Dear Editor, During positive pressure ventilation a peak inspiratory pressure >50-60 cm H2O may result in barotrauma [1]. Animal experiments have demonstrated that even a peak inspiratory pressure >30-40 cm H2O may cause pulmonary interstitial edema, elevated vascular permeability and inflammation, a picture that resembles acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS) [2]. Since peak inspiratory pressure is significantly lower during pressure-control ventilation (PCV) than during volume-control ventilation (VCV), one might expect PC modes of ventilation to be superior to VC modes [3]. Nevertheless, there is ample evidence that PCV is superior to VCV in terms of clinical outcome - only one study suggested a better outcome for ARDS-patients ventilated with PCV compared with VCV [4]. Meanwhile, PCV is increasingly being used: while only 1-5% of physicians expressed preference for PCV between 1992 and 1998 [5-7], one epidemiologic study in 2004 demonstrated >15% of physicians used PCV in their daily practice [8]. Fujita et al. investigated the effect of peak inspiratory flow in a rabbit acute lung injury model [9]. In their study, animals were randomly assigned to two ventilation groups: one group ventilated with pressure-regulated volume-control ventilation (PRVC) and one group receiving VCV. In the PRVC group, peak inspiratory flow was significantly higher than in the second group, as was to be expected. After development of lung injury and start of either ventilation strategy to the end of the experiment, PaO2 values remained significantly higher in the VC group than in the PRVC group. Wet-to-dry ratio and upper lobe tissue injury scores were higher in the PRVC group. The authors conclude form their experiments that high inspiratory flow is associated with greater deterioration in gas exchange and lung injury. We have some concerns regarding this conclusion. First, we wonder whether solely differences in peak inspiratory flow are responsible for the findings as described. Of importance, mean airway pressures were also higher with PRVC ventilation as compared with VCV, which in itself may be partly responsible for the detrimental effects. In this context, it can and must be noted that mammals, including humans, have a flow pattern resembling PRVC ventilation: alike the airflow pattern during PRVC ventilation, airflow during spontaneous breathing follows a "decelerating" pattern - fast contraction of the diaphragm and intercostal muscles enlarges the thorax volume, causing a negative intra-thoracic/intra-pulmonary pressure which results in a fast incline of inspiratory airflow. After reaching the peak, airflow rapidly declines until equilibration of intra-thoracic/intra-pulmonary pressure and environmental pressure. In contrast to PCV, VCV is characterized by a constant airflow during inspiration. Secondly, the tidal volumes used in this study merit closer attention. In intensive care medicine tidal volumes over the past decades have progressively decreased from >12-15 ml/kg actual body weight (ABW) [10,11] to Nevertheless, the findings by Fujita et al. are remarkable, and call for additional animal studies. If confirmed, a trial comparing PCV with VCV in patients that are to be ventilated for substantial periods of time, for instance patients with ALI/ARDS, seems warranted. Sincerely, Marcus J. Schultz, Peter E. Spronk, Michael A. Kuiper References: 1. Slutsky AS. Mechanical ventilation. American College of Chest Physicians' Consensus Conference. Chest, 1993; 104: 1833-59 2. Webb HH, Tierney DF: Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis, 1974; 110: 556-65 3. Guldager H, Nielsen SL, Carl P, Soerensen MB: A comparison of volume control and pressure-regulated volume control ventilation in acute respiratory failure. Crit Care (Lond), 1997; 1: 75-77 4. Esteban A, Alia I, Gordo F et al: Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure Collaborative Group. Chest, 2000; 117: 1690-96 5. Esteban A, Alia I, Ibanez J et al: Modes of mechanical ventilation and weaning. A national survey of Spanish hospitals. The Spanish Lung Failure Collaborative Group. Chest, 1994; 106: 1188-93 6. Esteban A, Anzueto A, Alia I et al: How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med, 2000; 161: 1450-58 7. Esteban A, Anzueto A, Frutos F et al: Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA, 2002; 287: 345-55 8. Ferguson ND, Meade MO, Esteban A et al: Influence of Randomized Trials on usual Clinical Practice. The International Study of Mechanical Ventilation. Proc Am Thor Soc, 2006; 3: A831 9. Fujita Y, Fujino Y, Uchiyama A et al: High peak inspiratory flow can aggravate ventilator-induced lung injury in rabbits. Med Sci Monit, 2007: 13(4): BR95-100 10. Suter PM, Fairley B, Isenberg MD: Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med, 1975; 292: 284-89 11. Jardin F, Farcot JC, Boisante L et al: Influence of positive end-expiratory pressure on left ventricular performance. N Engl J Med, 1981; 304: 387-92 12. Brun-Buisson C, Minelli C, Bertolini G et al: Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med, 2004; 30: 51-61 13. Sakr Y, Vincent JL, Reinhart K et al: High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest, 2005; 128: 3098-108 14. Amato MB, Barbas CS, Medeiros DM et al: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med, 1998; 338: 347-54 15. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med, 2000; 342: 1301-8 16. Dellinger RP, Carlet JM, Masur H et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med, 2004; 32: 858-73 LE 10486 str6-7 Detrimental factors during positive-pressure ventilation: pressure, flow, and/or volume? - in reply Dear Editor, We thank Dr. Schultz for the comments and appreciate the opportunity to reply. As Dr. Schultz pointed out, the mean airway pressure (mPaw) differed between the groups [1]. While the difference was about 2 cmH2O, it was higher when Paw during inspiratory phase was concerned. We agree with Dr. Schultz that mPaw might have been partly responsible for the injury. Flow pattern also differed between the groups. We know that flow pattern in spontaneous breathing is decelerating, and it is close to that of pressure-regulated volume control (PRVC). However, peak inspiratory flow in ARDS patients is much higher than that of healthy persons, because respiratory center in ARDS is stimulated [2]. In ARDS, the decelerating flow pattern is superior to a square waveform from the view point of work of breathing [3]. However, physiological rational is not always best in critically ill patients. In ARDS fairly amount of the lung was collapsed, and it is considered to increase shear stress between open and collapsed alveoli [4-6]. We speculated that higher the inspiratory flow, larger the shearing stress. While it could be possible to ventilate the animals in PRVC with a high peak flow in square flow pattern, when the setting peak flow is very high, inspiratory time is really short. We do not think very high peak flow in VC could have led the different results. We know that tidal volume (VT) used in our study (20 ml/kg) was high comparing to a standard of ventilatory management in ICU. We totally agree with Dr. Schultz on the point, and this is the most important issue in our study. However, in animal studies, we do not necessarily follow ventilatory management for patients. We have learned a lot from ventilator-induced lung injury with high PIP up to 40 cmH2O [7]. If we could ventilate the animals with lower VT for longer period like 3 days or longer, we could have had the results as Dr. Schultz commented. However, it was impossible in our laboratory. Nevertheless, we totally agree with Dr. Schultz comment on the point. Sincerely, Yasuki Fujita1, Yuji Fujino1, Akinori Uchiyama1, Takashi Mashimo2, Masaji Nishimura3 1 Intensive Care Unit, Osaka University Hospital, Suita, Osaka, Japan 2 Department of Anesthesiology, Osaka University Medical school, Suita, Osaka, Japan 3 Emergency and Critical Care Medicine, The University of Tokushima Graduate School, Tokushima, Japan Referenses: 1. Fujita Y, Fujino Y, Uchiyama A et al: High peak inspiratory flow can aggravate ventilator-induced lung injury in rabbits. Med Sci Monit, 2007; 13(4): BR95-100 2. Hering R, Zinserling J, Wrigge H et al: Effects of spontaneous breathing during airway pressure release ventilation on respiratory work and muscle blood flow in experimental lung injury. Chest, 2005; 128: 2991-98 3. Kallet RH, Campbell AR, Alonso JA et al: The effects of pressure control versus volume control assisted ventilation on patient work of breathing in acute lung injury and acute respiratory distress syndrome. Respir Care, 2000; 45: 1085-1096 4. Puybasset L, Cluzel P, Chao N et al. and the CT scan ARDS study group. A computed tomography scan assessment of regional lung volume in acute lung injury. Am J Respir Crit Care Med, 1998; 158: 1644-55 5. Muscedere JG, Mullen JBM, Gan K, Slutsky AS: Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med, 1994; 149: 1327-34 6. (ABSTRACT TRUNCATED)

Keywords: Positive-Pressure Respiration, Pressure, Respiratory Distress Syndrome, Adult - pathology, Tidal Volume, Positive-Pressure Respiration, Pressure, Respiratory Distress Syndrome, Adult - pathology, Tidal Volume