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Perioperative Medicine  |   January 2013
Effects of Recruitment Maneuver and Positive End-expiratory Pressure on Respiratory Mechanics and Transpulmonary Pressure during Laparoscopic Surgery
Author Affiliations & Notes
  • Gilda Cinnella, M.D.
    *
  • Salvatore Grasso, M.D., Ph.D.
  • Savino Spadaro, M.D.
  • Michela Rauseo, M.D.
    §
  • Lucia Mirabella, M.D. Ph.D.
    #
  • Potito Salatto, M.D.
  • Antonella De Capraris, M.D.
  • Luigi Nappi, M.D.
    ††
  • Pantaleo Greco, M.D.
    **
  • Michele Dambrosio, M.D., Ph.D.
    ‡‡
  • Professor of Anesthesia and Intensive Care, Resident of Anesthesia and Intensive Care, §Fellow Anesthesiologist, Staff Anesthesiologist, #Assistant Professor of Anesthesia and Intensive Care, ‡‡Professor of Anesthesia and Intensive Care, Department of Anesthesia and Intensive Care, **Professor of Gynecology, ††Assistant Professor of Gynecology, Department of Gynecology, University of Foggia, Foggia, Italy. Assistant Professor of Anesthesia and Intensive Care, Department of Anesthesia and Intensive Care, University of Bari, Bari, Italy.
Article Information
Perioperative Medicine / Ambulatory Anesthesia / Respiratory System
Perioperative Medicine   |   January 2013
Effects of Recruitment Maneuver and Positive End-expiratory Pressure on Respiratory Mechanics and Transpulmonary Pressure during Laparoscopic Surgery
Anesthesiology 1 2013, Vol.118, 114-122. doi:10.1097/ALN.0b013e3182746a10
Anesthesiology 1 2013, Vol.118, 114-122. doi:10.1097/ALN.0b013e3182746a10
What We Already Know about This Topic
  • Trendelenburg position and pneumoperitoneum worsen chest wall elastance and gas exchange during laparoscopic pelvic surgeries

What This Article Tells Us That Is New
  • Open lung strategy, consisting of a recruitment maneuver followed by the application of positive end-expiratory pressure, in 29 consecutive American Society of Anesthesiologists 1 and 2 nonobese patients, led to significant alveolar recruitment and improved chest wall and lung elastance in all the patients

Laparoscopy is a well-established procedure for pelvic gynecologic surgery often performed in Trendelenburg position.1,2 To facilitate laparoscopic surgical manipulation, a pneumoperitoneum is usually induced through carbon dioxide inflation. Both the increase in abdominal pressure as a result of carbon dioxide inflation and the head down body position have been shown to impair the respiratory function during the procedure, mainly inducing atelectasis formation in the dependent lung regions.1,3–6 The resulting decrease in functional residual capacity poses patients at risk of perioperative complications, particularly if they are obese and/or submitted to intricate surgical procedures.4,7 In fact, ventilation at low lung volumes may generate tidal alveolar recruiting (i.e.  , some alveolar units that are collapsed at end-expiration are cyclically reopened during tidal inflation), a mechanism generating an alveolar shear stress known as “atelectrauma”.8 Furthermore, in presence of atelectasis, delivering the tidal volume to the limited amount of patient lung parenchyma may induce alveolar stress and strain.9 Both stress, strain and atelectrauma are main mechanisms underlying ventilator-induced lung injury.9,10 Despite definitive evidences that ventilator-induced lung injury may play a role when ventilating normal lungs (as generally done during anesthesia) are lacking,11 the hypothesis that a lung-protective ventilatory strategy should be applied during general anesthesia is sound and widely debated.1,6,7,12–14 
Several ventilatory strategies aiming at improving arterial oxygenation and respiratory mechanics during laparoscopic surgery have been investigated: the application of positive end-expiratory pressure (PEEP) has been shown to counterbalance the diaphragm cranial shift increasing functional residual capacity and decreasing respiratory system elastance (ERS).12,13,15–17 Recently, translating the concept of lung-protective ventilatory strategy from the adult respiratory distress syndrome context,9,14,18–20 the application of an “open lung” strategy consisting in a recruiting maneuver (RM) followed by the subsequent application of PEEP has been suggested to effectively reexpand pneumoperitoneum-induced atelectasis and improve oxygenation during laparoscopic surgery.21–25 However, to our knowledge, the effects of the open lung strategy on respiratory mechanics partitioned between its chest wall and lung components (i.e.  , the relative effect exerted by the open lung strategy on lung and chest wall mechanics) have not been thoroughly investigated.26–28 This is of particular interest because classical physiologic concepts29 and recent experimental and clinical data clearly show that chest wall mechanical impairment has a deep impact on the response to any open lung strategy.9,16,20,30 In fact, during controlled positive pressure ventilation, the real lung-distending pressure is the transpulmonary pressure (PL), that is, the difference between airways opening pressure (PAO) and the pressure required to expand the chest wall,28,29,31 clinically estimated by measuring esophageal pressure (PES) as a surrogate of pleural pressure.32 
The hypothesis of the current study is that during laparoscopic gynecologic surgery, both the Trendelenburg position and pneumoperitoneum worsen chest wall elastance (ECW), concomitantly decreasing PL, and that an open lung strategy consisting of an RM followed by ventilation with PEEP applied after pneumoperitoneum induction, by increasing PL, would result in alveolar recruitment and improvement in respiratory mechanics and gas exchange.
Materials and Methods
After approval of the Policlinico Riuniti, Foggia, Italy, ethics committee and written informed consent from each patient, the study was performed in consecutive patients scheduled to undergo elective gynecologic laparoscopic surgery from January to July 2011. Inclusion criteria were age more than 18 yr and American Society of Anesthesiology physical status I and II. Patients with preexisting lung or cardiac disease, pathologic lung function, or obesity (body mass index ≥ 30 Kg/m2) were excluded from the study.
On their arrival in the operating room, patients were premedicated with midazolam 0.03–0.04 mg/kg. After applying standard monitoring device (electrocardiogram and pulse oximeter [Intellivue MP40 monitor, Philips, Boeblingen, Germany]), the radial artery was cannulated (Radial Artery Catheterization Set, Arrow International, Reading, PA) for continuous monitoring of blood pressure. The arterial line was connected to the FloTrac sensor and the Vigileo monitor (Edwards Life Sciences LLC, Irwine, CA, software version 03.10), which allows cardiac output and stroke volume estimation from the arterial pressure waveform and computes the stroke volume variation (SVV) in response to positive pressure mechanical ventilation as an index of cardiac preload and fluid responsiveness.33 
Patients were given 8 ml/kg of normal saline intravenously before the induction of anesthesia and were then maintained with 5 ml·kg–1·h–1of normal saline solution. Anesthesia was induced with propofol 2 mg/kg, fentanyl 3 ng/kg, and succinylcholine 1 mg/kg. After induction, the trachea was intubated with an endotracheal tube of appropriate size (Rushelit Rush AG Lab, Waiblingen, Germany). Anesthesia was maintained with an infusion of propofol 150–200 γ·kg–1·min–1, remifentanil 0.1–0.2 γ·kg–1·min–1, and cisatracurium 1.5 γ·kg–1·min–1. The level of anesthesia was assessed through bispectral index monitoring (Aspect A-2000®; Aspect Medical System, Newton, MA). The infusion rate of propofol was varied to target a bispectral index value between 50 and 60. The lungs were ventilated through a Servo Ventilator 900C (Siemens-Elema AB, Berlin, Germany) with a square flow waveform with a tidal volume (Vt) of 8 ml/kg ideal body weight, respiratory rate of 12 breath/min, inspiratory time of 33%, and an inspiratory pause of 20%. Patients were ventilated using oxygen in air with an inspiratory oxygen fraction set at 40% as needed to maintain the SaO2≥ 95%. No PEEP was initially added.
An esophageal thin latex balloon-tipped catheter (Compliance catheter, Microtek Medical B.V. Zutphen, The Netherlands) was inserted through the mouth, advanced into the esophagus and connected by means of a polyethylene catheter to a pressure transducer (Digima-Clic, Nordlingen, Germany), to measure PES. The esophageal balloon was filled with 1–1.5 ml of air, and its correct positioning in the lower third of the esophagus was verified according to literature, by allowing a brief period of spontaneous breathing after the induction of anesthesia and comparing the esophageal and the airway opening pressure traces.32 In addition, the correct balloon position in the lower third of the esophagus was confirmed by the presence of appropriate esophageal pressure deflections induced by mechanical ventilation and moderate push on the abdomen. All the data were controlled on the computer software of recording and analysis (ICU Lab, KleisTEK Engineering, Bari, Italy) through an optimal waveform.
A standardized protocol for hemodynamic management was applied to ensure fluid volume optimization. In brief, if SVV was lower than 13%, no additional fluids were given, whereas if SVV was higher than 13%, additional boluses of 250 ml of artificial colloid were infused over 15–20 min. After each bolus, SVV was re-evaluated, and a further bolus was administered if stroke volume increased by more than 10%, until reaching an SVV lower than 13%.33 
Study Protocol
About 15 min after pneumoperitoneum induction, if the patients were hemodynamically stable, that is, with mean blood pressure ≥ 80 mmHg, heart rate ≥ 60 beats/min, and SVV < 13%, the open lung strategy was applied as already described.34 In brief, the ventilator was switched to pressure-control ventilation, inspiratory time was increased to 50%, the peak inspiratory pressure gradient (above PEEP) was set at 20 cm H2O, and PEEP was progressively increased to obtain a stepwise increase of peak inspiratory to 30, 35, and 40 cm H2O every three breaths. The final recruiting pressure of 40 cm H2O was applied for six breaths. After ward, the ventilator switched again to the volume-control ventilation with baseline settings but with a PEEP level of 5 cm H2O that was maintained after abdominal deflation until the end of surgery. Overall, the RM procedure lasted approximately 1 min. Measurements were obtained (1) 15 min after anesthesia induction in supine position before inducing the pneumoperitoneum (TBSL); (2) 15 min after pneumoperitoneum induction (abdominal carbon dioxide inflation to obtain and intra-abdominal pressure of 10 mmHg) with the patient positioned at 20° head down (TpreOLS); (3) 20 min after the application of the open lung strategy (TpostOLS); and (4) at the end of surgery, after abdominal deflation and in supine position with a PEEP level of 5 cm H2O.
Measurements
Hemodynamic and respiratory mechanics parameters were recorded, digitized, and collected on a personal computer through a 12-bit analog-to digital converter board (DAQCard 700; National Instrument, Austin, TX) at a sample rate of 200 Hz (ICU Lab, KleisTEK Engineering).
Blood pressure was measured through a radial catheter connected to the pressure transducer of the MP40 monitor. Hemodynamic parameters obtained through the Vigileo monitor included stroke volume, cardiac output, and SVV, whereas stroke volume index and cardiac index were calculated using standard formulae. All intravascular pressure measurements were zeroed to the mid-axillary line. Analysis of arterial blood gases was performed (ABL 330; Radiometer, Copenhagen, Denmark).
Flow was measured with a heated pneumotachograph (Fleisch no. 2; Fleisch, Lausanne, Switzerland), connected to a differential pressure transducer (Diff-Cap, ±1 cm H2O; Special Instruments, Nordlingen, Germany) inserted between the Y-piece of the ventilator circuit and the endotracheal tube. The pneumotachograph was linear over the experimental range of flow. Volume was obtained by numerical integration of the flow signal. PAOwas measured proximal to the endotracheal tube with a pressure transducer (Special Instruments Digima-Clic ± 100 cm H2O; Nordlingen, Germany). The difference between the level of the PEEP set on the ventilator (read as the PAOvalue at the end of a regular breath) (PEEPexternal) and the pressure in PAOduring a 3- to 5-s end-expiratory occlusion (PEEPtotRS) was measured and regarded as the static intrinsic PEEP of the respiratory system according to Pepe.35 The end-expiratory occlusion was performed through the expiratory hold on the Servo 900C ventilator.
Static ERSwas calculated using:
ERS= PplatRS–PEEPtotRS/Vt(1)
where PplatRSis the value of PAOobtained by adding an end-inspiratory pause of 2–3 s through the inspiratory hold of the ventilator.
Static ECWwas calculated as:
ECW= (PplatCW− PEEPtotCW)/Vt, (2)
where PplatCWis the value of PESobtained contemporaneously to PplatRSduring the end-inspiratory pause. Lung static elastance (EL) was calculated as:
EL= ERS– ECW(3)
Transpulmonary end-inspiratory pressure (PplatL) was computed, according to Gattinoni et al  .9,29 as:
PplatL= PplatRS× EL/(EL+ ECW) (4)
Transpulmonary end-expiratory pressure (PEEPtotL) was computed during the end-expiratory pause as:
PEEPtotL= PEEPtotRS× EL/(EL+ ECW) (5)
Alveolar recruitment was measured though a physiologic method originally described by Ranieri et al  .,36 subsequently applied in several physiologic clinical studies18,28,34,37–39 and recently validated by Dellamonica et al  .40 In brief, for each experimental condition, we first measured the quasistatic volume–pressure curves of the respiratory system through the low-flow inflation technique as originally described by Lu et al  .41 and subsequently measured the delta end-expiratory lung volume as the difference between the end-expiratory lung volume during mechanical ventilation and the elastic equilibrium volume of the respiratory system at zero end-expiratory pressure, or relaxation volume (Vr) or functional residual capacity. The delta end-expiratory lung volume was measured by disconnecting the patient from the ventilator circuit distally from the pneumotachograph and allowing a prolonged expiration (15–20 s; fig. 1). Of note, this method does not measure Vrper se  but assumes that any alveolar recruitment obtained by applying RM or PEEP does not modify Vrand that therefore Vrremains the same in all the experimental conditions.36 Knowing the respective delta end-expiratory lung volume, the quasistatic volume–pressure curves obtained before and after the RM were plotted on the same volume–pressure axis and referred to Vr(fig. 2). To do so, each volume–pressure curve started at a point corresponding to PEEPTOT(referred to the X axis) and to the end-expiratory lung volume (referred to the Y axis) (fig. 2). The recruited volume (the gas volume of collapsed or fluid-filled alveolar units eventually reaerated by the open lung strategy) was computed as the difference in lung volume at the same static PAOread on the two pressure–volume curves (fig. 2).
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
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Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black  curve) and the higher PEEP strategy (gray  curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line  indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black 
	curve) and the higher PEEP strategy (gray 
	curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line 
	indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black  curve) and the higher PEEP strategy (gray  curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line  indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
×
Total airways resistances were calculated as the difference between PpeakRSand PplatRSdivided by the inspiratory airflow.37,41 
Statistical Analysis
A sample size calculation was performed using data from the study by Grasso et al  .18 on the effects of RMs in patients with adult respiratory distress syndrome ventilated with protective ventilatory strategy. On the basis of these data, the significant recruitment was designated as a 100-ml increase in end-expiratory lung volume with an SD of 116.7. By using a one-sample, one-sided test, the sample size calculated was of 23 patients; this number was increased to 31 to allow for an expected dropout of around one third of patients and was used for patient enrolment. The α and β errors for the sample size were chosen as 0.05 and 90%, respectively. Because only two patients dropped out from the analysis (fig. 3), the study power was 99%.
Fig. 3. Flow diagram of the progress through the phases of the trial.
Fig. 3. Flow diagram of the progress through the phases of the trial.
Fig. 3. Flow diagram of the progress through the phases of the trial.
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Statistical comparison of respiratory mechanics, hemodynamic, and gas exchange data was performed between the four study steps: data were tested for normal distribution by the Kolmogorov–Smirnov goodness-of-fit test and are presented as mean ± SD. Data analysis was performed using repeated-measures one-way ANOVA; if significant, the test of Tukey was applied for post hoc  comparison between the different experimental conditions. A P  value of less than 0.05 was considered statistically significant. Statistical analysis was performed using Statistica 8.0 (Statsoft Italia srl 2008, Vigonza Padova, Italy).
Results
Twenty-nine of 35 patients initially candidate for enrolment were included in the study. The enrolment flow diagram is reported in figure 3. Demographic characteristics of the population studied are presented in table 1. The study was completed successfully in every patient without complications or adverse events as a result of the study protocol. Data are presented as mean ± SD).
Table 1. Patients Demographic Characteristics
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Table 1. Patients Demographic Characteristics
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Respiratory Mechanics
Compared with the baseline (table 2), the induction of pneumoperitoneum and the Trendelenburg position worsened ECWand ELresulting in an overall increase of ERS(P =  0.00015 on TpreOLSvs.  TBSL, respectively). The open lung strategy decreased both ECWand EL(P =  0.0007 on TpostOLSvs  . TpreOLS, for both parameters). Both end-inspiratory and end-expiratory transpulmonary pressure (PplatLand PEEPtotL, respectively) decreased at TpreOLScompared with TBSL(P =  0.008) and both increased on TpostOLS(P =  0.008 vs.  TpreOLS).
Table 2. Breathing Pattern and Gas Exchange Parameters during the Different Experimental Conditions
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Table 2. Breathing Pattern and Gas Exchange Parameters during the Different Experimental Conditions
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Figure 4shows the quasistatic volume–pressure curves of the respiratory system measured immediately before and 20 min after the application of open lung strategy and plotted on the same volume–pressure axis (see Materials and Methods), in a representative patient. Of note, the curve obtained during the open lung strategy is shifted upward on the volume axis, clearly indicating the occurrence of alveolar recruitment. Overall, the open lung strategy resulted in a significant alveolar recruitment in all patients (194 + 80 ml, range 65–323 ml).
Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black  curve) and after (gray  curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black 
	curve) and after (gray 
	curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black  curve) and after (gray  curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
×
Gas Exchanges
The PaO2/inspiratory oxygen fraction ratio (table 2) worsened at TpreOLScompared with TBSL(P =  0.008) and returned to baseline values at TpostOLS(P =  0.008 vs.  TpreOLS). Despite alveolar minute ventilation remained unchanged, PaCO2increased at TpreOLScompared with TBSL(P =  0.008) and returned to baseline value after the application of the open lung strategy.
Hemodynamics
During the RM (table 3), cardiac index decreased by approximately 20% compared with TpreOLS(P =  0.0007), returned to TpreOLSvalues immediately after the RM and remained stable thereafter. SVV was 8.10 ± 2.37% on TBSLand remained stable throughout all the experimental conditions. Mean blood pressure and heart rate remained stable throughout the study.
Table 3. Hemodynamic Parameters during the Different Experimental Conditions
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Table 3. Hemodynamic Parameters during the Different Experimental Conditions
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Discussion
Our data show that in patients submitted to pelvic laparoscopic surgery in Trendelenburg position under general anesthesia, the application of an RM followed by PEEP after pneumoperitoneum induction leads to alveolar recruitment and improvement of chest wall and lung elastance.
Because the diaphragm is mechanically coupled to the abdominal wall, any increase in abdominal pressure may decrease functional residual capacity.28,42 During laparoscopy, the raised abdominal pressure distends the abdominal wall, increases its elastance, shifts cranially the diaphragm, and moves a large part of the ventilation-related volume changes through the rib cage.7,26,27 The Trendelenburg position often needed to perform pelvic surgery facilitates the transmission of the abdominal weight to the lung parenchyma. Our data confirm the pneumoperitoneum and Trendelenburg position–related worsening of respiratory mechanics: ECWincreased by 30%, whereas ELincreased by 20%, and furthermore, static intrinsic PEEP of the respiratory system and total airways resistances increased compared with those recorded at baseline, after the induction of anesthesia in supine position. On the other hand, we did record a worsening in PaO2/inspiratory oxygen fraction ratio that although significant was never clinically relevant (table 2). However, severe hypoxemia is not an hallmark of pneumoperitoneum-induced worsening of respiratory function during laparoscopy in healthy subjects, and moreover, oxygenation has been shown to be a poor indicator of the extent of pneumoperitoneum-induced lung collapse.
Several strategies have been proposed to counterbalance the derangements in respiratory mechanics induced by pneumoperitoneum during laparoscopic surgery. External PEEP alone has been repeatedly shown to have beneficial but transient effects, whereas recently Valenza et al  .22 showed that the combination of beach chair position and PEEP in morbidly obese patients during pneumoperitoneum improves oxygenation. This strategy, however, is not feasible in surgical settings in which other positions are needed. Futier et al  .24 demonstrated that an RM applied after pneumoperitoneum induction and followed by the application of PEEP provides significant improvements in ERSand oxygenation both in healthy and obese patients. We confirm the ability of a recruiting strategy to induce alveolar recruitment accompanied by a substantial improvement of respiratory mechanics in patients undergoing laparoscopic surgery in Trendelenburg position. Our focus in partitioning respiratory mechanics between lung and chest wall revealed that the amount of pressure applied to the airway opening that was dissipated to distend the chest wall increased after the induction of pneumoperitoneum in Trendelenburg position, resulting in a decrease in both end-inspiratory and end-expiratory PL. As expected, the RM reopened collapsed lung units and subsequently PEEP kept them opened by increasing PL. However, we must point out that the physiologic method used in the current study to estimate alveolar recruitment36,37 has been shown to underestimate alveolar recruitment in some instances (see below for the limitations).43 
Interestingly, we document that the open lung strategy decreased ECW. To explain this result, we speculate that PEEP, applied after the RM, at least partially counterbalanced the diaphragm cranial shift induced by pneumoperitoneum and Trendelenburg position and that the corresponding lung expansion lead to a more physiologic chest wall shape leading to the observed reduction in ECW.
It has recently been demonstrated in patients with adult respiratory distress syndrome19,20,30,31 that customizing to PEEP and RM accommodate for individual variations in lung and chest wall mechanics, to target an “optimal” end-expiratory20,31 or end-expiratory PL9,30,38, improves lung aeration and oxygenation. In patients with adult respiratory distress syndrome, targeting either a PEEPtotLbetween 0 and 10 cm H2O and or a PplatLthreshold of 24 cm H2O has been shown to maximize oxygenation without inducing barotrauma.9,20,30 Data on PLin healthy patients submitted to general anesthesia for laparoscopic surgery are scanty. We show that monitoring PLover time would be important to better understand the complex interplay between respiratory mechanics, anesthesia, pneumoperitoneum, and Trendelenburg position. An intriguing hypothesis is that optimizing PLon individual basis during laparoscopic surgery would be a physiologically sound strategy to obtain maximal alveolar recruitment and respiratory mechanics improvement. Nevertheless, we must point out that our study was not designed to test this hypothesis, and instead, we applied a standardized open lung strategy successfully tested in a different context.34 Further studies are required to define the “optimal” end-expiratory and end-inspiratory PLtargets and to test a PL-based ventilatory strategy in this setting.
Despite the increase in intrathoracic pressure induced by the open lung strategy, patients’ hemodynamic status remained stable. Cardiac output was only transiently affected by the RM itself (it decreased by about 20% during the maneuver and returned to its baseline values immediately after, despite the application of PEEP; table 3). An important issue to explain our finding is that, by protocol, in our patients cardiac preload was optimized before the open lung strategy (see Materials and Methods).
The current study has some limitations: (1) our patients were otherwise healthy women undergoing elective surgery and therefore more studies are required to study the effects of the open lung strategy on partitioned respiratory mechanics in patients with coexisting cardiopulmonary diseases; (2) some inhomogeneity in the surgical procedures among our patients must be taken into account when interpreting our data; (3) we cannot prove that, after the RM and the subsequent PEEP application, the position of the esophageal balloon in the esophagus remained the same. Nevertheless, at least to our knowledge, in all the previous clinical studies, after the correct balloon position was checked at baseline, the esophageal balloon position was not changed thereafter because it was assumed that the application of RM and/or different PEEP levels did not influence PESmeasurements.9,20,27–31,38 Furthermore, in our study, according to the “Gattinoni method,”9,29 we did not trust on the absolute PESvalues, but instead, we used the positive tidal PESexcursions to calculate ECWand subsequently calculated PLbased on the ration between ECWand EL.29 Furthermore, for the same reason, our PLmeasurement is likely less prone than the absolute PESto be influenced by different degrees of lung atelectasis; (4) in our study, we applied a standardized open lung strategy consisting in an RM followed by PEEP 5 cm H2O. Although our data show that such strategy resulted in significant alveolar recruitment and improvement in lung mechanics, we must point out that the PEEP level applied in our study was likely inadequate to maximize alveolar recruitment. As we discussed above, tailoring PEEP to optimize alveolar recruitment is an important issue that deserves further studies; (5) to estimate open lung strategy–induced alveolar recruitment, we used the method originally proposed by Ranieri et al  .36 We point out that although this method is useful to indicate that recruitment occurred, it may fail to precisely estimate the amount of alveolar recruitment in some instances, as recently shown by Patroniti et al  .43 We acknowledge this as a limitation of our study; and (6) the FloTrac/Vigileo has not been thoroughly validated in the surgical context and furthermore is validated to monitor the trend of cardiac output rather than its absolute values.33,44 
In conclusion, we document the physiologic effects of a ventilatory strategy aiming at reversing pneumoperitoneum-induced alveolar collapse in patients with normal lung function undergoing laparoscopic surgery in Trendelenburg position. It should be emphasized that this was a physiologic study not designed to evaluate the impact of the tested open lung strategy on meaningful outcome parameters and therefore any extrapolation of our results to the clinical scenario must be conducted with caution.
References
Valenza F, Chevallard G, Fossali T, Salice V, Pizzocri M, Gattinoni L. Management of mechanical ventilation during laparoscopic surgery. Best Pract Res Clin Anaesthesiol. 2010;24:227–41
Sharma KC, Brandstetter RD, Brensilver JM, Jung LD. Cardiopulmonary physiology and pathophysiology as a consequence of laparoscopic surgery. Chest. 1996;110:810–5
Strang CM, Hachenberg T, Fredén F, Hedenstierna G. Development of atelectasis and arterial to end-tidal PCO2-difference in a porcine model of pneumoperitoneum. Br J Anaesth. 2009;103:298–303
Fahy BG, Barnas GM, Flowers JL, Nagle SE, Njoku MJ. The effects of increased abdominal pressure on lung and chest wall mechanics during laparoscopic surgery. Anesth Analg. 1995;81:744–50
Hedenstierna G, Edmark L. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31:1327–35
Hedenstierna G, Rothen HU. Atelectasis formation during anesthesia: Causes and measures to prevent it. J Clin Monit Comput. 2000;16:329–35
Perilli V, Sollazzi L, Bozza P, Modesti C, Chierichini A, Tacchino RM, Ranieri R. The effects of the reverse trendelenburg position on respiratory mechanics and blood gases in morbidly obese patients during bariatric surgery. Anesth Analg. 2000;91:1520–5
Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med. 1994;149:1327–34
Chiumello D, Carlesso E, Cadringher P, Caironi P, Valenza F, Polli F, Tallarini F, Cozzi P, Cressoni M, Colombo A, Marini JJ, Gattinoni L. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med. 2008;178:346–55
Del Sorbo L, Goffi A, Ranieri VM. Mechanical ventilation during acute lung injury: Current recommendations and new concepts. Presse Med. 2011;40(12 Pt 2):e569–83
Curley GF, Contreras M, Higgins B, O’Kane C, McAuley DF, O’Toole D, Laffey JG. Evolution of the inflammatory and fibroproliferative responses during resolution and repair after ventilator-induced lung injury in the rat. ANESTHESIOLOGY. 2011;115:1022–32
Meininger D, Byhahn C, Mierdl S, Westphal K, Zwissler B. Positive end-expiratory pressure improves arterial oxygenation during prolonged pneumoperitoneum. Acta Anaesthesiol Scand. 2005;49:778–83
Maracajà-Neto LF, Verosai N, Erosa A, Roncally AC, Giannella A, Bozza A, Lessa MA. Beneficial effects of high positive end-expiratory pressure in lung respiratory mechanics during laparoscopic surgery. Acta Anaesthesiol Scand. 2009;53:210–7
Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna G. Re-expansion of atelectasis during general anaesthesia: A computed tomography study. Br J Anaesth. 1993;71:788–95
Pelosi P, Ravagnan I, Giurati G, Panigada M, Bottino N, Tredici S, Eccher G, Gattinoni L. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. ANESTHESIOLOGY. 1999;91:1221–31
Talab HF, Zabani IA, Abdelrahman HS, Bukhari WL, Mamoun I, Ashour MA, Sadeq BB, El Sayed SI. Intraoperative ventilatory strategies for prevention of pulmonary atelectasis in obese patients undergoing laparoscopic bariatric surgery. Anesth Analg. 2009;109:1511–6
Perilli V, Sollazzi L, Modesti C, Annetta MG, Sacco T, Bocci MG, Tacchino RM, Proietti R. Comparison of positive end-expiratory pressure with reverse Trendelenburg position in morbidly obese patients undergoing bariatric surgery: Effects on hemodynamics and pulmonary gas exchange. Obes Surg. 2003;13:605–9
Grasso S, Fanelli V, Cafarelli A, Anaclerio R, Amabile M, Ancona G, Fiore T. Effects of high versus  low positive end-expiratory pressures in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;171:1002–8
Constantin JM, Grasso S, Chanques G, Aufort S, Futier E, Sebbane M, Jung B, Gallix B, Bazin JE, Rouby JJ, Jaber S. Lung morphology predicts response to recruitment maneuver in patients with acute respiratory distress syndrome. Crit Care Med. 2010;38:1108–17
Talmor D, Sarge T, Malhotra A, O’Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008;359:2095–104
Whalen FX, Gajic O, Thompson GB, Kendrick ML, Que FL, Williams BA, Joyner MJ, Hubmayr RD, Warner DO, Sprung J. The effects of the alveolar recruitment maneuver and positive end-expiratory pressure on arterial oxygenation during laparoscopic bariatric surgery. Anesth Analg. 2006;102:298–305
Valenza F, Vagginelli F, Tiby A, Francesconi S, Ronzoni G, Guglielmi M, Zappa M, Lattuada E, Gattinoni L. Effects of the beach chair position, positive end-expiratory pressure, and pneumoperitoneum on respiratory function in morbidly obese patients during anesthesia and paralysis. ANESTHESIOLOGY. 2007;107:725–32
Cakmakkaya OS, Kaya G, Altintas F, Hayirlioglu M, Ekici B. Restoration of pulmonary compliance after laparoscopic surgery using a simple alveolar recruitment maneuver. J Clin Anesth. 2009;21:422–6
Futier E, Constantin JM, Pelosi P, Chanques G, Kwiatkoskwi F, Jaber S, Bazin JE. Intraoperative recruitment maneuver reverses detrimental pneumoperitoneum-induced respiratory effects in healthy weight and obese patients undergoing laparoscopy. ANESTHESIOLOGY. 2010;113:1310–9
Park HP, Hwang JW, Kim YB, Jeon YT, Park SH, Yun MJ, Do SH. Effect of pre-emptive alveolar recruitment strategy before pneumoperitoneum on arterial oxygenation during laparoscopic hysterectomy. Anaesth Intensive Care. 2009;37:593–7
Loring SH, Mead J. Action of the diaphragm on the rib cage inferred from a force-balance analysis. J Appl Physiol. 1982;53:756–60
Polese G, Rossi A, Appendini L, Brandi G, Bates JH, Brandolese R. Partitioning of respiratory mechanics in mechanically ventilated patients. J Appl Physiol. 1991;71:2425–33
Ranieri VM, Brienza N, Santostasi S, Puntillo F, Mascia L, Vitale N, Giuliani R, Memeo V, Bruno F, Fiore T, Brienza A, Slutsky AS. Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension. Am J Respir Crit Care Med. 1997;156(4 Pt 1):1082–91
Gattinoni L, Chiumello D, Carlesso E, Valenza F. Bench-to-bedside review: Chest wall elastance in acute lung injury/acute respiratory distress syndrome patients. Crit Care. 2004;8:350–5
Grasso S, Terragni P, Birocco A, Urbino R, Del Sorbo L, Filippini C, Mascia L, Pesenti A, Zangrillo A, Gattinoni L, Ranieri VM. ECMO criteria for influenza A (H1N1)-associated ARDS: Role of transpulmonary pressure. Intensive Care Med. 2012;38:395–403
Talmor D, Sarge T, O’Donnell CR, Ritz R, Malhotra A, Lisbon A, Loring SH. Esophageal and transpulmonary pressures in acute respiratory failure. Crit Care Med. 2006;34:1389–94
Baydur A, Behrakis PK, Zin WA, Jaeger M, Milic-Emili J. A simple method for assessing the validity of the esophageal balloon technique. Am Rev Respir Dis. 1982;126:788–91
Benes J, Chytra I, Altmann P, Hluchy M, Kasal E, Svitak R, Pradl R, Stepan M. Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: Results of prospective randomized study. Crit Care. 2010;14:R118
Cinnella G, Grasso S, Natale C, Sollitto F, Cacciapaglia M, Angiolillo M, Pavone G, Mirabella L, Dambrosio M. Physiological effects of a lung-recruiting strategy applied during one-lung ventilation. Acta Anaesthesiol Scand. 2008;52:766–75
Pepe PE, Marini JJ. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: The auto-PEEP effect. Am Rev Respir Dis. 1982;126:166–70
Ranieri VM, Eissa NT, Corbeil C, Chassé M, Braidy J, Matar N, Milic-Emili J. Effects of positive end-expiratory pressure on alveolar recruitment and gas exchange in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1991;144(3 Pt 1):544–51
Ranieri VM, Giuliani R, Fiore T, Dambrosio M, Milic-Emili J. Volume-pressure curve of the respiratory system predicts effects of PEEP in ARDS: “Occlusion”versus  “costant flow” technique. Am J Resp Crit Care Med. 1994;149:9–27
Staffieri F, Stripoli T, De Monte V, Crovace A, Sacchi M, De Michele M, Trerotoli P, Terragni P, Ranieri VM, Grasso S. Physiological effects of an open lung ventilatory strategy titrated on elastance-derived end-inspiratory transpulmonary pressure: Study in a pig model*. Crit Care Med. 2012;40:2124–31
Maggiore SM, Jonson B, Richard JC, Jaber S, Lemaire F, Brochard L. Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: Comparison with the lower inflection point, oxygenation, and compliance. Am J Respir Crit Care Med. 2001;164:795–801
Dellamonica J, Lerolle N, Sargentini C, Beduneau G, Di Marco F, Mercat A, Richard JC, Diehl JL, Mancebo J, Rouby JJ, Lu Q, Bernardin G, Brochard L. PEEP-induced changes in lung volume in acute respiratory distress syndrome. Two methods to estimate alveolar recruitment. Intensive Care Med. 2011;37:1595–604
Lu Q, Vieira SR, Richecoeur J, Puybasset L, Kalfon P, Coriat P, Rouby JJ. A simple automated method for measuring pressure-volume curves during mechanical ventilation. Am J Respir Crit Care Med. 1999;159:275–82
Sprung J, Whalley DG, Falcone T, Wilks W, Navratil JE, Bourke DL. The effects of tidal volume and respiratory rate on oxygenation and respiratory mechanics during laparoscopy in morbidly obese patients. Anesth Analg. 2003;97:268–74.
Patroniti N, Bellani G, Cortinovis B, Foti G, Maggioni E, Manfio A, Pesenti A. Role of absolute lung volume to assess alveolar recruitment in acute respiratory distress syndrome patients. Crit Care Med. 2010;38:1300–7
Concha MR, Mertz VF, Cortínez LI, González KA, Butte JM. Pulse contour analysis and transesophageal echocardiography: A comparison of measurements of cardiac output during laparoscopic colon surgery. Anesth Analg. 2009;109:114–8
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
Fig. 1. Measurement of the difference (ΔEELV) between EELV during mechanical ventilation and elastic equilibrium Vr. Records of Flow, Pao, and lung volume are shown. To allow for complete lung emptying to Vr, the patient was disconnected from the ventilator circuit distally from the pneumotachograph after a prolonged end-inspiratory pause and a prolonged (15–20 s) expiration to atmospheric pressure was allowed. EELV = end-expiratory lung volume; ΔEELV = delta end-expiratory lung volume; Pao = airway opening pressure; Vr= volume of the respiratory system.
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Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black  curve) and the higher PEEP strategy (gray  curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line  indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black 
	curve) and the higher PEEP strategy (gray 
	curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line 
	indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
Fig. 2. Illustration of the method used to measure recruited volume. Quasistatic volume–pressure relationship of the respiratory system during low-flow tidal inflation, obtained during the lower positive end-expiratory pressure (PEEP) strategy (black  curve) and the higher PEEP strategy (gray  curve) were referred to the static relaxation Vrand plotted on the same volume–pressure axis. The volume at the starting point of each curve is the end-expiratory lung volume during lower and higher PEEP strategy (points A and B, respectively). The dotted line  indicates the amount of alveolar recruitment measured as the volume difference at the same pressure (20 cm H2O) between the two curves. Vr= volume of the respiratory system; Pao = airway opening pressure.
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Fig. 3. Flow diagram of the progress through the phases of the trial.
Fig. 3. Flow diagram of the progress through the phases of the trial.
Fig. 3. Flow diagram of the progress through the phases of the trial.
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Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black  curve) and after (gray  curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black 
	curve) and after (gray 
	curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
Fig. 4. Quasistatic volume–pressure relationship of the respiratory system during low-flow inflation, obtained before (black  curve) and after (gray  curve) the recruiting maneuver (RM) in a representative patient. The elastic equilibrium volume of the respiratory system was used as a reference for the volume–pressure curves. The volume–pressure curve measured after the RM is shifted upward along the volume axis, suggesting alveolar recruitment. Recruited volume, measured as the difference in lung volume for the same static Pao (15 cm H2O), is indicated by the dotted line. Please note that, on the curve pre-OLS, PEEPtot was higher than zero (4.34 cm H2O) indicating the presence of air trapping. Because in the RM external PEEP was applied, in this condition, PEEPtot is equal to PEEPi. On the other hand, the curve obtained after the RM (with a PEEP of 5 cm H2O) shows a PEEPtot of 6.79 cm H2O, with a PEEPi of 1.79 cm H2O. OLS = open lung strategy; Pao = airway opening pressure; PEEP = positive end-expiratory pressure; Vr= volume of the respiratory system.
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Table 1. Patients Demographic Characteristics
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Table 1. Patients Demographic Characteristics
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Table 2. Breathing Pattern and Gas Exchange Parameters during the Different Experimental Conditions
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Table 2. Breathing Pattern and Gas Exchange Parameters during the Different Experimental Conditions
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Table 3. Hemodynamic Parameters during the Different Experimental Conditions
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Table 3. Hemodynamic Parameters during the Different Experimental Conditions
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