Nonconventional ventilation techniques

Transcription

1 REVIEW C URRENT OPINION Nonconventional ventilation techniques Ricardo Luiz Cordioli a,b, Evangelia Akoumianaki a, and Laurent Brochard a,c,d Purpose of review Mechanical ventilation is one of the most important life support tools in the ICU, but it may also be harmful by causing ventilator-induced lung injury (VILI) and other deleterious effects. Advances in ventilator technology have allowed the introduction of numerous ventilator modes in an effort to improve gas exchange, reduce the risk of VILI, and finally improve outcome. In this review, we will summarize the studies evaluating some of the nonconventional ventilation techniques and discuss their possible use in clinical practice. Recent findings Proportional assist ventilation and neurally adjusted ventilator assist are able to improve patient ventilator synchrony, possibly sleep, and may be better tolerated than pressure support ventilation; both integrate the physiological concept of respiratory variability like noisy ventilation. Experimental or short-term clinical studies have shown physiological benefits with the application of biphasic pressure modes. Some of the automated weaning algorithms may reduce time spent on ventilator and decrease ICU stay, especially in a busy environment. Summary Apart from the physiological and clinical attractiveness demonstrated in animals and small human studies, most of the nonconventional ventilator modes must prove their clinical benefits in large prospective trials before being applied in daily clinical practice. Keywords airway pressure release ventilation, automated ventilation, noisy ventilation, nonconventional ventilation, proportional ventilation INTRODUCTION Nowadays, it is well recognized that mechanical ventilation can potentially cause lung injury through a phenomenon described as ventilator-induced lung injury (VILI), which can contribute to organ dysfunction and death [1]. Furthermore, improper settings and/or inadequate modes can promote patient ventilator asynchrony, suppress normal breathing variability, and contribute to diaphragmatic dysfunction. Moreover, weaning from mechanical ventilation might be challenging due to patient-related factors and also due to undue prolongation of mechanical ventilation combined with a lack of well defined criteria [2]. Technological developments have resulted in novel nonconventional ventilator modes as an attempt to attenuate several of these problems. Nonconventional modes discussed in this review include proportional assist ventilation (PAV) and neurally adjusted ventilator assist (NAVA), airway pressure release ventilation (APRV), automated modes, and noisy ventilation [3]. The article reviews some of the recent data concerning nonconventional modes of ventilation cited above that seem to represent technological options with important physiological attractiveness. PROPORTIONAL MODES OF MECHANICAL VENTILATION The goals of assisted mechanical ventilation in the modern era should extend beyond the simple amelioration of arterial blood gas abnormalities and decreased work of breathing. Ideal ventilation should also incorporate the principles of patient ventilator synchrony, optimal diaphragmatic a Intensive Care Unit, University Hospital of Geneva, Geneva, Switzerland, b Hospital Israelita Albert Einstein, São Paulo, Brazil, c INSERM U955, Université Paris Est, Créteil, France and d School of Medicine, University of Geneva, Geneva, Switzerland Correspondence to Professor Laurent Brochard, Intensive Care Unit, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Switzerland. Tel: ; fax: ; Laurent.Brochard@hcuge.ch Curr Opin Crit Care 2013, 19:31 37 DOI: /MCC.0b013e32835c517d ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins

2 Respiratory system KEY POINTS Proportional modes of ventilation offer an adaptation to both changes in respiratory mechanics and changes in ventilatory demand. They also restore natural variability. Modes like noisy ventilation also introduce variability during mechanical ventilation. Some automated modes have proven that their routine clinical use is feasible and have even proven some advantages for reduction in the duration of ventilatory support. An important difference between all pressure-targeted modes is their degree of synchronization with patient s effort. unloading, lung-protective management, and preservation of normal respiratory pattern and variability. To fulfill these aims, the ventilator should be able to adapt both to changes in mechanics and changes in ventilatory demand, and act more as an amplifier of the respiratory controller s output rather than as a constant assistance provider. This is the theoretical background of the proportional modes of mechanical ventilation, in which the pressure applied to the airways during inspiration is proportional either to the inspiratory muscles pressure in PAV, or to the electrical activity of the diaphragm (EA DI ) in NAVA, according to a multiplicative factor named PAV gain or NAVA level, respectively [4]. PROPORTIONAL ASSIST VENTILATION WITH LOAD-ADJUSTABLE GAIN FACTORS (PAVR) Under patient-assisted mechanical ventilation, the total airway pressure (P TOT ) equals to the sum of muscle pressure (P MUS ) and ventilator pressure (P AW ); the equation of motion describing this relationship can be written as follows: P MUS þ P AW ¼ P 0 þ V 0 R RS þ V T E RS where E RS, R RS, and P 0 are the respiratory system s elastance and resistance and total positive end expiratory pressure (PEEP T ), respectively. In PAVþ (Puritan Bennett 840, Covidien, Colorado, USA), the ventilator automatically estimates E RS and R RS, every 4 10 breaths, and the physician sets the proportionality factor (PAV gain), which balances ventilator s (P AW ) and patient s (P MUS ) contribution to P TOT. P AW =P MUS ¼ %gain=ð100 %gainþ Consequently, P MUS, the only unknown variable, can be instantaneously calculated. The ventilator cycle during PAVþ is pneumatically triggered (P AW or flow criterion). Transition to expiration is driven by the gradual P MUS decline and the resulting decrease in inspiratory flow [5]. In a small group of difficult to wean patients, PAVþ improved patient ventilator interaction compared to pressure support ventilation (PSV), significantly reducing the incidence of end-expiratory asynchrony and increasing the time of synchrony during the breaths [6]. In a large study on 208 critically ill patients randomized to either PSV or PAVþ the failure rate of assisted mechanical ventilation, defined as a switch to controlled mechanical ventilation (CMV), was two times higher in the PSV group (22%) as compared to the PAVþ group (11%) [7]. In a retrospective analysis of their data, the authors found that PAVþ was associated with fewer modifications of the ventilator settings and fewer adjustments in the dose of sedatives [8]. The advantages of PAVþ over conventional PSV are not limited to patient ventilator interaction. PAVþ could have a lung-protective role in acute lung injury or acute respiratory distress syndrome (ALI/ ARDS) patients for several reasons. Firstly, it does not interfere with neural reflexes, allowing the inhibition of inspiratory muscle activity when lung distension exceeds a certain limit (Hering-Breuer reflex activation). Indeed, the study by Xirouchaki et al. [7] showed that during PAVþ 94% of end-inspiratory plateau pressures remained below 26 cmh 2 O. Secondly, by adjusting the pressure provided to instantaneous P MUS, PAV preserves V T variability, which has been associated with improvements in gas exchange and lung mechanics. Spieth et al. [9] reported that both noisy PSV (described below) and PAV restored normal V T variability and improved oxygenation and venous admixture in an experimental study. Pulmonary inflammatory response and lung damage, however, did not differ among the three modes [9]. Proportional assist ventilation has also been shown to improve sleep quality compared with PSV in difficult to wean patients exhibiting high number of asynchronies [10]. Nevertheless, in a more recent study PAVþ and PSV had comparable effects on sleep architecture in sedated and nonsedated critically ill patients [11]. Moreover, high levels of assist equally promoted unstable breathing in some patients irrespectively of the ventilator mode. Further studies are needed to clarify the impact of PAVþ on sleep in mechanically ventilated patients. NEURALLY ADJUSTED VENTILATOR ASSIST In NAVA, ventilator support is coupled with the neural component of the respiratory effort, as 32 Volume 19 Number 1 February 2013

3 Nonconventional ventilation techniques Cordioli et al. expressed by the electrical activity of the diaphragm (EA DI ) (NAVA, Maquet Critical Care, Solna, Sweden). An EA DI increase above a predetermined value (EA DI trigger) triggers pressure delivery (P AW ), which is, at any instance, an amplification of the measured EA DI : P AW ðcmh 2 OÞ¼NAVA level ðcmh 2 O=mVÞ EA DI ðmvþ The end of the inspiratory phase is triggered by a fractional decrease of EA DI from its maximum value [4]. The caregiver selects the triggering and cyclingoff criterion, as well as the NAVA level, that is the amplification factor of the EA DI. It follows that optimal positioning of the EA DI catheter is crucial for NAVA s proper function. A formula based on the distance between nose, ear lobe, and xiphoid process allows adequate catheter placement in two-thirds of patients, and the signal acquired is relatively stable even after small diaphragmatic shifts induced by body position, PEEP or intra-abdominal pressure changes [12]. Large alterations in the above parameters, however, necessitate rechecking catheter position. Probably the most challenging issue when implementing NAVA is the titration of NAVA level. Presetting the NAVA level with the ventilator s preview tool ( NAVA preview, Maquet Critical Care, Solna, Sweden) is far from ideal and may contribute to overestimation of the required support [13]. Brander et al. [14] described a two-phase response during NAVA level escalation: initially P AW and V T increase up to a point beyond which EA DI downregulation by feedback control mechanisms maintains P AW and V T relatively stable. They proposed that the optimal NAVA level (NAVA AL ) lies on the inflection point from the first to the second response [14]. A mathematical model which estimates automatically the NAVA AL corresponding to this zone has been recently developed [15]. Alternatively, NAVA level could be adapted to achieve a 60% reduction in maximum EA DI recorded during a spontaneous breathing trial equivalent (PSV of 7 cmh 2 O with no PEEP) [16 & ]. More recently, the patient ventilator breath contribution index introduced by Grasselli et al. [17] could reliably partition ventilator s and patient s contribution to the volume generated during NAVA. In the clinical setting this index could further help to quantify and standardize the adjustment of assist [17]. Compared to PSV, NAVA consistently improved patient ventilator synchrony in pediatric and adult patients by reducing the total number of asynchronies, triggering delay and delayed cycling [18 &,19,20]. NAVA abolished ineffective efforts and premature cycling and decreased expiratory delay by more than 50%. In some studies, however, double triggering was higher than in PSV due to a biphasic shaped EA DI signal [18 & ]. Similarly, when applied noninvasively, NAVA enhanced patient ventilator synchrony compared to PSV [21 23]. Whether the favorable effects of NAVA in patient ventilator interaction would be translated into better sleep quality has been examined in a small crossover study: sleep fragmentation, sleep architecture, and sleep quality were all better with NAVA compared to PSV. The inferiority of PSV was attributed to the combined effect of over-assistance, ineffective efforts and central apneas, all being absent during NAVA ventilation [24]. Similarly to PAV, the physiological neural variability of breathing pattern is well maintained with NAVA [25 27]. Increasing NAVA levels increase tidal volume, EA DI, and airway pressure variability [26,28]. Even at high levels of assist, EA DI downregulation resulting from the activation of inhibitory reflexes protects patients from inordinate increase in V T and P AW [14,26]. Notwithstanding these reassuring observations, the clinician must be aware that excessive NAVA levels might disturb this neuro-ventilator feedback mechanism resulting in periods of apnea and, occasionally, in high volume and pressure cycles [28,29]. AIRWAY PRESSURE RELEASE VENTILATION APRV is a pressure-targeted, time-triggered, and time-cycled ventilator mode. Its operation is based on the rotation between two pressure levels: a high (P HIGH ) and a low (PEEP) airway pressure. The frequency of the cycling, resembling the ventilator s rate when using conventional ventilation and the time spent at each pressure level, is determined by the physician. Initially APRV was described as a way to deliver high continuous positive airway pressure with intermittent release of the pressure to increase alveolar ventilation. Although initially used with long portions of the duty cycle at P HIGH, more recently it has been used in a much broader fashion with normal I/E ratios as a pressure-controlled mode on top of which can be superimposed spontaneous breathing activity [30]. In the absence of spontaneous respiratory efforts APRV and pressure assist control (PAC) function identically. What distinguishes APRV, however, is the presence of a constantly active expiratory valve, allowing unrestricted spontaneous breathing at any point of the phase cycle. This feature is considered as crucial for the potential beneficial effects attributed to APRV over traditional ventilator ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 33

4 Respiratory system modes: recruitment of dependent lung regions, improvements in ventilation perfusion matching and oxygenation, better hemodynamic profile and cardiac performance, higher renal blood flow and glomerular filtration rate, and possibly lower levels of sedation and better hemodynamics [30 32,33 & ]. Both de-escalation of sedatives and facilitation of spontaneous efforts enhance secretion clearance and are possibly related to the finding that APRV reduced the risk of ventilator-associated pneumonia in patients with pulmonary contusion [34]. The promising results of Putensen et al. on clinical outcomes were, nevertheless, not reproduced when APRV was compared with lung protective volume assist control ventilation neither in a large international retrospective study [35] nor in a more recent prospective one [36]. In a recent trial, combining prone position with APRV ventilation improved hypoxemia and limited end-organ dysfunction in a small retrospective study of patients with severe H 1 N 1 -related ARDS [37]. Despite the extended research on pressure-targeted modes of ventilation, great confusion still exists regarding their operational differences. This is especially true for APRV and biphasic positive airway pressure (BIPAP). In an attempt to identify the definitional criteria of APRV and BIPAP, Rose and Hawkins [38] concluded that ambiguity exists in the criteria that distinguish APRV and BIPAP. In many review articles, APRV is described as an inverse ratio BIPAP [33 &,39] but not in many of the clinical trials [30]. This perception has been recently challenged by our group, which classified the various pressure-targeted modes according to the ability of spontaneous efforts to trigger the ventilator: in nonsynchronized modes, such as APRV, spontaneous breaths are not synchronized with pressure delivery from the ventilator while in synchronized modes, such as PAC, all efforts trigger the ventilator. BIPAP lies between the two extremities, allowing some effortstobesynchronizedwith the ventilator and others not. Testing our hypothesis in a bench model of ARDS we found that, with the same ventilator settings, all pressure-targeted modes function identically in the absence of spontaneous breathing. In contrast, in the presence of neural breaths, V T and transpulmonary pressure (P TP ) increase in parallel to synchronization augmentation. The opposite is true for V T variability, which decreases with synchronization [40]. Hence, this difference between BIPAP (partially synchronized) and APRV (nonsynchronized) in the resulting V T and P TP could be hazardous in ARDS patients presenting diaphragmatic contractions. In conclusion, experimental or short-term clinical studies have shown physiologic benefits with the application of APRV, but the effects on clinical outcomes are less clear. Further research to precisely define the functional features of this mode and, more importantly, their clinical consequences, in comparison to the other pressure-targeted modes, will better clarify its role in the treatment of critically ill patients. NOISY VENTILATION Conventional mechanical ventilation has a monotonous pattern not reflecting the physiologic variability: life support systems may therefore benefit from introduction of noise in the system of assistance [41]. Numerous studies in animals showed promising results with biologically variable or noisy ventilation compared to CMV: improved gas exchange and lung function in different conditions [42 44], reduced histological damage [45], and attenuated inflammatory response [46]. Different mechanisms could explain why noisy ventilation improves lung function: stochastic resonance [41], increase respiratory sinus arrhythmia [47], endogenous release surfactant [48], dynamic effects on the pressure-volume curve [49], and a better perfusion ventilation match [50]. Recently, the effects of conventional PSV, noisy PSV, and pressure-controlled ventilation (PCV) were compared in 24 surfactant-depleted pigs suffering from ALI. Noisy PSV was associated with a significant higher coefficient of variation of V T and airway pressure, and resulted in lower levels of partial pressure of carbon dioxide (PaCO 2 ), decreased inspiratory effort, reduced alveolar edema in overall lung as well as reduced inflammation in the nondependent parts of the lungs [51]. Another study from the same group showed significantly better oxygenation and reduced venous admixture when comparing noisy PSV with conventional PSV and protective PCV [50]. Both patient-assisted ventilation modes reduced the cyclic opening and closure of lung units and tidal hyperinflation compared to PCV with a redistribution of the pulmonary perfusion from dorsal to ventral lung regions; noisy PSV also redistributed the pulmonary perfusion from caudal to cranial zones compared to other ventilator strategies. Very recently, Spieth et al. [9] evaluated 24 pigs where ALI was induced by lung lavage, after animals were randomized to 6 h of assisted ventilation with PSV or PAV or noisy PSV. PAV and noisy PSV improved oxygenation and venous admixture and produced a higher V T variability compared with PSV. PAV produced the higher work of breathing as well as higher number of breaths with peak inspiratory airway pressure greater than 40 cmh 2 O and V T 34 Volume 19 Number 1 February 2013

5 Nonconventional ventilation techniques Cordioli et al. greater than 15 ml/kg. However, pulmonary inflammatory response and diffuse alveolar damage score were similar among the three groups. The study is discussed in an interesting editorial where the author advocates that the use of noisy ventilation is an obvious phenomenon which will be adopted both in controlled or assisted mechanical ventilation and that this may happen sooner than we believe [52]. Unfortunately, evidence from critically ill patients is still lacking but, like other modes of ventilation cited above (PAVþ and NAVA), in the future mechanical ventilation will probably take more advantage of the physiological variability of breathing [53]. AUTOMATED VENTILATION Automated ventilation is an attractive strategy to simplify daily ICU practice, especially in units where the physician or nurse to patient ratio is low. A clinical trial of 144 patients comparing an automated pressure support and weaning ventilation vs. a physician-controlled weaning process showed that automated pressure support and weaning was able to reduce the median duration of weaning and the total duration of mechanical ventilation and ICU stay without any adverse effects [54]. SmartCare/PS version 1.1 (Dräger Medical, Lübeck, Germany) was recently compared to a standardized protocol in an unselected surgical patient population. Three hundred patients were randomized and the results showed an overall ventilation time not significantly different between automated pressure support and weaning and the control group, with a small trend toward fewer tracheostomies and a faster first spontaneous breathing trial in the group randomized to automated pressure support and weaning. In the subgroup which underwent cardiac surgery (n ¼ 132) there was a significantly shorter overall ventilation time with the automated pressure support and weaning vs. standardized protocol [55]. The WEAN study [56] compared automated pressure support and weaning (SmartCare) with a protocolized weaning in 93 critically ill adults and showed a similar compliance for weaning with these different approaches. In the automated pressure support and weaning group, patients experienced significantly shorter median times to first spontaneous breathing trial and to successful extubation with similar hospital stay. The final publication of these results will help to give an overall idea of the efficacy of this system. Recently, Arnal et al. [57] compared adaptive support ventilation (ASV) and a new automated mode, the IntelliVent-ASV (Hamilton Medical, Rhäzüns, Switzerland), which automatically adjusts not only ventilation but also oxygenation, according to SpO 2 recordings. There was no safety issue requiring premature interruption of IntelliVent-ASV and this model delivered ventilation with lower V T, inspiratory pressure, inspiratory fraction of oxygen (FiO 2 ), and PEEP with similar arterial blood gases as compared to ASV. In a preliminary study, Garnero et al. [58] studied 100 patients, categorized as having normal lung, ALI/ARDS, or chronic obstructive pulmonary disease all invasively ventilated using IntelliVent- ASV and followed them from study inclusion to weaning or death. The median mechanical ventilation duration was 3.0 days without any safety issue. They also studied if the clinical manual setting would be the same in these 100 patients cited above and they found that V T delivered by IntelliVent-ASV would be only a little higher than the V T manually set by the clinician. Minute volume, PEEP, and FiO 2 automatically selected by IntelliVent-ASV were not statistically different as compared to the clinician s manual settings [59]. Finally, three modes of automated pressure support and weaning were compared in a bench study mimicking several breathing patterns [60]: ASV on Hamilton G5 ventilator (HamiltonMedical, Rhäzüns, Switzerland), mandatory rate ventilation (MRV) on Taema Horus (Air Liquide, Paris, France), and Smartcare on Evita XL (Dräger, Lübeck, Germany). All were identically able to identify weaning success and failure even with anxiety or irregular breathing, but all failed to identify a weaning success in the presence of Cheyne-Stokes breathing pattern. ASV showed a more accentuated variation of pressure support over the time. Automated ventilation, especially automated weaning, seems to be really attractive in that it can reduce time spent on ventilator, decrease ICU stay, and may improve clinical outcomes when implemented in uncomplicated patients in a busy ICU environment. Only a few randomized clinical trials applied this technology, especially in more severe patients or during prolonged ventilation periods. Of note, in a recent clinical study enrolling 304 patients to test a weaning strategy based on biomarkers, the SmartCareAW technique was used in both arms as a way to standardize the weaning approach [61]. FUTURE PERSPECTIVES Despite the growing interest for nonconventional ventilator modes their spread in clinical practice is still limited. This is partly attributed to the fact that some of them are commercially implemented in just ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 35

6 Respiratory system one type of ventilator. Also, a clear outcome benefit over conventional modes has not been demonstrated so far. Finally, the ideal time to institute these modes during the course of critical illness, which patients will most likely benefit and how to solve several practical issues remain mostly unanswered. Large clinical trials in the near future will hopefully address these issues. New technologies that can help to upgrade the translation from clinical knowledge to automatic closed-loop ventilation during specific disease state and to adjust strategies to personal therapeutic preferences of the intensivist or therapeutic guidelines are also currently developed [62]. CONCLUSION Technology of mechanical ventilation keeps developing and appealing new modes are now available. Apart from being a life-saving procedure, mechanical ventilation per se can be deleterious and if not well applied it can contribute to organ dysfunction. Different patients, different diseases, different ICU organizations need different options of mechanical ventilation, so nonconventional modes of mechanical ventilation might be a better option in some circumstances. In this review, we discussed some recent data on some of the nonconventional modes of mechanical ventilation representing different interesting options. Unfortunately, apart from animals or small clinical trials showing physiologic or clinical benefits, most often these nonconventional modes of ventilation must still show their real clinical benefits in large clinical trials before being applied for a routine practice method of ventilation. Acknowledgements None. Conflicts of interest L. Brochard s laboratory has received research grants over the last 5 years with the following companies for specific research projects: Maquet (NAVA), Covidien (PAV), Drager (SmartCare), General Electric (FRC), Philips Respironics (NIV). REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 68). 1. Lionetti V, Recchia FA, Ranieri VM. Overview of ventilator-induced lung injury mechanisms. Curr Opin Crit Care 2005; 11: Epstein SK. Weaning from ventilatory support. Curr Opin Crit Care 2009; 15: Lellouche F, Brochard L. Advanced closed loops during mechanical ventilation (PAV, NAVA, ASV, SmartCare). Best Pract Res Clin Anaesthesiol 2009; 23: Moerer O. Effort-adapted modes of assisted breathing. Curr Opin Crit Care 2012; 18: Younes M. Proportional assist ventilation, a new approach to ventilatory support. Theory Am Rev Respir Dis 1992; 145: Costa R, Spinazzola G, Cipriani F, et al. A physiologic comparison of proportional assist ventilation with load-adjustable gain factors (PAVþ) versus pressure support ventilation (PSV). Intensive Care Med 2011; 37: Xirouchaki N, Kondili E, Vaporidi K, et al. Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support. Intensive Care Med 2008; 34: Xirouchaki N, Kondili E, Klimathianaki M, Georgopoulos D. Is proportionalassist ventilation with load-adjustable gain factors a user-friendly mode? Intensive Care Med 2009; 35: Spieth PM, Guldner A, Beda A, et al. Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury. Crit Care Med 2012; 40: Bosma K, Ferreyra G, Ambrogio C, et al. Patient-ventilator interaction and sleep in mechanically ventilated patients: pressure support versus proportional assist ventilation. Crit Care Med 2007; 35: Alexopoulou C, Kondili E, Vakouti E, et al. Sleep during proportional-assist ventilation with load-adjustable gain factors in critically ill patients. Intensive Care Med 2007; 33: Barwing J, Pedroni C, Quintel M, Moerer O. Influence of body position, PEEP and intra-abdominal pressure on the catheter positioning for neurally adjusted ventilatory assist. Intensive Care Med 2011; 37: Barwing J, Linden N, Ambold M, et al. Neurally adjusted ventilatory assist vs. pressure support ventilation in critically ill patients: an observational study. Acta Anaesthesiol Scand 2011; 55: Brander L, Leong-Poi H, Beck J, et al. Titration and implementation of neurally adjusted ventilatory assist in critically ill patients. Chest 2009; 135: Ververidis D, Van Gils M, Passath C, et al. Identification of adequate neurally adjusted ventilatory assist (NAVA) during systematic increases in the NAVA level. IEEE Trans Biomed Eng 2011; 58: & Roze H, Lafrikh A, Perrier V, et al. Daily titration of neurally adjusted ventilatory assist using the diaphragm electrical activity. Intensive Care Med 2011; 37: In 15 patients, the feasibility of daily titration of the NAVA level as being 60% of the maximal diaphragmatic electrical activity measured during a spontaneous breathing trial during PSV was evaluated. It proved feasible and well tolerated until extubation. 17. Grasselli G, Beck J, Mirabella L, et al. Assessment of patient-ventilator breath contribution during neurally adjusted ventilatory assist. Intensive Care Med 2012; 38: & Piquilloud L, Vignaux L, Bialais E, et al. Neurally adjusted ventilatory assist improves patient-ventilator interaction. Intensive Care Med 2011; 37: Compared with standard pressure support in 22 patients, NAVA can improve patient ventilator synchrony in intubated spontaneously breathing intensive care patients. 19. Clement KC, Thurman TL, Holt SJ, Heulitt MJ. Neurally triggered breaths reduce trigger delay and improve ventilator response times in ventilated infants with bronchiolitis. Intensive Care Med 2011; 37: Alander M, Peltoniemi O, Pokka T, Kontiokari T. Comparison of pressure-, flow-, and NAVA-triggering in pediatric and neonatal ventilatory care. Pediatr Pulmonol 2012; 47: Cammarota G, Olivieri C, Costa R, et al. Noninvasive ventilation through a helmet in postextubation hypoxemic patients: physiologic comparison between neurally adjusted ventilatory assist and pressure support ventilation. Intensive Care Med 2011; 37: Schmidt M, Dres M, Raux M, et al. Neurally adjusted ventilatory assist improves patient-ventilator interaction during postextubation prophylactic noninvasive ventilation. Crit Care Med 2012; 40: Piquilloud L, Tassaux D, Bialais E, et al. Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator interaction during noninvasive ventilation delivered by face mask. Intensive Care Med 2012; 38: Delisle S, Ouellet P, Bellemare P, et al. Sleep quality in mechanically ventilated patients: comparison between NAVA and PSV modes. Ann Intensive Care 2011; 1: Coisel Y, Chanques G, Jung B, et al. Neurally adjusted ventilatory assist in critically ill postoperative patients: a crossover randomized study. Anesthesiology 2010; 113: Schmidt M, Demoule A, Cracco C, et al. Neurally adjusted ventilatory assist increases respiratory variability and complexity in acute respiratory failure. Anesthesiology 2010; 112: Moorhead KT, Piquilloud L, Lambermont B, et al. NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand. J Clin Monit Comput [Epub ahead of print] 36 Volume 19 Number 1 February 2013

7 Nonconventional ventilation techniques Cordioli et al. 28. Patroniti N, Bellani G, Saccavino E, et al. Respiratory pattern during neurally adjusted ventilatory assist in acute respiratory failure patients. Intensive Care Med 2012; 38: Allo JC, Beck JC, Brander L, et al. Influence of neurally adjusted ventilatory assist and positive end-expiratory pressure on breathing pattern in rabbits with acute lung injury. Crit Care Med 2006; 34: Putensen C, Zech S, Wrigge H, et al. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med 2001; 164: Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome. Crit Care 2001; 5: Yoshida T, Rinka H, Kaji A, et al. The impact of spontaneous ventilation on distribution of lung aeration in patients with acute respiratory distress syndrome: airway pressure release ventilation versus pressure support ventilation. Anesth Analg 2009; 109: & Daoud EG, Farag HL, Chatburn RL. Airway pressure release ventilation: what do we know? Respir Care 2012; 57: This study reviews the different methods proposed for APRV settings, and summarizes the different studies comparing APRV and BIPAP, and the potential benefits and pitfalls for APRV. 34. Walkey AJ, Nair S, Papadopoulos S, et al. Use of airway pressure release ventilation is associated with a reduced incidence of ventilator-associated pneumonia in patients with pulmonary contusion. J Trauma 2011; 70:E42 E Gonzalez M, Arroliga AC, Frutos-Vivar F, et al. Airway pressure release ventilation versus assist-control ventilation: a comparative propensity score and international cohort study. Intensive Care Med 2010; 36: Maxwell RA, Green JM, Waldrop J, et al. A randomized prospective trial of airway pressure release ventilation and low tidal volume ventilation in adult trauma patients with acute respiratory failure. J Trauma 2010; 69: ; discussion Sundar KM, Thaut P, Nielsen DB, et al. Clinical course of ICU patients with severe pandemic 2009 influenza A (H1N1) pneumonia: single center experience with proning and pressure release ventilation. J Intensive Care Med 2012; 27: Rose L, Hawkins M. Airway pressure release ventilation and biphasic positive airway pressure: a systematic review of definitional criteria. Intensive Care Med 2008; 34: Modrykamien A, Chatburn RL, Ashton RW. Airway pressure release ventilation: an alternative mode of mechanical ventilation in acute respiratory distress syndrome. Cleve Clin J Med 2011; 78: Akoumianaki E, Lefebvre JC, Lyazidi A, et al. Impact of type or pressure controlled ventilation on lung protection: a bench study. Intensive Care Med 2012; 38 (1 Supp):S Suki B, Alencar AM, Sujeer MK, et al. Life-support system benefits from noise. Nature 1998; 393: Mutch WA, Eschun GM, Kowalski SE, et al. Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth 2000; 84: Mutch WA, Buchman TG, Girling LG, et al. Biologically variable ventilation improves gas exchange and respiratory mechanics in a model of severe bronchospasm. Crit Care Med 2007; 35: Mutch WA, Harms S, Ruth Graham M, et al. Biologically variable or naturally noisy mechanical ventilation recruits atelectatic lung. Am J Respir Crit Care Med 2000; 162: Spieth PM, Carvalho AR, Pelosi P, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med 2009; 179: Thammanomai A, Hueser LE, Majumdar A, et al. Design of a new variableventilation method optimized for lung recruitment in mice. J Appl Physiol 2008; 104: Mutch WA, Graham MR, Girling LG, Brewster JF. Fractal ventilation enhances respiratory sinus arrhythmia. Respir Res 2005; 6: Arold SP, Suki B, Alencar AM, et al. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol 2003; 285:L370 L Ma B, Suki B, Bates JH. Effects of recruitment/derecruitment dynamics on the efficacy of variable ventilation. J Appl Physiol 2011; 110: Carvalho AR, Spieth PM, Guldner A, et al. Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol 2011; 110: Spieth PM, Carvalho AR, Guldner A, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med 2011; 39: Allardet-Servent J. Adding noise to mechanical ventilation: so obvious! Crit Care Med 2012; 40: Kacmarek RM, Villar J. When it comes to ventilation, noisy is better than quiet and variability is healthier than constant! Crit Care Med 2011; 39: Lellouche F, Mancebo J, Jolliet P, et al. A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation. Am J Respir Crit Care Med 2006; 174: Schadler D, Engel C, Elke G, et al. Automatic control of pressure support for ventilator weaning in surgical intensive care patients. Am J Respir Crit Care Med 2012; 185: Burns KEA, Lellouche F, Lessard M, et al. Wean earlier and automatically with new technology: preliminary results of the wean study. Am J Respir Crit Care Med 2012; Arnal JM, Wysocki M, Novotni D, et al. Safety and efficacy of a fully closedloop control ventilation (IntelliVent-ASV(R)) in sedated ICU patients with acute respiratory failure: a prospective randomized crossover study. Intensive Care Med 2012; 38: Garnero A, Arnal JM, Wysocky M, et al. Routine use of a fully close loop ventilation mode in long term ventilated ICU patients: a prospective study. Am J Respir Crit Care Med 2012; Arnal JM, Garnero A, Wysocki M, et al. Comparison of settings automatically by a full close loop ventilation mode with clinician manual settings in ICU patients. Am J Respir Crit Care Med 2012; Morato JB, Sakuma MT, Ferreira JC, Caruso P. Comparison of 3 modes of automated weaning from mechanical ventilation: a bench study. J Crit Care [Epub ahead of print] 61. Mekontso Dessap A, Roche-Campo F, Kouatchet A, et al. Natriuretic peptidedriven fluid management during ventilator weaning: a randomized controlled trial. Am J Respir Crit Care Med [Epub ahead of print] 62. Lozano-Zahonero S, Gottlieb D, Haberthur C, et al. Automated mechanical ventilation: adapting decision making to different disease states. Med Biol Eng Comput 2011; 49: ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 37