preparing patients for weaning by shortening the total MV and weaning duration with a fewer number of manual settings of the ventilator. Further studies are needed to test the positive impact of these new technologies on outcomes such as patient ventilator interaction, patient comfort, ICU cost, and mortality.

Author contributions: C. K. is the guarantor of the manuscript and takes responsibility for its content, including the data, analysis, review and writing of the manuscript. I. N. contributed to the study design and data collection, analysis and review of the manuscript and O. E., D. T., A. B., and E. T. contributed substantially to the data collection and the review and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We thank the American Thoracic Society’s Methods in Epidemiologic, Clinical and Operations Research (MECOR) Program for stimulating our interest in this research and for advice on the manuscript.

ASV

adaptive support ventilation

MinVol

minute volume

MV

mechanical ventilation

NIV

noninvasive ventilation

P-ACV

pressure assist/control ventilation

PEEP

positive end-expiratory pressure

PS

pressure support

PSV

pressure support ventilation

RR

respiratory rate

SBT

spontaneous breathing trial

Vt

tidal volume

Rose L, Schultz MJ, Cardwell CR, Jouvet P, McAuley DF, Blackwood B. Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children. Cochrane Database Syst Rev. 2013;6:CD009235. [PubMed]
 
Sulzer CF, Chioléro R, Chassot PG, Mueller XM, Revelly JP. Adaptive support ventilation for fast tracheal extubation after cardiac surgery: a randomized controlled study. Anesthesiology. 2001;95(6):1339-1345. [CrossRef] [PubMed]
 
Petter AH, Chioléro RL, Cassina T, Chassot PG, Müller XM, Revelly JP. Automatic “respirator/weaning” with adaptive support ventilation: the effect on duration of endotracheal intubation and patient management. Anesth Analg. 2003;97(6):1743-1750. [CrossRef] [PubMed]
 
Gruber PC, Gomersall CD, Leung P, et al. Randomized controlled trial comparing adaptive-support ventilation with pressure-regulated volume-controlled ventilation with automode in weaning patients after cardiac surgery. Anesthesiology. 2008;109(1):81-87. [CrossRef] [PubMed]
 
Kirakli C, Ozdemir I, Ucar ZZ, Cimen P, Kepil S, Ozkan SA. Adaptive support ventilation for faster weaning in COPD: a randomised controlled trial. Eur Respir J. 2011;38(4):774-780. [CrossRef] [PubMed]
 
Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol. 1950;2(11):592-607. [PubMed]
 
Jacobi J, Fraser GL, Coursin DB, et al; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1):119-141. [CrossRef] [PubMed]
 
Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;29(5):1033-1056. [CrossRef] [PubMed]
 
Esteban A, Alía I, Gordo F, et al; The Spanish Lung Failure Collaborative Group. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. Am J Respir Crit Care Med. 1997;156(2 pt 1):459-465. [CrossRef] [PubMed]
 
Frutos-Vivar F, Esteban A. When to wean from a ventilator: an evidence-based strategy. Cleve Clin J Med. 2003;70(5):389. [CrossRef] [PubMed]
 
Agarwal R, Srinivasan A, Aggarwal AN, Gupta D. Adaptive support ventilation for complete ventilatory support in acute respiratory distress syndrome: a pilot, randomized controlled trial. Respirology. 2013;18(7):1108-1115. [PubMed]
 
Chen CW, Wu CP, Dai YL, et al. Effects of implementing adaptive support ventilation in a medical intensive care unit. Respir Care. 2011;56(7):976-983. [CrossRef] [PubMed]
 
Arnal JM, Wysocki M, Nafati C, et al. Automatic selection of breathing pattern using adaptive support ventilation. Intensive Care Med. 2008;34(1):75-81. [CrossRef] [PubMed]
 
Esteban A, Frutos F, Tobin MJ, et al; Spanish Lung Failure Collaborative Group. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med. 1995;332(6):345-350. [CrossRef] [PubMed]
 
Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335(25):1864-1869. [CrossRef] [PubMed]
 
Rose L, Presneill JJ, Johnston L, Cade JF. A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartCare/PS. Intensive Care Med. 2008;34(10):1788-1795. [CrossRef] [PubMed]
 
Marelich GP, Murin S, Battistella F, Inciardi J, Vierra T, Roby M. Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses: effect on weaning time and incidence of ventilator-associated pneumonia. Chest. 2000;118(2):459-467. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Flow of patients throughout the study. ASV = adaptive support ventilation; MV = mechanical ventilation; P-ACV = pressure assist/control ventilation.Grahic Jump Location
Figure Jump LinkFigure 2 –  Total MV duration expressed as a Kaplan-Meier curve in the ASV and conventional ventilation groups. (Patients who were self-extubated or died before planned extubation are censored.) See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 –  Weaning duration expressed as a Kaplan-Meier curve in the ASV and conventional ventilation groups. (Patients who were self-extubated or died before planned extubation are censored.) See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of the Two Groups at the Time of Inclusion

Data are presented as median (interquartile range), No. (%), or No. Respiratory function tests are for the patients with obstructive and restrictive lung disease only. Arterial blood gas results are the ones just before intubation. APACHE = Acute Physiologic and Chronic Health Evaluation; ASV = adaptive support ventilation; MV = mechanical ventilation; P-ACV = pressure assist/control ventilation.

Table Graphic Jump Location
TABLE 2 ]  Comparison of ASV and Conventional Ventilation Groups

Data are presented as No. (%) or median (IQR). Mean ± SD is also presented for some variables because of the skewed distribution of the data. LOS = length of stay; VAP = ventilator-associated pneumonia. See Table 1 legend for expansion of other abbreviations.

Table Graphic Jump Location
TABLE 3 ]  Weaning Status of the Two Groups

Data are presented as No. (%). See Table 1 legend for expansion of abbreviations.

a 

n = 114.

b 

n = 115.

c 

n = 78.

d 

n = 79.

e 

Simple group when compared with difficult and prolonged group.

References

Rose L, Schultz MJ, Cardwell CR, Jouvet P, McAuley DF, Blackwood B. Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children. Cochrane Database Syst Rev. 2013;6:CD009235. [PubMed]
 
Sulzer CF, Chioléro R, Chassot PG, Mueller XM, Revelly JP. Adaptive support ventilation for fast tracheal extubation after cardiac surgery: a randomized controlled study. Anesthesiology. 2001;95(6):1339-1345. [CrossRef] [PubMed]
 
Petter AH, Chioléro RL, Cassina T, Chassot PG, Müller XM, Revelly JP. Automatic “respirator/weaning” with adaptive support ventilation: the effect on duration of endotracheal intubation and patient management. Anesth Analg. 2003;97(6):1743-1750. [CrossRef] [PubMed]
 
Gruber PC, Gomersall CD, Leung P, et al. Randomized controlled trial comparing adaptive-support ventilation with pressure-regulated volume-controlled ventilation with automode in weaning patients after cardiac surgery. Anesthesiology. 2008;109(1):81-87. [CrossRef] [PubMed]
 
Kirakli C, Ozdemir I, Ucar ZZ, Cimen P, Kepil S, Ozkan SA. Adaptive support ventilation for faster weaning in COPD: a randomised controlled trial. Eur Respir J. 2011;38(4):774-780. [CrossRef] [PubMed]
 
Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol. 1950;2(11):592-607. [PubMed]
 
Jacobi J, Fraser GL, Coursin DB, et al; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1):119-141. [CrossRef] [PubMed]
 
Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;29(5):1033-1056. [CrossRef] [PubMed]
 
Esteban A, Alía I, Gordo F, et al; The Spanish Lung Failure Collaborative Group. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. Am J Respir Crit Care Med. 1997;156(2 pt 1):459-465. [CrossRef] [PubMed]
 
Frutos-Vivar F, Esteban A. When to wean from a ventilator: an evidence-based strategy. Cleve Clin J Med. 2003;70(5):389. [CrossRef] [PubMed]
 
Agarwal R, Srinivasan A, Aggarwal AN, Gupta D. Adaptive support ventilation for complete ventilatory support in acute respiratory distress syndrome: a pilot, randomized controlled trial. Respirology. 2013;18(7):1108-1115. [PubMed]
 
Chen CW, Wu CP, Dai YL, et al. Effects of implementing adaptive support ventilation in a medical intensive care unit. Respir Care. 2011;56(7):976-983. [CrossRef] [PubMed]
 
Arnal JM, Wysocki M, Nafati C, et al. Automatic selection of breathing pattern using adaptive support ventilation. Intensive Care Med. 2008;34(1):75-81. [CrossRef] [PubMed]
 
Esteban A, Frutos F, Tobin MJ, et al; Spanish Lung Failure Collaborative Group. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med. 1995;332(6):345-350. [CrossRef] [PubMed]
 
Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335(25):1864-1869. [CrossRef] [PubMed]
 
Rose L, Presneill JJ, Johnston L, Cade JF. A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartCare/PS. Intensive Care Med. 2008;34(10):1788-1795. [CrossRef] [PubMed]
 
Marelich GP, Murin S, Battistella F, Inciardi J, Vierra T, Roby M. Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses: effect on weaning time and incidence of ventilator-associated pneumonia. Chest. 2000;118(2):459-467. [CrossRef] [PubMed]
 
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