1 Département d'Anesthésie Réanimation, Hôpitaux Sud, Marseille, France. 2 Service de Réanimation, Hôpital d'Instruction des Armées Laveran, Marseille, France. 3 Service de Chirurgie Thoracique, Hôpitaux Sud, Marseille, France. 4 Service de Réanimation Médicale, Hôpitaux Sud, Marseille, France. 5 Laboratoire de Physiologie Respiratoire, UPRES EA 2201, Université de la Méditerranée, France
* Corresponding author: Réanimation Polyvalente, Hôpital Sainte-Marguerite, 13274 Marseille Cedex 9, France. E-mail: pierre.michelet{at}mail.ap-hm.fr
Accepted for publication April 12, 2005.
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Abstract |
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Methods. Twenty pigs were studied during open-chest, left OLV. Arterial blood gases and haemodynamic variables were measured at different levels of PEEP (0, 5, 10 and 15 cm H2O) applied in random order with or without iNO 4 p.p.m. Pressurevolume curves were measured at each level of PEEP.
Results. PEEP5 and PEEP10 improved /
ratio (P<0.005) and shunt (P<0.005) regardless of the presence of iNO. PEEP15 improved oxygenation and shunt only when it was associated with iNO (P<0.001). Whereas PEEP5, PEEP10 and PEEP15 were associated with a significant increase in end-expiratory volume (P<0.001), only PEEP5 and PEEP10 were associated with continuous lung volume recruitment (P<0.01). Moreover, PEEP15 induced a significant decrease in linear compliance (P<0.001).
Conclusions. In a healthy porcine lung model of OLV-RH, moderate PEEP can improve oxygenation. This effect implies both expiratory and inspiratory pulmonary recruitment. Co-administration of 4 p.p.m. iNO was ineffective.
Keywords: complications, hypoxaemia ; model, pig ; nitric oxide ; ventilation, one lung ; ventilation, possible end-expiratory pressure
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Introduction |
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The aim of this study was therefore to study the relationship between oxygenation improvement and PEEP during OLV and to test the effectiveness of the addition of iNO 4 p.p.m. in a pig model with intact lungs.
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Methods |
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General procedures
After premedication with i.m. midazolam 2 mg kg1, anaesthesia was induced and maintained by i.v. infusion of midazolam, fentanyl and pancuronium. Saline solution 7 ml1 kg1 h1 was infused continuously throughout the protocol. Animals were tracheotomized and a tracheostomy cannula (ID 8.0 mm, Mallinckrodt Medical, Hazelwood, MO, USA) was placed. Two-lung volume-controlled ventilation was first performed with a tidal volume of 10 ml kg1, a of 0.4 (oxygen and nitrogen mixture), an inspiration: expiration ratio of 1:2 and no PEEP (Servo 900C; Siemens, Elema, Sweden). Respiratory rate was adjusted to obtain arterial
between 35 and 45 mm Hg.
After stabilization under two-lung ventilation, the tracheostomy cannula was removed and a single-lumen reinforced tracheal tube with cuff (ID 7.0 mm; Rüsch manufacturing, N. Ireland, UK) was advanced through the tracheostomy orifice. It was blocked in the left main stem bronchus using fibre-optic bronchoscopy in order to exclude the right lung from ventilation. Left OLV was initiated with a tidal volume of 7 ml kg1 and with an inspiration:expiration ratio of 1:2 without PEEP. The respiratory rate was adjusted to obtain arterial not exceeding 55 mm Hg. After stabilization, animals were turned left and a right thoracotomy was performed. The right lung was exposed by placing a chest retractor between the fourth and fifth ribs. The effectiveness of right lung exclusion was checked by continuous inspection. The
was maintained at 0.4 throughout the experiment.
NO in nitrogen was used at a concentration of 450 p.p.m. (Air Liquide®; Meudon, France) and was delivered sequentially during inspiration within the inspiratory limb of the ventilator (Opti-NO; Taema, Antony, France). Intratracheal gas was sampled by continuous aspiration through the endotracheal tube (suction flow 1 litre min1) so as to allow continuous monitoring of inspiratory, expiratory and mean NO and NO2 concentrations using a chemiluminescence method (NOX 4000; Sérés, Aix-en-Provence, France). A flowmeter delivering flows within a range of 1 to 999 ml min1 (Air Liquide; Meudon) was set to achieve an inspiratory tracheal concentration of 4 p.p.m. Changes in potentially induced by the inhalation of NO were monitored continuously using an oxygen analyser (NOX 4000).
Experimental design
After the onset of baseline left OLV in PEEP 0 cm H2O, the left lung was ventilated with PEEP levels of 0, 5, 10 and 15 cm H2O (0 cm H2O=ZEEP; 5 cm H2O=PEEP5; 10 cm H2O=PEEP10; 15 cm H2O=PEEP15) in a random order with or without iNO 4 p.p.m. This resulted in eight periods of 20 min with an interval of 5 min at ZEEP between each period.
Data recording and oxygenation measurements
The primary end-point was oxygenation, as assessed by :
ratio. Arterial and mixed venous pH,
,
and
were measured using a blood gas analyser (278 blood gas system; Ciba Corning, Medfield, MA, USA). Indexed pulmonary vascular resistances (PVRI) and intrapulmonary shunt or venous admixture (Qva/Qt) were calculated using standard formula.
Data recording and pulmonary mechanics measurements
A pulmonary mechanical study of the left lung was performed in semi-static conditions at the end of the PEEP-iNO trial (i.e. after the pigs had been tested with the four levels of PEEP with and without iNO) and for each level of PEEP. In order to do this, the lung volume history was firstly standardized: the level of PEEP was reset at 0 cm H2O and, after 3 min of mechanical ventilation with unchanged Vt, a recruitment manoeuvre was performed by increasing airway pressure to 45 cm H2O for 15 s. Thereafter, a pneumotachograph (Hans Rudolf 4813, Kansas City, MO, USA) with an integral pressure transducer was connected on the tracheal tube. Volume changes were obtained by integration of the flow signal recorded on the MP100 data acquisition system (Biopac Systems, Goleta, CA, USA) and analysed using the Acknowledge software program (Biopac Systems).18 The different pressures were measured with another differential pressure transducer. Dynamic measurements of tidal volume (Vt), respiratory rate (RR), maximal inspiratory pressure (Paw), inspiratory to expiratory ratio (I/E) were recorded continuously. Intrinsic PEEP was measured at the end of a 5 s end-expiratory occlusion.
Variation in FRC was evaluated by measurement of the variation in end-expiratory lung volume (EELVv)1921 and performed at each level of PEEP. The EELVv was calculated as the difference between the volume measured during a 6 s prolonged expiration from PEEP to ZEEP and a 6 s prolonged expiration at PEEP (to subtract the volume related to intrinsic PEEP, if any).
A study of the pressurevolume (P-V) relationship was performed at each level of PEEP in order to evaluate the respective lung inspiratory recruitment and potential overdistension related to PEEP. A 2-litre syringe filled with pure oxygen was connected to the tracheal tube at the end of expiration in PEEP. The left lung was inflated in a stepwise fashion with 100 ml increments of oxygen up to a volume of 1500 ml or a maximum plateau airway pressure of 45 cm H2O.22 At the end of each increment, an end-expiratory pause of 3 s was held. Plateau airway pressure was defined as the pressure value measured at the 3rd second of pause.23 At each level of PEEP tested, P-V curves were traced, starting from the pressure point recorded during an end-expiratory occlusion and the corresponding EELVv. Inspiratory lung volume recruited by PEEP was defined as the difference between the volume measured on the curve starting from each level of PEEP and the volume measured on the corresponding curve starting from ZEEP, plotted on the same volume axis.21 Inspiratory lung recruitment was calculated at several values of plateau airway pressure ranging from 15 to 35 cm H2O, which represented the range of pressures available for all animals. Measurement of static compliance (Cpl) of the respiratory system was made in the linear segment of the P-V curve.24
Data recording and haemodynamic measurements
A 5 F catheter was inserted in the left carotid artery to monitor systemic pressures and arterial blood gases. A pulmonary artery catheter (Baxter Healthcare, Irvine, CA, USA) was inserted via the right external jugular vein to monitor mean pulmonary arterial pressure (MPAP) and cardiac index (CI) by pulmonary thermodilution. Systemic and pulmonary arterial pressures and pulmonary artery occlusion pressure (PAOP) were measured at end-expiration. Cardiac output was measured by injection of three 10 ml boluses of 5% glucose solution at 6 to 10°C via a closed system (Co-set; Baxter Healthcare) at end-inspiration. Study data correspond to the mean of three measurements.
Body surface area (BSA, m2) was calculated using the following formula: BSA=K/weight (kg)2/3, where K was 0.112 for pigs. At the end of the experiment, pigs were killed with an overdose of thiopental.
Statistical analysis
Statistical analysis was performed using the SPSS 11.0 software package (SPSS, Chicago, IL, USA) and distribution of data was confirmed. Results were expressed as mean (SD). Changes in ventilatory settings were assessed with paired Student's t-tests. Two-way repeated measures analysis of variance (ANOVA) was used to evaluate the effects of PEEP, iNO and their interaction. The influence of the order of PEEP levels was assessed by a two-way ANOVA taking into account PEEP level and order. Tukey's post hoc test was used to compare times and groups when there was statistical significance. For all tests, a P-value equal to or less than 0.05 was considered statistically significant.
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Results |
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There was a significant effect of PEEP on (P<0.001, ANOVA). Post hoc analysis revealed that this decrease in
was related to PEEP5 and PEEP10 (P<0.001 for each, post hoc Tukey test; Table 2). Statistical analysis did not show an effect of iNO or interaction between PEEP and iNO on
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Similarly, there was a statistical influence of PEEP on lung inspiratory volumes (P<0.001, ANOVA; Fig. 2).
Effects of PEEP levels and iNO on haemodynamic parameters
ANOVA showed that PEEP modified cardiac index (P<0.01), which significantly decreased at PEEP10 and PEEP15 (P<0.05, post hoc Tukey test; Table 2) regardless of the presence of iNO. In addition, ANOVA showed that both PEEP (P<0.05; Table 3) and iNO (P<0.02; Table 3) modified MPAP, which decreased with PEEP5 (P<0.05, post hoc Tukey test; Table 2) and with iNO regardless of the presence of PEEP for ZEEP, PEEP10 and PEEP15 (P<0.02, post hoc Tukey test; Table 2). Similarly, the PVRI was influenced both by PEEP (P<0.05, ANOVA; Table 2) and by iNO (P<0.01, ANOVA; Table 2). Whereas PEEP5 was associated with a decrease in PVRI (P<0.05, post hoc Tukey test; Table 2), PEEP15 induced a significant increase compared with PEEP5 (P<0.05, post hoc Tukey test). iNO induced a decrease in PVRI only at ZEEP and PEEP15 (P<0.02, post hoc Tukey test; Table 2). Mean arterial pressure and heart rate were not affected by PEEP or iNO.
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Discussion |
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Our results are in agreement with previous data showing a beneficial effect of PEEP on oxygenation during OLV.2 6 25 26 The PEEP-related increase in EELV reported in the current study suggests that an increase in FRC could participate in the improvement in oxygenation. This mechanism has already been suggested in patients by Slinger and colleagues,6 who demonstrated that PEEP5 increased oxygenation in the case of a PEEP-related increase in plateau end-expiratory pressure towards the lower inflection point of the static compliance curve. A PEEP-related increase in FRC was also described by Cohen and Eisenkraft1 to explain the oxygenation improvement of several hypoxaemic patients ventilated with PEEP10. In addition, and as we hypothesized, we demonstrate here that the increase in oxygenation was associated with a significant lung inspiratory recruitment. Whereas the increase in PEEP leads to a continuous increase in EELV, only PEEP5 and PEEP10 induced a significant increase in oxygenation and continuous inspiratory lung recruitment. Conversely, PEEP15 was associated with the higher level of EELV but did not further improve oxygenation, whereas it induced limited lung inspiratory recruitment. Therefore, the observation that oxygenation improved only at PEEP levels associated with lung inspiratory recruitment suggests that inspiratory rather than expiratory recruitment is involved in the oxygenation increase. To our knowledge, the effect of lung inspiratory recruitment on oxygenation improvement related to PEEP has not been reported before in this specific setting. Indeed, in injured lungs, the beneficial effect of PEEP on oxygenation has been related both to an increase in FRC and to lung inspiratory recruitment above the FRC.14 15 23 This phenomenon was explained by an increase in airway and alveolar collapse during expiration in ZEEP, with higher pressure needed to reopen the collapsed areas above FRC during the inspiratory phase.14 15 Conversely, the preservation of FRC in PEEP promotes inspiratory recruitment for the same tidal volume.14 15 23 However, this mechanism is commonly judged as secondary to the PEEP-induced increase in FRC during OLV.2 6 25
The absence of further improvement in oxygenation with PEEP15 could be explained by overdistension, which was seen, as in previous reports, as the increase in plateau pressure and associated with a decrease in linear compliance and a dramatic increase in airway pressures.14 2729 As already demonstrated during two-lung ventilation,27 high levels of PEEP might lead to redistribution of pulmonary blood flow from overdistended lung units to lung areas with a low ventilation:perfusion ratio or pulmonary shunt, resulting in a worsening in oxygenation and pulmonary shunting. Although this mechanism has been reported to explain the discrepancies between studies related to the efficiency of PEEP on oxygenation during OLV,6 in our study the overdistension was limited to PEEP15. The occurrence of this adverse effect only for the higher level of PEEP could result from the tidal volumes used. Our ventilatory strategy included a moderate reduction of Vt at 7 ml kg1 after pulmonary exclusion that has been demonstrated previously to prevent PEEP-related overdistension in an experimental model of OLV in healthy lung.30 Conversely, the traditional OLV procedure includes the use of tidal volumes almost as high as during two-lung ventilation (i.e. 1012 ml kg1).31 In this setting, the application of external PEEP can promote rapid overdistension during the inspiratory phase with a consequent ineffectiveness PEEP on oxygenation.30 32 These results led us to consider that a moderate reduction in tidal volume associated with PEEP ranging from 5 to 10 cm H2O could be the better compromise to optimize oxygenation during OLV in healthy lung. Nevertheless, whereas our study protocol did not include different levels of tidal volume, this interpretation is limited and requires further investigation to test the respective influences of tidal volume and PEEP on oxygenation and lung mechanics.
Recent experimental data suggest that 4 p.p.m. iNO could be efficient for oxygenation during OLV, notably by diverting blood flow from non-ventilated towards ventilated lung.9 Furthermore, several studies reported that PEEP-induced alveolar recruitment could be considered a factor determining iNO-induced improvement in arterial oxygenation.16 17 Indeed, iNO could optimize the perfusion of newly recruited areas and reduce the ventilationperfusion mismatch.17 Our results do not support this hypothesis in the setting of OLV, since at PEEP5 and PEEP10 iNO did not affect oxygenation, while these levels of PEEP were associated with significant pulmonary recruitment. Moreover, the addition of iNO to PEEP5 and PEEP10 did not result in a reduction in PVRI compared with PEEP alone. Conversely, the addition of iNO to ZEEP and PEEP15 resulted in a significant reduction in PVRI associated with oxygenation improvement for PEEP15. Although these results were unexpected regarding our study hypothesis, several factors could explain these observations. For PEEP5 and PEEP10, the decrease in hypoxic pulmonary vasoconstriction was probably sufficient to optimize blood flow in the recruited areas, so iNO could not overact. In agreement, iNO-induced reduction in PVRI and improvement in has been correlated with the level of hypoxic pulmonary vasoconstriction.16 In addition, the increase in PVRI related to PEEP-induced overdistension25 could have also interacted. This mechanism could explain the lack of PVRI decrease at PEEP10 despite a similar oxygenation improvement compared with PEEP5 and the significant increase in PVRI at PEEP15 compared with PEEP5 and PEEP10. Interestingly, the higher level of PVRI at PEEP15 was associated with an effect of iNO on PVRI and oxygenation. As these effects were not associated with a modification in cardiac index, one can presume that the effect of iNO on oxygenation was related to a correction of ventilationperfusion mismatching induced by overdistension.
Study limitations
During OLV, oxygenation depends on FRC variation and pulmonary recruitment, but also on haemodynamic effects. Our work did not include measurements of the distribution of pulmonary perfusion. Therefore, we could not determine the ventilationperfusion distribution. Moreover, the goal of mechanical ventilation during OLV is a compromise between the need for alveolar recruitment and the risk of excessive alveolar overdistension. The absence of an evaluation of the distribution of pulmonary recruitment and hyperinflation during the respiratory cycle represents another limitation of our study and should be assessed in further studies, notably by computed tomography.33 34
Conclusion
Our results show that, during OLV-related hypoxaemia in a healthy lung model, increasing PEEP should have a beneficial effect on oxygenation, based on its effect on lung inspiratory recruitment and its ability to preserve EELV. Cases of PEEP ineffectiveness during OLV could be related to PEEP-induced overdistension that could probably be limited by reducing the Vt. Whereas the association with iNO did not result in oxygenation improvement in the case of PEEP-related effectiveness, this agent could be useful when overdistension occurs. It is essential to demonstrate the clinical efficiency of such a strategy in clinical studies.
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References |
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2 Inomata S, Nishikawa T, Saito S, Kihara S. Best PEEP during one-lung ventilation. Br J Anaesth 1997; 78: 7546
3 Slinger P, Suissa S, Triolet W. Predicting arterial oxygenation during one lung anaesthesia. Can J Anaesth 1992; 39: 10305[Abstract]
4 Watanabe S, Noguchi E, Yamada S, Hamada N, Kano T. Sequential changes of arterial oxygen tension in the supine position during one-lung ventilation. Anesth Analg 2000; 90: 2834
5 Moutafis M, Liu N, Dalibon N, et al. The effects on inhaled nitric oxide and its combination with intravenous almitrine on during one-lung ventilation in patients undergoing thoracoscopic procedures. Anesth Analg 1997; 85: 11305[Abstract]
6 Slinger P, Kruger M, McRae K, Winton T. Relation of the static compliance curve and positive end-expiratory pressure to oxygenation during one-lung ventilation. Anesthesiology 2001; 95: 1096102[ISI][Medline]
7 Fujiwara M, Abe K, Mashimo T. The effect of positive end-expiratory pressure and continuous positive airway pressure on the oxygenation and shunt fraction during one-lung ventilation with propofol anesthesia. J Clin Anesth 2001; 13: 4737[CrossRef][ISI][Medline]
8 Groh J, Kuhnle G, Ney L, Sckell A, Goetz A. Effects of isoflurane on regional pulmonary blood flow during one-lung ventilation. Br J Anaesth 1995; 74: 20916
9 Sticher J, Scholz S, Böning O, et al. Small-dose nitric oxide improves oxygenation during one-lung ventilation: an experimental study. Anesth Analg 2002; 95: 155762
10 Tokics L, Hedenstierna G, Strandberg A, Brismar B, Lundquist H. Lung collapse and gas exchange during general anesthesia: effects of spontaneous breathing, muscle paralysis, and positive end-expiratory pressure. Anesthesiology 1987; 66: 15767[ISI][Medline]
11 Pelosi P, Ravagnan I, Giurati G, et al. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology 1999; 91: 122131[ISI][Medline]
12 Hedenstierna G, Rothen HU. Atelectasis formation during anesthesia: causes and measures to prevent it. J Clin Monit Comput 2000; 16: 32935[CrossRef][ISI][Medline]
13 Neumann P, Rothen H, Berglund J, Valtysson J, Magnusson A, Hedenstierna G. Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesth Scand 1999; 43: 295301[CrossRef][ISI][Medline]
14 Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L. Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med 1999; 159: 11728
15 Gattinoni L, Pelosi P, Crotti S, Valenza F. Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. Am J Respir Crit Care Med 1995; 151: 180714[Abstract]
16 Puybasset L, Rouby J, Mourgeon E, et al. Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure. Am J Respir Crit Care Med 1995; 152: 31828[Abstract]
17 Johannigman J, Davis K, Campbell R, Luchette F, Frame S, Branson R. Positive end-expiratory pressure and response to inhaled nitric oxide: changing nonresponders to responders. Surgery 2000; 127: 3904[CrossRef][ISI][Medline]
18 Gainnier M, Michelet P, Thirion X, Arnal J, Sainty J, Papazian L. Prone position and positive end expiratory pressure in acute respiratory distress syndrome. Crit Care Med 2003; 31: 271926[CrossRef][ISI][Medline]
19 Riou Y, Storme L, Leclerc F, Neve V, Logier R, Lequien P. Comparison of four methods for measuring elevation of FRC in mechanically ventilated infants. Intensive Care Med 1999; 25: 111825[CrossRef][ISI][Medline]
20 Richard J, Maggiore S, Jonson B, Mancebo J, Lemaire F, Brochard L. Influence of tidal volume on alveolar recruitment. Respective role of PEEP and a recruitment maneuver. Am J Respir Crit Care Med 2001; 163: 160913
21 Richard J, Brochard L, Vandelet P, et al. Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury. Crit Care Med 2003; 31: 8992[CrossRef][ISI][Medline]
22 Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure: computed tomographic scan study. Am Rev Respir Dis 1987; 136: 7306[ISI][Medline]
23 Dambrosio M, Roupie E, Mollet J, et al. Effects of positive end-expiratory pressure and different tidal volumes on alveolar recruitment and hyperinflation. Anesthesiology 1997; 87: 495503[ISI][Medline]
24 Maggiore S, Jonson B, Richard J, Jaber S, Lemaire F, Brochard L. Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury. Am J Respir Crit Care Med 2001; 164: 795801
25 Benumof J. Conventional and differential lung management of one-lung ventilation. In: Anesthesia for Thoracic Surgery, 2nd edn. Philadelphia: Saunders, 1994; 41324
26 Eisenkraft J, Cohen E, Neustein S. Anesthesia for thoracic surgery. In: Barash P, Cullen B, Stoelting R, eds. Clinical Anesthesia, 3rd edn. Philadelphia: Lippincott-Raven, 1997; 77984
27 Ranieri V, Mascia L, Fiore T, Bruno F, Brienza A, Giuliani R. Cardiorespiratory effects of positive end-expiratory pressure during progressive tidal volume reduction (permissive hypercapnia) in patients with acute respiratory distress syndrome. Anesthesiology 1995; 83: 71020[CrossRef][ISI][Medline]
28 Dambrosio M, Roupie E, Mollet JJ, et al. Effects of positive end-expiratory pressure and different tidal volumes on alveolar recruitment and hyperinflation. Anesthesiology 1997; 87: 495503[ISI][Medline]
29 Lu Q, Rouby JJ. Measurement of pressure-volume curves in patients on mechanical ventilation: methods and significance. Crit Care 2000; 4: 91100[CrossRef][ISI][Medline]
30 Gama de Abreu M, Heintz M, Heller A, Széchenyi R, Albrecht D, Koch T. One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model. Anesth Analg 2003; 96: 2208
31 Brodsky JB, Fitzmaurice B. Modern anesthetic techniques for thoracic operations. World J Surg 2001; 25: 1626[CrossRef][ISI][Medline]
32 Katz J, Laverne R, Fairley H, Thomas A. Pulmonary oxygen exchange during endobronchial anesthesia: effects of tidal volume and PEEP. Anesthesiology 1982; 56: 16471[ISI][Medline]
33 Vieira SR, Puybasset L, Richecoeur J, et al. A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension. Am J Respir Crit Care Med 1998; 158: 15717
34 Victorino JA, Borges JB, Okamoto VN, et al. Imbalances in regional lung ventilation: a validation study on electrical impedance tomography. Am J Respir Crit Care Med 2004; 169: 791800