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Use of the Pulmonary Artery Catheter Is Not Associated With Worse Outcome in the ICU^*

Yasser Sakr, MB BCh, MSc; Jean-Louis Vincent, MD, PhD, FCCP; Konrad Reinhart, MD, PhD; Didier Payen, MD; Christian J. Wiedermann, MD; Durk F. Zandstra, MD; Charles L. Sprung, MD; on behalf of the Sepsis Occurrence in Acutely Ill Patients Investigators

^* From the Department of Intensive Care (Drs. Sakr and Vincent), Erasme Hospital, Free University of Brussels, Belgium; Department of Anesthesiology and Intensive Care (Dr. Reinhart), Friedrich-Schiller-University Jena, Germany; Department of Anesthesiology and Intensive Care (Dr. Payen), Centre Hospitalier Universitaire Lariboisiere, Paris, France; Department of Internal Medicine (Dr. Wiedermann), University of Innsbruck, Innsbruck, Austria; Department of Intensive Care (Dr. Zandstra), Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands; and Department of Anesthesiology and Critical Care Medicine (Dr. Sprung), Hadassah Hebrew University Medical Center, Jerusalem, Israel. A list of the SOAP Investigators is given in the ^Appendix.

Correspondence to: Jean-Louis Vincent, MD, PhD, FCCP, Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium; e-mail: jlvincen{at}ulb.ac.be

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 
Study objectives: In critically ill patients, the impact of pulmonary artery catheter (PAC) use on outcome is debatable. We investigated the epidemiology of PAC use in European ICUs and its relation to outcome.

Design: International cohort, observational study

Setting: One hundred ninety-eight European ICUs participating in the Sepsis Occurrence in Acutely Ill Patients Study.

Patients: All 3,147 adult patients admitted to one of the participating ICUs between May 1, 2002, and May 15, 2002.

Interventions: None.

Measurements and results: Patients were classified according to whether or not they had a PAC at any time during their ICU stay, and were followed up until death, hospital discharge, or for 60 days. Propensity score case matching was performed, and matched pairs were examined for baseline characteristics and outcome. Of 3,147 patients, 481 patients (15.3%) had a PAC. Patients with a PAC were older, had a higher incidence of heart failure, a lower incidence of cancer, and were more commonly surgical admissions. Fluid balance was comparable between the two groups. ICU and hospital mortality rates were higher in patients with a PAC (28.1% vs 16.8% and 32.5% vs 22.5%, respectively; p < 0.001). However, PAC use was not an independent risk factor for 60-day mortality in multivariate analysis, and in 453 propensity-matched pairs ICU and hospital mortality rates were comparable between groups (26.7% vs 26.3% and 31.4% vs 32.8%, p = not significant). Survival to 60 days was similar between the two matched groups (log rank = 0.02; p = 0.894).

Conclusions: This observational study suggests that PAC use is not associated with increased mortality in this heterogeneous population.

Key Words: critically ill • hemodynamic monitoring • intensive care • survival • Swan-Ganz catheter

	Introduction

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The pulmonary artery catheter (PAC) is a valuable tool for monitoring patient condition and guiding therapy in ICUs worldwide. It was introduced clinically > 3 decades ago¹ and provides a number of physiologic variables that have been shown to be more accurate than clinical judgment and basic hemodynamic monitoring.^2345678 Although the impact of PAC insertion on patient outcome has been questioned in several investigations, no clear conclusion has been reached. Several studies⁹¹⁰¹¹ have suggested that the use of the PAC in critically ill patients may result in worse outcomes, although others^12131415 have not confirmed these findings. A particularly famous, prospective cohort study by Connors et al,⁹ which involved a mixed population of medical and surgical ICU patients, suggested increased mortality, length of stay, and costs associated with the use of PAC. This study⁹ and the accompanying editorial¹⁶ caused turmoil among intensivists and generated intense interest in the lay press.¹⁷ The results of this study⁹ have been widely debated,¹⁸ and a call for either a moratorium or randomized control studies was even proposed by some authors.¹⁶¹⁹

A French multicenter, randomized controlled study²⁰ noted that early PAC use in patients with shock or ARDS did not significantly affect mortality or morbidity, similar to the results of an earlier, smaller study²¹ in the United Kingdom. Another controlled study²² in high-risk surgical patients failed to show any benefit of PAC use. However, controlled studies could be limited by methodologic problems, including selection bias, noncompliance by physicians, and crossover from the control group to use of PAC.²³ Observational studies may, therefore, provide beneficial information; however, careful consideration and correction for all possible confounding variables is mandatory.

In this large cohort of critically ill patients included in the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study, we addressed the epidemiology of PAC use in European ICUs and examined the possible association between PAC use and outcome. We applied two methods to test for adjusting for confounding variables: multivariate regression analysis and propensity score case matching.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 
Study Design
This report is the result of a substudy from the SOAP database, a prospective, multicenter, observational study that was designed to evaluate the epidemiology of sepsis in European countries and was initiated by a working group of the European Society of Intensive Care Medicine. Institutional recruitment for participation was by open invitation from the study steering committee to European ICUs. Since this epidemiologic, observational study did not require any deviation from routine medical practice, institutional review board approval was either waived or expedited in participating institutions, and informed consent was not required. We included all adult patients (> 15 years old) admitted to the participating centers (a list of participating countries and centers is given in the ^Appendix) between May 1, 2002, and May 15, 2002. Patients were followed up until death, hospital discharge, or for 60 days. Those who stayed in the ICU for < 24 h for routine postoperative observation were excluded.

Data Management
Data were collected prospectively using preprinted case report forms. Detailed instructions, explaining the aim of the study, instructions for data collection, and definitions for various important items were available for all participants at www.intensive.org before starting data collection and throughout the study period. The steering committee processed all queries during data collection.

Data were entered centrally by medical personnel using statistical software (SPSS version 11.0 for Windows; SPSS; Chicago, IL). A random sample of 5% of data were re-entered by a different encoder and revised by a third encoder; a consistency of > 99.5% per variable and 98.5% per patient was observed during the whole process of data entry. In case of inconsistency, data were verified and corrected. Daily frequency tables were revised for all variables, and the investigators were questioned when data values were either questionable or missing for required fields. Data collection on admission included demographic data and comorbid diseases. Clinical and laboratory data for simplified acute physiology score (SAPS) II²⁴ were reported as the worst value within 24 h after hospital admission. Microbiologic and clinical infections were reported daily as well as the antibiotics administrated. A daily evaluation of organ function that was based on a set of laboratory and clinical parameters according to the sequential organ failure assessment (SOFA) score²⁵ was performed, with the most abnormal value for each of the six organ systems (ie, respiratory, renal, cardiovascular, hepatic, coagulation, and neurologic) being collected on admission and every 24 h thereafter. For a single missing value, a replacement was calculated using the mean value of the results on either side of the absent result. When first or last values were missing, the nearest value was carried backward or forward respectively. When more than one consecutive result was missing, it was considered to be a missing value in the analysis.

Definitions
Infection was defined as the presence of a pathogenic microorganism or clinical infection necessitating antibiotic administration. Sepsis, severe sepsis, and septic shock were defined according to the American College of Chest Physicians/Society of Critical Care Medicine consensus conference definitions.²⁶ Circulatory shock was defined as a cardiovascular SOFA score > 2; ie, the use of dopamine at a dose > 5 µg/kg/min and/or epinephrine or norepinephrine at any dose. To allow for the difference between colloid and crystalloid solutions,²⁷ we calculated the adjusted fluid balance by multiplying the amount of colloid given by three.

Statistical Methods
Data were analyzed using statistical software (SPSS version 11.0 for Windows; SPSS). Descriptive statistics were computed for all study variables. The Kolmogorov-Smirnov test was used, and stratified distribution plots were examined to verify the normality of distribution of continuous variables. Nonparametric tests of comparison were used for variables evaluated as not normally distributed. Difference testing between groups was performed using the two-tailed t test, Mann-Whitney U test, ² test, and Fisher Exact Test as appropriate. To determine the relative hazard of death (RH) due to PAC use, a multivariate Cox proportional hazard model²⁸ was constructed with time to death right censored at 60 days as the dependent factor in the overall population. Variables considered for the Cox regression analysis included the following: age, gender, comorbid diseases and SAPS II score on hospital admission, the extent of organ failure as assessed by the SOFA, daily fluid balance, and the use of various vasopressors and colloids. Variables were introduced in the multivariate model if significantly associated with a higher risk of 60-day mortality on a univariate basis at a p value < 0.2. Coliniarity between variables was excluded prior to modeling. The time-dependent covariate method²⁸ was used to check the proportional hazard assumption of the model; an extended Cox model was constructed, adding interaction terms that involve time, ie, time-dependent variables, computed as the byproduct of time and individual covariates in the model (time x covariate). Individual time-dependent covariates were introduced one by one and in combinations in the extended model, none of which was found to be significant (Wald ² statistics). A forward stepwise approach was used, and the use of PAC was entered as the last step in the model after adjustment for other factors. Kaplan-Meier survival curves were plotted and compared using the signed log-rank test in the overall population and in the propensity score matched pairs. Propensity scores²⁹ were obtained through logistic regression of patient characteristics on PAC status (ie, actual use of PAC). A greedy matching technique³⁰ was used to match unique patients with PAC with unique patients without PAC based on propensity scores. The best-matched propensity score was identical to five digits. Once a match was made, the control patient was removed from the pool. This process was then repeated using four-digit matching, then three-digit matching, etc. If a PAC patient matched with more than one control, a match was randomly selected. The process proceeded sequentially to a single-digit match on propensity score. If a match was not obtained at this point, the patient with PAC was excluded. All statistics were two tailed, and p < 0.05 was considered to be significant.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 
Study Population
Of 3,147 patients included in the SOAP study, 481 patients (15.3%) had a PAC inserted, including 367 patients (11.7%) who had it introduced on the day of hospital admission, and 114 patients (3.6%) later. The median duration of PAC use was 3 days (interquartile range [IQR], 2 to 6 days), accounting for 1,917 of the total reported ICU days (8.7%). The characteristics of the study group on hospital admission are presented in Table 1 . Patients with a PAC were older, had a higher incidence of heart failure, a lower incidence of cancer, and were more commonly surgical admissions than patients without a PAC. The SAPS II and SOFA scores and the incidence of sepsis syndromes were higher in the PAC group. Figure 1 represents the percentage of PAC use in the contributing countries.

View larger version (25K): [in this window] [in a new window] [Download PPT slide]   Figure 1.. Bar chart representing the percentage of PAC use in the various contributing countries; only countries including > 50 patients are considered. UK = United Kingdom.

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 2.. Top, A: Kaplan-Meier survival curves in patients with PAC (lower dashed curve) and those without PAC (upper continuous curve). Patients with PAC had a significantly lower 60-day survival (log rank = 14.04; p < 0.001) than those without PAC. Bottom, B: Kaplan-Meier survival curves in patients with PAC (lower dashed curve) and their propensity matched pairs without a PAC (upper continuous curve). No difference in 60-day survival between patients with PAC (log rank = 0.02; p = 0.894) and their propensity-matched controls.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

There can be large international variations in the use of the PAC. Even in Europe, PAC use can vary markedly; in our study the overall incidence was 15.3% at any time during the ICU stay, mostly (11.7%) on the admission day. This incidence is comparable with another large European study performed 10 years ago, the European Prevalence of Infection in Intensive Care study,³¹ involving > 10,000 patients, of which 12.8% had a PAC on the study day, suggesting that PAC use has remained relatively stable over time. However, these figures contrast with the high incidence in the north American study by Connors et al,⁹ in which 38% of patients had a PAC within the first 24 h of hospital admission, raising the question of overzealous insertion and subsequent selection bias involving unnecessary insertion in patients who may suffer the complications of PAC rather than being able to benefit from it. Also, Connors et al⁹ excluded 5% of patients who had a PAC inserted after 24 h of hospital admission with no rational explanation for this exclusion. These patients most probably represent a subgroup that might, in fact, have benefited from the PAC, as the authors alluded to in their discussion. We elected to include patients with a PAC inserted at any time during the ICU stay to avoid any selection bias.

In our study, the reason for the increased mortality and decreased survival in patients managed with a PAC is quite evident. As expected, patients with a PAC were older, had a higher incidence of heart failure, higher SAPS II and SOFA scores, and a greater incidence of sepsis syndromes. We used two methods to adjust for possible confounders: a multivariate logistic regression analysis using the Cox model, and propensity score case matching. In a multivariate analysis, the use of the PAC was not associated with an independent higher risk of death in our patients (n = 4,147) after adjusting for age, sex, comorbidities on admission, type of admission, SAPS II score, the degree of organ failure assessed by the SOFA score, and the presence of sepsis syndromes on hospital admission. Factors independently associated with a higher risk of death at 60-day mortality included higher SAPS II score, liver cirrhosis, medical admission, older age, HIV infection, hematologic cancer, but not the use of a PAC.

Propensity score technology, introduced by Rosenbaum and Rubin,²⁹ controls for naturally occurring systematic differences in the background characteristics between the treatment group (PAC group) and the control group (patients without PAC), by reducing the entire collection of these characteristics to a single composite that approximately summarizes the collection. This reduction from many characteristics to one composite characteristic allows the straightforward assessment of whether the treatment and control groups overlap enough with respect to background characteristics to allow a sensible estimation of treatment vs control effects from the data set.³² The propensity score is found by predicting treatment group membership (the use of PAC) from the confounding covariates, for example, by a logistic regression analysis. Each person in the database then has an estimated propensity score, which is the estimated probability (as determined by that person’s covariate values). Applications include matched sampling, subclassification, and covariate adjustment according to the propensity score.²⁹³³ We used a multivariate logistic regression analysis with PAC use as the dependent factor. We adjusted for age, sex, comorbidities on admission, SAPS II score, the degree of organ failure assessed by the SOFA score, procedures on hospital admission, and presence of sepsis syndromes on hospital admission. The 453 propensity-matched pairs had comparable baseline characteristics. ICU and hospital mortality rates were comparable between the PAC group and their matched pairs, and survival to 60 days was similar between the two groups.

The same technique of propensity score matching was used by Connors et al⁹; however, of the 2,184 patients with a PAC in that study, only 1,008 patients (46.2%) were matched. The possible reason for this may be a failure of the 53.8% of patients with a PAC to match with patients from the control group due to defective overlap between the two groups, or the presence of missing values of the covariates included in the propensity score calculation. This defective matching could have introduced a major selection bias comparing the propensity-matched groups and raises questions about how representative these data are. In our study, as many as 94.2% of the patients with a PAC were matched to control patients, likely due to sufficient overlap between the two groups and the small number of missing values (< 1%). Also, we excluded uncomplicated patients admitted for postoperative monitoring < 24 h. Accordingly, selection bias is markedly minimized in our study compared with that by Connors et al.⁹ In another study by Yu et al,¹⁴ the authors also used propensity case matching and noted no negative effects of PAC insertion on outcome. However, this study used data that are now > 10 years old.

Several randomized controlled trials²⁰²¹²² have found no differences in outcome between patients with and those without PACs. In high-risk surgical patients, Sandham et al²² showed no significant difference in mortality between patients managed with a PAC and those without a PAC (7.7% vs 7.8%, p = not significant). Similarly, in patients with shock or ARDS, Richard et al²⁰ noted that there were no significant differences in mortality with or without the PAC at day 14 or day 90. These authors also noted no differences in organ failure-free days, renal support, vasoactive agents, hospital or ICU stay, or mechanical ventilation use, although an earlier meta-analysis³⁴ of randomized controlled trials showed a significant reduction in morbidity, in terms of organ dysfunction, using PAC-guided strategies. Most recently, the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial, which included 433 patients with class IV advanced heart failure from 26 sites in the United States and Canada who were randomized to assessment with or without a PAC, found no differences in mortality rates or days hospitalized in patients with or without a PAC.³⁵

The study by Sandham and colleagues²² reported a higher rate of pulmonary embolism in the catheter group than in the standard care group, although the cause effect relationship is questionable. In the French study,²⁰ there were few major complications, PAC-related infections occurred in 10 patients (2.8%), and there were no cases of pulmonary embolism. In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness study,³⁵ approximately 4% of patients undergoing pulmonary artery catheterization had complications, including cardiac arrest and infection, but there were no PAC-related deaths. PAC-associated complications were difficult to assess in our study. However, complications of catheterization have not been emphasized in the literature.¹⁸²⁰

Our study is limited by the observational design. However, both the multivariate regression analysis and the propensity score matching yielded similar results. Other confounders not reported in our study could have contributed to either more beneficial or more deleterious effects due to PAC insertion. The heterogeneity of patients in our study is another important limitation, but it is difficult to identify a homogenous population in the ICU milieu due to marked overlap of disease processes.

It should be emphasized that we are evaluating a monitoring tool and not a new therapy. Proper collection and interpretation of data provided by the PAC with subsequent implementation of the results in clinical practice is mandatory to ensure a clear beneficial effect. Prognosis cannot be improved by catheter insertion per se. Accordingly, the call for a moratorium for the PAC use in the ICU is unjustified, and randomized controlled studies in specific subgroups of critically ill patients are impractical due to marked overlap between the different disease processes in the ICU. Improved training and proper implementation of the data provided by the PAC should reduce the complications related to its use and increase the beneficial effects.

	Conclusion

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 
In this multicenter, observational European study, a PAC was inserted in 15.3% of patients. PAC use was not associated with a worse prognosis after adjustment for possible confounders.

	Appendix

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 
SOAP Investigators
Austria: University Hospital of Vienna (G. Delle Karth); LKH Steyr (V. Draxler); LKH-Deutschlandsberg (G. Filzwieser); Otto Wagner Spital of Vienna (W. Heindl); Krems of Donau (G. Kellner, T. Bauer); Barmherzige Bruede of Linz (K. Lenz); KH Floridsdorf of Vienna (E. Rossmann); University Hospital of Innsbruck (C. Wiedermann); Belgium: CHU of Charleroi (P. Biston); Hôpitaux Iris Sud of Brussels (D. Chochrad); Clinique Europe Site St Michel of Brussels (V. Collin); CHU of Liège (P. Damas); University Hospital Ghent (J. Decruyenaere, E. Hoste); CHU Brugmann of Brussels (J. Devriendt); Centre Hospitalier Jolimont-Lobbes of Haine St. Paul (B. Espeel); CHR Citadelle of Liege (V. Fraipont); UCL Mont-Godinne of Yvoir (E. Installe); ACZA Campus Stuivenberg (M. Malbrain); OLV Ziekenhuis Aalst (G. Nollet); RHMS Ath-Baudour-Tournai (J.C. Preiser); AZ St. Augustinus of Wilrijk (J. Raemaekers); CHU Saint-Pierre of Brussels (A. Roman); Cliniques du Sud-Luxembourg of Arlon (M. Simon); Academic Hospital Vrije Universiteit Brussels (H. Spapen); AZ Sint-Blasius of Dendermonde (W. Swinnen); Clinique Notre-Dame of Tournai (F. Vallot); Erasme University Hospital of Brussels (J.L. Vincent); Czech Republic: University Hospital of Plzen (I. Chytra); U SV.Anny of Brno (L. Dadak); Klaudians of Mlada Boleslav (I. Herold); General Faculty Hospital of Prague (F. Polak); City Hospital of Ostrava (M. Sterba); Denmark: Gentofte Hospital, University of Copenhagen (M. Bestle); Rigshospitalet of Copenhagen (K. Espersen); Amager Hospital of Copenhagen (H. Guldager); Rigshospitalet, University of Copenhagen (K-L. Welling); Finland: Aland Central Hospital of Mariehamn (D. Nyman); Kuopio University Hospital (E. Ruokonen); Seinajoki Central Hospital (K. Saarinen); France: Raymond Poincare of Garches (D. Annane); Institut Gustave Roussy of Villejuif (P. Catogni); Jacques Monod of Le Havre (G. Colas); CH Victor Jousselin of Dreux (F. Coulomb); Hôpital St. Joseph & St. Luc of Lyon (R. Dorne); Saint Joseph of Paris (M. Garrouste); Hôpital Pasteur of Nice (C. Isetta); CHU Brabois of Vandoeuvre Les Nancy (J. Larché); Saint Louis of Paris (J-R. LeGall); CHU de Grenoble (H. Lessire); CHU Pontchaillou of Rennes (Y. Malledant); Hôpital des Hauts Clos of Troyes (P. Mateu); CHU of Amiens (M. Ossart); Hôpital Lariboisière of Paris (D. Payen); CHD Félix Gyuon of Saint Denis La Reunion (P. Schlossmacher); Hôpital Bichat of Paris (J-F. Timsit); Hôpital Saint Andre of Bordeaux (S. Winnock); Hôpital Victor Dupouy of Argentueil (J-P. Sollet); CH Auch (L. Mallet); CHU Nancy-Brabois of Vandoeuvre (P. Maurer); CH William Morey of Chalon (J-M. Sab); Victor Dupouy of Argenteuil (J-P. Sollet); Germany: University Hospital Heidelberg (G. Aykut); Friedrich Schiller University Jena (F. Brunkhorst); University Clinic Hamburg-Eppendorf (A. Nierhaus); University Hospital Mainz (M. Lauterbach); University Hospital Carl Gustav Carus of Dresden (M. Ragaller); Hans Sushemihl Krankenhaus of Emden (R. Gatz); Vivantes-Klinikum Neukoelln of Berlin (H. Gerlach); University Hospital RWTH Aachen (D. Henzler); Kreisklinik Langen-Seligenstadt (H-B Hopf); GKH Bonn (H. Hueneburg); Zentralklinik Bad Berka (W. Karzai); Neuwerk of Moenchengladbach (A. Keller); Philipps University of Marburg (U. Kuhlmann); University Hospital Regensburg (J. Langgartner); ZKH Links der Weser of Bremen (C. Manhold); University Hospital of Dresden (M. Ragaller); Universtiy of Wuerzburg (B. Reith); Hannover Medical School (T. Schuerholz); Universitätsklinikum Charité Campus Mitte of Berlin (C. Spies); Bethanien Hospital of Moers (R. Stögbauer); KhgmbH Schongau (J. Unterburger); Greece: Thriassio Hospital of Athens (P-M. Clouva-Molyvdas); Sismanoglion General Hospital of Athens (G. Giokas); KAT General Hospital of Athens (E. Ioannidou); G. Papanikolaou General Hospital of Thessaloniki (A. Lahana); Agios Demetrios of Thessaloniki (A. Liolios); Onassis Cardiac Surgery Center of Athens (K. Marathias); University Hospital of Ioannina (G. Nakos); Tzanio Hospital of Athens (A. Tasiou); Athens General Hospital Gennimatas (H. Tsangaris); Hungary: Peterfy Hospital of Budapest (P. Tamasi); Ireland: Mater Hospital of Dublin (B. Marsh); Beaumont Hospital of Dublin (M. Power); Israel: Hadassah Hebrew University Medical Center (C. Sprung); Italy: Azienda Ospedaliera Senese o Siena (B. Biagioli); S. Martino of Genova (F. Bobbio Pallavicini); Azienda Ospedaliera S. Gerardo dei Tintori of Monza (A. Pesenti); Osp Regionale of Saronno (C. Capra); Ospedale Maggiore - University A. Avogadro of Novara (F. Della Corte); Osp. Molinette of Torino (P.P. Donadio); A.O. Umberto I Ancona, Rianimazione Clinica (A. Donati); Azienda Ospedaliera Universitaria Policlinico of Palermo (A. Giarratano); San Giovanni Di Dio of Florence (T. Giorgio); H San Raffaele IRCCS of Milano (D. Giudici); Ospedale Di Busto Arsizio (S. Greco); Civile Di Massa (A. Guadagnucci); San Paolo of Milano (G. Lapichino); S.Giovanni Bosco Torino (S. Livigni); Osp. San Giovanni of Sesto (G. Moise); S Camillo of Roma (G. Nardi); Vittorio Emanuele of Catania (E. Panascia); Hospital of Piacenza (M. Pizzamiglio); Universita di Torino-Ospedale S. Giovanni Battista (V.M. Ranieri); Policlinico Le Scotte of Siena (R. Rosi); Ospedale Maggiore Policlinico IRCCS of Milano (A. Sicignano); A. Uboldo of Cernusco Sul Naviglio (M. Solca); P.O. Civile Carrara of Massa (G. Vignali); San Giovanni of Roma (I. Volpe Rinonapoli); Netherlands: Boven IJ Ziekenhuis of Amsterdam (M. Barnas); UMC St. Radboud of Nijmegen (E.E. De Bel); Academic Medical Center of Amsterdam (A-C. De Pont); VUMC of Amsterdam (J. Groeneveld); Groningen University Hospital (M. Nijsten); Waterlandziekenhuis of Purmerend (L. Sie); OLVG of Amsterdam (D.F. Zandstra); Norway: Sentralsjukehuset i Rogaland of Stavanger (S. Harboe); Sykehuset Østfold of Fredrikstad (S. Lindén); Aker University Hospital of Oslo (R.Z. Lovstad); Ulleval University Hospitalof Oslo (H. Moen); Akershus University Hospital of Nordbyhagen (N. Smith-Erichsen); Poland: Pediatric University Hospital of Lodz (A. Piotrowski); Central Clinic Hospital SLAM of Katowice (E. Karpel); Portugal: Garcia de Orta of Almada (E. Almeida); Hospital de St. António dos Capuchos of Lisboa (R. Moreno); Hospital de Santa Maria of Lisboa (A. Pais-De-Lacerda); Hospital S.Joao of Porto (J.A. Paiva); Fernado Fonseca of Masama (I. Serra); São Teotonio Viseu (A. Pimentel); Romania: Inst of Cardiovascular Diseases of Bucharest (D. Filipescu); Serbia and Montenegro: Military Medical Academy of Belgrade (K. Jovanovic); Slovakia: SUSCH of Bratislava (P. Malik); Slovenia: General Hospital of Novo Mesto (K. Lucka); General Hospital of Celje (G. Voga); Spain: Hospital Universitario Rio Hortega of Valladolid (C. Aldecoa Alvarez-Santullano); Sabadell Hospital (A. Artigas); Hospital Clinic of Barcelona (E. Zavala, A. Escorsell, J. Nicolas); Virgen del Camino of Pamplona (J. J. Izura Cea); Virgen de la Salud of Toledo (L. Marina); 12 de Octubre of Madrid (J. Montejo); Gregorio Maranon of Madrid (E. Palencia); General Universitario de Elche (F. Santos); Puerta del Mar of Cadiz (R. Sierra-Camerino); Fundación Jiménez Díaz of Madrid (F. Sipmann); Hospital Clinic of Barcelona (E. Zavala); Sweden: Central Hospital of Kristianstad (K. Brodersen); Stockholm Soder Hospital (J. Haggqvist); Sunderby Hospital of Luleå (D. Hermansson); Huddinge University Hospital of Stockholm (H. Hjelmqvist); Switzerland: Kantonsspital Luzern (K. Heer); Hirslanden Klinik Beau-Site of Bern (G. Loderer); University Hospital of Zurich (M. Maggiorini); Hôpital de la ville of La Chaux-de-Fonds (H. Zender); United Kingdom: Western General Hospital of Edinburgh (P. Andrews); Peterborough Hospitals NHS Trust of Peterborough (B. Appadu); University Hospital Lewisham, London (C. Barrera Groba); Bristol Royal Infirmary (J. Bewley); Queen Elizabeth Hospital Kings Lynn (K. Burchett); Milton Keynes General (P. Chambers); Homerton University Hospital of London (J. Coakley); Charing Cross Hospital of London (D. Doberenz); North Staffordshire Hospital of Stoke On Trent (N. Eastwood); Antrim Area Hospital (A. Ferguson); Royal Berkshire Hospital of Reading (J. Fielden); The James Cook University Hospital of Middlesbrough (J. Gedney); Addenbookes of Cambridge (K. Gunning); Rotherham DGH (D. Harling); St.Helier of Carshalton (S. Jankowski); Southport & Formby (D. Jayson); Freeman of Newcastle On Tyne (A. Kilner); University Hospital of North Tees at Stockton on Tees (V. Krishna-Kumar); St.Thomas Hospital of London (K. Lei); Royal Infirmary of Edinburgh (S. Mackenzie); Derriford of Plymouth (P. Macnaughton); Royal Liverpool University Hospital (G. Marx); Stirling Royal Infirmary (C. McCulloch); University Hospital of Wales, Cardiff (P. Morgan); St. George’s Hospital of London (A. Rhodes); Gloucestershire Royal Hospital (C. Roberts); St. Peters of Chertsey (M. Russell); James Paget Hospital of Great Yarmouth (D. Tupper-Carey, M. Wright); Kettering General Hospital (L. Twohey); Burnley DGH (J. Watts); Northampton General Hospital (R. Webster); Dumfries Royal Infirmary (D. Williams)

	Footnotes

 
Abbreviations: IQR = interquartile range; PAC = pulmonary artery catheter; RH = relative hazard of death; SAPS = simplified acute physiology score; SOAP = Sepsis Occurrence in Acutely ill Patients; SOFA = sequential organ failure assessment

This study was endorsed by the European Society of Intensive Care Medicine and supported by an unrestricted grant from Abbott, Baxter, Eli Lilly, GlaxoSmithKline and NovoNordisk.

Received for publication November 19, 2004. Accepted for publication May 1, 2005.

	References

TOP Abstract Introduction Materials and Methods Results Discussion Conclusion Appendix References

 

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