recent studies have shown that lung protective strategies using low tidal volumes and high levels of positive end - expiratory pressure ( peep ) reduce mortality and are becoming standard practice in patients with acute respiratory distress syndrome ( ards ) . although peep improves arterial oxygenation , it can adversely affect systemic hemodynamics , reducing venous return and cardiac output . the splanchnic perfusion is particularly sensitive , and any reduction can compromise its barrier function , promote bacterial translocation , and contribute to the development of multiple organ failure . in experimental models , peep has markedly decreased mesenteric and portal blood flow , despite only moderate reductions in cardiac output [ 4 - 8 ] . these effects are usually dose related , becoming more pronounced with peep levels around 20 cmh2o . kiefer reported that peep did not significantly alter splanchnic blood flow in six patients with acute lung injury . nevertheless , caution should be exercised in extending these results to clinical practice , because only hemodynamically stable patients without adrenergic drugs were studied , and peep levels never exceeded 14 cmh2o . our aim was to evaluate the effects of peep levels up to 20 cmh2o on gastric mucosal perfusion and systemic hemodynamics in mechanically ventilated patients with ards under hemodynamic support . the study was approved by the ethics committee of the medicine faculty and was performed in the surgical intensive care unit of the catholic university hospital of chile . adult mechanically ventilated patients were considered eligible for the study if they met the following criteria for ards during the 24 hours that preceded the study : acute onset of respiratory failure ; diffuse bilateral infiltrates in the chest radiograph ; a ratio of partial pressure of o2 ( pao2 ) to fraction of inspired oxygen ( fio2 ) of less than 200 mmhg ; and a pulmonary arterial occlusion pressure less than 18 mmhg and no cardiac failure . hemodynamic monitoring included an arterial line and a pulmonary artery catheter ( baxter edwards critical - care , irvine , ca ) . patients could be under vasopressor or inotropic support , but had to be hemodynamically stable for at least 3 hours before starting the protocol . patients were excluded if they had any of the following conditions : pregnancy , pre - existing respiratory dysfunction , cardiac index of less than 2.5 l minm , or were receiving enteral nutrition . a nasogastric tonometer ( triptonometry catheter 14f , with biofilter connector for tonocap monitor ) was inserted into the stomach and connected to air automated tonometry ( tonocap monitor ; datex - engstrom , helsinki , finland ) . patients were connected to volume - controlled mechanical ventilation ( servo 900 c ; siemens , solna , sweden ) . a pressure  volume curve was obtained for each patient by the airway occlusion technique , and ideal peep was defined as the lower inflection point + 2 cmh2o , or 12 cmh2o if no lower inflection point was found . peep levels of 10 , 15 , 20 cmh2o , and ideal peep , with tidal volumes of 8 ml kg , were applied in four consecutive 30 min periods , respectively . respiratory rate was modified to maintain end tidal co2 within  10 mmhg of basal . all patients were receiving a constant infusion of 6% hetastarch before the beginning of the study ( 4080 ml h ) . cardiac output was optimized before and during the trial by determining the respiratory variation of systolic arterial pressure . whenever the variation was more than 10% a 100 ml bolus of 6% hetastarch was infused and the volume status was reassessed . no change in adrenergic support was allowed during the protocol . if hypotension ( mean arterial pressure < 65 mmhg ) persisted for more than 1 min , the protocol was stopped . at baseline , and at the end of each period , hemodynamic , ventilatory and tonometric measurements were performed , and arterial blood samples withdrawn . hemodynamic records included mean arterial pressure , heart rate , cardiac output , pulmonary artery occlusion pressure , central venous pressure and left ventricular stroke work index . cardiac output was measured by thermodilution as the average of three values obtained after injections of 10 ml of 5% dextrose in water at room temperature . the co2 gap ( gastric partial pressure of co2 [ pco2 ] minus arterial pco2 ) was calculated by comparing simultaneous measurements of tonometric gastric mucosal pco2 and arterial pco2 . data were analyzed with a friedman test followed by a wilcoxon signed - rank test if necessary . the study was approved by the ethics committee of the medicine faculty and was performed in the surgical intensive care unit of the catholic university hospital of chile . adult mechanically ventilated patients were considered eligible for the study if they met the following criteria for ards during the 24 hours that preceded the study : acute onset of respiratory failure ; diffuse bilateral infiltrates in the chest radiograph ; a ratio of partial pressure of o2 ( pao2 ) to fraction of inspired oxygen ( fio2 ) of less than 200 mmhg ; and a pulmonary arterial occlusion pressure less than 18 mmhg and no cardiac failure . hemodynamic monitoring included an arterial line and a pulmonary artery catheter ( baxter edwards critical - care , irvine , ca ) . patients could be under vasopressor or inotropic support , but had to be hemodynamically stable for at least 3 hours before starting the protocol . patients were excluded if they had any of the following conditions : pregnancy , pre - existing respiratory dysfunction , cardiac index of less than 2.5 l minm , or were receiving enteral nutrition . a nasogastric tonometer ( triptonometry catheter 14f , with biofilter connector for tonocap monitor ) was inserted into the stomach and connected to air automated tonometry ( tonocap monitor ; datex - engstrom , helsinki , finland ) . patients were connected to volume - controlled mechanical ventilation ( servo 900 c ; siemens , solna , sweden ) . a pressure  volume curve was obtained for each patient by the airway occlusion technique , and ideal peep was defined as the lower inflection point + 2 cmh2o , or 12 cmh2o if no lower inflection point was found . peep levels of 10 , 15 , 20 cmh2o , and ideal peep , with tidal volumes of 8 ml kg , were applied in four consecutive 30 min periods , respectively . respiratory rate was modified to maintain end tidal co2 within  10 mmhg of basal . all patients were receiving a constant infusion of 6% hetastarch before the beginning of the study ( 4080 ml h ) . cardiac output was optimized before and during the trial by determining the respiratory variation of systolic arterial pressure . whenever the variation was more than 10% a 100 ml bolus of 6% hetastarch was infused and the volume status was reassessed . no change in adrenergic support was allowed during the protocol . if hypotension ( mean arterial pressure < 65 mmhg ) persisted for more than 1 min , the protocol was stopped . at baseline , and at the end of each period , hemodynamic , ventilatory and tonometric measurements were performed , and arterial blood samples withdrawn . hemodynamic records included mean arterial pressure , heart rate , cardiac output , pulmonary artery occlusion pressure , central venous pressure and left ventricular stroke work index . cardiac output was measured by thermodilution as the average of three values obtained after injections of 10 ml of 5% dextrose in water at room temperature . the co2 gap ( gastric partial pressure of co2 [ pco2 ] minus arterial pco2 ) was calculated by comparing simultaneous measurements of tonometric gastric mucosal pco2 and arterial pco2 . data were analyzed with a friedman test followed by a wilcoxon signed - rank test if necessary . they had a median ( range ) age of 63.5 years ( 2386 ) , and an acute physiology and chronic health evaluation ii score of 14 ( 720 ) at admission to the intensive care unit . on the day of the study they had a median sepsis - related organ failure assessment ( sofa ) all patients fulfilled criteria for ards , as defined by the inclusion criteria , during the 24 hours before the study and they had been on mechanical ventilation for 32 ( 1272 ) hours . they were being ventilated with a median peep level of 9 ( 412 ) cmh2o , they had a pao2/fio2 ratio of 235 ( 144388 ) mmhg and their respiratory system compliance was 45 ( 2760 ) ml per cmh2o . seven patients had sepsis ( two pneumonia and five extrapulmonary sepsis ) , and one a severe thoracic trauma . baseline characteristics of the patients apache , acute physiology and chronic health evaluation ; crs , respiratory system compliance ; dbt , dobutamine ; dp , dopamine ; lip , lower inflection point ; ne , norepinephrine ( noradrenaline ) ; nl , no lip found ; ns , not significant ; peep , positive end - expiratory pressure ; s , significant ; sofa , sepsis - related organ failure assessment . no changes in cardiac index or in co2 gap were found at any of the study periods ( table 2 ) . oxygenation index , mean arterial pressure , pulmonary mean arterial pressure , pulmonary artery occlusion pressure , central venous pressure and left ventricular stroke work index also remained stable through the study . only mean airway pressure and pao2/fio2 ratio differed between periods , as expected . five patients required a 100 ml bolus of hetastarch during the trial ; in no patient was it necessary to repeat it . individual changes in co2 gap and cardiac index are presented in figs 1 and 2 , respectively . at baseline after starting the protocol with 10 cmh2o peep , patient 6 , who was previously being ventilated with 4 cmh2o peep , had a further increase in co2 gap . when peep was increased from 10 to 15 cmh2o , six patients decreased their co2 gap and two increased it . when peep was increased from 15 to 20 cmh2o , three patients increased their co2 gap , three decreased it and in one patient it remained unchanged . patient 4 did not complete the protocol because of moderate hypotension ( mean arterial pressure 60 mmhg ) when peep was increased to 20 cmh2o . this patient recovered after an increased dose of norepinephrine ( noradrenaline ) and a return of peep to baseline levels . cvp , central venous pressure ; co2 gap , arterial partial pressure of co2 [ pco2 ] minus gastric pco2 ; fio2 , fraction of inspired oxygen ; lvswi , left ventricular stroke work index ; map , mean arterial pressure ; oi , oxygenation index , defined as mean airway pressure  fio2  100/arterial pco2 ; pao2 , partial pressure of o2 ; paco2 , partial pressure of co2 ; paop , pulmonary arterial occlusion pressure ; peep , positive end - expiratory pressure . p < 0.05 for all comparisons except baseline versus peep 10 and peep 10 versus ideal peep . p < 0.05 for all comparisons except baseline versus peep 10 , baseline versus peep 15 , baseline versus ideal peep , and peep 15 versus ideal peep . the median length of stay in the intensive care unit was 17 ( 1034 ) days and the median duration of mechanical ventilation was 9 ( 534 ) days . individual changes in co2 gap ( gastric pco2 minus arterial pco2 ) with different positive end - expiratory pressure levels . our results show that high peep levels ( up to 20 cmh2o ) do not compromise gastric mucosal perfusion , as assessed by tonometry , and do not affect systemic hemodynamics in most patients with ards . this is consistent with the findings of two other studies on the effects of peep on splanchnic perfusion in patients with ards . nevertheless , in contrast with our study , neither of those studies included patients in septic shock or under adrenergic support . this is an important issue , because hemodynamic safety concerns could preclude the use of high or optimal peep levels in that setting , even if necessary . a major finding of our study is that peep levels up to 20 cmh2o can be well tolerated , even in patients with ards and septic shock . nevertheless , our trial was relatively short and we can not exclude the possibility that keeping high peep levels for a longer period might result in increased fluid requirements , which could be deleterious in the longer term . experimental and clinical research has demonstrated that in mechanically ventilated subjects without lung injury , peep decreases venous return and , secondarily , cardiac output [ 17 - 19 ] . in addition , trager and colleagues showed that , in patients with acute respiratory failure associated with septic shock , high peep levels induced a decrease in cardiac output . in contrast , we found no decrease in cardiac output in our patients tested with increasing peep levels when fluid administration was optimized according to respiratory variation in systolic arterial pressure . possible explanations for these contradictory results are a higher rate of fluid administration and the use of lower tidal volumes in the latter studies . although we did not determine the upper inflection point of the pressure  volume curve , we think that by keeping tidal volume at 8 ml kgany overdistension of the lungs was minimized . thus , it seems that it is possible to preserve cardiac output in patients with ards , despite the use of high peep levels , by optimizing fluid administration and limiting tidal volumes . gastric mucosal perfusion , as assessed by co2 gap , also remained unchanged during the peep trial . this is consistent with the results reported by kiefer and akinci in similar studies . in all these studies cardiac output remained unchanged . in contrast , trager reported , in a series of septic shock patients with acute respiratory failure , that an increase in peep from 5 to 15 cmh2o induced a decrease in cardiac output associated to a decrease in hepatic vein o2 saturation and in hepatic glucose production . it therefore seems that by avoiding decreases in cardiac output , splanchnic perfusion can be preserved in the majority of the patients . in spite of the fact that no significant changes in co2 gap or cardiac index were found during the protocol , when looking at the individual data certain patients evidenced an adverse effect when their peep level was increased . patient 4 , who had an extrapulmonary ards , presented hypotension when 20 cmh2o peep was applied . in this case , no simultaneous records of cardiac output or co2 gap could be made for safety reasons ( we immediately proceeded to decrease peep level ) . patient 6 , who had a pulmonary ards and who before starting the study had a 30 mmhg co2 gap while being ventilated with 4 cmh2o peep , presented a further deterioration in co2 gap after starting the protocol with 10 cmh2o peep , which was not associated with a decrease in cardiac output . these events suggest that not all patients with ards can tolerate high peep levels ; if required , careful hemodynamic monitoring including assessment of regional perfusion should be applied . one major limitation of our study is the small number of patients studied . we did not perform any a priori power analysis because we had no estimation of the possible magnitude of the effects that peep could have on gastric tonometry . although all patients fulfilled criteria for ards during the 24 hours that preceded the study , at inclusion their pao2/fio2 ratio and their respiratory system compliance were only moderately decreased . they show in patients diagnosed with ards that after a few hours of treatment with peep or a high fio2 , more than half of the patients present a pao2/fio2 ratio of more than 200 mmhg . in addition , respiratory system compliance increased by more than 10 ml per cmh2o after 6 hours of treatment with peep . at inclusion our patients had already been ventilated with a median peep level of 9 cmh2o for more than 12 hours , which could have explained the rather improved respiratory performance at baseline . in any event , this improvement demonstrated a less severe ards . it is possible that more severely compromised patients might present a lower tolerance to high peep levels . other limitation is that tonometry was the sole method used to assess gastric mucosal perfusion . nevertheless , elizalde and colleagues showed that gastric mucosal blood flow , measured by laser doppler flowmetry and by reflectance spectrophotometry , is well correlated with gastric intramucosal acidosis in mechanically ventilated patients . our study supports the findings of previous studies suggesting that high peep levels do not affect splanchnic perfusion and are hemodynamically well tolerated in most patients with ards . furthermore , our study shows that gastric mucosal perfusion can be well preserved while high peep levels are applied even in patients presenting cardiovascular dysfunction and receiving adrenergic support , which is a frequent occurrence in critical care . nevertheless , two of the eight patients studied exhibited adverse effects during the peep trial , which highlights the importance of a close monitoring of systemic and regional perfusion while applying high peep levels to patients with ards . future studies should assess the effects of peep on splanchnic perfusion in a longer term . high peep levels do not affect gastric mucosal perfusion and are hemodinamically well tolerated in most patients with ards ards = acute respiratory distress syndrome ; co2 gap = gastric pco2 minus arterial pco2 ; fio2 = fraction of inspired oxygen ; pao2 = partial pressure of o2 ; pco2 = partial pressure of co2 ; peep = positive end - expiratory pressure .
introductionpositive end - expiratory pressure ( peep ) improves oxygenation and can prevent ventilator - induced lung injury in patients with acute respiratory distress syndrome ( ards ) . 
 nevertheless , peep can also induce detrimental effects by its influence on the cardiovascular system . 
 the purpose of this study was to assess the effects of peep on gastric mucosal perfusion while applying a protective ventilatory strategy in patients with ards.methodseight patients were included . 
 a pressure  volume curve was traced and ideal peep , defined as lower inflection point + 2 cmh2o , was determined . 
 gastric tonometry was measured continuously ( tonocap ) . after baseline measurements , 10 , 15 and 20 
 cmh2o peep and ideal peep were applied for 30 min each . by the end of each period , 
 hemodynamic , co2 gap ( gastric minus arterial partial pressures ) , and ventilatory measurements were performed.resultspeep had no effect on co2 gap ( median [ range ] , baseline : 19 [ 230 ] mmhg ; peep 10 : 19 [ 040 ] mmhg ; peep 15 : 18 [ 039 ] mmhg ; peep 20 : 17 [ 439 ] mmhg ; ideal peep : 19 [ 939 ] mmhg ; p = 0.18 ) . 
 cardiac index also remained unchanged ( baseline : 4.6 [ 2.56.3 ] l min-1 m-2 ; peep 10 : 4.5 [ 2.56.9 ] l min-1 m-2 ; peep 15 : 4.3 [ 26.8 ] l min-1 m-2 ; peep 20 : 4.7 [ 2.46.2 ] l min-1 m-2 ; ideal peep : 5.1 [ 2.16.3 ] l min-1 m-2 ; p = 0.08 ) . 
 one patient did not complete the protocol because of hypotension.conclusionpeep of 1020 cmh2o does not affect gastric mucosal perfusion and is hemodynamically well tolerated in most patients with ards , including those receiving adrenergic drugs .