netherlands journal of critical care

Copyright ©2008, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received July 2008 ; Accepted July 2008 e d i t o r i a l Should our patients with ALI or ARDS be ventilated at higher PEEP levels?

D Gommers

Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands

In patients with the acute respiratory syndrome (ARDS), the lung is maximum to above 30 cm H2O [5]. In the ExPress atelectatic or consolidated, particularly in dependent regions, so that trial, no recruitment manoeuvres were performed. For both studies, it cannot participate in gas exchange. During , the primary outcome was the effect on mortality in comparison with the less affected lung regions must therefore accommodate most of the the established low-tidal volume strategy from ARDS network trials. tidal volume, with the risk of tidal hyperinflation. The ARDS network In both studies, the 28-day mortality rate was 28% in the trial established the importance of hyperinflation by demonstrating intervention group and 32% in the controls, but this difference that ventilation using lower tidal volumes (6 versus 12 mL/kg) and was not significant [4,5]. The intervention group appeared to have maintaining a plateau pressure of no more than 30 cm H2O, improves improved secondary endpoints in both trials, such as oxygenation survival [1]. In a second trial of the ARDS network group, the ALVEOLI and less use of rescue therapies. Moreover, the recruitment ventilation trial, it was shown that application of higher positive end-expiratory strategy in the ExPress trial resulted in more -free days and pressure (PEEP) levels improved oxygenation but did not have an organ failure-free days [5]. In the latter trial, post-hoc analyses based impact on survival, suggesting that higher PEEP does not confer on oxygenation impairment at study enrolment showed that mortality additional mortality benefit when low tidal volume ventilation is used tended to improve and extubation occurred earlier in patients with [2]. This specific low-tidal-volume strategy has become the standard ARDS, whereas the opposite trend was observed in patients with ALI nowadays and is called ‘protective ventilation’ strategy. [5]. Therefore, it was suggested that the strategy of a high level of Atelectotrauma (cyclic atelectasis) has been shown to be another PEEP and low tidal volume should be used with caution in patients important contributor to ventilator-induced lung injury in ARDS. with ALI not reaching the criteria for ARDS. Atelectotrauma may be mitigated by recruitment manoeuvres to The outcome of the three trials (ALVEOLI, LOV and ExPress) open up collapsed alveoli followed by application of high levels of that applied higher PEEP levels in patients with ALI or ARDS, was PEEP to prevent further collapse. In theory, ventilation strategies that comparable for survival but differed in the secondary endpoints combine low tidal volumes and high PEEP levels and that prevent [2,4,5]. However, the secondary endpoints were different: all trials atelectotrauma, would be the ideal ventilation strategy for lung showed improved oxygenation but the LOV and ExPress trial also protection in ARDS [3]. However, the debate continues as to whether showed less use of rescue therapy and, in addition the ExPress trial hyperinflation is of more importance than cyclic atelectasis inthe resulted in more ventilator-free days and organ failure-free days in the development of , which is known to induce distal organ high-PEEP group. The reason for this is not known, but the three trials dysfunction and, ultimately, multi-organ failure. differed in study design. The ALVEOLI and LOV trials used a scale of Because application of higher PEEP levels may increase the risk PEEP versus FiO2 whereas the ExPress trial applied a PEEP level based of hyperinflation, a compromise must be found between PEEP- on plateau pressure, individually dosed and regardless of its effect on induced alveolar recruitment and prevention of hyperinflation. This oxygenation. editorial discusses the results of two studies (both published in the It has been shown that application of the use of a scale of PEEP vs. JAMA in February 2008) in which higher PEEP levels were used in FiO2 according to the ARDSnet trial resulted in alveolar hyperinflation patients with acute lung injury (ALI) or ARDS in order to increase (as indicated by the stress index), with impaired cardiac output and alveolar recruitment while avoiding excessive hyperinflation. [4,5]. increased levels of cytokines (Il-6 and 8) in patients with ARDS [6]. The first study is called the ‘lung open ventilation’ (LOV) trial and Therefore, it has been suggested that in applying PEEP properly not a was performed in 30 intensive care units (ICUs) in Canada, Australia, universal level of PEEP should be used, but rather the best PEEP level and Saudi Arabia [4]. This was a randomized, controlled trial in 983 that the individual patient actually needs at a certain time point. This patients with ALI or ARDS and the experimental ventilation strategy implies constant re-evaluation of the individual ventilator settings, included: tidal volumes of 6 mL/kg, plateau pressures below 40 cm often a difficult task in the hectic ICU environment. However, H2O, recruitment manoeuvres (40-second breath-hold at 40 cm H2O ignoring the latter monitoring by, for instance, not adjusting PEEP airway pressure), and a table-based PEEP using a scale of PEEP versus levels when lung function improves or by using a universal high FiO2 [4]. The second study called the Expiratory Pressure (ExPress) PEEP for all patients, may eventually result in ventilating lungs with trial, was performed in 767 patients with ALI and was conducted in pressures higher than necessary and thus causing overdistention. 37 ICUs in France [5]. The recruitment strategy consisted of tidal This was probably the case in the ALVEOLI trial because mean PEEP volumes of 6 mL/kg, and PEEP levels were adjusted based on airway levels on Day 1 were around 15 cm H2O in the intervention group in pressure and were kept as high as possible without increasing the all three studies, and PEEP was decreased to below 10 cm H2O within one week in the LOV and the ExPress trials, but was still 13 cm H2O in

Correspondence the ALVEOLI trial on Day 7 [2,4,5]. In the LOV trial, a recruitment manoeuvre (a 40-second breath- D Gommers hold at 40 cm H2O) was performed in order to open up the lung [4]. E-mail: [email protected]

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Different recruitment manoeuvres have been tested in patients with meaningful outcome is not yet available [6]. Another strategy for ARDS and it has become clear that each patient has his own opening individual titration of PEEP could be the simultaneous measurement pressure. Further, it has been shown that pressures exceeding 60 of dead space and compliance. Recently, Maisch and colleagues [10] cm H2O are required to re-open some atelectatic regions [7]. In the performed a recruitment manoeuvre in combination with different LOV trial all patients underwent the same recruitment manoeuvre, levels of PEEP in patients with healthy lungs undergoing general and its efficacy on lung function was not monitored. In addition, it anaesthesia, and found that the ‘optimal’ PEEP was indicated by is of special importance to use an adequate level of PEEP to prevent the highest compliance in combination with the lowest dead space re-collapse directly after a recruitment manoeuvre [7]. Again, this fraction. However, alveolar dead space is not only influenced by is not a universally high level of PEEP based on FiO2, but the PEEP alveolar hyperinflation but also by intrapulmonary shunting. The level should be dosed and monitored in order to avoid overdistention. latter is of more importance in patients with ARDS. It therefore still Therefore, it is likely that a significant proportion of patients in the needs to be tested whether assessing dead space is sensitive enough LOV trial who underwent the recruitment manoeuvre failed to ‘open for PEEP dosing in patients with ARDS. up the lung and keep the lung open’ with the experimental study Thus, strategies with higher levels of PEEP appear to be safe and protocol used. beneficial, especially in patients with ARDS who the sickest. Although The PEEP which prevents re-collapse after a recruitment manoeuvre, the mortality rate did not differ, the higher PEEP strategy resulted in but avoids overdistention while optimizing lung mechanics, can be fewer patients with severe hypoxaemia leading to fewer pulmonary defined as the ‘optimal’ PEEP. In practice, what tool should we use to deaths, and this could account for the 3 to 4% difference in mortality find the ‘optimal’ PEEP? Blood gases have shown to be inappropriate rate in favour of the higher PEEP group observed in both the LOV and imaging techniques such as computed tomography (CT) cannot and the ExPress trials, in comparison with the low PEEP arm [11]. In be used as a bedside tool for daily monitoring [8,9]. The stress index, addition, Gattinoni et al. [12] have shown that the capacity for opening obtained from the shape of the global airway pressure-time curves, collapsed lung units varies greatly among patients with ARDS. Thus, can be used to detect tidal recruitment or tidal hyperinflation, but ‘optimal’ PEEP can only be achieved by using individual settings that only during controlled constant-flow ventilation [6]. In patients with differ from patient to patient and from time to time. Therefore, we are ARDS, it was shown that adjusting PEEP based on the stress index waiting for simple validated bedside tools to better individualize the reduced the risk of alveolar hyperinflation, but data on clinically PEEP levels for our patients with ALI/ARDS.

References 1. ARDSnet. 2000. Ventilation with lower tidal vol- tive end-expiratory pressure setting in adults with 9. Cressoni M, Caironi P, Polli F et al. 2008. Anatomi- umes as compared with traditional tidal volumes acute lung injury and acute respiratory distress cal and functional intrapulmonary shunt in acute for acute lung injury and the acute respiratory syndrome. JAMA. 299:646-655. respiratory distress syndrome. Crit Care Med. distress syndrome. The Acute Respiratory Distress 6. Grasso S, Stripoli T, De Michele M, et al. 2007. ARD- 36:669-675. Syndrome Network. N Engl J Med. 342:1301-1308. Snet ventilatory protocol and alveolar hyperinfla- 10. Maisch S, Reissmann H, Fuellekrug B, Weismann D, 2. ARDSnet. 2004. Higher versus lower end-expirato- tion: the role of positive end-expiratory pressure. Rutkowski T, Tusman G, Bohm SH. 2008. Compli- ry pressures in patients with the acute respiratory Am J Respir Crit Care Med. 176:761-767. ance and dead space fraction indicate an optimal distress syndrome. N Engl J Med. 351:327-336. 7. Borges JB, Okamoto VN, Matos GFJ, et al. 2006. level of positive end-expiratory pressure after 3. Lachmann B. 1992. Open up the lung and keep the Reversibility of lung collapse and hypoxemia in recruitment in anesthetized patients. Anesth lung open. Intensive Care Med. 18:319-321. early acute respiratory distress syndrome. Am J Analg. 106:175-181. 4. Meade MO, Cook DJ, Guyatt GH et al. 2008. Ven- Respir Crit Care Med. 174:268-278. 11. Gattinoni L, Caironi P. 2008. Refining ventilatory tilation strategy using low tidal volumes, recruit- 8. Groeneveld ABJ, Schneider AJ. 2008. The relation- treatment for acute lung injury and acute respira- ment maneuvers, and high positive-end expiratory ship between arterial Po2 and mixed venous Po2 tory distress syndrome. JAMA. 299:691-693. pressure for acute lung injury and acute respira- in response to changes in positive end-expiratory 12. Gattinoni L, Caironi P, Cressoni M, et al. 2006. Lung tory distress syndrome. JAMA. 299:637-645. pressure in ventilated patients. Anaesthesia. recruitment in patients with the acute respiratory 5. Mercat A, Richard J-CM, Vielle B et al. 2008. Posi- 63:488-499. distress syndrome. 354:1775-1786.

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