Serveur d'exploration autour du libre accès en Belgique

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment

Identifieur interne : 000288 ( Pmc/Corpus ); précédent : 000287; suivant : 000289

Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment

Auteurs : Colin Cordemans ; Inneke De Laet ; Niels Van Regenmortel ; Karen Schoonheydt ; Hilde Dits ; Greg Martin ; Wolfgang Huber ; Manu Lng Malbrain

Source :

RBID : PMC:3390296

Abstract

Introduction

Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI).

Methods

In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix®) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality.

Results

At baseline, no significant intergroup differences were found, except for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7, p = 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg, p = 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg, p = 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg, p = 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL, p < 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days, p = 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034).

Conclusion

PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.


Url:
DOI: 10.1186/2110-5820-2-S1-S15
PubMed: 22873416
PubMed Central: 3390296

Links to Exploration step

PMC:3390296

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment</title>
<author>
<name sortKey="Cordemans, Colin" sort="Cordemans, Colin" uniqKey="Cordemans C" first="Colin" last="Cordemans">Colin Cordemans</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="De Laet, Inneke" sort="De Laet, Inneke" uniqKey="De Laet I" first="Inneke" last="De Laet">Inneke De Laet</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Regenmortel, Niels" sort="Van Regenmortel, Niels" uniqKey="Van Regenmortel N" first="Niels" last="Van Regenmortel">Niels Van Regenmortel</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Schoonheydt, Karen" sort="Schoonheydt, Karen" uniqKey="Schoonheydt K" first="Karen" last="Schoonheydt">Karen Schoonheydt</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dits, Hilde" sort="Dits, Hilde" uniqKey="Dits H" first="Hilde" last="Dits">Hilde Dits</name>
</author>
<author>
<name sortKey="Martin, Greg" sort="Martin, Greg" uniqKey="Martin G" first="Greg" last="Martin">Greg Martin</name>
<affiliation>
<nlm:aff id="I2">Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huber, Wolfgang" sort="Huber, Wolfgang" uniqKey="Huber W" first="Wolfgang" last="Huber">Wolfgang Huber</name>
<affiliation>
<nlm:aff id="I3">II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Malbrain, Manu Lng" sort="Malbrain, Manu Lng" uniqKey="Malbrain M" first="Manu Lng" last="Malbrain">Manu Lng Malbrain</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">22873416</idno>
<idno type="pmc">3390296</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390296</idno>
<idno type="RBID">PMC:3390296</idno>
<idno type="doi">10.1186/2110-5820-2-S1-S15</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000288</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment</title>
<author>
<name sortKey="Cordemans, Colin" sort="Cordemans, Colin" uniqKey="Cordemans C" first="Colin" last="Cordemans">Colin Cordemans</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="De Laet, Inneke" sort="De Laet, Inneke" uniqKey="De Laet I" first="Inneke" last="De Laet">Inneke De Laet</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Regenmortel, Niels" sort="Van Regenmortel, Niels" uniqKey="Van Regenmortel N" first="Niels" last="Van Regenmortel">Niels Van Regenmortel</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Schoonheydt, Karen" sort="Schoonheydt, Karen" uniqKey="Schoonheydt K" first="Karen" last="Schoonheydt">Karen Schoonheydt</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dits, Hilde" sort="Dits, Hilde" uniqKey="Dits H" first="Hilde" last="Dits">Hilde Dits</name>
</author>
<author>
<name sortKey="Martin, Greg" sort="Martin, Greg" uniqKey="Martin G" first="Greg" last="Martin">Greg Martin</name>
<affiliation>
<nlm:aff id="I2">Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huber, Wolfgang" sort="Huber, Wolfgang" uniqKey="Huber W" first="Wolfgang" last="Huber">Wolfgang Huber</name>
<affiliation>
<nlm:aff id="I3">II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Malbrain, Manu Lng" sort="Malbrain, Manu Lng" uniqKey="Malbrain M" first="Manu Lng" last="Malbrain">Manu Lng Malbrain</name>
<affiliation>
<nlm:aff id="I1">Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Annals of Intensive Care</title>
<idno type="eISSN">2110-5820</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Introduction</title>
<p>Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI).</p>
</sec>
<sec>
<title>Methods</title>
<p>In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix
<sup>®</sup>
) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality.</p>
</sec>
<sec>
<title>Results</title>
<p>At baseline, no significant intergroup differences were found, except for lower PaO
<sub>2</sub>
/FIO
<sub>2 </sub>
and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7,
<italic>p </italic>
= 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg,
<italic>p </italic>
= 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg,
<italic>p </italic>
= 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg,
<italic>p </italic>
= 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL,
<italic>p </italic>
< 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days,
<italic>p </italic>
= 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%,
<italic>p </italic>
= 0.034).</p>
</sec>
<sec>
<title>Conclusion</title>
<p>PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.</p>
</sec>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Murphy, Cv" uniqKey="Murphy C">CV Murphy</name>
</author>
<author>
<name sortKey="Schramm, Ge" uniqKey="Schramm G">GE Schramm</name>
</author>
<author>
<name sortKey="Doherty, Ja" uniqKey="Doherty J">JA Doherty</name>
</author>
<author>
<name sortKey="Reichley, Rm" uniqKey="Reichley R">RM Reichley</name>
</author>
<author>
<name sortKey="Gajic, O" uniqKey="Gajic O">O Gajic</name>
</author>
<author>
<name sortKey="Afessa, B" uniqKey="Afessa B">B Afessa</name>
</author>
<author>
<name sortKey="Micek, St" uniqKey="Micek S">ST Micek</name>
</author>
<author>
<name sortKey="Kollef, Mh" uniqKey="Kollef M">MH Kollef</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rivers, Ep" uniqKey="Rivers E">EP Rivers</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Prowle, Jr" uniqKey="Prowle J">JR Prowle</name>
</author>
<author>
<name sortKey="Echeverri, Je" uniqKey="Echeverri J">JE Echeverri</name>
</author>
<author>
<name sortKey="Ligabo, Ev" uniqKey="Ligabo E">EV Ligabo</name>
</author>
<author>
<name sortKey="Ronco, C" uniqKey="Ronco C">C Ronco</name>
</author>
<author>
<name sortKey="Bellomo, R" uniqKey="Bellomo R">R Bellomo</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schrier, Rw" uniqKey="Schrier R">RW Schrier</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bagshaw, Sm" uniqKey="Bagshaw S">SM Bagshaw</name>
</author>
<author>
<name sortKey="Brophy, Pd" uniqKey="Brophy P">PD Brophy</name>
</author>
<author>
<name sortKey="Cruz, D" uniqKey="Cruz D">D Cruz</name>
</author>
<author>
<name sortKey="Ronco, C" uniqKey="Ronco C">C Ronco</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rivers, E" uniqKey="Rivers E">E Rivers</name>
</author>
<author>
<name sortKey="Nguyen, B" uniqKey="Nguyen B">B Nguyen</name>
</author>
<author>
<name sortKey="Havstad, S" uniqKey="Havstad S">S Havstad</name>
</author>
<author>
<name sortKey="Ressler, J" uniqKey="Ressler J">J Ressler</name>
</author>
<author>
<name sortKey="Muzzin, A" uniqKey="Muzzin A">A Muzzin</name>
</author>
<author>
<name sortKey="Knoblich, B" uniqKey="Knoblich B">B Knoblich</name>
</author>
<author>
<name sortKey="Peterson, E" uniqKey="Peterson E">E Peterson</name>
</author>
<author>
<name sortKey="Tomlanovich, M" uniqKey="Tomlanovich M">M Tomlanovich</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sakr, Y" uniqKey="Sakr Y">Y Sakr</name>
</author>
<author>
<name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name>
</author>
<author>
<name sortKey="Reinhart, K" uniqKey="Reinhart K">K Reinhart</name>
</author>
<author>
<name sortKey="Groeneveld, J" uniqKey="Groeneveld J">J Groeneveld</name>
</author>
<author>
<name sortKey="Michalopoulos, A" uniqKey="Michalopoulos A">A Michalopoulos</name>
</author>
<author>
<name sortKey="Sprung, Cl" uniqKey="Sprung C">CL Sprung</name>
</author>
<author>
<name sortKey="Artigas, A" uniqKey="Artigas A">A Artigas</name>
</author>
<author>
<name sortKey="Ranieri, Vm" uniqKey="Ranieri V">VM Ranieri</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
<author>
<name sortKey="Cheatham, Ml" uniqKey="Cheatham M">ML Cheatham</name>
</author>
<author>
<name sortKey="Kirkpatrick, A" uniqKey="Kirkpatrick A">A Kirkpatrick</name>
</author>
<author>
<name sortKey="Sugrue, M" uniqKey="Sugrue M">M Sugrue</name>
</author>
<author>
<name sortKey="Parr, M" uniqKey="Parr M">M Parr</name>
</author>
<author>
<name sortKey="De Waele, J" uniqKey="De Waele J">J De Waele</name>
</author>
<author>
<name sortKey="Balogh, Z" uniqKey="Balogh Z">Z Balogh</name>
</author>
<author>
<name sortKey="Leppaniemi, A" uniqKey="Leppaniemi A">A Leppaniemi</name>
</author>
<author>
<name sortKey="Olvera, C" uniqKey="Olvera C">C Olvera</name>
</author>
<author>
<name sortKey="Ivatury, R" uniqKey="Ivatury R">R Ivatury</name>
</author>
<author>
<name sortKey="D Amours, S" uniqKey="D Amours S">S D'Amours</name>
</author>
<author>
<name sortKey="Wendon, J" uniqKey="Wendon J">J Wendon</name>
</author>
<author>
<name sortKey="Hillman, K" uniqKey="Hillman K">K Hillman</name>
</author>
<author>
<name sortKey="Johansson, K" uniqKey="Johansson K">K Johansson</name>
</author>
<author>
<name sortKey="Kolkman, K" uniqKey="Kolkman K">K Kolkman</name>
</author>
<author>
<name sortKey="Wilmer, A" uniqKey="Wilmer A">A Wilmer</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name>
</author>
<author>
<name sortKey="Sakr, Y" uniqKey="Sakr Y">Y Sakr</name>
</author>
<author>
<name sortKey="Sprung, Cl" uniqKey="Sprung C">CL Sprung</name>
</author>
<author>
<name sortKey="Ranieri, Vm" uniqKey="Ranieri V">VM Ranieri</name>
</author>
<author>
<name sortKey="Reinhart, K" uniqKey="Reinhart K">K Reinhart</name>
</author>
<author>
<name sortKey="Gerlach, H" uniqKey="Gerlach H">H Gerlach</name>
</author>
<author>
<name sortKey="Moreno, R" uniqKey="Moreno R">R Moreno</name>
</author>
<author>
<name sortKey="Carlet, J" uniqKey="Carlet J">J Carlet</name>
</author>
<author>
<name sortKey="Le Gall, Jr" uniqKey="Le Gall J">JR Le Gall</name>
</author>
<author>
<name sortKey="Payen, D" uniqKey="Payen D">D Payen</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rosenberg, Al" uniqKey="Rosenberg A">AL Rosenberg</name>
</author>
<author>
<name sortKey="Dechert, Re" uniqKey="Dechert R">RE Dechert</name>
</author>
<author>
<name sortKey="Park, Pk" uniqKey="Park P">PK Park</name>
</author>
<author>
<name sortKey="Bartlett, Rh" uniqKey="Bartlett R">RH Bartlett</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Payen, D" uniqKey="Payen D">D Payen</name>
</author>
<author>
<name sortKey="De Pont, Ac" uniqKey="De Pont A">AC de Pont</name>
</author>
<author>
<name sortKey="Sakr, Y" uniqKey="Sakr Y">Y Sakr</name>
</author>
<author>
<name sortKey="Spies, C" uniqKey="Spies C">C Spies</name>
</author>
<author>
<name sortKey="Reinhart, K" uniqKey="Reinhart K">K Reinhart</name>
</author>
<author>
<name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wiedemann, Hp" uniqKey="Wiedemann H">HP Wiedemann</name>
</author>
<author>
<name sortKey="Wheeler, Ap" uniqKey="Wheeler A">AP Wheeler</name>
</author>
<author>
<name sortKey="Bernard, Gr" uniqKey="Bernard G">GR Bernard</name>
</author>
<author>
<name sortKey="Thompson, Bt" uniqKey="Thompson B">BT Thompson</name>
</author>
<author>
<name sortKey="Hayden, D" uniqKey="Hayden D">D Hayden</name>
</author>
<author>
<name sortKey="Deboisblanc, B" uniqKey="Deboisblanc B">B deBoisblanc</name>
</author>
<author>
<name sortKey="Connors, Af" uniqKey="Connors A">AF Connors</name>
</author>
<author>
<name sortKey="Hite, Rd" uniqKey="Hite R">RD Hite</name>
</author>
<author>
<name sortKey="Harabin, Al" uniqKey="Harabin A">AL Harabin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Alsous, F" uniqKey="Alsous F">F Alsous</name>
</author>
<author>
<name sortKey="Khamiees, M" uniqKey="Khamiees M">M Khamiees</name>
</author>
<author>
<name sortKey="Degirolamo, A" uniqKey="Degirolamo A">A DeGirolamo</name>
</author>
<author>
<name sortKey="Amoateng Adjepong, Y" uniqKey="Amoateng Adjepong Y">Y Amoateng-Adjepong</name>
</author>
<author>
<name sortKey="Manthous, Ca" uniqKey="Manthous C">CA Manthous</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Berkowitz, Dm" uniqKey="Berkowitz D">DM Berkowitz</name>
</author>
<author>
<name sortKey="Danai, Pa" uniqKey="Danai P">PA Danai</name>
</author>
<author>
<name sortKey="Eaton, S" uniqKey="Eaton S">S Eaton</name>
</author>
<author>
<name sortKey="Moss, M" uniqKey="Moss M">M Moss</name>
</author>
<author>
<name sortKey="Martin, Gs" uniqKey="Martin G">GS Martin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kuzkov, Vv" uniqKey="Kuzkov V">VV Kuzkov</name>
</author>
<author>
<name sortKey="Kirov, My" uniqKey="Kirov M">MY Kirov</name>
</author>
<author>
<name sortKey="Sovershaev, Ma" uniqKey="Sovershaev M">MA Sovershaev</name>
</author>
<author>
<name sortKey="Kuklin, Vn" uniqKey="Kuklin V">VN Kuklin</name>
</author>
<author>
<name sortKey="Suborov, Ev" uniqKey="Suborov E">EV Suborov</name>
</author>
<author>
<name sortKey="Waerhaug, K" uniqKey="Waerhaug K">K Waerhaug</name>
</author>
<author>
<name sortKey="Bjertnaes, Lj" uniqKey="Bjertnaes L">LJ Bjertnaes</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Phillips, Cr" uniqKey="Phillips C">CR Phillips</name>
</author>
<author>
<name sortKey="Chesnutt, Ms" uniqKey="Chesnutt M">MS Chesnutt</name>
</author>
<author>
<name sortKey="Smith, Sm" uniqKey="Smith S">SM Smith</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sakka, Sg" uniqKey="Sakka S">SG Sakka</name>
</author>
<author>
<name sortKey="Ruhl, Cc" uniqKey="Ruhl C">CC Ruhl</name>
</author>
<author>
<name sortKey="Pfeiffer, Uj" uniqKey="Pfeiffer U">UJ Pfeiffer</name>
</author>
<author>
<name sortKey="Beale, R" uniqKey="Beale R">R Beale</name>
</author>
<author>
<name sortKey="Mcluckie, A" uniqKey="Mcluckie A">A McLuckie</name>
</author>
<author>
<name sortKey="Reinhart, K" uniqKey="Reinhart K">K Reinhart</name>
</author>
<author>
<name sortKey="Meier Hellmann, A" uniqKey="Meier Hellmann A">A Meier-Hellmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sakka, Sg" uniqKey="Sakka S">SG Sakka</name>
</author>
<author>
<name sortKey="Klein, M" uniqKey="Klein M">M Klein</name>
</author>
<author>
<name sortKey="Reinhart, K" uniqKey="Reinhart K">K Reinhart</name>
</author>
<author>
<name sortKey="Meier Hellmann, A" uniqKey="Meier Hellmann A">A Meier-Hellmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Martin, Gs" uniqKey="Martin G">GS Martin</name>
</author>
<author>
<name sortKey="Eaton, S" uniqKey="Eaton S">S Eaton</name>
</author>
<author>
<name sortKey="Mealer, M" uniqKey="Mealer M">M Mealer</name>
</author>
<author>
<name sortKey="Moss, M" uniqKey="Moss M">M Moss</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mitchell, Jp" uniqKey="Mitchell J">JP Mitchell</name>
</author>
<author>
<name sortKey="Schuller, D" uniqKey="Schuller D">D Schuller</name>
</author>
<author>
<name sortKey="Calandrino, Fs" uniqKey="Calandrino F">FS Calandrino</name>
</author>
<author>
<name sortKey="Schuster, Dp" uniqKey="Schuster D">DP Schuster</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Martin, Gs" uniqKey="Martin G">GS Martin</name>
</author>
<author>
<name sortKey="Moss, M" uniqKey="Moss M">M Moss</name>
</author>
<author>
<name sortKey="Wheeler, Ap" uniqKey="Wheeler A">AP Wheeler</name>
</author>
<author>
<name sortKey="Mealer, M" uniqKey="Mealer M">M Mealer</name>
</author>
<author>
<name sortKey="Morris, Ja" uniqKey="Morris J">JA Morris</name>
</author>
<author>
<name sortKey="Bernard, Gr" uniqKey="Bernard G">GR Bernard</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bernard, Gr" uniqKey="Bernard G">GR Bernard</name>
</author>
<author>
<name sortKey="Artigas, A" uniqKey="Artigas A">A Artigas</name>
</author>
<author>
<name sortKey="Brigham, Kl" uniqKey="Brigham K">KL Brigham</name>
</author>
<author>
<name sortKey="Carlet, J" uniqKey="Carlet J">J Carlet</name>
</author>
<author>
<name sortKey="Falke, K" uniqKey="Falke K">K Falke</name>
</author>
<author>
<name sortKey="Hudson, L" uniqKey="Hudson L">L Hudson</name>
</author>
<author>
<name sortKey="Lamy, M" uniqKey="Lamy M">M Lamy</name>
</author>
<author>
<name sortKey="Legall, Jr" uniqKey="Legall J">JR Legall</name>
</author>
<author>
<name sortKey="Morris, A" uniqKey="Morris A">A Morris</name>
</author>
<author>
<name sortKey="Spragg, R" uniqKey="Spragg R">R Spragg</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Deeren, Dh" uniqKey="Deeren D">DH Deeren</name>
</author>
<author>
<name sortKey="Zachee, P" uniqKey="Zachee P">P Zachee</name>
</author>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Le Gall, Jr" uniqKey="Le Gall J">JR Le Gall</name>
</author>
<author>
<name sortKey="Lemeshow, S" uniqKey="Lemeshow S">S Lemeshow</name>
</author>
<author>
<name sortKey="Saulnier, F" uniqKey="Saulnier F">F Saulnier</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Knaus, Wa" uniqKey="Knaus W">WA Knaus</name>
</author>
<author>
<name sortKey="Draper, Ea" uniqKey="Draper E">EA Draper</name>
</author>
<author>
<name sortKey="Wagner, Dp" uniqKey="Wagner D">DP Wagner</name>
</author>
<author>
<name sortKey="Zimmerman, Je" uniqKey="Zimmerman J">JE Zimmerman</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name>
</author>
<author>
<name sortKey="De Mendonca, A" uniqKey="De Mendonca A">A de Mendonca</name>
</author>
<author>
<name sortKey="Cantraine, F" uniqKey="Cantraine F">F Cantraine</name>
</author>
<author>
<name sortKey="Moreno, R" uniqKey="Moreno R">R Moreno</name>
</author>
<author>
<name sortKey="Takala, J" uniqKey="Takala J">J Takala</name>
</author>
<author>
<name sortKey="Suter, Pm" uniqKey="Suter P">PM Suter</name>
</author>
<author>
<name sortKey="Sprung, Cl" uniqKey="Sprung C">CL Sprung</name>
</author>
<author>
<name sortKey="Colardyn, F" uniqKey="Colardyn F">F Colardyn</name>
</author>
<author>
<name sortKey="Blecher, S" uniqKey="Blecher S">S Blecher</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cuthbertson, Dp" uniqKey="Cuthbertson D">DP Cuthbertson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cerda, J" uniqKey="Cerda J">J Cerda</name>
</author>
<author>
<name sortKey="Sheinfeld, G" uniqKey="Sheinfeld G">G Sheinfeld</name>
</author>
<author>
<name sortKey="Ronco, C" uniqKey="Ronco C">C Ronco</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Elbers, Pw" uniqKey="Elbers P">PW Elbers</name>
</author>
<author>
<name sortKey="Ince, C" uniqKey="Ince C">C Ince</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Nieuwenhuijzen, Ga" uniqKey="Nieuwenhuijzen G">GA Nieuwenhuijzen</name>
</author>
<author>
<name sortKey="Knapen, Mf" uniqKey="Knapen M">MF Knapen</name>
</author>
<author>
<name sortKey="Oyen, Wj" uniqKey="Oyen W">WJ Oyen</name>
</author>
<author>
<name sortKey="Hendriks, T" uniqKey="Hendriks T">T Hendriks</name>
</author>
<author>
<name sortKey="Corstens, Fh" uniqKey="Corstens F">FH Corstens</name>
</author>
<author>
<name sortKey="Goris, Rj" uniqKey="Goris R">RJ Goris</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dalfino, L" uniqKey="Dalfino L">L Dalfino</name>
</author>
<author>
<name sortKey="Tullo, L" uniqKey="Tullo L">L Tullo</name>
</author>
<author>
<name sortKey="Donadio, I" uniqKey="Donadio I">I Donadio</name>
</author>
<author>
<name sortKey="Malcangi, V" uniqKey="Malcangi V">V Malcangi</name>
</author>
<author>
<name sortKey="Brienza, N" uniqKey="Brienza N">N Brienza</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Simmons, Rs" uniqKey="Simmons R">RS Simmons</name>
</author>
<author>
<name sortKey="Berdine, Gg" uniqKey="Berdine G">GG Berdine</name>
</author>
<author>
<name sortKey="Seidenfeld, Jj" uniqKey="Seidenfeld J">JJ Seidenfeld</name>
</author>
<author>
<name sortKey="Prihoda, Tj" uniqKey="Prihoda T">TJ Prihoda</name>
</author>
<author>
<name sortKey="Harris, Gd" uniqKey="Harris G">GD Harris</name>
</author>
<author>
<name sortKey="Smith, Jd" uniqKey="Smith J">JD Smith</name>
</author>
<author>
<name sortKey="Gilbert, Tj" uniqKey="Gilbert T">TJ Gilbert</name>
</author>
<author>
<name sortKey="Mota, E" uniqKey="Mota E">E Mota</name>
</author>
<author>
<name sortKey="Johanson, Wg" uniqKey="Johanson W">WG Johanson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
<author>
<name sortKey="Chiumello, D" uniqKey="Chiumello D">D Chiumello</name>
</author>
<author>
<name sortKey="Pelosi, P" uniqKey="Pelosi P">P Pelosi</name>
</author>
<author>
<name sortKey="Bihari, D" uniqKey="Bihari D">D Bihari</name>
</author>
<author>
<name sortKey="Innes, R" uniqKey="Innes R">R Innes</name>
</author>
<author>
<name sortKey="Ranieri, Vm" uniqKey="Ranieri V">VM Ranieri</name>
</author>
<author>
<name sortKey="Del Turco, M" uniqKey="Del Turco M">M Del Turco</name>
</author>
<author>
<name sortKey="Wilmer, A" uniqKey="Wilmer A">A Wilmer</name>
</author>
<author>
<name sortKey="Brienza, N" uniqKey="Brienza N">N Brienza</name>
</author>
<author>
<name sortKey="Malcangi, V" uniqKey="Malcangi V">V Malcangi</name>
</author>
<author>
<name sortKey="Cohen, J" uniqKey="Cohen J">J Cohen</name>
</author>
<author>
<name sortKey="Japiassu, A" uniqKey="Japiassu A">A Japiassu</name>
</author>
<author>
<name sortKey="De Keulenaer, Bl" uniqKey="De Keulenaer B">BL De Keulenaer</name>
</author>
<author>
<name sortKey="Daelemans, R" uniqKey="Daelemans R">R Daelemans</name>
</author>
<author>
<name sortKey="Jacquet, L" uniqKey="Jacquet L">L Jacquet</name>
</author>
<author>
<name sortKey="Laterre, Pf" uniqKey="Laterre P">PF Laterre</name>
</author>
<author>
<name sortKey="Frank, G" uniqKey="Frank G">G Frank</name>
</author>
<author>
<name sortKey="De Souza, P" uniqKey="De Souza P">P de Souza</name>
</author>
<author>
<name sortKey="Cesana, B" uniqKey="Cesana B">B Cesana</name>
</author>
<author>
<name sortKey="Gattinoni, L" uniqKey="Gattinoni L">L Gattinoni</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gattinoni, L" uniqKey="Gattinoni L">L Gattinoni</name>
</author>
<author>
<name sortKey="Caironi, P" uniqKey="Caironi P">P Caironi</name>
</author>
<author>
<name sortKey="Cressoni, M" uniqKey="Cressoni M">M Cressoni</name>
</author>
<author>
<name sortKey="Chiumello, D" uniqKey="Chiumello D">D Chiumello</name>
</author>
<author>
<name sortKey="Ranieri, Vm" uniqKey="Ranieri V">VM Ranieri</name>
</author>
<author>
<name sortKey="Quintel, M" uniqKey="Quintel M">M Quintel</name>
</author>
<author>
<name sortKey="Russo, S" uniqKey="Russo S">S Russo</name>
</author>
<author>
<name sortKey="Patroniti, N" uniqKey="Patroniti N">N Patroniti</name>
</author>
<author>
<name sortKey="Cornejo, R" uniqKey="Cornejo R">R Cornejo</name>
</author>
<author>
<name sortKey="Bugedo, G" uniqKey="Bugedo G">G Bugedo</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Luecke, T" uniqKey="Luecke T">T Luecke</name>
</author>
<author>
<name sortKey="Roth, H" uniqKey="Roth H">H Roth</name>
</author>
<author>
<name sortKey="Herrmann, P" uniqKey="Herrmann P">P Herrmann</name>
</author>
<author>
<name sortKey="Joachim, A" uniqKey="Joachim A">A Joachim</name>
</author>
<author>
<name sortKey="Weisser, G" uniqKey="Weisser G">G Weisser</name>
</author>
<author>
<name sortKey="Pelosi, P" uniqKey="Pelosi P">P Pelosi</name>
</author>
<author>
<name sortKey="Quintel, M" uniqKey="Quintel M">M Quintel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Garcia Delgado, M" uniqKey="Garcia Delgado M">M Garcia-Delgado</name>
</author>
<author>
<name sortKey="Touma Fernandez, A" uniqKey="Touma Fernandez A">A Touma-Fernandez</name>
</author>
<author>
<name sortKey="Chamorro Marin, V" uniqKey="Chamorro Marin V">V Chamorro-Marin</name>
</author>
<author>
<name sortKey="Ruiz Aguilar, A" uniqKey="Ruiz Aguilar A">A Ruiz-Aguilar</name>
</author>
<author>
<name sortKey="Aguilar Alonso, E" uniqKey="Aguilar Alonso E">E Aguilar-Alonso</name>
</author>
<author>
<name sortKey="Fernandez Mondejar, E" uniqKey="Fernandez Mondejar E">E Fernandez-Mondejar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ruiz Bailen, M" uniqKey="Ruiz Bailen M">M Ruiz-Bailen</name>
</author>
<author>
<name sortKey="Fernandez Mondejar, E" uniqKey="Fernandez Mondejar E">E Fernandez-Mondejar</name>
</author>
<author>
<name sortKey="Hurtado Ruiz, B" uniqKey="Hurtado Ruiz B">B Hurtado-Ruiz</name>
</author>
<author>
<name sortKey="Colmenero Ruiz, M" uniqKey="Colmenero Ruiz M">M Colmenero-Ruiz</name>
</author>
<author>
<name sortKey="Rivera Fernandez, R" uniqKey="Rivera Fernandez R">R Rivera-Fernandez</name>
</author>
<author>
<name sortKey="Guerrero Lopez, F" uniqKey="Guerrero Lopez F">F Guerrero-Lopez</name>
</author>
<author>
<name sortKey="Vazquez Mata, G" uniqKey="Vazquez Mata G">G Vazquez-Mata</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chen, Ym" uniqKey="Chen Y">YM Chen</name>
</author>
<author>
<name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
<author>
<name sortKey="Qiu, Hb" uniqKey="Qiu H">HB Qiu</name>
</author>
<author>
<name sortKey="Li, Jq" uniqKey="Li J">JQ Li</name>
</author>
<author>
<name sortKey="Huang, Yz" uniqKey="Huang Y">YZ Huang</name>
</author>
<author>
<name sortKey="Xu, Xt" uniqKey="Xu X">XT Xu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
<author>
<name sortKey="Wilmer, A" uniqKey="Wilmer A">A Wilmer</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Starling, Eh" uniqKey="Starling E">EH Starling</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cribbs, Sk" uniqKey="Cribbs S">SK Cribbs</name>
</author>
<author>
<name sortKey="Martin, Gs" uniqKey="Martin G">GS Martin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mangialardi, Rj" uniqKey="Mangialardi R">RJ Mangialardi</name>
</author>
<author>
<name sortKey="Martin, Gs" uniqKey="Martin G">GS Martin</name>
</author>
<author>
<name sortKey="Bernard, Gr" uniqKey="Bernard G">GR Bernard</name>
</author>
<author>
<name sortKey="Wheeler, Ap" uniqKey="Wheeler A">AP Wheeler</name>
</author>
<author>
<name sortKey="Christman, Bw" uniqKey="Christman B">BW Christman</name>
</author>
<author>
<name sortKey="Dupont, Wd" uniqKey="Dupont W">WD Dupont</name>
</author>
<author>
<name sortKey="Higgins, Sb" uniqKey="Higgins S">SB Higgins</name>
</author>
<author>
<name sortKey="Swindell, Bb" uniqKey="Swindell B">BB Swindell</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lum, H" uniqKey="Lum H">H Lum</name>
</author>
<author>
<name sortKey="Siflinger Birnboim, A" uniqKey="Siflinger Birnboim A">A Siflinger-Birnboim</name>
</author>
<author>
<name sortKey="Blumenstock, F" uniqKey="Blumenstock F">F Blumenstock</name>
</author>
<author>
<name sortKey="Malik, Ab" uniqKey="Malik A">AB Malik</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Qiao, Rl" uniqKey="Qiao R">RL Qiao</name>
</author>
<author>
<name sortKey="Ying, X" uniqKey="Ying X">X Ying</name>
</author>
<author>
<name sortKey="Bhattacharya, J" uniqKey="Bhattacharya J">J Bhattacharya</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name>
</author>
<author>
<name sortKey="Voglis, S" uniqKey="Voglis S">S Voglis</name>
</author>
<author>
<name sortKey="Kim, Ch" uniqKey="Kim C">CH Kim</name>
</author>
<author>
<name sortKey="Slutsky, As" uniqKey="Slutsky A">AS Slutsky</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Powers, Ka" uniqKey="Powers K">KA Powers</name>
</author>
<author>
<name sortKey="Kapus, A" uniqKey="Kapus A">A Kapus</name>
</author>
<author>
<name sortKey="Khadaroo, Rg" uniqKey="Khadaroo R">RG Khadaroo</name>
</author>
<author>
<name sortKey="He, R" uniqKey="He R">R He</name>
</author>
<author>
<name sortKey="Marshall, Jc" uniqKey="Marshall J">JC Marshall</name>
</author>
<author>
<name sortKey="Lindsay, Tf" uniqKey="Lindsay T">TF Lindsay</name>
</author>
<author>
<name sortKey="Rotstein, Od" uniqKey="Rotstein O">OD Rotstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Malbrain, Ml" uniqKey="Malbrain M">ML Malbrain</name>
</author>
<author>
<name sortKey="Chiumello, D" uniqKey="Chiumello D">D Chiumello</name>
</author>
<author>
<name sortKey="Pelosi, P" uniqKey="Pelosi P">P Pelosi</name>
</author>
<author>
<name sortKey="Wilmer, A" uniqKey="Wilmer A">A Wilmer</name>
</author>
<author>
<name sortKey="Brienza, N" uniqKey="Brienza N">N Brienza</name>
</author>
<author>
<name sortKey="Malcangi, V" uniqKey="Malcangi V">V Malcangi</name>
</author>
<author>
<name sortKey="Bihari, D" uniqKey="Bihari D">D Bihari</name>
</author>
<author>
<name sortKey="Innes, R" uniqKey="Innes R">R Innes</name>
</author>
<author>
<name sortKey="Cohen, J" uniqKey="Cohen J">J Cohen</name>
</author>
<author>
<name sortKey="Singer, P" uniqKey="Singer P">P Singer</name>
</author>
<author>
<name sortKey="Japiassu, A" uniqKey="Japiassu A">A Japiassu</name>
</author>
<author>
<name sortKey="Kurtop, E" uniqKey="Kurtop E">E Kurtop</name>
</author>
<author>
<name sortKey="De Keulenaer, Bl" uniqKey="De Keulenaer B">BL De Keulenaer</name>
</author>
<author>
<name sortKey="Daelemans, R" uniqKey="Daelemans R">R Daelemans</name>
</author>
<author>
<name sortKey="Del Turco, M" uniqKey="Del Turco M">M Del Turco</name>
</author>
<author>
<name sortKey="Cosimini, P" uniqKey="Cosimini P">P Cosimini</name>
</author>
<author>
<name sortKey="Ranieri, M" uniqKey="Ranieri M">M Ranieri</name>
</author>
<author>
<name sortKey="Jacquet, L" uniqKey="Jacquet L">L Jacquet</name>
</author>
<author>
<name sortKey="Laterre, Pf" uniqKey="Laterre P">PF Laterre</name>
</author>
<author>
<name sortKey="Gattinoni, L" uniqKey="Gattinoni L">L Gattinoni</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kula, R" uniqKey="Kula R">R Kula</name>
</author>
<author>
<name sortKey="Szturz, P" uniqKey="Szturz P">P Szturz</name>
</author>
<author>
<name sortKey="Sklienka, P" uniqKey="Sklienka P">P Sklienka</name>
</author>
<author>
<name sortKey="Neiser, J" uniqKey="Neiser J">J Neiser</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Milberg, Ja" uniqKey="Milberg J">JA Milberg</name>
</author>
<author>
<name sortKey="Davis, Dr" uniqKey="Davis D">DR Davis</name>
</author>
<author>
<name sortKey="Steinberg, Kp" uniqKey="Steinberg K">KP Steinberg</name>
</author>
<author>
<name sortKey="Hudson, Ld" uniqKey="Hudson L">LD Hudson</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article" xml:lang="en">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Ann Intensive Care</journal-id>
<journal-id journal-id-type="iso-abbrev">Ann Intensive Care</journal-id>
<journal-title-group>
<journal-title>Annals of Intensive Care</journal-title>
</journal-title-group>
<issn pub-type="epub">2110-5820</issn>
<publisher>
<publisher-name>Springer</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">22873416</article-id>
<article-id pub-id-type="pmc">3390296</article-id>
<article-id pub-id-type="publisher-id">2110-5820-2-S1-S15</article-id>
<article-id pub-id-type="doi">10.1186/2110-5820-2-S1-S15</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" id="A1">
<name>
<surname>Cordemans</surname>
<given-names>Colin</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>colincordemans@gmail.com</email>
</contrib>
<contrib contrib-type="author" id="A2">
<name>
<surname>De laet</surname>
<given-names>Inneke</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>inneke.delaet@zna.be</email>
</contrib>
<contrib contrib-type="author" id="A3">
<name>
<surname>Van Regenmortel</surname>
<given-names>Niels</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>niels.vanregenmortel@zna.be</email>
</contrib>
<contrib contrib-type="author" id="A4">
<name>
<surname>Schoonheydt</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>karen.schoonheydt@zna.be</email>
</contrib>
<contrib contrib-type="author" id="A5">
<name>
<surname>Dits</surname>
<given-names>Hilde</given-names>
</name>
<email>hilde.dits@zna.be</email>
</contrib>
<contrib contrib-type="author" id="A6">
<name>
<surname>Martin</surname>
<given-names>Greg</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>greg.martin@emory.edu</email>
</contrib>
<contrib contrib-type="author" id="A7">
<name>
<surname>Huber</surname>
<given-names>Wolfgang</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<email>Wolfgang.Huber@lrz.tu-muenchen.de</email>
</contrib>
<contrib contrib-type="author" corresp="yes" id="A8">
<name>
<surname>Malbrain</surname>
<given-names>Manu LNG</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>manu.malbrain@skynet.be</email>
</contrib>
</contrib-group>
<aff id="I1">
<label>1</label>
Department of Intensive Care, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Campus Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerpen 6, Belgium</aff>
<aff id="I2">
<label>2</label>
Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA, USA</aff>
<aff id="I3">
<label>3</label>
II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</aff>
<pub-date pub-type="collection">
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>5</day>
<month>7</month>
<year>2012</year>
</pub-date>
<volume>2</volume>
<issue>Suppl 1</issue>
<supplement>
<named-content content-type="supplement-title">Diagnosis and management of intra-abdominal hypertension and abdominal compartment syndrome</named-content>
<named-content content-type="supplement-editor">MLNG Malbrain, R Ivatury, BL De Keulenaer and P Pelosi</named-content>
</supplement>
<fpage>S15</fpage>
<lpage>S15</lpage>
<permissions>
<copyright-statement>Copyright ©2012 Cordemans et al.; licensee Springer</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>Cordemans et al.; licensee Springer</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0">
<license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.annalsofintensivecare.com/content/2/S1/S15"></self-uri>
<abstract>
<sec>
<title>Introduction</title>
<p>Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI).</p>
</sec>
<sec>
<title>Methods</title>
<p>In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix
<sup>®</sup>
) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality.</p>
</sec>
<sec>
<title>Results</title>
<p>At baseline, no significant intergroup differences were found, except for lower PaO
<sub>2</sub>
/FIO
<sub>2 </sub>
and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7,
<italic>p </italic>
= 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg,
<italic>p </italic>
= 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg,
<italic>p </italic>
= 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg,
<italic>p </italic>
= 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL,
<italic>p </italic>
< 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days,
<italic>p </italic>
= 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%,
<italic>p </italic>
= 0.034).</p>
</sec>
<sec>
<title>Conclusion</title>
<p>PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.</p>
</sec>
</abstract>
<kwd-group>
<kwd>abdominal pressure</kwd>
<kwd>extravascular lung water</kwd>
<kwd>fluid balance</kwd>
<kwd>fluid management</kwd>
<kwd>capillary leak</kwd>
<kwd>organ failure</kwd>
<kwd>treatment</kwd>
<kwd>conservative late fluid management</kwd>
<kwd>albumin</kwd>
<kwd>PEEP.</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec>
<title>Introduction</title>
<p>Both early and late fluid management affect outcome in acute lung injury (ALI), sepsis, and trauma [
<xref ref-type="bibr" rid="B1">1</xref>
-
<xref ref-type="bibr" rid="B5">5</xref>
]. After initial filling to reverse distributive shock [
<xref ref-type="bibr" rid="B6">6</xref>
], emphasis shifts to limitation and elimination of interstitial edema in vital organs. Indeed, a positive fluid balance resulting from third spacing is independently associated with impaired organ function and worse outcome [
<xref ref-type="bibr" rid="B7">7</xref>
-
<xref ref-type="bibr" rid="B11">11</xref>
]. Conversely, achievement of negative fluid balances predicts survival and improves lung function [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B13">13</xref>
].</p>
<p>Bedside measurement of extravascular lung water index (EVLWI) performed by transpulmonary thermodilution allows to estimate the extent of capillary leak and fluid overload [
<xref ref-type="bibr" rid="B14">14</xref>
-
<xref ref-type="bibr" rid="B17">17</xref>
]. Accordingly, EVLWI correlates well with organ function and survival [
<xref ref-type="bibr" rid="B15">15</xref>
,
<xref ref-type="bibr" rid="B16">16</xref>
,
<xref ref-type="bibr" rid="B18">18</xref>
,
<xref ref-type="bibr" rid="B19">19</xref>
]. Moreover, fluid management aimed at EVLWI reduction results in a more negative fluid balance and improved outcomes [
<xref ref-type="bibr" rid="B20">20</xref>
]. In order to achieve a negative fluid balance, previous prospective trials excluded patients with hypotension and renal failure [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B20">20</xref>
,
<xref ref-type="bibr" rid="B21">21</xref>
].</p>
<p>In this study, we aimed for a negative fluid balance in mechanically ventilated patients with ALI presenting with severe hypoxemia, increased EVLWI, and intra-abdominal pressure (IAP) using a restrictive fluid management, referred to in our institution as "PAL-treatment". PAL-treatment combines high levels of positive end-expiratory pressure (PEEP), small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix
<sup>®</sup>
) or ultrafiltration during continuous renal replacement therapy (CRRT).</p>
</sec>
<sec sec-type="methods">
<title>Methods</title>
<sec>
<title>Study design</title>
<p>In this retrospective matched case-control single center study, patients with PAL-treatment were compared to a matched control group for 1 week from the onset of ALI. Outcomes were assessed at day 28 after enrolment or at the day of death or hospital discharge, whichever occurred first. The primary outcome parameter was hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, development of intra-abdominal hypertension (IAH), duration of mechanical ventilation (MV) and cumulative fluid balance, organ dysfunction, and vasopressor therapy requirements after 1 week.</p>
</sec>
<sec>
<title>Patients</title>
<p>Data of 114 patients treated in two ICU's in Ziekenhuis Netwerk Antwerpen, ZNA Campus Stuivenberg, Antwerp, Belgium were collected from March 2004 to August 2007 (control group) and from March 2008 to February 2010 (PAL group). Patients were consecutively included if they were intubated and MV and if monitoring with transpulmonary thermodilution technique was performed.</p>
<p>The PAL group consisted of 57 patients with ALI according to international criteria [
<xref ref-type="bibr" rid="B22">22</xref>
], in whom a negative daily fluid balance was deemed necessary, according to clinical appraisal of low P
<sub>a</sub>
O
<sub>2</sub>
/FIO
<sub>2 </sub>
ratio and increased EVLWI and IAP. All patients were included at the onset of ALI.</p>
<p>The historical cohort consisted of 123 MV patients with thermodilution catheter monitoring, of which 65 patients met the criteria of ALI [
<xref ref-type="bibr" rid="B22">22</xref>
] and had data available from the onset of ALI. We used an automatic case-control matching software module to abstract 57 control patients from this group. In this way, controls were matched to PAL-treated patients with regard to demographics, etiology of lung injury, severity of illness, organ dysfunction, fluid balance, and EVLWI at baseline.</p>
</sec>
<sec>
<title>Treatment protocol</title>
<p>Approval for this epidemiologic study was granted by our institutional review board (EC approval number 3766). Due to the observational and retrospective character of this study, informed consent was waived. Standard treatment was based on recent ICU guidelines and did not differ between the two groups.</p>
<p>Patients in the PAL group received a combination therapy aiming for negative daily fluid balances. First, application of PEEP was titrated to counterbalance increased IAP (best PEEP in cmH
<sub>2</sub>
O = IAP in mmHg). Next, hyperoncotic albumin (20%) solution was administered by 200-ml boluses over 60 min twice on the first day and subsequently titrated toward a serum albumin level of 30 g/L. Finally, a furosemide drip was initiated with an intravenous loading dose of 60 mg, followed by a continuous infusion at 60 mg/h for the first 4 h and 5-10 mg/h thereafter, according to hemodynamic tolerance. In anuric patients, CRRT was initiated with an ultrafiltration rate resulting in neutral to negative daily fluid balances.</p>
</sec>
<sec>
<title>Data collection</title>
<p>Demographic, clinical, and laboratory data were registered in an electronic database, supplemented with daily fluid balance, sepsis-related organ failure assessment (SOFA) score, IAP, MV settings, and hemodynamic variables. Finally, data on total duration of MV, CRRT, ICU stay, hospital stay, and mortality on day 28 were added to the database.</p>
<p>Capillary leak index (CLI) was defined as C-reactive protein (CRP; milligrams per deciliter) over albumin (grams per liter) ratio, multiplied by 100 [
<xref ref-type="bibr" rid="B23">23</xref>
]. Requirement of vasopressor therapy was determined by the need of norepinephrine with a dose ≥ 0.1 μg/kg/min.</p>
<p>Severity of illness on ICU admission was described by an averaged simplified acute physiology (SAPS II) score [
<xref ref-type="bibr" rid="B24">24</xref>
], acute physiology and chronic health evaluation (APACHE II) score [
<xref ref-type="bibr" rid="B25">25</xref>
], and SOFA score [
<xref ref-type="bibr" rid="B26">26</xref>
]. Daily fluid balance was calculated by subtracting the fluid output (diuresis, ultrafiltration volume in case of CRRT, and any loss from drainage tubes) from the fluid intake (IV and enteral fluid administration); each day the cumulative fluid balance was computed by the addition of daily fluid balances.</p>
<p>IAP was the mean of two daily IAP measurements via a Foley bladder catheter, as described previously [
<xref ref-type="bibr" rid="B27">27</xref>
]. IAH was defined as persistent increase of IAP ≥ 12 mmHg and abdominal perfusion pressure (APP) as mean arterial pressure (MAP) minus IAP according to consensus definitions [
<xref ref-type="bibr" rid="B8">8</xref>
].</p>
<p>A central venous catheter and a thermistor-tipped arterial thermodilution catheter (Pulsiocath 5F) inserted into the femoral artery and attached to a PiCCOplus
<sup>® </sup>
system (Pulsion Medical Systems, Munich, Germany) were already in place for each patient. Transpulmonary thermodilution measurements were obtained by central venous injection of three 20-mL boluses of cooled saline (< 8°C). For each set of thermodilution determinations, the mean values were used for statistical analysis. Cardiac output (CO), global end diastolic volume (GEDV), extravascular lung water (EVLW), global ejection fraction (GEF), pulmonary vascular permeability index, stroke volume variation (SVV), and pulse pressure variation were calculated using the PiCCOplus
<sup>® </sup>
[
<xref ref-type="bibr" rid="B17">17</xref>
]. EVLW was indexed to body weight (EVLWI) and CO and GEDV to body surface area (cardiac index (CI), GEDVI).</p>
</sec>
<sec>
<title>Statistical analysis</title>
<p>A priori analyses were performed to stratify patient groups by demographics, etiology of lung injury, severity of illness, organ dysfunction, fluid balance, and EVLWI at baseline. We analyzed data on intent-to-treat basis comparing outcomes on different time points within groups and between groups during 1 week.</p>
<p>Continuous data were expressed by mean ± standard deviation (SD), and intergroup differences were determined by one-way analysis of variance (ANOVA) analyses day by day for 1 week (univariate analysis). Categorical data were expressed as frequency distributions and/or percentages, and the
<italic>χ</italic>
<sup>2 </sup>
test was used to determine intergroup differences. Two-sided
<italic>p </italic>
values of 0.05 or less were considered to indicate statistical significance.</p>
<p>Time course of PEEP, albumin, P
<sub>a</sub>
O
<sub>2</sub>
/FIO
<sub>2 </sub>
ratio, EVLWI, daily and cumulative fluid balance, SOFA score, and IAP was described by clustered error bar graphs representing mean ± standard error. The Kaplan-Meier method was used to analyze differences in cumulative survival and duration of mechanical ventilation. We used SPSS software package (version 17.0.1; SPSS, Chicago, IL, USA). Automatic case-control matching was performed with the fuzzy extension (
<ext-link ext-link-type="uri" xlink:href="http://www.spss.com/devcentral">http://www.spss.com/devcentral</ext-link>
).</p>
</sec>
</sec>
<sec sec-type="results">
<title>Results</title>
<sec>
<title>Baseline characteristics</title>
<p>We included 114 mainly medical (
<italic>n </italic>
= 102) mechanically ventilated patients with ALI. Fifty-five patients (48.2%) required vasopressor therapy, and 50 patients (43.9%) received CRRT at baseline.</p>
<p>The PAL group had on average lower PaO
<sub>2</sub>
/FIO
<sub>2 </sub>
(higher respiratory SOFA score), increased IAP, and higher PEEP level. Otherwise, the two groups were similar (Table
<xref ref-type="table" rid="T1">1</xref>
).</p>
<table-wrap id="T1" position="float">
<label>Table 1</label>
<caption>
<p>Baseline characteristics</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left">Variable</th>
<th align="left">Control group (
<italic>n </italic>
= 57)</th>
<th align="left">PAL group (
<italic>n </italic>
= 57)</th>
<th align="left">
<italic>p </italic>
value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left">Age (year)</td>
<td align="left">61.4 ± 16.8</td>
<td align="left">63.0 ± 14.3</td>
<td align="left">0.598</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Male sex (%)</td>
<td align="left">73.7</td>
<td align="left">66.7</td>
<td align="left">0.539</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">BMI</td>
<td align="left">25.2 ± 4.0</td>
<td align="left">26.1 ± 6.0</td>
<td align="left">0.366</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Primary lung injury (%)</td>
<td></td>
<td></td>
<td align="left">0.607</td>
</tr>
<tr>
<td align="left"> Sepsis</td>
<td align="left">43.9</td>
<td align="left">47.4</td>
<td></td>
</tr>
<tr>
<td align="left"> Pneumonia</td>
<td align="left">22.8</td>
<td align="left">26.3</td>
<td></td>
</tr>
<tr>
<td align="left"> Aspiration</td>
<td align="left">12.3</td>
<td align="left">8.8</td>
<td></td>
</tr>
<tr>
<td align="left"> Burns</td>
<td align="left">5.3</td>
<td align="left">7.0</td>
<td></td>
</tr>
<tr>
<td align="left"> Trauma</td>
<td align="left">7.0</td>
<td align="left">3.5</td>
<td></td>
</tr>
<tr>
<td align="left"> Other</td>
<td align="left">8.8</td>
<td align="left">7.0</td>
<td></td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Medical ICU (%)</td>
<td align="left">87.7</td>
<td align="left">91.2</td>
<td align="left">0.344</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" colspan="4">Severity of disease</td>
</tr>
<tr>
<td align="left"> SAPS II</td>
<td align="left">52.3 ± 17.3</td>
<td align="left">47.9 ± 18.4</td>
<td align="left">0.188</td>
</tr>
<tr>
<td align="left"> APACHE II</td>
<td align="left">22.7 ± 11.1</td>
<td align="left">22.9 ± 11.4</td>
<td align="left">0.934</td>
</tr>
<tr>
<td align="left" colspan="4"> SOFA score</td>
</tr>
<tr>
<td align="left">  Respiratory</td>
<td align="left">1.9 ± 1.4</td>
<td align="left">2.4 ± 1.3</td>
<td align="left">0.037</td>
</tr>
<tr>
<td align="left">  Coagulation</td>
<td align="left">0.9 ± 1.2</td>
<td align="left">1.0 ± 1.2</td>
<td align="left">0.488</td>
</tr>
<tr>
<td align="left">  Liver</td>
<td align="left">0.6 ± 1.0</td>
<td align="left">0.8 ± 1.2</td>
<td align="left">0.302</td>
</tr>
<tr>
<td align="left">  Cardiovascular</td>
<td align="left">2.9 ± 1.5</td>
<td align="left">3.0 ± 1.2</td>
<td align="left">0.640</td>
</tr>
<tr>
<td align="left">  Nervous</td>
<td align="left">2.5 ± 1.7</td>
<td align="left">2.6 ± 1.6</td>
<td align="left">0.867</td>
</tr>
<tr>
<td align="left">  Renal</td>
<td align="left">1.5 ± 1.6</td>
<td align="left">1.5 ± 1.6</td>
<td align="left">0.864</td>
</tr>
<tr>
<td align="left">  Total</td>
<td align="left">10.2 ± 4.2</td>
<td align="left">11.3 ± 4.0</td>
<td align="left">0.160</td>
</tr>
<tr>
<td align="left"> Number of organs failing</td>
<td align="left">2.1 ± 1.1</td>
<td align="left">2.5 ± 1.2</td>
<td align="left">0.061</td>
</tr>
<tr>
<td align="left" colspan="4"> Hemodynamic variables</td>
</tr>
<tr>
<td align="left">  HR (bpm)</td>
<td align="left">98.0 ± 18.0</td>
<td align="left">96.5 ± 19.4</td>
<td align="left">0.733</td>
</tr>
<tr>
<td align="left">  Mean arterial pressure (mmHg)</td>
<td align="left">83.3 ± 13.5</td>
<td align="left">84.9 ± 11.0</td>
<td align="left">0.502</td>
</tr>
<tr>
<td align="left">  Vasopressor use (%)</td>
<td align="left">58.0</td>
<td align="left">52.0</td>
<td align="left">0.688</td>
</tr>
<tr>
<td align="left">  CI (L/min/m
<sup>2</sup>
)</td>
<td align="left">3.4 ± 0.9</td>
<td align="left">3.8 ± 0.9</td>
<td align="left">0.145</td>
</tr>
<tr>
<td align="left">  SVV (%)</td>
<td align="left">15.5 ± 8.4</td>
<td align="left">12.0 ± 5.5</td>
<td align="left">0.088</td>
</tr>
<tr>
<td align="left">  GEF (%)</td>
<td align="left">19.7 ± 6.6</td>
<td align="left">22.1 ± 7.6</td>
<td align="left">0.260</td>
</tr>
<tr>
<td align="left">  GEDVI (mL/m
<sup>2</sup>
)</td>
<td align="left">736.8 ± 141.5</td>
<td align="left">807.5 ± 189.3</td>
<td align="left">0.163</td>
</tr>
<tr>
<td align="left">  EVLWI (mL/kg)</td>
<td align="left">12.0 ± 6.1</td>
<td align="left">13.4 ± 6.2</td>
<td align="left">0.326</td>
</tr>
<tr>
<td align="left" colspan="4"> Respiratory variables</td>
</tr>
<tr>
<td align="left">  Tidal volume (mL/kg of PBW)</td>
<td align="left">8.6 ± 1.8</td>
<td align="left">7.9 ± 1.9</td>
<td align="left">0.119</td>
</tr>
<tr>
<td align="left">  Plateau pressure (cmH
<sub>2</sub>
O)</td>
<td align="left">25.1 ± 9.1</td>
<td align="left">25.3 ± 7.4</td>
<td align="left">0.914</td>
</tr>
<tr>
<td align="left">  PEEP (cmH
<sub>2</sub>
O)</td>
<td align="left">6.7 ± 2.4</td>
<td align="left">10.2 ± 2.9</td>
<td align="left">< 0.001</td>
</tr>
<tr>
<td align="left">  Dynamic compliance (mL/cmH
<sub>2</sub>
O)</td>
<td align="left">39.4 ± 17.4</td>
<td align="left">42.8 ± 22.4</td>
<td align="left">0.402</td>
</tr>
<tr>
<td align="left">  PaO
<sub>2</sub>
/FIO
<sub>2</sub>
</td>
<td align="left">256.5 ± 152.7</td>
<td align="left">174.5 ± 84.5</td>
<td align="left">0.001</td>
</tr>
<tr>
<td align="left" colspan="4"> Renal and metabolic variables</td>
</tr>
<tr>
<td align="left">  Creatinine (mg/dL)</td>
<td align="left">2.1 ± 2.2</td>
<td align="left">1.8 ± 1.5</td>
<td align="left">0.393</td>
</tr>
<tr>
<td align="left">  Urine output (mL/day)</td>
<td align="left">1,366 ± 1,273</td>
<td align="left">1,591 ± 1,139</td>
<td align="left">0.323</td>
</tr>
<tr>
<td align="left">  CRRT (%)</td>
<td align="left">47.4</td>
<td align="left">40.4</td>
<td align="left">0.571</td>
</tr>
<tr>
<td align="left">  Albumin (g/L)</td>
<td align="left">25.3 ± 8.0</td>
<td align="left">26.7 ± 6.6</td>
<td align="left">0.297</td>
</tr>
<tr>
<td align="left">  pH</td>
<td align="left">7.33 ± 0.12</td>
<td align="left">7.35 ± 0.11</td>
<td align="left">0.430</td>
</tr>
<tr>
<td align="left" colspan="4"> Immune system</td>
</tr>
<tr>
<td align="left">  CRP (mg/dL)</td>
<td align="left">14.7 ± 13.5</td>
<td align="left">15.3 ± 10.1</td>
<td align="left">0.806</td>
</tr>
<tr>
<td align="left" colspan="4"> Central nervous system</td>
</tr>
<tr>
<td align="left">  Glasgow Coma Score</td>
<td align="left">8.2 ± 5.4</td>
<td align="left">7.6 ± 5.1</td>
<td align="left">0.557</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Capillary leak index</td>
<td align="left">68.9 ± 66.3</td>
<td align="left">62.9 ± 48.4</td>
<td align="left">0.589</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Intra-abdominal pressure (mmHg)</td>
<td align="left">8.0 ± 3.7</td>
<td align="left">10.0 ± 4.2</td>
<td align="left">0.013</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Abdominal perfusion pressure (mmHg)</td>
<td align="left">75.3 ± 14.0</td>
<td align="left">75.1 ± 12.9</td>
<td align="left">0.933</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Fluid balance day before enrolment (mL)</td>
<td align="left">2,504 ± 2,704</td>
<td align="left">1,659 ± 4,419</td>
<td align="left">0.224</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>BMI, body mass index; ICU, intensive care unit; SAPS, simplified acute physiology score; APACHE, acute physiology and chronic health evaluation; SOFA, sepsis and organ failure assessment; HR, heart rate; CI, cardiac index; SVV, stroke volume variation; GEF, global ejection fraction; GEDVI, global end diastolic volume index; EVLWI, extravascular lung water index; PEEP, positive end-expiratory pressure; CRRT, continuous renal replacement therapy; CRP, C-reactive protein; PBW, predicted body weight; HR, heart rate.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Direct treatment effects (Figure
<xref ref-type="fig" rid="F1">1</xref>
and Table
<xref ref-type="table" rid="T2">2</xref>
)</title>
<p>Serum albumin concentration averaged 26.0 ± 7.4 g/L in the total group. From day 2, patients in the PAL group had significantly higher concentrations, rising to 33.0 ± 7.3 g/L on day 7 (
<italic>p </italic>
< 0.001). Controls had no significant increase in albumin after 1 week (25.3 ± 8.0 vs 26.4 ± 5.0 g/L,
<italic>p </italic>
= 0.399).</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption>
<p>
<bold>Mean ± standard error of variables directly affected by 1 week of PAL-treatment</bold>
. PAL-treated patients are depicted by a full line and control patients by a dotted line. *
<italic>p </italic>
< 0.05, day-by-day pairwise compared between the PAL group and the control group (one-way ANOVA).</p>
</caption>
<graphic xlink:href="2110-5820-2-S1-S15-1"></graphic>
</fig>
<table-wrap id="T2" position="float">
<label>Table 2</label>
<caption>
<p>Mean absolute change of selected variables after 1 week</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left">Variable</th>
<th align="left">Control group</th>
<th align="left">PAL group</th>
<th align="left">
<italic>p </italic>
value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left">SOFA score</td>
<td></td>
<td></td>
<td></td>
</tr>
<tr>
<td align="left"> Respiratory</td>
<td align="left">0.0 ± 1.7</td>
<td align="left">-0.8 ± 1.6</td>
<td align="left">0.015</td>
</tr>
<tr>
<td align="left"> Coagulation</td>
<td align="left">0.4 ± 1.1</td>
<td align="left">0.1 ± 0.9</td>
<td align="left">0.181</td>
</tr>
<tr>
<td align="left"> Liver</td>
<td align="left">0.3 ± 1.1</td>
<td align="left">0.4 ± 0.8</td>
<td align="left">0.553</td>
</tr>
<tr>
<td align="left"> Cardiovascular</td>
<td align="left">-0.5 ± 1.9</td>
<td align="left">-1.2 ± 2.0</td>
<td align="left">0.087</td>
</tr>
<tr>
<td align="left"> Nervous</td>
<td align="left">0.2 ± 2.0</td>
<td align="left">-0.2 ± 1.8</td>
<td align="left">0.271</td>
</tr>
<tr>
<td align="left"> Renal</td>
<td align="left">0.2 ± 1.8</td>
<td align="left">0.3 ± 1.5</td>
<td align="left">0.693</td>
</tr>
<tr>
<td align="left"> Total</td>
<td align="left">0.7 ± 5.4</td>
<td align="left">-1.3 ± 5.0</td>
<td align="left">0.057</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Number of organs failing</td>
<td align="left">-0.1 ± 1.6</td>
<td align="left">-0.6 ± 1.5</td>
<td align="left">0.115</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Hemodynamic variables</td>
<td></td>
<td></td>
<td></td>
</tr>
<tr>
<td align="left"> HR (bpm)</td>
<td align="left">-11.5 ± 16.3</td>
<td align="left">11.1 ± 95.2</td>
<td align="left">0.183</td>
</tr>
<tr>
<td align="left"> Mean arterial pressure (mmHg)</td>
<td align="left">4.1 ± 13.6</td>
<td align="left">0.6 ± 15.5</td>
<td align="left">0.247</td>
</tr>
<tr>
<td align="left"> CI (L/min/m
<sup>2</sup>
)</td>
<td align="left">0.9 ± 0.2</td>
<td align="left">1.0 ± 0.2</td>
<td align="left">0.274</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Respiratory variables</td>
<td></td>
<td></td>
<td></td>
</tr>
<tr>
<td align="left"> Plateau pressure (cmH
<sub>2</sub>
O)</td>
<td align="left">2.2 ± 8.6</td>
<td align="left">0.7 ± 8.9</td>
<td align="left">0.431</td>
</tr>
<tr>
<td align="left"> PEEP (cmH
<sub>2</sub>
O)</td>
<td align="left">2.1 ± 3.6</td>
<td align="left">0.5 ± 3.8</td>
<td align="left">0.050</td>
</tr>
<tr>
<td align="left"> Dynamic compliance (mL/cmH
<sub>2</sub>
O)</td>
<td align="left">1.6 ± 24.3</td>
<td align="left">5.3 ± 31.4</td>
<td align="left">0.548</td>
</tr>
<tr>
<td align="left"> PaO
<sub>2</sub>
/FIO
<sub>2 </sub>
ratio</td>
<td align="left">-12.3 ± 166.4</td>
<td align="left">99.9 ± 110.5</td>
<td align="left">< 0.001</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">EVLWI (mL/kg)</td>
<td align="left">-1.1 ± 3.7</td>
<td align="left">-4.2 ± 5.6</td>
<td align="left">0.006</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Albumin (g/L)</td>
<td align="left">1.1 ± 9.0</td>
<td align="left">6.3 ± 8.9</td>
<td align="left">0.008</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Creatinine (mg/dL)</td>
<td align="left">-0.5 ± 2.0</td>
<td align="left">-0.1 ± 1.1</td>
<td align="left">0.171</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Capillary leak index</td>
<td align="left">-17.1 ± 75.5</td>
<td align="left">-31.0 ± 47.4</td>
<td align="left">0.111</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Intra-abdominal pressure (mmHg)</td>
<td align="left">1.8 ± 3.8</td>
<td align="left">-0.4 ± 3.6</td>
<td align="left">0.007</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Abdominal perfusion pressure (mmHg)</td>
<td align="left">0.4 ± 14.4</td>
<td align="left">1.3 ± 15.5</td>
<td align="left">0.785</td>
</tr>
<tr>
<td colspan="4">
<hr></hr>
</td>
</tr>
<tr>
<td align="left">Cumulative fluid balance (mL/day)</td>
<td align="left">8,027 ± 5,254</td>
<td align="left">-1,451 ± 7,761</td>
<td align="left">< 0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>SOFA, sepsis and organ failure assessment; HR, heart rate; CI, cardiac index; PEEP, positive end-expiratory pressure; EVLWI, extravascular lung water.</p>
</table-wrap-foot>
</table-wrap>
<p>CLI was significantly reduced during 1 week of PAL-treatment (62.9 ± 48.4 vs 31.9 ± 25.5,
<italic>p </italic>
< 0.001), in contrast to non-significant reductions in the control group (68.9 ± 66.3 vs 51.8 ± 42.5,
<italic>p </italic>
= 0.139).</p>
<p>In the PAL group, average PEEP for the entire week was significantly higher (11.0 ± 2.8 vs 7.9 ± 2.9 cmH
<sub>2</sub>
O,
<italic>p </italic>
< 0.001) compared to controls. PEEP level correlated with average IAP of 10.0 ± 3.4 mmHg (
<italic>R </italic>
= 0.293,
<italic>p </italic>
< 0.001).</p>
<p>After the day of enrolment, patients in the PAL group had significantly lower daily fluid balances on each day; a negative daily fluid balance was achieved on average by day 4. PAL-treated patients had a trend toward higher average urine output (1,844 ± 1,714 vs 1,681 ± 1,635 mL,
<italic>p </italic>
= 0.182). Resulting cumulative fluid balance after 1 week was significantly higher in the control group.</p>
</sec>
<sec>
<title>Effects on organ function (Figure
<xref ref-type="fig" rid="F2">2</xref>
and Table
<xref ref-type="table" rid="T2">2</xref>
)</title>
<p>Respiratory function improved significantly in the PAL group. The PaO
<sub>2</sub>
/FIO
<sub>2 </sub>
ratio increased from 174.5 ± 84.5 to 274.4 ± 116.9 (
<italic>p </italic>
< 0.001) after 1 week in PAL-treated patients but remained unchanged in the control group (256.6 ± 152.7 vs 244.2 ± 98.3,
<italic>p </italic>
= 0.641). Accordingly, respiratory SOFA score after 1 week decreased only in the PAL group. EVLWI was reduced from 12.0 ± 6.1 to 10.9 ± 3.2 mL/kg (
<italic>p </italic>
= 0.021) in the control group and from 13.4 ± 6.2 to 9.2 ± 3.6 mL/kg (
<italic>p </italic>
= 0.006) in the PAL group. Except for a higher setting of PEEP, respiratory mechanics were similar between groups at all time points.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption>
<p>
<bold>Assessment of respiratory, cardiovascular, and renal functions</bold>
. Mean ± standard error for change to baseline in respiratory function (reflected by P/F ratio and EVLWI), cardiovascular function reflected by MAP/heart rate ratio, and renal function as assessed with renal SOFA score during 1 week of PAL-treatment. PAL-treated patients are depicted by a full line and control patients by a dotted line. *
<italic>p </italic>
< 0.05, day-by-day pairwise compared between the PAL group and the control group (one-way ANOVA).</p>
</caption>
<graphic xlink:href="2110-5820-2-S1-S15-2"></graphic>
</fig>
<p>Overall hemodynamic impact assessed with cardiovascular SOFA score shows a significant improvement after 1 week in the PAL group (3.0 ± 1.2 vs 1.8 ± 1.6,
<italic>p </italic>
< 0.001) and a modest but insignificant decrease in the control group (2.9 ± 1.5 vs 2.4 ± 1.5,
<italic>p </italic>
= 0.099). Time course of the MAP/heart rate ratio is shown in Figure
<xref ref-type="fig" rid="F2">2</xref>
. Other hemodynamic monitoring variables were not significantly affected.</p>
<p>After 1 week, a higher percentage of patients required vasopressor therapy in the PAL group (Table
<xref ref-type="table" rid="T3">3</xref>
). Furthermore, average dose of norepinephrine for the entire week was greater in the PAL group (0.281 ± 0.284 vs 0.180 ± 0.129 μg/kg/min,
<italic>p </italic>
= 0.005).</p>
<table-wrap id="T3" position="float">
<label>Table 3</label>
<caption>
<p>Major outcomes</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th></th>
<th align="center">Control group</th>
<th align="center">PAL group</th>
<th align="center">
<italic>p </italic>
value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left">Death at day 28 (%)</td>
<td align="center">49.1</td>
<td align="center">28.1</td>
<td align="center">0.034</td>
</tr>
<tr>
<td align="left">ICU stay (day)</td>
<td align="center">37.1 ± 19.9</td>
<td align="center">23.6 ± 15</td>
<td align="center">0.006</td>
</tr>
<tr>
<td align="left">Hospital stay (day)</td>
<td align="center">82.5 ± 57.6</td>
<td align="center">69.8 ± 66.9</td>
<td align="center">0.475</td>
</tr>
<tr>
<td align="left">Vasopressor therapy after 1 week (%)</td>
<td align="center">30.6</td>
<td align="center">60.8</td>
<td align="center">0.003</td>
</tr>
<tr>
<td align="left">Duration mechanical ventilation (day)</td>
<td align="center">25.5 ± 20.2</td>
<td align="center">14.6 ± 10.7</td>
<td align="center">0.020</td>
</tr>
<tr>
<td align="left">Duration CRRT (day)</td>
<td align="center">6.2 ± 8.8</td>
<td align="center">10.0 ± 3.8</td>
<td align="center">0.437</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>ICU, intensive care unit; CRRT, continuous renal replacement therapy.</p>
</table-wrap-foot>
</table-wrap>
<p>Changes in renal function as assessed with renal SOFA score were similar in both groups. However, average serum creatinine during the observed week was higher in PAL-treated patients (1.9 ± 3.3 vs 1.6 ± 1.3 mg/dL,
<italic>p </italic>
= 0.038) (Table
<xref ref-type="table" rid="T2">2</xref>
).</p>
<p>As shown in Table
<xref ref-type="table" rid="T2">2</xref>
and Figure
<xref ref-type="fig" rid="F3">3</xref>
, IAP increased in the control group but remained stable in the PAL group. The APP remained unchanged during the whole week. During observation, 33.6% of patients developed IAH, 39.6% in the PAL group, and 27.8% in the control group (
<italic>p </italic>
= 0.224).</p>
<fig id="F3" position="float">
<label>Figure 3</label>
<caption>
<p>
<bold>Mean ± standard error for intra-abdominal pressure during 1 week of PAL-treatment</bold>
. IAP increases significantly in control patients and remains stable in PAL-treated patients. According to PAL-treatment protocol, PEEP level was titrated to IAP (best PEEP equals IAP) resulting in a mean PEEP of 11.0 ± 2.8 cmH
<sub>2</sub>
O. PAL-treated patients are depicted by a full line and control patients by a dotted line. *
<italic>p </italic>
< 0.05, day-by-day pairwise compared between the PAL group and the control group (one-way ANOVA).</p>
</caption>
<graphic xlink:href="2110-5820-2-S1-S15-3"></graphic>
</fig>
</sec>
<sec>
<title>Major outcomes (Table
<xref ref-type="table" rid="T3">3</xref>
and Figure
<xref ref-type="fig" rid="F4">4</xref>
)</title>
<p>A total of 44 patients (38.6%) died, with more deaths in the control group than in the PAL group (49.1 vs 28.1%,
<italic>p </italic>
= 0.034). Patients in the PAL group surviving their ICU stay required fewer days of ICU admission and days on MV. Total hospital stay and days with CRRT were similar in both groups.</p>
<fig id="F4" position="float">
<label>Figure 4</label>
<caption>
<p>
<bold>Kaplan-Meier plot for cumulative survival and days on mechanical ventilation</bold>
. PAL-treated patients are depicted by a full line and control patients by a dotted line.</p>
</caption>
<graphic xlink:href="2110-5820-2-S1-S15-4"></graphic>
</fig>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>In this study, we demonstrated that a multi-modal approach using PAL-treatment in patients with ALI achieves negative cumulative fluid balance without compromising organ function. Furthermore, compared to a matched control group, we found improved oxygenation, EVLWI and IAP reduction, fewer days on mechanical ventilation, shorter ICU stay, and reduced 28-day mortality in the PAL group.</p>
<p>The idea behind PAL-treatment aiming for negative fluid balance in a setting of capillary leak is based on the recently rediscovered concept of the ebb and flow phase [
<xref ref-type="bibr" rid="B2">2</xref>
,
<xref ref-type="bibr" rid="B13">13</xref>
,
<xref ref-type="bibr" rid="B28">28</xref>
,
<xref ref-type="bibr" rid="B29">29</xref>
]. The ebb phase represents a distributive shock characterized by increased capillary permeability and albumin leak [
<xref ref-type="bibr" rid="B2">2</xref>
,
<xref ref-type="bibr" rid="B28">28</xref>
,
<xref ref-type="bibr" rid="B30">30</xref>
]. Excess interstitial fluid leads to organ dysfunction [
<xref ref-type="bibr" rid="B31">31</xref>
], including ALI, secondary IAH [
<xref ref-type="bibr" rid="B8">8</xref>
], and associated acute kidney injury [
<xref ref-type="bibr" rid="B32">32</xref>
]. Shock reversal and subsequent hemodynamic and renal recovery sets in the transition to the flow phase resulting in mobilization of excess extravascular (lung) water [
<xref ref-type="bibr" rid="B2">2</xref>
]. Previously, a neutral to negative cumulative balance [
<xref ref-type="bibr" rid="B1">1</xref>
,
<xref ref-type="bibr" rid="B7">7</xref>
,
<xref ref-type="bibr" rid="B10">10</xref>
,
<xref ref-type="bibr" rid="B13">13</xref>
,
<xref ref-type="bibr" rid="B33">33</xref>
,
<xref ref-type="bibr" rid="B34">34</xref>
] and reduction of EVLWI were shown to correlate with improved survival [
<xref ref-type="bibr" rid="B15">15</xref>
,
<xref ref-type="bibr" rid="B16">16</xref>
,
<xref ref-type="bibr" rid="B18">18</xref>
,
<xref ref-type="bibr" rid="B19">19</xref>
].</p>
<p>PAL-treatment intends to initiate the flow phase, limiting capillary leak and promoting interstitial fluid removal while ensuring organ perfusion at the same time. Therefore, it is a specific form of restrictive fluid management, combining open lung ventilation, small volume resuscitation with hyperoncotic albumin, and aggressive fluid removal.</p>
<p>Open lung ventilation strategy in ALI signifies application of high levels of PEEP [
<xref ref-type="bibr" rid="B35">35</xref>
] and is correlated with decreases in EVLWI [
<xref ref-type="bibr" rid="B36">36</xref>
]. Both the percentage of potentially recruitable lung and EVLWI are related to outcome [
<xref ref-type="bibr" rid="B15">15</xref>
,
<xref ref-type="bibr" rid="B16">16</xref>
,
<xref ref-type="bibr" rid="B18">18</xref>
,
<xref ref-type="bibr" rid="B19">19</xref>
,
<xref ref-type="bibr" rid="B35">35</xref>
]. The open lung strategy in ALI is associated with increased alveolar fluid clearance and reduced EVLWI [
<xref ref-type="bibr" rid="B37">37</xref>
-
<xref ref-type="bibr" rid="B39">39</xref>
]. In this study, PAL-treatment was initiated in patients with low oxygenation index and high EVLWI, potentially indicating a higher proportion of recruitable lung. Within the concept of the polycompartment syndrome, we set PEEP level (cmH
<sub>2</sub>
O) equal to IAP (mmHg) in order to counteract IAP [
<xref ref-type="bibr" rid="B40">40</xref>
] (Figure
<xref ref-type="fig" rid="F3">3</xref>
).</p>
<p>Induction of the flow phase with PAL-treatment implies vascular refilling from the interstitium and subsequent removal of fluids from the body producing a net negative fluid balance. In this context, addition of small volume resuscitation with hyperoncotic albumin to a fluid removal regimen resulted in a greater negative fluid balance while maintaining better hemodynamic stability [
<xref ref-type="bibr" rid="B21">21</xref>
]. Moreover, restoration of colloid osmotic pressure in absence of elevated hydrostatic pressure may prevent further interstitial edema formation [
<xref ref-type="bibr" rid="B41">41</xref>
,
<xref ref-type="bibr" rid="B42">42</xref>
]. Accordingly, hypoproteinemia is highly predictive of positive fluid balance and development of ALI in patients with sepsis [
<xref ref-type="bibr" rid="B43">43</xref>
]. In view of PAL-treatment as a therapy for capillary leak, beneficial effects of albumin on the microcirculation may be of particular interest, attenuating capillary permeability and pulmonary inflammation [
<xref ref-type="bibr" rid="B44">44</xref>
-
<xref ref-type="bibr" rid="B47">47</xref>
].</p>
<p>PAL-treatment proved to be effective to achieve negative fluid balance. After 1 week, PAL-treated patients had a net negative cumulative fluid balance while control patients added up to a positive cumulative fluid balance, similar to other cohorts [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B20">20</xref>
]. In contrast to previous studies, negative fluid balance was pursued as a specific goal. One week of PAL-treatment did not significantly worsen cardiovascular function. Yet, more patients required vasopressor therapy and administered doses were higher. Furthermore, although renal SOFA score on each day was similar in both groups, the PAL group had higher average creatinine for the observed week. In line with previous reports, successful restrictive fluid strategy with PAL-treatment led to improved oxygenation and shortened duration of MV [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B21">21</xref>
]. Moreover, PAL-treated patients had a significant greater reduction of EVLWI. This observation possibly reflects improved healing of lung injury, better shock reversal with transition to the flow phase [
<xref ref-type="bibr" rid="B15">15</xref>
,
<xref ref-type="bibr" rid="B16">16</xref>
,
<xref ref-type="bibr" rid="B18">18</xref>
,
<xref ref-type="bibr" rid="B19">19</xref>
]. We found PAL-treated patients to have a significant reduction of CLI as a result of restoration of serum albumin.</p>
<p>Overzealous fluid therapy in a setting of capillary leak is an important risk factor for IAH, associated with organ failure and increased mortality [
<xref ref-type="bibr" rid="B48">48</xref>
]. Therefore, a fluid strategy aimed at negative fluid balance and avoiding crystalloid over-resuscitation may play an important role in preventing and even treating IAH [
<xref ref-type="bibr" rid="B49">49</xref>
]. In this context, our observations demonstrated a significant increase of IAP in controls, whereas IAP dropped in PAL-treated patients.</p>
<p>Our study has several important limitations. First, the use of historical controls may raise difficulties to ensure that obtained differences in outcome are related to the studied treatment. Indeed, we cannot deny that continuous evolving standard care has led to better outcomes in patients with acute lung injury [
<xref ref-type="bibr" rid="B50">50</xref>
]. In particular, there are indices that a more protective ventilation (not only higher PEEP as per protocol) was applied in the PAL group since at baseline controls had slightly higher tidal volumes and lower PEEP levels. However, as patients were selected for PAL-treatment based on low oxygenation indices and high EVLWI, they may have had a higher percentage of potentially recruitable lung, requiring higher PEEP levels [
<xref ref-type="bibr" rid="B35">35</xref>
].</p>
<p>Second, the large difference in mortality between the two groups has to be placed in context. Expected mortality in the control group and PAL group was 47% and 48%, computing a standardized mortality ratio of 1.04 and 1.70, respectively. Apart from the presumed better standard care over time, a selection bias may have been introduced by including only mechanically ventilated patients with thermodilution catheter monitoring. Thus, we selected a specific case mix of severely ill ALI patients prone to exhibit fluid retention, in which attention to fluid balance may be expected to have great potential benefit. In this regard, we note a considerable high cumulative fluid balance after 1 week in controls (8,027 mL), albeit similar to earlier reports [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B20">20</xref>
]. Third, since this was an open trial in which fluid therapy decisions were made by the treating physician, the lack of a strict protocol to guide fluid therapy may have introduced bias. Fourth, our database did not supply detailed information on amounts of fluids administrated in the first 6 h. The fluid balance on the day before enrolment was almost 1 L higher in controls, possibly indicating a more aggressive initial volume replacement. Exact data on the type of fluid used and the rate of hourly ultrafiltration in patients with CRRT were not recorded either.</p>
</sec>
<sec sec-type="conclusions">
<title>Conclusion</title>
<p>PAL-treatment in patients with ALI results in a negative cumulative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes. Repercussions on cardiovascular and renal function were limited. Within the concept of dual response to inflammatory injury, we conclude that PAL-treatment could safely and effectively promote the transition to flow phase. Future double-blinded trials confirming these observations and investigating PAL-treatment in other settings of capillary leak are warranted.</p>
</sec>
<sec>
<title>Abbreviations</title>
<p>ALI: acute lung injury; ANOVA: analysis of variance; APACHE: acute physiology and chronic health evaluation; APP: abdominal perfusion pressure; CI: cardiac index; CLI: capillary leak index; CO: cardiac output; CRP: C-reactive protein; CRRT: continuous renal replacement therapy; EVLW(I): extravascular lung water (index); GEDV(I): global end diastolic volume (index); GEF: global ejection fraction; IAH: intra-abdominal hypertension; IAP: intra-abdominal pressure; ICU: intensive care unit; MAP: mean arterial pressure; MV: mechanical ventilation; PAL-treatment: PEEP + albumin + Lasix (furosemide); PEEP: positive end-expiratory pressure; SAPS: simplified acute physiology score; SOFA: sepsis and organ failure assessment; SVV: stroke volume variation; vs: versus.</p>
</sec>
<sec>
<title>Competing interests</title>
<p>GM, WH, and MM are members of the medical advisory board of Pulsion Medical Systems (Munich, Germany), a monitoring company. The other authors declare that they have no competing interests.</p>
</sec>
<sec>
<title>Authors' contributions</title>
<p>CC, IDL, NVR, KS, HD, and MM planned the study and were responsible for the design, coordination, and drafting the manuscript. GM and WH participated in the study design and helped to draft the manuscript. CC and MM performed the statistical analysis and helped to draft the manuscript. All authors read and approved the final manuscript.</p>
</sec>
</body>
<back>
<sec>
<title>Acknowledgements</title>
<p>This article has been published as part of
<italic>Annals of Intensive Care </italic>
Volume 2 Supplement 1, 2012: Diagnosis and management of intra-abdominal hypertension and abdominal compartment syndrome. The full contents of the supplement are available online at
<ext-link ext-link-type="uri" xlink:href="http://www.annalsofintensivecare.com/supplements/2/S1">http://www.annalsofintensivecare.com/supplements/2/S1</ext-link>
</p>
<p>The authors are indebted to Ms. Harriet Adamson for her advice and technical assistance with the preparation of this manuscript. The authors also wish to thank the study nurses Ms. Anita Jans and Ms. Kim Serneels (ICU, ZNA Stuivenberg, Antwerp, Belgium) for their fantastic work in keeping the database up-to-date. There was no funding for this study.</p>
<p>The study is supported by the Council of Internal Medicine (head Prof Dr Pierre Zachée, MD, PhD), ZNA Stuivenberg Hospital, who paid for the open access publication fee.</p>
</sec>
<ref-list>
<ref id="B1">
<mixed-citation publication-type="journal">
<name>
<surname>Murphy</surname>
<given-names>CV</given-names>
</name>
<name>
<surname>Schramm</surname>
<given-names>GE</given-names>
</name>
<name>
<surname>Doherty</surname>
<given-names>JA</given-names>
</name>
<name>
<surname>Reichley</surname>
<given-names>RM</given-names>
</name>
<name>
<surname>Gajic</surname>
<given-names>O</given-names>
</name>
<name>
<surname>Afessa</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Micek</surname>
<given-names>ST</given-names>
</name>
<name>
<surname>Kollef</surname>
<given-names>MH</given-names>
</name>
<article-title>The importance of fluid management in acute lung injury secondary to septic shock</article-title>
<source>Chest</source>
<year>2009</year>
<volume>136</volume>
<issue>1</issue>
<fpage>102</fpage>
<lpage>109</lpage>
<pub-id pub-id-type="doi">10.1378/chest.08-2706</pub-id>
<pub-id pub-id-type="pmid">19318675</pub-id>
</mixed-citation>
</ref>
<ref id="B2">
<mixed-citation publication-type="journal">
<name>
<surname>Rivers</surname>
<given-names>EP</given-names>
</name>
<article-title>Fluid-management strategies in acute lung injury - liberal, conservative, or both?</article-title>
<source>The New England journal of medicine</source>
<year>2006</year>
<volume>354</volume>
<issue>24</issue>
<fpage>2598</fpage>
<lpage>2600</lpage>
<pub-id pub-id-type="doi">10.1056/NEJMe068105</pub-id>
<pub-id pub-id-type="pmid">16714769</pub-id>
</mixed-citation>
</ref>
<ref id="B3">
<mixed-citation publication-type="journal">
<name>
<surname>Prowle</surname>
<given-names>JR</given-names>
</name>
<name>
<surname>Echeverri</surname>
<given-names>JE</given-names>
</name>
<name>
<surname>Ligabo</surname>
<given-names>EV</given-names>
</name>
<name>
<surname>Ronco</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Bellomo</surname>
<given-names>R</given-names>
</name>
<article-title>Fluid balance and acute kidney injury</article-title>
<source>Nature reviews</source>
<year>2010</year>
<volume>6</volume>
<issue>2</issue>
<fpage>107</fpage>
<lpage>115</lpage>
</mixed-citation>
</ref>
<ref id="B4">
<mixed-citation publication-type="journal">
<name>
<surname>Schrier</surname>
<given-names>RW</given-names>
</name>
<article-title>Fluid administration in critically ill patients with acute kidney injury</article-title>
<source>Clin J Am Soc Nephrol</source>
<year>2010</year>
<volume>5</volume>
<issue>4</issue>
<fpage>733</fpage>
<lpage>739</lpage>
<pub-id pub-id-type="doi">10.2215/CJN.00060110</pub-id>
<pub-id pub-id-type="pmid">20167687</pub-id>
</mixed-citation>
</ref>
<ref id="B5">
<mixed-citation publication-type="journal">
<name>
<surname>Bagshaw</surname>
<given-names>SM</given-names>
</name>
<name>
<surname>Brophy</surname>
<given-names>PD</given-names>
</name>
<name>
<surname>Cruz</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Ronco</surname>
<given-names>C</given-names>
</name>
<article-title>Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury</article-title>
<source>Critical care</source>
<year>2008</year>
<volume>12</volume>
<issue>4</issue>
<fpage>169</fpage>
<pub-id pub-id-type="doi">10.1186/cc6948</pub-id>
<pub-id pub-id-type="pmid">18671831</pub-id>
</mixed-citation>
</ref>
<ref id="B6">
<mixed-citation publication-type="journal">
<name>
<surname>Rivers</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Nguyen</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Havstad</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Ressler</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Muzzin</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Knoblich</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Peterson</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Tomlanovich</surname>
<given-names>M</given-names>
</name>
<article-title>Early goal-directed therapy in the treatment of severe sepsis and septic shock</article-title>
<source>The New England journal of medicine</source>
<year>2001</year>
<volume>345</volume>
<issue>19</issue>
<fpage>1368</fpage>
<lpage>1377</lpage>
<pub-id pub-id-type="doi">10.1056/NEJMoa010307</pub-id>
<pub-id pub-id-type="pmid">11794169</pub-id>
</mixed-citation>
</ref>
<ref id="B7">
<mixed-citation publication-type="journal">
<name>
<surname>Sakr</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Vincent</surname>
<given-names>JL</given-names>
</name>
<name>
<surname>Reinhart</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Groeneveld</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Michalopoulos</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Sprung</surname>
<given-names>CL</given-names>
</name>
<name>
<surname>Artigas</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Ranieri</surname>
<given-names>VM</given-names>
</name>
<article-title>High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury</article-title>
<source>Chest</source>
<year>2005</year>
<volume>128</volume>
<issue>5</issue>
<fpage>3098</fpage>
<lpage>3108</lpage>
<pub-id pub-id-type="doi">10.1378/chest.128.5.3098</pub-id>
<pub-id pub-id-type="pmid">16304249</pub-id>
</mixed-citation>
</ref>
<ref id="B8">
<mixed-citation publication-type="journal">
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Cheatham</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Kirkpatrick</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Sugrue</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Parr</surname>
<given-names>M</given-names>
</name>
<name>
<surname>De Waele</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Balogh</surname>
<given-names>Z</given-names>
</name>
<name>
<surname>Leppaniemi</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Olvera</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Ivatury</surname>
<given-names>R</given-names>
</name>
<name>
<surname>D'Amours</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Wendon</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Hillman</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Johansson</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kolkman</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Wilmer</surname>
<given-names>A</given-names>
</name>
<article-title>Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. I. Definitions</article-title>
<source>Intensive care medicine</source>
<year>2006</year>
<volume>32</volume>
<issue>11</issue>
<fpage>1722</fpage>
<lpage>1732</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-006-0349-5</pub-id>
<pub-id pub-id-type="pmid">16967294</pub-id>
</mixed-citation>
</ref>
<ref id="B9">
<mixed-citation publication-type="journal">
<name>
<surname>Vincent</surname>
<given-names>JL</given-names>
</name>
<name>
<surname>Sakr</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Sprung</surname>
<given-names>CL</given-names>
</name>
<name>
<surname>Ranieri</surname>
<given-names>VM</given-names>
</name>
<name>
<surname>Reinhart</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Gerlach</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Moreno</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Carlet</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Le Gall</surname>
<given-names>JR</given-names>
</name>
<name>
<surname>Payen</surname>
<given-names>D</given-names>
</name>
<article-title>Sepsis in European intensive care units: results of the SOAP study</article-title>
<source>Critical care medicine</source>
<year>2006</year>
<volume>34</volume>
<issue>2</issue>
<fpage>344</fpage>
<lpage>353</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000194725.48928.3A</pub-id>
<pub-id pub-id-type="pmid">16424713</pub-id>
</mixed-citation>
</ref>
<ref id="B10">
<mixed-citation publication-type="journal">
<name>
<surname>Rosenberg</surname>
<given-names>AL</given-names>
</name>
<name>
<surname>Dechert</surname>
<given-names>RE</given-names>
</name>
<name>
<surname>Park</surname>
<given-names>PK</given-names>
</name>
<name>
<surname>Bartlett</surname>
<given-names>RH</given-names>
</name>
<article-title>Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort</article-title>
<source>Journal of intensive care medicine</source>
<year>2009</year>
<volume>24</volume>
<issue>1</issue>
<fpage>35</fpage>
<lpage>46</lpage>
<pub-id pub-id-type="pmid">19103612</pub-id>
</mixed-citation>
</ref>
<ref id="B11">
<mixed-citation publication-type="journal">
<name>
<surname>Payen</surname>
<given-names>D</given-names>
</name>
<name>
<surname>de Pont</surname>
<given-names>AC</given-names>
</name>
<name>
<surname>Sakr</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Spies</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Reinhart</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Vincent</surname>
<given-names>JL</given-names>
</name>
<article-title>A positive fluid balance is associated with a worse outcome in patients with acute renal failure</article-title>
<source>Critical care</source>
<year>2008</year>
<volume>12</volume>
<issue>3</issue>
<fpage>R74</fpage>
<pub-id pub-id-type="doi">10.1186/cc6916</pub-id>
<pub-id pub-id-type="pmid">18533029</pub-id>
</mixed-citation>
</ref>
<ref id="B12">
<mixed-citation publication-type="journal">
<name>
<surname>Wiedemann</surname>
<given-names>HP</given-names>
</name>
<name>
<surname>Wheeler</surname>
<given-names>AP</given-names>
</name>
<name>
<surname>Bernard</surname>
<given-names>GR</given-names>
</name>
<name>
<surname>Thompson</surname>
<given-names>BT</given-names>
</name>
<name>
<surname>Hayden</surname>
<given-names>D</given-names>
</name>
<name>
<surname>deBoisblanc</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Connors</surname>
<given-names>AF</given-names>
<suffix>Jr</suffix>
</name>
<name>
<surname>Hite</surname>
<given-names>RD</given-names>
</name>
<name>
<surname>Harabin</surname>
<given-names>AL</given-names>
</name>
<article-title>Comparison of two fluid-management strategies in acute lung injury</article-title>
<source>The New England journal of medicine</source>
<year>2006</year>
<volume>354</volume>
<issue>24</issue>
<fpage>2564</fpage>
<lpage>2575</lpage>
<pub-id pub-id-type="pmid">16714767</pub-id>
</mixed-citation>
</ref>
<ref id="B13">
<mixed-citation publication-type="journal">
<name>
<surname>Alsous</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Khamiees</surname>
<given-names>M</given-names>
</name>
<name>
<surname>DeGirolamo</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Amoateng-Adjepong</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Manthous</surname>
<given-names>CA</given-names>
</name>
<article-title>Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study</article-title>
<source>Chest</source>
<year>2000</year>
<volume>117</volume>
<issue>6</issue>
<fpage>1749</fpage>
<lpage>1754</lpage>
<pub-id pub-id-type="doi">10.1378/chest.117.6.1749</pub-id>
<pub-id pub-id-type="pmid">10858412</pub-id>
</mixed-citation>
</ref>
<ref id="B14">
<mixed-citation publication-type="journal">
<name>
<surname>Berkowitz</surname>
<given-names>DM</given-names>
</name>
<name>
<surname>Danai</surname>
<given-names>PA</given-names>
</name>
<name>
<surname>Eaton</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Moss</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Martin</surname>
<given-names>GS</given-names>
</name>
<article-title>Accurate characterization of extravascular lung water in acute respiratory distress syndrome</article-title>
<source>Critical care medicine</source>
<year>2008</year>
<volume>36</volume>
<issue>6</issue>
<fpage>1803</fpage>
<lpage>1809</lpage>
<pub-id pub-id-type="doi">10.1097/CCM.0b013e3181743eeb</pub-id>
<pub-id pub-id-type="pmid">18496374</pub-id>
</mixed-citation>
</ref>
<ref id="B15">
<mixed-citation publication-type="journal">
<name>
<surname>Kuzkov</surname>
<given-names>VV</given-names>
</name>
<name>
<surname>Kirov</surname>
<given-names>MY</given-names>
</name>
<name>
<surname>Sovershaev</surname>
<given-names>MA</given-names>
</name>
<name>
<surname>Kuklin</surname>
<given-names>VN</given-names>
</name>
<name>
<surname>Suborov</surname>
<given-names>EV</given-names>
</name>
<name>
<surname>Waerhaug</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Bjertnaes</surname>
<given-names>LJ</given-names>
</name>
<article-title>Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury</article-title>
<source>Critical care medicine</source>
<year>2006</year>
<volume>34</volume>
<issue>6</issue>
<fpage>1647</fpage>
<lpage>1653</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000218817.24208.2E</pub-id>
<pub-id pub-id-type="pmid">16625129</pub-id>
</mixed-citation>
</ref>
<ref id="B16">
<mixed-citation publication-type="journal">
<name>
<surname>Phillips</surname>
<given-names>CR</given-names>
</name>
<name>
<surname>Chesnutt</surname>
<given-names>MS</given-names>
</name>
<name>
<surname>Smith</surname>
<given-names>SM</given-names>
</name>
<article-title>Extravascular lung water in sepsis-associated acute respiratory distress syndrome: indexing with predicted body weight improves correlation with severity of illness and survival</article-title>
<source>Critical care medicine</source>
<year>2008</year>
<volume>36</volume>
<issue>1</issue>
<fpage>69</fpage>
<lpage>73</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000295314.01232.BE</pub-id>
<pub-id pub-id-type="pmid">18090369</pub-id>
</mixed-citation>
</ref>
<ref id="B17">
<mixed-citation publication-type="journal">
<name>
<surname>Sakka</surname>
<given-names>SG</given-names>
</name>
<name>
<surname>Ruhl</surname>
<given-names>CC</given-names>
</name>
<name>
<surname>Pfeiffer</surname>
<given-names>UJ</given-names>
</name>
<name>
<surname>Beale</surname>
<given-names>R</given-names>
</name>
<name>
<surname>McLuckie</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Reinhart</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Meier-Hellmann</surname>
<given-names>A</given-names>
</name>
<article-title>Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution</article-title>
<source>Intensive care medicine</source>
<year>2000</year>
<volume>26</volume>
<issue>2</issue>
<fpage>180</fpage>
<lpage>187</lpage>
<pub-id pub-id-type="doi">10.1007/s001340050043</pub-id>
<pub-id pub-id-type="pmid">10784306</pub-id>
</mixed-citation>
</ref>
<ref id="B18">
<mixed-citation publication-type="journal">
<name>
<surname>Sakka</surname>
<given-names>SG</given-names>
</name>
<name>
<surname>Klein</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Reinhart</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Meier-Hellmann</surname>
<given-names>A</given-names>
</name>
<article-title>Prognostic value of extravascular lung water in critically ill patients</article-title>
<source>Chest</source>
<year>2002</year>
<volume>122</volume>
<issue>6</issue>
<fpage>2080</fpage>
<lpage>2086</lpage>
<pub-id pub-id-type="doi">10.1378/chest.122.6.2080</pub-id>
<pub-id pub-id-type="pmid">12475851</pub-id>
</mixed-citation>
</ref>
<ref id="B19">
<mixed-citation publication-type="journal">
<name>
<surname>Martin</surname>
<given-names>GS</given-names>
</name>
<name>
<surname>Eaton</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Mealer</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Moss</surname>
<given-names>M</given-names>
</name>
<article-title>Extravascular lung water in patients with severe sepsis: a prospective cohort study</article-title>
<source>Critical care</source>
<year>2005</year>
<volume>9</volume>
<issue>2</issue>
<fpage>R74</fpage>
<lpage>82</lpage>
<pub-id pub-id-type="doi">10.1186/cc3025</pub-id>
<pub-id pub-id-type="pmid">15774053</pub-id>
</mixed-citation>
</ref>
<ref id="B20">
<mixed-citation publication-type="journal">
<name>
<surname>Mitchell</surname>
<given-names>JP</given-names>
</name>
<name>
<surname>Schuller</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Calandrino</surname>
<given-names>FS</given-names>
</name>
<name>
<surname>Schuster</surname>
<given-names>DP</given-names>
</name>
<article-title>Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization</article-title>
<source>The American review of respiratory disease</source>
<year>1992</year>
<volume>145</volume>
<issue>5</issue>
<fpage>990</fpage>
<lpage>998</lpage>
<pub-id pub-id-type="doi">10.1164/ajrccm/145.5.990</pub-id>
<pub-id pub-id-type="pmid">1586077</pub-id>
</mixed-citation>
</ref>
<ref id="B21">
<mixed-citation publication-type="journal">
<name>
<surname>Martin</surname>
<given-names>GS</given-names>
</name>
<name>
<surname>Moss</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Wheeler</surname>
<given-names>AP</given-names>
</name>
<name>
<surname>Mealer</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Morris</surname>
<given-names>JA</given-names>
</name>
<name>
<surname>Bernard</surname>
<given-names>GR</given-names>
</name>
<article-title>A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury</article-title>
<source>Critical care medicine</source>
<year>2005</year>
<volume>33</volume>
<issue>8</issue>
<fpage>1681</fpage>
<lpage>1687</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000171539.47006.02</pub-id>
<pub-id pub-id-type="pmid">16096441</pub-id>
</mixed-citation>
</ref>
<ref id="B22">
<mixed-citation publication-type="journal">
<name>
<surname>Bernard</surname>
<given-names>GR</given-names>
</name>
<name>
<surname>Artigas</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Brigham</surname>
<given-names>KL</given-names>
</name>
<name>
<surname>Carlet</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Falke</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Hudson</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Lamy</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Legall</surname>
<given-names>JR</given-names>
</name>
<name>
<surname>Morris</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Spragg</surname>
<given-names>R</given-names>
</name>
<article-title>The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination</article-title>
<source>American journal of respiratory and critical care medicine</source>
<year>1994</year>
<volume>149</volume>
<issue>3 Pt 1</issue>
<fpage>818</fpage>
<lpage>824</lpage>
<pub-id pub-id-type="pmid">7509706</pub-id>
</mixed-citation>
</ref>
<ref id="B23">
<mixed-citation publication-type="journal">
<name>
<surname>Deeren</surname>
<given-names>DH</given-names>
</name>
<name>
<surname>Zachee</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<article-title>Granulocyte colony-stimulating factor-induced capillary leak syndrome confirmed by extravascular lung water measurements</article-title>
<source>Annals of hematology</source>
<year>2005</year>
<volume>84</volume>
<issue>2</issue>
<fpage>89</fpage>
<lpage>94</lpage>
<pub-id pub-id-type="doi">10.1007/s00277-004-0946-8</pub-id>
<pub-id pub-id-type="pmid">15365768</pub-id>
</mixed-citation>
</ref>
<ref id="B24">
<mixed-citation publication-type="journal">
<name>
<surname>Le Gall</surname>
<given-names>JR</given-names>
</name>
<name>
<surname>Lemeshow</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Saulnier</surname>
<given-names>F</given-names>
</name>
<article-title>A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study</article-title>
<source>Jama</source>
<year>1993</year>
<volume>270</volume>
<issue>24</issue>
<fpage>2957</fpage>
<lpage>2963</lpage>
<pub-id pub-id-type="doi">10.1001/jama.1993.03510240069035</pub-id>
<pub-id pub-id-type="pmid">8254858</pub-id>
</mixed-citation>
</ref>
<ref id="B25">
<mixed-citation publication-type="journal">
<name>
<surname>Knaus</surname>
<given-names>WA</given-names>
</name>
<name>
<surname>Draper</surname>
<given-names>EA</given-names>
</name>
<name>
<surname>Wagner</surname>
<given-names>DP</given-names>
</name>
<name>
<surname>Zimmerman</surname>
<given-names>JE</given-names>
</name>
<article-title>APACHE II: a severity of disease classification system</article-title>
<source>Critical care medicine</source>
<year>1985</year>
<volume>13</volume>
<issue>10</issue>
<fpage>818</fpage>
<lpage>829</lpage>
<pub-id pub-id-type="doi">10.1097/00003246-198510000-00009</pub-id>
<pub-id pub-id-type="pmid">3928249</pub-id>
</mixed-citation>
</ref>
<ref id="B26">
<mixed-citation publication-type="journal">
<name>
<surname>Vincent</surname>
<given-names>JL</given-names>
</name>
<name>
<surname>de Mendonca</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Cantraine</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Moreno</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Takala</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Suter</surname>
<given-names>PM</given-names>
</name>
<name>
<surname>Sprung</surname>
<given-names>CL</given-names>
</name>
<name>
<surname>Colardyn</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Blecher</surname>
<given-names>S</given-names>
</name>
<article-title>Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine</article-title>
<source>Critical care medicine</source>
<year>1998</year>
<volume>26</volume>
<issue>11</issue>
<fpage>1793</fpage>
<lpage>1800</lpage>
<pub-id pub-id-type="doi">10.1097/00003246-199811000-00016</pub-id>
<pub-id pub-id-type="pmid">9824069</pub-id>
</mixed-citation>
</ref>
<ref id="B27">
<mixed-citation publication-type="journal">
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<article-title>Different techniques to measure intra-abdominal pressure (IAP): time for a critical re-appraisal</article-title>
<source>Intensive care medicine</source>
<year>2004</year>
<volume>30</volume>
<issue>3</issue>
<fpage>357</fpage>
<lpage>371</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-003-2107-2</pub-id>
<pub-id pub-id-type="pmid">14730376</pub-id>
</mixed-citation>
</ref>
<ref id="B28">
<mixed-citation publication-type="journal">
<name>
<surname>Cuthbertson</surname>
<given-names>DP</given-names>
</name>
<article-title>Post-shock metabolic response</article-title>
<source>Lancet</source>
<year>1942</year>
<volume>i</volume>
<fpage>433</fpage>
<lpage>447</lpage>
</mixed-citation>
</ref>
<ref id="B29">
<mixed-citation publication-type="journal">
<name>
<surname>Cerda</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Sheinfeld</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Ronco</surname>
<given-names>C</given-names>
</name>
<article-title>Fluid overload in critically ill patients with acute kidney injury</article-title>
<source>Blood purification</source>
<year>2010</year>
<volume>29</volume>
<issue>4</issue>
<fpage>331</fpage>
<lpage>338</lpage>
<pub-id pub-id-type="doi">10.1159/000287776</pub-id>
<pub-id pub-id-type="pmid">20173320</pub-id>
</mixed-citation>
</ref>
<ref id="B30">
<mixed-citation publication-type="journal">
<name>
<surname>Elbers</surname>
<given-names>PW</given-names>
</name>
<name>
<surname>Ince</surname>
<given-names>C</given-names>
</name>
<article-title>Mechanisms of critical illness - classifying microcirculatory flow abnormalities in distributive shock</article-title>
<source>Critical care</source>
<year>2006</year>
<volume>10</volume>
<issue>4</issue>
<fpage>221</fpage>
<pub-id pub-id-type="doi">10.1186/cc4969</pub-id>
<pub-id pub-id-type="pmid">16879732</pub-id>
</mixed-citation>
</ref>
<ref id="B31">
<mixed-citation publication-type="journal">
<name>
<surname>Nieuwenhuijzen</surname>
<given-names>GA</given-names>
</name>
<name>
<surname>Knapen</surname>
<given-names>MF</given-names>
</name>
<name>
<surname>Oyen</surname>
<given-names>WJ</given-names>
</name>
<name>
<surname>Hendriks</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Corstens</surname>
<given-names>FH</given-names>
</name>
<name>
<surname>Goris</surname>
<given-names>RJ</given-names>
</name>
<article-title>Organ damage is preceded by changes in protein extravasation in an experimental model of multiple organ dysfunction syndrome</article-title>
<source>Shock</source>
<year>1997</year>
<volume>7</volume>
<issue>2</issue>
<fpage>98</fpage>
<lpage>104</lpage>
<pub-id pub-id-type="doi">10.1097/00024382-199702000-00005</pub-id>
<pub-id pub-id-type="pmid">9035285</pub-id>
</mixed-citation>
</ref>
<ref id="B32">
<mixed-citation publication-type="journal">
<name>
<surname>Dalfino</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Tullo</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Donadio</surname>
<given-names>I</given-names>
</name>
<name>
<surname>Malcangi</surname>
<given-names>V</given-names>
</name>
<name>
<surname>Brienza</surname>
<given-names>N</given-names>
</name>
<article-title>Intra-abdominal hypertension and acute renal failure in critically ill patients</article-title>
<source>Intensive care medicine</source>
<year>2008</year>
<volume>34</volume>
<issue>4</issue>
<fpage>707</fpage>
<lpage>713</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-007-0969-4</pub-id>
<pub-id pub-id-type="pmid">18157662</pub-id>
</mixed-citation>
</ref>
<ref id="B33">
<mixed-citation publication-type="journal">
<name>
<surname>Simmons</surname>
<given-names>RS</given-names>
</name>
<name>
<surname>Berdine</surname>
<given-names>GG</given-names>
</name>
<name>
<surname>Seidenfeld</surname>
<given-names>JJ</given-names>
</name>
<name>
<surname>Prihoda</surname>
<given-names>TJ</given-names>
</name>
<name>
<surname>Harris</surname>
<given-names>GD</given-names>
</name>
<name>
<surname>Smith</surname>
<given-names>JD</given-names>
</name>
<name>
<surname>Gilbert</surname>
<given-names>TJ</given-names>
</name>
<name>
<surname>Mota</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Johanson</surname>
<given-names>WG</given-names>
<suffix>Jr</suffix>
</name>
<article-title>Fluid balance and the adult respiratory distress syndrome</article-title>
<source>The American review of respiratory disease</source>
<year>1987</year>
<volume>135</volume>
<issue>4</issue>
<fpage>924</fpage>
<lpage>929</lpage>
<pub-id pub-id-type="pmid">3565940</pub-id>
</mixed-citation>
</ref>
<ref id="B34">
<mixed-citation publication-type="journal">
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Chiumello</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Pelosi</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Bihari</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Innes</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Ranieri</surname>
<given-names>VM</given-names>
</name>
<name>
<surname>Del Turco</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Wilmer</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Brienza</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Malcangi</surname>
<given-names>V</given-names>
</name>
<name>
<surname>Cohen</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Japiassu</surname>
<given-names>A</given-names>
</name>
<name>
<surname>De Keulenaer</surname>
<given-names>BL</given-names>
</name>
<name>
<surname>Daelemans</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Jacquet</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Laterre</surname>
<given-names>PF</given-names>
</name>
<name>
<surname>Frank</surname>
<given-names>G</given-names>
</name>
<name>
<surname>de Souza</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Cesana</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Gattinoni</surname>
<given-names>L</given-names>
</name>
<article-title>Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study</article-title>
<source>Critical care medicine</source>
<year>2005</year>
<volume>33</volume>
<issue>2</issue>
<fpage>315</fpage>
<lpage>322</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000153408.09806.1B</pub-id>
<pub-id pub-id-type="pmid">15699833</pub-id>
</mixed-citation>
</ref>
<ref id="B35">
<mixed-citation publication-type="journal">
<name>
<surname>Gattinoni</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Caironi</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Cressoni</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Chiumello</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Ranieri</surname>
<given-names>VM</given-names>
</name>
<name>
<surname>Quintel</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Russo</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Patroniti</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Cornejo</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Bugedo</surname>
<given-names>G</given-names>
</name>
<article-title>Lung recruitment in patients with the acute respiratory distress syndrome</article-title>
<source>The New England journal of medicine</source>
<year>2006</year>
<volume>354</volume>
<issue>17</issue>
<fpage>1775</fpage>
<lpage>1786</lpage>
<pub-id pub-id-type="doi">10.1056/NEJMoa052052</pub-id>
<pub-id pub-id-type="pmid">16641394</pub-id>
</mixed-citation>
</ref>
<ref id="B36">
<mixed-citation publication-type="journal">
<name>
<surname>Luecke</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Roth</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Herrmann</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Joachim</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Weisser</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Pelosi</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Quintel</surname>
<given-names>M</given-names>
</name>
<article-title>PEEP decreases atelectasis and extravascular lung water but not lung tissue volume in surfactant-washout lung injury</article-title>
<source>Intensive care medicine</source>
<year>2003</year>
<volume>29</volume>
<issue>11</issue>
<fpage>2026</fpage>
<lpage>2033</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-003-1906-9</pub-id>
<pub-id pub-id-type="pmid">12897993</pub-id>
</mixed-citation>
</ref>
<ref id="B37">
<mixed-citation publication-type="journal">
<name>
<surname>Garcia-Delgado</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Touma-Fernandez</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Chamorro-Marin</surname>
<given-names>V</given-names>
</name>
<name>
<surname>Ruiz-Aguilar</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Aguilar-Alonso</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Fernandez-Mondejar</surname>
<given-names>E</given-names>
</name>
<article-title>Alveolar fluid clearance in healthy pigs and influence of positive end-expiratory pressure</article-title>
<source>Critical care</source>
<year>2010</year>
<volume>14</volume>
<issue>2</issue>
<fpage>R36</fpage>
<pub-id pub-id-type="doi">10.1186/cc8914</pub-id>
<pub-id pub-id-type="pmid">20233408</pub-id>
</mixed-citation>
</ref>
<ref id="B38">
<mixed-citation publication-type="journal">
<name>
<surname>Ruiz-Bailen</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Fernandez-Mondejar</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Hurtado-Ruiz</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Colmenero-Ruiz</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Rivera-Fernandez</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Guerrero-Lopez</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Vazquez-Mata</surname>
<given-names>G</given-names>
</name>
<article-title>Immediate application of positive-end expiratory pressure is more effective than delayed positive-end expiratory pressure to reduce extravascular lung water</article-title>
<source>Critical care medicine</source>
<year>1999</year>
<volume>27</volume>
<issue>2</issue>
<fpage>380</fpage>
<lpage>384</lpage>
<pub-id pub-id-type="doi">10.1097/00003246-199902000-00046</pub-id>
<pub-id pub-id-type="pmid">10075064</pub-id>
</mixed-citation>
</ref>
<ref id="B39">
<mixed-citation publication-type="journal">
<name>
<surname>Chen</surname>
<given-names>YM</given-names>
</name>
<name>
<surname>Yang</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Qiu</surname>
<given-names>HB</given-names>
</name>
<name>
<surname>Li</surname>
<given-names>JQ</given-names>
</name>
<name>
<surname>Huang</surname>
<given-names>YZ</given-names>
</name>
<name>
<surname>Xu</surname>
<given-names>XT</given-names>
</name>
<article-title>[Effect of protective ventilation and open lung strategy on extravascular lung water in rabbits with acute respiratory distress syndrome]</article-title>
<source>Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases</source>
<year>2005</year>
<volume>28</volume>
<issue>9</issue>
<fpage>615</fpage>
<lpage>618</lpage>
<pub-id pub-id-type="pmid">16207430</pub-id>
</mixed-citation>
</ref>
<ref id="B40">
<mixed-citation publication-type="journal">
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Wilmer</surname>
<given-names>A</given-names>
</name>
<article-title>The polycompartment syndrome: towards an understanding of the interactions between different compartments!</article-title>
<source>Intensive care medicine</source>
<year>2007</year>
<volume>33</volume>
<issue>11</issue>
<fpage>1869</fpage>
<lpage>1872</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-007-0843-4</pub-id>
<pub-id pub-id-type="pmid">17786404</pub-id>
</mixed-citation>
</ref>
<ref id="B41">
<mixed-citation publication-type="journal">
<name>
<surname>Starling</surname>
<given-names>EH</given-names>
</name>
<article-title>On the absorption of fluids from the connective tissue spaces</article-title>
<source>The Journal of physiology</source>
<year>1896</year>
<volume>19</volume>
<issue>4</issue>
<fpage>312</fpage>
<lpage>326</lpage>
</mixed-citation>
</ref>
<ref id="B42">
<mixed-citation publication-type="journal">
<name>
<surname>Cribbs</surname>
<given-names>SK</given-names>
</name>
<name>
<surname>Martin</surname>
<given-names>GS</given-names>
</name>
<article-title>Fluid balance and colloid osmotic pressure in acute respiratory failure: optimizing therapy</article-title>
<source>Expert review of respiratory medicine</source>
<year>2009</year>
<volume>3</volume>
<issue>6</issue>
<fpage>651</fpage>
<lpage>662</lpage>
<pub-id pub-id-type="doi">10.1586/ers.09.49</pub-id>
<pub-id pub-id-type="pmid">20477354</pub-id>
</mixed-citation>
</ref>
<ref id="B43">
<mixed-citation publication-type="journal">
<name>
<surname>Mangialardi</surname>
<given-names>RJ</given-names>
</name>
<name>
<surname>Martin</surname>
<given-names>GS</given-names>
</name>
<name>
<surname>Bernard</surname>
<given-names>GR</given-names>
</name>
<name>
<surname>Wheeler</surname>
<given-names>AP</given-names>
</name>
<name>
<surname>Christman</surname>
<given-names>BW</given-names>
</name>
<name>
<surname>Dupont</surname>
<given-names>WD</given-names>
</name>
<name>
<surname>Higgins</surname>
<given-names>SB</given-names>
</name>
<name>
<surname>Swindell</surname>
<given-names>BB</given-names>
</name>
<article-title>Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group</article-title>
<source>Critical care medicine</source>
<year>2000</year>
<volume>28</volume>
<issue>9</issue>
<fpage>3137</fpage>
<lpage>3145</lpage>
<pub-id pub-id-type="doi">10.1097/00003246-200009000-00001</pub-id>
<pub-id pub-id-type="pmid">11008971</pub-id>
</mixed-citation>
</ref>
<ref id="B44">
<mixed-citation publication-type="journal">
<name>
<surname>Lum</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Siflinger-Birnboim</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Blumenstock</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Malik</surname>
<given-names>AB</given-names>
</name>
<article-title>Serum albumin decreases transendothelial permeability to macromolecules</article-title>
<source>Microvascular research</source>
<year>1991</year>
<volume>42</volume>
<issue>1</issue>
<fpage>91</fpage>
<lpage>102</lpage>
<pub-id pub-id-type="doi">10.1016/0026-2862(91)90077-O</pub-id>
<pub-id pub-id-type="pmid">1921757</pub-id>
</mixed-citation>
</ref>
<ref id="B45">
<mixed-citation publication-type="journal">
<name>
<surname>Qiao</surname>
<given-names>RL</given-names>
</name>
<name>
<surname>Ying</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Bhattacharya</surname>
<given-names>J</given-names>
</name>
<article-title>Effects of hyperoncotic albumin on endothelial barrier properties of rat lung</article-title>
<source>The American journal of physiology</source>
<year>1993</year>
<volume>265</volume>
<issue>1 Pt 2</issue>
<fpage>H198</fpage>
<lpage>204</lpage>
<pub-id pub-id-type="pmid">7688190</pub-id>
</mixed-citation>
</ref>
<ref id="B46">
<mixed-citation publication-type="journal">
<name>
<surname>Zhang</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Voglis</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>CH</given-names>
</name>
<name>
<surname>Slutsky</surname>
<given-names>AS</given-names>
</name>
<article-title>Effects of albumin and Ringer's lactate on production of lung cytokines and hydrogen peroxide after resuscitated hemorrhage and endotoxemia in rats</article-title>
<source>Critical care medicine</source>
<year>2003</year>
<volume>31</volume>
<issue>5</issue>
<fpage>1515</fpage>
<lpage>1522</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000065271.23556.FF</pub-id>
<pub-id pub-id-type="pmid">12771627</pub-id>
</mixed-citation>
</ref>
<ref id="B47">
<mixed-citation publication-type="journal">
<name>
<surname>Powers</surname>
<given-names>KA</given-names>
</name>
<name>
<surname>Kapus</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Khadaroo</surname>
<given-names>RG</given-names>
</name>
<name>
<surname>He</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Marshall</surname>
<given-names>JC</given-names>
</name>
<name>
<surname>Lindsay</surname>
<given-names>TF</given-names>
</name>
<name>
<surname>Rotstein</surname>
<given-names>OD</given-names>
</name>
<article-title>Twenty-five percent albumin prevents lung injury following shock/resuscitation</article-title>
<source>Critical care medicine</source>
<year>2003</year>
<volume>31</volume>
<issue>9</issue>
<fpage>2355</fpage>
<lpage>2363</lpage>
<pub-id pub-id-type="doi">10.1097/01.CCM.0000084846.45830.AA</pub-id>
<pub-id pub-id-type="pmid">14501967</pub-id>
</mixed-citation>
</ref>
<ref id="B48">
<mixed-citation publication-type="journal">
<name>
<surname>Malbrain</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Chiumello</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Pelosi</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Wilmer</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Brienza</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Malcangi</surname>
<given-names>V</given-names>
</name>
<name>
<surname>Bihari</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Innes</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Cohen</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Singer</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Japiassu</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Kurtop</surname>
<given-names>E</given-names>
</name>
<name>
<surname>De Keulenaer</surname>
<given-names>BL</given-names>
</name>
<name>
<surname>Daelemans</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Del Turco</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Cosimini</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Ranieri</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Jacquet</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Laterre</surname>
<given-names>PF</given-names>
</name>
<name>
<surname>Gattinoni</surname>
<given-names>L</given-names>
</name>
<article-title>Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study</article-title>
<source>Intensive care medicine</source>
<year>2004</year>
<volume>30</volume>
<issue>5</issue>
<fpage>822</fpage>
<lpage>829</lpage>
<pub-id pub-id-type="doi">10.1007/s00134-004-2169-9</pub-id>
<pub-id pub-id-type="pmid">14758472</pub-id>
</mixed-citation>
</ref>
<ref id="B49">
<mixed-citation publication-type="journal">
<name>
<surname>Kula</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Szturz</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Sklienka</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Neiser</surname>
<given-names>J</given-names>
</name>
<article-title>Negative fluid balance in patients with abdominal compartment syndrome - case reports</article-title>
<source>Acta chirurgica Belgica</source>
<year>2008</year>
<volume>108</volume>
<issue>3</issue>
<fpage>346</fpage>
<lpage>349</lpage>
<pub-id pub-id-type="pmid">18710113</pub-id>
</mixed-citation>
</ref>
<ref id="B50">
<mixed-citation publication-type="journal">
<name>
<surname>Milberg</surname>
<given-names>JA</given-names>
</name>
<name>
<surname>Davis</surname>
<given-names>DR</given-names>
</name>
<name>
<surname>Steinberg</surname>
<given-names>KP</given-names>
</name>
<name>
<surname>Hudson</surname>
<given-names>LD</given-names>
</name>
<article-title>Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993</article-title>
<source>Jama</source>
<year>1995</year>
<volume>273</volume>
<issue>4</issue>
<fpage>306</fpage>
<lpage>309</lpage>
<pub-id pub-id-type="doi">10.1001/jama.1995.03520280052039</pub-id>
<pub-id pub-id-type="pmid">7815658</pub-id>
</mixed-citation>
</ref>
</ref-list>
</back>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Belgique/explor/OpenAccessBelV2/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000288 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000288 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Belgique
   |area=    OpenAccessBelV2
   |flux=    Pmc
   |étape=   Corpus
   |type=    RBID
   |clé=     PMC:3390296
   |texte=   Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i   -Sk "pubmed:22873416" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd   \
       | NlmPubMed2Wicri -a OpenAccessBelV2 

Wicri

This area was generated with Dilib version V0.6.25.
Data generation: Thu Dec 1 00:43:49 2016. Site generation: Wed Mar 6 14:51:30 2024