The pressure-volume curve of the respiratory system is a phys-iologic method used to describe the mechanical properties ofthe respiratory system. A renewal of interest in the pressure-volume curve has recently appeared because of experimentalevidence regarding the information conveyed by the curve, abetter understanding of the pathophysiologic factors influenc-ing its interpretation, and the beneficial results of clinical trialsbased on the use of the pressure-volume curve for ventilatorymanagement of acute respiratory distress syndrome. Thisarticle discusses the techniques for tracing the pressure-volume curves and reviews the studies evaluating recentadvances concerning its use, interpretation, and clinical rele-vance in critically ill patients. Curr Opin Crit Care 2000, 6:1–10 © 2000

Lippincott Williams & Wilkins, Inc.

Department of Medical Intensive Care, University of Paris XII, Créteil, France

Correspondence to Salvatore M. Maggiore, MD, Department of MedicalIntensive Care, University of Paris XII, Henri Mondor Hospital, 51, avenue du Mal

de Lattre de Tassigny, 94010 Créteil, France; e-mail: smmaggiore@post.club-internet.fr

Current Opinion in Critical Care 2000, 6:1–10

Abbreviations

ALI acute lung injuryARDS acute respiratory distress syndromeLIP lower inflection pointP-V pressure-volumePEEP positive end-expiratory pressureUIP upper inflection pointZEEP zero end-expiratory pressure

ISSN 1070–5295 © 2000 Lippincott Williams & Wilkins, Inc.

The pressure-volume (P-V) curve of the respiratorysystem is a classic physiologic method used to describethe mechanical properties of the respiratory system. Itsinterest as pulmonary function test in the most severesituations encountered in pulmonary disease was envis-aged relatively early [1], and its use as a monitoring toolwas introduced some years after the first description ofthe acute respiratory distress syndrome (ARDS) [2].Nevertheless, describing the elastic properties of thewhole respiratory system with a single curve is aschematic approach, because the curve is influenced bynumerous factors that complicate its interpretation [3,4].Thus, for several years, despite the relative simplicity ofthe acquisition procedure, this approach was limitedessentially to the clinical research field. More recently, arenewal of interest in the P-V curve has appearedbecause of experimental evidence of the informationconveyed by the curve [5,6], the beneficial results ofclinical trials based on the use of the P-V curve forventilatory management of ARDS [7••,8] on the onehand, and the better understanding of the pathophysio-logic factors influencing its interpretation on the other[9••,10]. Moreover, the appearance of simple and, insome cases, almost automated methods contributes tothe renewed attention to the P-V curve as a diagnosticand monitoring tool available at the bedside [11]. Thisreview will focus briefly on the physiologic background,technique description, and recent advances concerningthe use and interpretation of the P-V curve in criticallyill patients.

Physiologic backgroundThe P-V relation describes the static behavior of therespiratory system and is used to get information aboutthe structures (lung, chest wall, and airways) of the system[12–14]. These mechanical structures can be described bytheir resistive and elastic properties [15]. When the lungsare principally involved in pathologic processes, the studyof the elastic properties of the respiratory system is rele-vant. To eliminate the resistive, nonelastic factorsincluded in the measured pressures, it is necessary toreach static or quasi-static conditions. Some of the differ-ences observed between P-V curves acquired under staticand dynamic conditions may depend not only on resistiveforces but also on the visco-elastic behavior of the system[16]. To study the elastic properties of the respiratorysystem, the investigator needs also to eliminate the influ-ence of the respiratory muscles. Patients are thereforeusually under deep sedation, and muscle relaxants aremost often administered [17–19••].

1

Pressure-volume curve in the critically illSalvatore M. Maggiore, MD, and Laurent Brochard, MD

In healthy humans, the P-V curve from residual volumeto total lung capacity has usually a sigmoidal shape (Fig.1). However, above the functional residual capacity (thelung volume at the end of a normal, quiet expiration), inthe volume range of tidal ventilation, the slope of thecurve is usually linear. In ARDS patients, the reductionof the number of normally ventilated alveolar unitsdecreases the range where tidal ventilation occurs,resulting in small variation of volume per unit of pres-sure change, and the entire curve is flattened (Fig. 1).

The S-shaped inspiratory P-V curve of ARDS patients canbe thought of as consisting of three segments (Fig. 2). Atlow lung volumes, the initial flat segment with very lowcompliance reflects the collapse of peripheral airways andlung units [17,20,21]. As insufflation proceeds, an inter-mediate linear segment with a steeper slope, ie, a greaterchord compliance, is observed. Compliance remainsstable over the linear portion [22]. At high pressures, butat much smaller lung volumes than in healthy subjects,the P-V curve flattens again with a fast decrease of theslope, ie, the compliance, in its third segment. The transi-tion between the first flat portion and the linear part ofthe curve is termed the lower inflection point (LIP), whichindicates the reopening of collapsed airways. In ARDSpatients, the LIP is usually supposed to represent themean critical pressure needed to reopen the previouslycollapsed airways and alveolar units, a phenomenondefined as alveolar recruitment [3,17,23,24]. Similarly, thepoint at the transition between the linear part and thethird segment, where the compliance begins to fall, istermed the upper inflection point (UIP). The UIP corre-

sponds to the volume at which overdistension of certainlung units happens and/or at which alveolar recruitmentends [22]. Then, lung ventilation occurring below the LIPor above the UIP carries the risk of generating repetitivecollapse/reopening or overdistension phenomena, both ofwhich are associated with the appearance and the progres-sion of lung injury. Hence, the segment between the LIPand the UIP may represent the zone over which tidalventilation in ARDS patients should preferentially occurin order to protect the lung from further injury [25•].

Techniques for pressure-volume curvemeasurementThe techniques used to trace the P-V curve can be staticand quasi-static, or dynamic. With the static methods(the supersyringe, the interrupter and the multipleocclusion techniques), the airway pressure is measuredduring an end-inspiratory pause, ie, at zero flow.Therefore, both the flow-resistive and inertial pressuresare eliminated. Conversely, with the dynamic, quasi-static method (the low flow technique), the resistive andthe visco-elastic phenomena are present during themeasurement of the curve; thus, for a correct evaluationof the elastic properties of the respiratory system it isessential to take these phenomena into account.Whatever the technique, the simultaneous measure-ment of the airway and esophageal pressure allows theinvestigator to trace the P-V curves of the lung and ofthe chest wall.

2 Respiratory system

Figure 1. Pressure-volume curve of respiratory system inhealthy subject and in patient with acute respiratory distresssyndrome

RV

FRC

TLC

0

Vol

ume,

L

Vital capacity

Pressure, cm H2O#50

ARDS

Healthy

Example of the pressure-volume relation of the respiratory system in a patientwith acute respiratory distress syndrome (ARDS) (bold line) compared to thepressure-volume curve of the respiratory system and to the respiratory volumesin a healthy subject (dotted line). FRC, functional residual capacity; RV, residualvolume; TLC, total lung capacity.

Figure 2. Typical inspiratory pressure-volume curve of therespiratory system in a patient with acute respiratory distresssyndrome

0

1000

500

1500

0

Vol

ume,

mL

10 20 30Pressure, cm H2O

40 50

LIP

PEEPi

UIP

Clin

Volumes are expressed relative to the end-expiratory lung volume at zero end-expiratory pressure (ZEEP). The curve consists of three segments identified bythe presence of a lower inflection point (LIP) and an upper inflection point (UIP).The intermediate linear segment has the steeper slope (interrupted line), ie, thegreater compliance (chord compliance or Clin). Note the presence of intrinsicpositive end-expiratory pressure (PEEPi), causing a rightward shift of the curve.

The supersyringe techniqueThe supersyringe technique was the first described forthe static P-V curve measurement in ARDS patients[17,26]. It consisted of an insufflation, starting from theresting volume of the respiratory system to the estimatedtotal lung capacity, accomplished with a calibratedsyringe of known volume ranging from 1.5 to 2 liters.Disconnection from the ventilator, allowing a completeexhalation to the resting volume of the respiratorysystem, was necessary before connection to the syringe.To trace the curve, the respiratory system was inflated ina stepwise manner from the starting volume, consideredto be the relaxation volume of the system, to a maximumof 40 to 50 cm H2O and then deflated [27,28].

The supersyringe technique has been largely used todescribe the modifications of the elastic properties of therespiratory system related to the severity and the stageof the ARDS [17]. Nevertheless, this method has draw-backs and limitations that have been well described[4,29]. The procedure is relatively long and the resultsmay be influenced by oxygen consumption, as well as bythe changes in gas temperature and humidity. The arti-facts and the cumbersome nature of the procedure havelimited the use of this method to the research field.

The multiple occlusion techniqueThe multiple occlusion technique uses the ventilatorcapabilities to perform volume and static pressuremeasurements, during occlusions performed with differ-ent inflated volumes delivered during constant flow-controlled ventilation [18,30–32]. After ensuring theabsence of leaks in the system, the intrinsic positiveend-expiratory pressure (PEEP) is measured during anend-expiratory pause before each studied insufflation toensure the stability of the end-expiratory volume andpressure [33–36]. The multiple end-inspiratory occlu-sions are performed using different tidal breaths startingfrom the same lung volume. The static pressure values,obtained after a few seconds pause, and the exhaledvolume after the occlusion release are read on the venti-lator monitor. The curve is then constructed by plottingthe volumes against the corresponding static pressures.By acquiring the P-V curves from zero end-expiratorypressure (ZEEP) and from PEEP together with themeasurement of the lung volume retained by PEEP, it ispossible to quantify the alveolar recruitment [18,37,38].

Compared to the supersyringe technique, the multipleocclusion method offers the advantages of not requiringspecial equipment, and the disconnection of the patientfrom the ventilator, also allowing the computation ofalveolar recruitment, when curves from PEEP andZEEP are performed. Apart from the relative complex-ity of the technique, however, the sequential insuffla-tion of the different tidal breaths can modify the lung

volume history, thus potentially influencing the shape ofthe curve. The need to ventilate at ZEEP for aprolonged period can also be poorly tolerated.

The low flow techniqueThe technical complexity and the cumbersome natureof the apparatus needed with the above describedmethods, led to an effort to simplify the measurement ofthe P-V curve. A dynamic technique using a lowconstant flow for the curve recording was proposed inthe 1970s [1,20,39]. This technique is based on theconcept that, during a passive lung inflation withconstant inspiratory flow, the rate of the airway pressurechange is inversely related to the compliance of therespiratory system [40]. However, for a correct analysisof the elastic properties of the system, it is necessary totake into account the resistive pressure. Differentauthors have found that results obtained with a suffi-ciently low flow were highly reproducible and similar tothose found with the supersyringe and multiple occlu-sion methods [37,41]. The initial part of the P-V curvewas also better visualized compared with other tech-niques [41]. Recently, Servillo et al. [11] described a newautomated low flow inflation method, performed with acommercial ventilator (Servo Ventilator 900C, Siemens-Elema AB, Sweden) controlled by a computer. Thismethod allowed a complete control of the eventspreceding the measurements as well as the calculationof the resistances related to the endotracheal tube andto the airway. After subtracting the resistive pressure tothe measured airway pressure, the authors showed agood agreement between the results of the automatedlow flow inflation method (15 L/min) and of the multi-ple occlusion technique, concerning the chord compli-ance and the LIP values. In some patients slight differ-ences existed at high lung volume (UIP), usually abovethe tidal range and thus with small practical relevance.This probably reflected the importance of the visco-elastic and/or of the pendelluft phenomena at the higherlung volume [16].

Rodriguez et al. [42] compared the multiple occlusionwith the low constant flow method performed with thestandard equipment of a commercial ventilator. Theyfound a good agreement between the P-V curves andthe linear compliance values with the two techniques,with a slight tendency to overestimate static pressurewith the low flow. The time needed for a complete P-Vcurve acquisition was 38 minutes with the multipleocclusion versus 3 minutes with the low flow technique.

The previous findings have been confirmed in a recentstudy by Lu et al. [43•]. These authors compared the P-V curves obtained with two constant flows of 3 and 9L/min with those acquired with the supersyringe andwith the multiple occlusion methods. The constant flow

Pressure-volume curve in the critically ill Maggiore and Brochard 3

technique was performed with a standard intensive careunit ventilator, allowing the simultaneous display of thecurve on the screen and the subsequent analysis usingcursors. The pulmonary and thoraco-pulmonary P-Vcurves measured with the supersyringe, the multipleocclusions, and the constant flow of 3 L/min were super-imposed. The curves obtained with 9 L/min wereslightly shifted to the right because of the flow-depen-dent resistive component, but this shift seemed to havelittle clinical relevance (the resistive airway pressureresulting from the administration of the 9 L/minconstant flow was less than 1 cm H2O). The thoracic P-V curves, as well as the values of chord compliance andLIP, were identical with all the methods.

Svantesson et al. [44] recently evaluated a similar tech-nique in healthy anesthetized subjects, using a low sinu-soidal flow to allow the exact computation of resistiveairway pressure. The inspiratory airway resistance deter-mined with the flow interruption technique and withthe sinusoidal flow was similar. Also, an excellent agree-ment between the values of chord compliance, LIP, andUIP measured with a low constant flow and with thesinusoidal flow was found. The modulated flow seemsto permit an accurate measurement of P-V curve indifferent situations, even in case of high resistances, andwithout needing a very low flow.

The automated low sinusoidal flow technique has beenused in patients with acute lung injury (ALI) by Jonsonet al. [19••] (Fig. 3). The authors found that themeasurement of inspiratory airway resistance by theflow modulation allowed an accurate determination ofthe elastic recoil pressures. Because it is a dynamicmeasurement, visco-elastic forces especially present athigh lung volumes are included in the calculated elasticpressures [45]. For this reason, a P-V curve acquiredunder dynamic conditions may give more realistic infor-mation about the pressures really exerted on peripherallung units during insufflation, and be more clinicallyrelevant than the static recordings. The control of the

lung volume history preceding the measurements,together with the automated and unbiased successiveanalysis of results, allowed to minimize methodologicalerrors.

In conclusion, the low flow technique offers manyadvantages compared with the other methods. It is easyto use at the bedside, requires much less time than themultiple occlusion technique, and can be done withoutspecial equipment other than a modern ventilator thatsupplies a low constant flow (<15 L/min) [46], withoutthe patient’s disconnection from the ventilator. Airwaypressure measurement allows the investigator to esti-mate the alveolar pressure when the resistive pressure isminimized or subtracted. Moreover, this techniqueallows P-V curves to be drawn for different ventilatorysettings and different levels of PEEP, and can be usedto quantify alveolar recruitment.

Alveolar recruitmentAlveolar recruitment, ie, the reopening of the previouslycollapsed lung units, is the cornerstone of some recentprotective ventilatory strategies in ARDS [47]. Indeed, ithas been suggested that the presence of atelectasis mayhave an injurious effect on the lung, causing the mainte-nance and the increase of lung and systemic inflammation(“atelectrauma”) [5,48••,49•]. Reversing such a deleteri-ous phenomenon and recruiting the collapsed alveoli,together with reducing the intrapulmonary shunt andimproving oxygenation, are goals of lung protection [25•].Therefore, the analysis of the effect of PEEP on alveolarrecruitment is of special concern in the management ofARDS patients. This important issue was addressed in aseries of studies by Ranieri et al. [18,37,38], who proposeda simple method to quantify alveolar recruitment by theanalysis of P-V curve. After acquiring the P-V curves atZEEP and at PEEP with the multiple occlusion tech-nique, the authors measured the end-expiratory lungvolume at PEEP above the relaxation volume. Thus, itwas possible to plot both the ZEEP and PEEP curves onthe same volume axis, referring them to the relaxation

4 Respiratory system

Schema illustrating the recording maneuvers for the acqui-sition of the pressure-volume curves at ZEEP and at PEEPwith the low sinusoidal flow technique. The flow (F),volume (V) and pressure (P) signals preceding the insuffla-tions, ie, the lung volume history, from ZEEP and fromPEEP are superimposable. After a prolonged expiration atZEEP or at PEEP, the insufflation at modulated flow allowsto trace the elastic P-V curves at ZEEP and at PEEP,respectively.EELV, end-expiratory lung volume, at PEEP; Pmax, safetymaximal pressure; RV, the resting or elastic equilibriumvolume, at ZEEP.Adapted from [19••], with permission.

0

0

2

60

30

1 F (L/s)

V (L)

P (cmH2O)

ZEEP

PEEP

EELV

Pmax

RV

Figure 3. Maneuvers for pressure-volume curve acquisition using the low sinusoidal flow technique

volume of the respiratory system that was assumed asconstant. Alveolar recruitment was then calculated as thedifference in lung volume between ZEEP and PEEP forthe same amount of airway pressure, eg, 20 cm H2O. Theauthors used this technique to analyze the effect of PEEPwith two different levels of tidal volume (small: 5–8mL/kg; high: 10–15 mL/kg) in ARDS patients [38]. Theyfound that the small tidal volume induced a decrease inlung volume compared with the high tidal volume atZEEP, whereas alveolar recruitment differed to a largeextent with the two volumes. This important studystressed the relation between PEEP and tidal volume interm of alveolar recruitment during mechanical ventilationof ARDS. Recently, Jonson et al. [19••] evaluated theamount of volume recruited by PEEP in ALI patients.The low sinusoidal flow technique was used to measurethe P-V curves at PEEP and, after a single prolonged expi-ration during which PEEP was eliminated, at ZEEP. Asignificant recruitment occurred with PEEP, ranging from205 mL at 15 cm H2O to 78 mL at 30 cm H2O, and a corre-lation was found between the LIP value and the amountof alveolar recruitment. Contrasting with standard notions,linear compliance was always lower on the curve recordedat PEEP than on the curve at ZEEP (Fig. 4). Indeed, anongoing continuous recruitment of collapsed lung unitsoccurs far above the LIP during insufflation, after a singleexpiration to ZEEP. These results have been confirmedby Hickling [9••], who analyzed the effect of PEEP on P-V curve, using a mathematical model of ARDS lungs. Inthis model, recruitment continued far above the LIP onthe steeper segment of the P-V curve from ZEEP,

whereas the P-V slope, ie, the chord compliance, of the P-V curve from PEEP was decreased, indicating optimalrecruitment of collapsed lung units. The effect of PEEPon the alveolar recruitment in ARDS patients has beenrecently analyzed in preliminary studies [50]. Comparedwith a high tidal volume, a low tidal ventilation inducedalveolar derecruitment when PEEP was set at LIP. Thealveolar derecruitment induced by the low tidal volumewas completely reversed by a re-expansion maneuver andpartially avoided by the application of the higher level ofPEEP. The same authors [51] also evaluated the amountof recruitment with decreasing PEEP levels and comparedthe recruitment directly measured from the curves, withthe simple analysis of the LIP on the P-V curve at ZEEP.It was found that recruitment was much greater above theLIP than below, although it occurred along a large range ofthe inspiratory capacity. These results show that PEEP-induced recruitment proceeds far above the LIP, while thepressure corresponding to the LIP indicates an increasebut not the beginning of alveolar recruitment. As previ-ously reported [3,52], this suggests that the ARDS lung ismade of compartments with very different critical openingpressures, while LIP may represent only the mean valueof these opening pressures [10]. The relation between theLIP and the alveolar recruitment in patients with ALI wasalso analyzed by Vieira et al. [53••]. In this well-designedstudy, the authors tried to correlate the presence and theabsence of the LIP on the P-V curve at ZEEP with differ-ent pulmonary morphology, as assessed by the computedtomography scanner, and analyzed the effect of two levelof PEEP on recruitment and overdistension in patientswith or without a LIP on the P-V curve. They found thatthe presence of LIP was associated with a diffuse andhomogeneous distribution of pathologic lung areas, with apredominance of poorly and nonaerated zones; the appli-cation of increasing PEEP levels resulted in a continuousand progressive recruitment without overdistension.Conversely, in patients without LIP there was a coexis-tence of normally aerated lung areas with nonaerated lungareas. In this last group of patients, the application of aPEEP of 10 or 15 cm H2O, while also inducing recruit-ment, resulted in overdistension, without additionalrecruitment above 10 cm H2O. The different responses toPEEP seemed to result from the different lung morphol-ogy. This study demonstrated that the simple analysis ofthe P-V curve may be helpful for understanding the patho-physiologic mechanisms underlying the lung injury, andfor finding appropriate ventilatory settings.

Role of the chest wallThe alterations of the mechanics of respiratory systemobserved in patients with ARDS are frequently consid-ered as the expression of the impaired lung mechanics[17,22]. Although chest wall impairment in acute respi-ratory failure had already been suggested [54], the influ-ence of the alterations of the chest wall mechanics on

Pressure-volume curve in the critically ill Maggiore and Brochard 5

Figure 4. Inspiratory elastic pressure-volume curves recordedfrom ZEEP and from PEEP in a patient with ARDS

0

750

500

250

1000

0

Vol

ume,

mL

10 20 30

Pressure, cm H2O40 50

PEEP

ZEEP

Vrecr

Volumes are expressed relative to the end-expiratory lung volume at ZEEP. Thechord compliance of the P-V curve from PEEP is lower than the curve fromZEEP. Recruitment of collapsed alveolar units causes an upward shift of thecurve from PEEP. Thus, the recruited lung volume (Vrecr) is expressed by thevolume difference between the P-V curve at ZEEP and the P-V curve at PEEP forthe same amount of airway pressure.ARDS, acute respiratory distress syndrome; PEEP, positive end-expiratory pres-sure; ZEEP, zero end-expiratory pressure.

the elastic properties of the respiratory system has beenemphasized recently [55–58]. The chest wall is coupled,by means of the diaphragm, to the abdominal compart-ment. Therefore, any pathologic process causing abdom-inal distension may affect directly chest wall and respira-tory mechanics.

In a recent paper, Mergoni et al. [57] investigated theimpact of chest wall mechanics on the shape of the P-Vcurve of the respiratory system, particularly concerningthe LIP, in 13 patients with acute respiratory failure.The partitioning of total respiratory system P-V curveinto the lung and the chest wall components was carriedout using the esophageal balloon technique togetherwith the supersyringe technique. The authors foundthat only in two patients was the LIP on the P-V curveof the respiratory system due exclusively to the lung,whereas in seven patients it was due only to the charac-teristics of the P-V curve of the chest wall. The applica-tion of PEEP up to 15 cm H2O reduced the LIP on allthe P-V curves but caused an improvement in oxygena-tion only in the group of patients who exhibited a LIPon the lung P-V curve. These results suggest that, insome cases, the impairment of the chest wall mayexplain the LIP seen on the P-V curve of the respiratorysystem, even if this seems to have limited clinical impli-cations (the higher LIP value found on the P-V curve ofthe chest-wall was 4.8 cm H2O). However, these resultswere not confirmed by Vieira et al. [53••] who foundthat, in eight patients with ALI, the LIP detected onthe P-V curve of the total respiratory system was presenton the lung P-V curve, and, in only two patients, also onthe chest wall P-V curve. Further studies with a greaternumber of patients are required on this aspect. Ranieri etal. [58] performed static P-V curves with partitioning ofchest wall and lung mechanics together with themeasurement of abdominal pressure to assess the rela-tive contribution of the chest wall, the lung, and theabdomen to the overall impairment of the P-V relationof respiratory system in ARDS patients. They foundthat the impairment of the elastic properties of therespiratory system varied with the underlying diseaseresponsible for ARDS. By contrast to patients withmedical ARDS, in patients with surgical ARDS, theinflating volume caused a decrease in the respiratorysystem and the lung compliance associated with alveolaroverdistension. Also, the chest wall and the abdomen P-V curves were different in the two groups. While themedical ARDS patients had normal chest wall andabdominal curves, patients with surgical ARDS hadchest wall and abdominal P-V curves shifted rightwardand flattened. This suggested that the flattening of theP-V curves of the respiratory system observed in someARDS patients may be secondary to abdominal disten-sion. A further evidence of the role of abdominal disten-sion was obtained in the five patients who required

surgical abdominal decompression. After surgery, the P-V curves of the respiratory system, chest wall andabdomen were shifted upward and leftward, indicatingan improvement in respiratory system compliance.

The role of the chest wall in the change of respiratorymechanics related to the prone position in patients withALI has been investigated by Pelosi et al. [59•]. Theend-inspiratory occlusion technique was used for themeasurement of the effective compliance (tidalvolume/end-inspiratory plateau pressure–PEEP) of therespiratory system, the lung, and the chest wall. It wasfound that the effective chest wall compliancedecreased in the prone position and the greater theeffective chest wall compliance in the supine position,the greater its decrease in the prone position. Thedecrease of effective chest wall compliance in the proneposition was also correlated with the improvement inoxygenation. The effective chest wall compliance in thesupine position then allowed to predict the oxygenationchanges in the prone position (r = 0.80, P <0.01). Usingthe same technical approach (the end-inspiratory occlu-sion technique) for the assessment of the effectivecompliance, Gattinoni et al. [60•] studied the differ-ences in respiratory mechanics between ARDS originat-ing from pulmonary (n = 12) and extrapulmonary (n = 9)disease. The effective compliance of the respiratorysystem was similar in both groups of patients, but thepulmonary ARDS group had a lower effective lungcompliance, whereas the extrapulmonary ARDSpatients showed a markedly decreased effective compli-ance of the chest wall and an increased intra-abdominalpressure. The increase of PEEP up to 15 cm H2Ocaused a further decrease of the effective lung andrespiratory system compliance with no alveolar recruit-ment in patients with pulmonary ARDS. Conversely,PEEP induced an improvement of the effective compli-ance of the lung, the chest wall and the respiratorysystem together with a consistent recruitment, in thegroup with extrapulmonary ARDS. Thus, pulmonaryARDS was characterized by lung tissue consolidationresulting in minimal PEEP-induced recruitment,whereas extrapulmonary ARDS had prevalent intersti-tial edema and alveolar collapse resulting in a betterrecruitment with PEEP. The authors concluded that thepartitioning of the respiratory mechanics may allow abetter characterization of the underlying pathology ofARDS, with a possible improvement in the clinicalmanagement. In a preliminary study, the values of thechord compliance measured on the P-V curves werecompared with the values of the effective compliance inpatients with ALI, mostly from pulmonary disease [61].It was found that the effective compliance, calculated asin Gattinoni’s paper, systematically underestimated thechord compliance (Fig. 5) and it was largely influencedby the size of tidal volume. Moreover, although PEEP

6 Respiratory system

induced a decrease of chord compliance, effectivecompliance increased with PEEP. In addition, the alve-olar recruitment calculated by the effective compliancesignificantly and systematically underestimated therecruitment measured on the P-V curves. Thissuggested that the effective compliance may not be areliable method to assess either the elastic properties ofthe respiratory system or the effect of PEEP on therecruitment, as suggested by others [62,63]. The nonlin-earity of the P-V relation thus makes difficult to use theeffective compliance at the bedside.

Clinical trialsAlthough the P-V curve was first described in the classicwork of Rahn et al. in the late 1940s [13], the relevanceof the P-V curve measurement in the clinical practicewas suggested only recently [7••,64,65••]. This was firstdue to recent, compelling data, which, in animal models,have clearly shown how mechanical ventilation itself candamage the lungs [66–72]. The detrimental effect of themechanical stretch caused by conventional ventilationwas also suggested in ARDS patients [73–76]. The firstcontrolled clinical trial of the effect of a protective venti-lation strategy based on the P-V curve of the respiratorysystem and designed to minimize ventilation-inducedlung injury was carried out by Amato et al. [7••]. In thislandmark paper, the authors randomized 53 patients tobe assigned to a conventional or protective mechanicalventilation. Conventional ventilation included a tidal

volume of 12 mL/kg and a minimal PEEP for accept-able oxygenation. In the protective strategy group, pres-sure-limited (40 cm H2O) ventilatory modes were usedwith a tidal volume of 6 mL/kg and a PEEP value set 2cm H2O above the LIP on the P-V curve measured fromZEEP. The results showed a major difference in the 28-day mortality (38% of patients in the protective ventila-tion group died, compared with 71% in the conventionalventilation group), although the difference in survival athospital discharge was not significant. A lower rate ofbarotraumatic complications (7% vs 42%) was alsoobserved in the pressure-limited group.

More recently, Ranieri et al. [65••] provided newevidence about ventilator-induced lung injury duringmechanical ventilation in ARDS. The authors carried outa randomized control trial in 37 ARDS patients assignedto receive a conventional (n = 19) or a lung-protective (n= 18) ventilation in which ventilatory settings were basedon the P-V curve of the respiratory system. The levels ofa variety of inflammatory cytokines measured in lunglavage and in the systemic circulation remained elevatedor increased at 24 and 36 hours in patients receivingconventional mechanical ventilation, whereas these para-meters progressively decreased in the lung-protectivestrategy group. These data provided direct evidence for aworsening of cellular injury (“biotrauma”) caused bymechanical ventilation, and for a possible mechanism ofmortality associated with ventilator-induced lung injuryin ARDS [77]. Furthermore, the results of this trial mayalso partly explain how mechanical ventilation may influ-ence the development of sepsis and multiple organfailure, which are the major causes of death in ARDSpatients [48••,49•,78–80].

Both of these trials emphasized the role of the P-V curveas a unique tool for a better understanding of the patho-physiology of the lung injury, as well as for the optimal,individualized ventilatory management according to theseverity of the lung disease and the elastic characteris-tics of the respiratory system, in critically ill patients.

ConclusionsRecent technical advances and insights into the mecha-nisms of respiratory system impairment, together withnew evidence of the relevance of respiratory mechanicsmeasurement, make the P-V curve of extreme interest fora physiologic approach to mechanical ventilation of thecritically ill. It is through a better understanding of theunderlying disease process and its effects on respiratorystructure and function that a significant improvement inoutcome can be expected [81]. Thus, the P-V curve, ifeasy to acquire at the bedside, can facilitate the individualtitration of ventilatory settings, taking into account theconstraints of the respiratory system, and may contributeto accomplish the goal of an improved outcome.

Pressure-volume curve in the critically ill Maggiore and Brochard 7

Figure 5. Comparison between pressure-volume curves andeffective compliance

0

800

400

1200

0

Vol

ume,

mL

10 20 30Pressure, cm H2O

40 50

}{VestVmes

Ceff

The heavy dotted line represents effective compliance (Ceff). The two pointsrepresent the values of the intrinsic positive end-expiratory pressure and of theplateau pressure, obtained after the insufflation of a given tidal volume, allowingfor the computation of the effective compliance. Because of the nonlinearity ofthe pressure-volume (P-V) relation, effective compliance systematically underesti-mates the chord compliance of the P-V curve at zero end-expiratory pressure.Similarly, the alveolar recruitment measured on the P-V curves (Vmes) is signifi-cantly underestimated when it is calculated by the effective compliance method(Vest).

References and recommended readingPapers of particular interest, published within the annual period of review,have been highlighted as:• Of special interest•• Of outstanding interest

1 Bone RC: Diagnosis of causes for acute respiratory distress by pressure-volume curves. Chest 1976, 70:740–746.

2 Ashbaugh DG, Bigelow DB, Petty TL, Levine BE: Acute respiratory distressin adults. Lancet 1967, 2:319–323.

3 Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M: Pressure-volumecurve of total respiratory system in acute respiratory failure: computedtomographic scan study. Am Rev Respir Dis 1987, 136:730–736.

4 Dall’Ava-Santucci J, Armaganidis A, Brunet F, Dhainaut JF, Chelucci GL,Monsallier JF, Lockhart A: Causes of error in respiratory pressure-volumecurves in paralyzed subjects. J Appl Physiol 1988, 64:42–49.

5 Muscedere JG, Mullen JBM, Gari K, Bryan AC, Slutsky AS: Tidal ventilationat low airway pressures can augment lung injury. Am J Respir Crit CareMed 1994, 149:1327–1334.

6 Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatorystrategies increase cytokines and c-fos m-RNA expression in an isolated ratlung model. J Clin Invest 1997, 99:944–952.

••7 Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino GdPP,

Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, TakagakiTY, Ribeiro Carvalho CR: Effect of a protective-ventilation strategy onmortality in the acute respiratory distress syndrome. N Engl J Med 1998,338:347–354.

This landmark paper showed survival benefit in patients with ARDS using a lungprotective ventilatory strategy based on the P-V curve of the respiratory system.

8 Grasso S, Puntillo F, Mascia L, Cafarelli A, Trotta T, Capobianco S, AnconaG, Bruno F, Slutsky A, Ranieri VM: Volume recruiting maneuver (VRM) inARDS patients. Intensive Care Med 1999 (suppl), 25:S111.

••9 Hickling KG: The pressure-volume curve is greatly modified by recruitment:

a mathematical model of ARDS lungs. Am J Respir Crit Care Med 1998,158:194–202.

An ARDS lung model study giving a possible explanation for the lower and theupper inflection points, and describing the effect of alveolar recruitment on theP-V curve.

10 Jonson B, Svantesson C: Elastic pressure-volume curves: what informationdo they convey? Thorax 1999, 54:82–87.

11 Servillo G, Svantesson C, Beydon L, Roupie E, Brochard L, Lemaire F,Jonson B: Pressure-volume curves in acute respiratory failure. Automatedlow flow inflation versus occlusion. Am J Respir Crit Care Med 1997,155:1629–1636.

12 Fenn WO: Mechanics of respiration. Am J Med 1951, 10:77–91.

13 Rahn H, Fenn WO, Otis AB: The pressure-volume diagram of the thoraxand the lung. Am J Physiol 1946, 146:161–178.

14 Radford E Jr: Static mechanical properties of mammalian lungs. InHandbook of Physiology, vol 1. Edited by Fenn WO. Washington, DC:American Physiological Society; 1964:429–449.

15 Rodarte JR, Rehder K: Dynamics of respiration. In Handbook of Physiology,vol 3. Edited by Macklem PT, Mead J. Bethesda: American PhysiologicalSociety; 1986:113–130.

16 Shardonofsky FR, Skaburskis M, Sato J, Zin WA, Milic-Emili J: Effects ofvolume history and vagotomy on pulmonary and chest wall mechanics incats. J Appl Physiol 1991, 71:498–508.

17 Matamis D, Lemaire F, Harf A, Brun-Buisson C, Ansquer JC, Atlan G: Totalrespiratory pressure-volume curves in the adult respiratory distresssyndrome. Chest 1984, 86:58–66.

18 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 gasexchange in patients with the adult respiratory distress syndrome. Am RevRespir Dis 1991, 144:544–551.

••19 Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L:

Pressure-volume curves and compliance in acute lung injury: evidence ofrecruitment above the lower inflection point. Am J Respir Crit Care Med1999, 159:1172–1178.

In this article, the low sinusoidal flow technique was used for acquisition of P-Vcurves in ALI patients, in order to evaluate the effect of PEEP on the alveolarrecruitment. PEEP induced a reduction of chord compliance as well as a contin-uous recruitment far above the lower inflection point.

20 Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver HB:Ventilation with positive end-expiratory pressure in acute lung disease. JClin Invest 1972, 51:2315–2323.

21 Petty TL, Silvers GW, Paul GW, Stanford RE: Abnormalities in lung elasticproperties and surfactant function in adult respiratory distress syndrome.Chest 1979, 75:571–575.

22 Roupie E, Dambrosio M, Servillo G, Mentec H, El Atrous S, Beydon L,Brun-Buisson C, Lemaire F, Brochard L: Titration of tidal volume andinduced hypercapnia in acute respiratory distress syndrome. Am J RespirCrit Care Med 1995, 152:121–128.

23 Gattinoni L, Pesenti A, Bombino M, Baglioni S, Rivolta M, Rossi F, Rossi G,Fumagalli R, Marcolin R, Mascheroni D, Torresin A: Relationships betweenlung computed tomographic density, gas exchange, and PEEP in acuterespiratory failure. Anesthesiology 1988, 69:824–832.

24 Dall’Ava-Santucci J, Armagandis A, Brunet F, Dhainault JF, Nouira S,Moriceau D, Lockhart A: Mechanical effects of PEEP in patients with adultrespiratory distress syndrome. J Appl Physiol 1990, 68:843–848.

•25 Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy

M, Marini JJ, Matthay MA, Pinsky MR, Spragg R, Suter PM: The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmaco-logic, supportive therapy, study design strategies, and issues related torecovery and remodeling. Am J Respir Crit Care Med 1998,157:1332–1347.

The actual recommendations for the management of ARDS patients introducingthe concept of the lung protection.

26 Janney CD: Super-syringe. Anesthesiology 1959, 1959:709–711.

27 Mancebo J, Calaf N, Benito S: Pulmonary compliance measurement inacute respiratory failure. Crit Care Med 1985, 13:589–591.

28 Benito S, Lemaire F: Pulmonary pressure-volume relationship in acuterespiratory distress syndrome in adults: role of positive end-expiratory pres-sure. J Crit Care 1990, 5:27–34.

29 Gattinoni L, Mascheroni D, Basilico E, Foti G, Pesenti A, Avalli L:Volume/pressure curve of total respiratory system in paralysed patients:artefacts and correction factors. Intensive Care Med 1987, 13:19–25.

30 Levy P, Similowski T, Corbeil C, Albala M, Pariente R, Milic-Emili J, JonsonB: A method for studying the static volume-pressure curves of the respira-tory system during mechanical ventilation. J Crit Care 1989, 4:83–89.

31 Sydow M, Burchardi H, Zinserling J, Ische H, Crozier TA, Weyland W:Improved determination of static compliance by automated single volumesteps in ventilated patients. Intensive Care Med 1991, 17:108–114.

32 Fernandez R, Blanch L, Artigas A: Inflation static pressure-volume curves ofthe total respiratory system determined without any instrumentation otherthan the mechanical ventilator. Intensive Care Med 1993, 19:33–38.

33 Rossi A, Gottfried SB, Zocchi L, Higgs BS, Lennox S, Calverley PMA,Begin P, Grassino A, Milic-Emili J: Measurement of static compliance of thetotal respiratory system in patients with acute respiratory failure duringmechanical ventilation: the effect of intrinsic positive end expiratory pres-sure. Am Rev Respir Dis 1985, 131:672–677.

34 Rossi A, Gottfried SB, Higgs BD, Zocchi L, Grassino A, Milic-Emili J:Respiratory mechanics in mechanically ventilated patients with respiratoryfailure. J Appl Physiol 1985, 58:1849–1858.

35 Jonson B, Nordström L, Olsson SG, Akerback D: Monitoring of ventilationand lung mechanics during automatic ventilation: a new device. BullPhysiopath Resp 1975, 11:729–743.

36 Pepe PE, Marini JJ: Occult positive end-expiratory pressure in mechanicallyventilated patients with airflow obstruction: the auto-PEEP effect. Am RevResp Dis 1982, 216:166–169.

37 Ranieri VM, Giuliani R, Fiore T, Dambrosio M, Milic-Emili J: Volume-pres-sure curve of the respiratory system predicts effects of PEEP in ARDS:“occlusion” versus “constant flow” technique. Am J Respir Crit Care Med1994, 149:19–27.

38 Ranieri VM, Mascia L, Fiore T, Bruno F, Brienza A, Giul iani R:Cardiorespiratory effects of positive end-expiratory pressure duringprogressive tidal volume reduction (permissive hypercapnia) in patientswith acute respiratory distress syndrome. Anesthesiology 1995,83:710–720.

39 Thomas L, Robert D, Gerard M: Routine use of pressure-volume loopsduring mechanical ventilation: determination of optimal combination of flow,tidal volume, and positive end-expiratory pressure. Chest 1979,75:743–744.

8 Respiratory system

40 Bates JHT, Rossi A, Milic-Emili J: Analysis of the behavior of the respiratorysystem with constant inspiratory f low. J Appl Physiol 1985,58:1840–1848.

41 Mankikian B, Lemaire F, Benito S, Brun-Buisson C, Harf A, Maillot JP,Becker J: A new device for measurement of pulmonary pressure-volumecurves in patients on mechanical ventilation. Crit Care Med 1983,11:897–901.

42 Rodriguez L, Marquer B, Mardrus P, Molenat F, Le Grand JL, Reboul M,Garrigues B: A new simple method to perform pressure-volume curvesobtained under quasi-static conditions during mechanical ventilation.Intensive Care Med 1999, 25:173–179.

•43 Lu Q, Vieira SRR, Richecoeur J, Puybasset L, Kalfon P, Coriat P, Rouby JJ:

A simple automated method for measuring pressure-volume curves duringmechanical ventilation. Am J Respir Crit Care Med 1999, 159:275–282.

This study shows the ease, safety, and reliability of the low constant flow tech-nique for the measurement of the P-V curve at the bedside.

44 Svantesson C, Drefeldt B, Sigurdsson S, Larsson A, Brochard L, Jonson B:A single computer-controlled mechanical insufflation allows determinationof the pressure-volume relationship of the respiratory system. J Clin MonitComput 1999, 15:9–16.

45 Beydon L, Svantesson C, Brauer K, Lemaire F, Jonson B: Respiratorymechanics in patients ventilated for critical lung disease. Eur Respir J1996, 9:262–273.

46 Guérin C, Blanc Q, Robert D: Automated pressure-volume curves: evaluationwith a new device [abstract]. Am J Respir Crit Care Med 1999, 159:A75.

47 Lachmann B: Open the lung and keep the lung open. Intensive Care Med1992, 18:319–321.

••48 Slutsky AS, Tremblay LN: Multiple system organ failure: is mechanical

ventilation a contributing factor? Am J Respir Crit Care Med 1998,157:1721–1725.

The authors review some clinical and experimental data supporting the hypothe-sis that mechanical ventilation may initiate and/or propagate a systemic inflam-mation response leading to multiple system organ failure.

•49 Chiumello D, Pristine G, Slutsky AS: Mechanical ventilation affects local

and systemic cytokines in an animal model of acute respiratory distresssyndrome. Am J Respir Crit Care Med 1999, 160:109–116.

This experimental study shows that a particular ventilatory strategy can affect therelease of cytokines into systemic circulation, thus potentially playing a role forthe development of multiple systemic organ failure.

50 Maggiore SM, Richard JC, Jaber S, Lefort Y, Jonson B, Mancebo J,Lemaire F, Brochard L: Alveolar derecruitment induced by low tidal volume(Vt) in ARDS patients: are PEEP or a re-expansion maneuver (RM) effective[abstract]? Am J Respir Crit Care Med 1999, 159:A458.

51 Maggiore SM, Richard JC, Jaber S, Jonson B, Lemaire F, Brochard L:Automatic PEEP titration using multiple pressure-volume (PV) curves analy-sis. Comparison with the lower inflection point (LIP)[abstract]. Am J RespirCrit Care Med 1999, 159:A75.

52 Gattinoni L, Pelosi P, Crotti S, Valenza F: Effects of positive end-expiratorypressure on regional distribution of tidal volume and recruitement in adultrespiratory distress syndrome. Am J Respir Crit Care Med 1995,151:1807–1814.

••53 Vieira SR, Puybasset L, Lu Q, Richecoeur J, Cluzel P, Coriat P, Rouby JJ: A

scanographic assessment of pulmonary morphology in acute lung injury:significance of the lower inflection point detected on the lung pressure-volume curve. Am J Respir Crit Care Med 1999, 159:1612–1623.

This study shows that the simple analysis of the P-V curve can be helpful forunderstanding the pathophysiology of lung injury, and for selecting appropriateventilatory settings.

54 Katz JA, Zinn SE, Ozanne GM, Fairley HV: Pulmonary, chest wall, and lung-thorax elastances in acute respiratory failure. Chest 1981, 80:304–311.

55 Mutoh T, Wayne J, Lamm E: Abdominal distension alters regional pleuralpressures and chest wall mechanics in pigs in vivo. J Appl Physiol 1991,70:2611–2618.

56 Pelosi P, Cereda M, Foti G, Giacomini M, Pesenti A: Alterations in lung andchest wall mechanics in patients with acute lung injury: effects of positiveend-expiratory pressure. Am J Respir Crit Care Med 1995, 152:531–537.

57 Mergoni M, Martelli A, Volpi A, Primavera S, Zuccoli P, Rossi A: Impact ofpositive end-expiratory pressure on chest wall and lung pressure volumecurve in acute respiratory failure. Am J Respir Crit Care Med 1997,156:846–854.

58 Ranieri VM, Brienza N, Santostasi S, Puntillo F, Mascia L, Vitale N, GiulianiR, Memeo V, Bruno F, Fiore T, Brienza A, Slutsky AS: Impairment of lung

and chest wall mechanics in patients with acute respiratory distresssyndrome: role of abdominal distension. Am J Respir Crit Care Med 1997,156:1082–1091.

•59 Pelosi P, Tubiolo D, Mascheroni D, Vicardi P, Crotti S, Valenza F, Gattinoni

L: Effects of the prone position on respiratory mechanics and gasexchange during acute lung injury. Am J Respir Crit Care Med 1998,157:387–393.

Prone position resulted in a reduction of the effective chest wall compliance. Thevalue of effective chest wall compliance in the supine position predicted theoxygenation changes in the prone position.

•60 Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, Lissoni A: Acute

respiratory distress syndrome caused by pulmonary and extrapulmonarydisease: different syndromes? Am J Respir Crit Care Med 1998,158:3–11.

Effective chest wall compliance allowed investigators to differentiate ARDS frompulmonary and from extrapulmonary disease and to predict the effect of PEEPon alveolar recruitment.

61 Richard JC, Maggiore SM, Carlucci A, Jaber S, Jonson B, Mancebo J,Lemaire F, Brochard L: Is effective compliance (Ceff) reliable to assess theeffect of PEEP in patients with acute lung injury (ALI) [abstract]. Am JRespir Crit Care Med 1999, 159:A75.

62 Suter PM, Fairley HB, Isenberg MD: Effect of tidal volume and positive end-expiratory pressure on compliance during mechanical ventilation. Chest1978, 73:158–162.

63 Amato MBP, Barbas CSV, Meyer EC, Grunauer MA, Magaldi RB, CarvalhoCRR: Setting the “best PEEP” in ARDS: limitations of choosing the PEEPaccording to the “best compliance” [abstract]. Am J Respir Crit Care Med1995, 151:A550.

64 Amato MBP, Barbas CSV, Medeiros DM, Schettino GdPP, Filho GL,Kairalla RA, Deheinzelin D, Morais C, Fernands EdO, Takagaki T, deCarvalho CRR: Beneficial effects of the “open lung approach” with lowdistending pressures in acute respiratory distress syndrome: a prospectiverandomized study on mechanical ventilation. Am J Respir Crit Care Med1995, 152:1835–1846.

••65 Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno

F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators inpatients with acute respiratory distress syndrome: a randomized controlledtrial. JAMA 1999, 282:54–61.

This randomized study provides new evidence about the role of ventilator-induced lung injury and supports previous experimental data about the mecha-nism of the development of multisystem organ failure during mechanical ventila-tion in ARDS patients. This study suggests a beneficial effect of a lungprotective ventilatory strategy based on the P-V curve.

66 Webb HH, Tierney DF: Experimental pulmonary edema due to intermittentpositive pressure ventilation with high inflation pressures: protection bypositive pressures end-expiratory pressure. Am Rev Respir Dis 1974,110:556–565.

67 Dreyfuss D, Basset G, Soler P, Saumon G: Intermittent positive-pressurehyperventilation with high inflation pressures produces pulmonarymicrovascular injury in rats. Am Rev Respir Dis 1985, 132:880–884.

68 Kolobow T, Moretti MP, Fumagalli R, Mascheroni D, Prato P, Chen V, JorisM: Severe impairment in lung function induced by high peak airway pres-sure during mechanical ventilation: an experimental study. Am Rev RespirDir 1987, 135:312–315.

69 Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressurepulmonary edema: respective effects of high airway pressure, high tidalvolume and positive end-expiratory pressure. Am Rev Respir Dis 1988,137:1159–1164.

70 Corbridge TC, Wood LDH, Crawford GP, Chudoba MJ, Yanos J, SznajderJI: Adverse effects of large tidal volume and low PEEP in canine acid aspi-ration. Am Rev Respir Dis 1990, 142:311–315.

71 Dreyfuss D, Saumon G: Role of tidal volume, FRC and end-inspiratoryvolume in the development of pulmonary edema following mechanical venti-lation. Am Rev Respir Dis 1993, 48:1184–1203.

72 Dreyfuss D, Soler P, Saumon G: Mechanical ventilation-induced pulmonaryedema. Interaction with previous lung alterations. Am J Respir Crit CareMed 1995, 151:1568–1575.

73 Hickling KG, Henderson SJ, Jackson R: Low mortality associated with lowvolume pressure limited ventilation with permissive hypercapnia in severeadult respiratory distress syndrome. Intensive Care Med 1990,16:372–377.

74 Hickling KG, Walsh J, Henderson SJ, Jackson R: Low mortality rate in adultrespiratory distress syndrome using low-volume, pressure-limited ventilation

Pressure-volume curve in the critically ill Maggiore and Brochard 9

with permissive hypercapnia: a prospective study. Crit Care Med 1994,22:1568–1578.

75 Gattinoni L, Pesenti A, Mascheroni D, Marcolin R, Fumagalli R, Rossi F,Iapichino G, Romagnoli G, Uziel L, Agostoni A: Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respi-ratory failure. JAMA 1986, 256:881–886.

76 Lee PC, Helsmoortel CM, Cohen SM, Fink MP: Are low tidal volumes safe?Chest 1990, 97:430–434.

77 Hudson L: Progress in understanding ventilator-induced lung injury. JAMA1999, 282:77–78.

78 Montgomery B, Stager M, Carrico J, Hudson L: Causes of mortality inpatients with the adult respiratory distress syndrome. Am Rev Respir Dis1985, 132:485–489.

79 Ferring M, Vincent JL: Is outcome from ARDS related to the severity ofrespiratory failure? Eur Respir J 1997, 10:1297–1300.

80 Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, LeeperK: Persistent elevation of inflammatory cytokines predicts a poor outcomein ARDS. Chest 1995, 107:1062–1073.

81 Hubmayr RD, Abel MD, Rehder K: Physiologic approach to mechanicalventilation. Crit Care Med 1990, 18:103–113.

10 Respiratory system