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Erschienen in: Intensive Care Medicine 12/2015

01.12.2015 | Systematic Review

Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs

verfasst von: Ming Bai, Meilan Zhou, Lijie He, Feng Ma, Yangping Li, Yan Yu, Pengbo Wang, Li Li, Rui Jing, Lijuan Zhao, Shiren Sun

Erschienen in: Intensive Care Medicine | Ausgabe 12/2015

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Abstract

Purpose

The purpose of this study was to evaluate the effect and safety of citrate versus heparin anticoagulation for continuous renal replacement therapy (CRRT) in critically ill patients by performing a meta-analysis of updated evidence.

Methods

Medline, Embase, and Cochrane databases were searched for eligible studies, and manual searches were also performed to identify additional trials. Randomized controlled trials (RCTs) assessing the effect of citrate versus heparin anticoagulation for CRRT were considered eligible for inclusion.

Results

Eleven RCTs with 992 patients and 1998 circuits met the inclusion criteria. Heparin was regionally delivered in two trials and systemically delivered in nine trials. Citrate for CRRT significantly reduced the risk of circuit loss compared to regional (HR 0.52, 95 % CI 0.35–0.77, P = 0.001) and systemic (HR 0.76, 95 % CI 0.59–0.98, P = 0.04) heparin. Citrate also reduced the incidence of filter failure (RR 0.70, 95 % CI 0.50–0.98, P = 0.04). The citrate group had a significantly lower bleeding risk than the systemic heparin group (RR 0.36, 95 % CI 0.21–0.60, P < 0.001) and a similar bleeding risk to the regional heparin group (RR 0.34, 95 % CI 0.01–8.24, P = 0.51). The incidences of heparin-induced thrombocytopenia (HIT) and hypocalcemia were increased in the heparin and citrate groups, respectively. No significant survival difference was observed between the groups.

Conclusions

Given the lower risk of circuit loss, filter failure, bleeding, and HIT, regional citrate should be considered a better anticoagulation method than heparin for CRRT in critically ill patients without any contraindication.
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Literatur
1.
Zurück zum Zitat Fealy N, Baldwin I, Bellomo R (2002) The effect of circuit “down-time” on uraemic control during continuous veno-venous haemofiltration. Crit Care Resusc 4:266–270PubMed Fealy N, Baldwin I, Bellomo R (2002) The effect of circuit “down-time” on uraemic control during continuous veno-venous haemofiltration. Crit Care Resusc 4:266–270PubMed
2.
Zurück zum Zitat Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R (2003) Continuous is not continuous: the incidence and impact of circuit “down-time” on uraemic control during continuous veno-venous haemofiltration. Intensive Care Med 29:575–578CrossRefPubMed Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R (2003) Continuous is not continuous: the incidence and impact of circuit “down-time” on uraemic control during continuous veno-venous haemofiltration. Intensive Care Med 29:575–578CrossRefPubMed
3.
Zurück zum Zitat Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCentralCrossRefPubMed Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCentralCrossRefPubMed
4.
Zurück zum Zitat Carr JA, Silverman N (1999) The heparin-protamine interaction. A review. J Cardiovasc Surg (Torino) 40:659–666 Carr JA, Silverman N (1999) The heparin-protamine interaction. A review. J Cardiovasc Surg (Torino) 40:659–666
5.
Zurück zum Zitat Syed S, Reilly RF (2009) Heparin-induced thrombocytopenia: a renal perspective. Nat Rev Nephrol 5:501–511CrossRefPubMed Syed S, Reilly RF (2009) Heparin-induced thrombocytopenia: a renal perspective. Nat Rev Nephrol 5:501–511CrossRefPubMed
6.
Zurück zum Zitat Pinnick RV, Wiegmann TB, Diederich DA (1983) Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 308:258–261CrossRefPubMed Pinnick RV, Wiegmann TB, Diederich DA (1983) Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 308:258–261CrossRefPubMed
7.
Zurück zum Zitat Mehta RL, McDonald BR, Aguilar MM, Ward DM (1990) Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int 38:976–981CrossRefPubMed Mehta RL, McDonald BR, Aguilar MM, Ward DM (1990) Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int 38:976–981CrossRefPubMed
8.
Zurück zum Zitat Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P (2004) Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Intensive Care Med 30:260–265CrossRefPubMed Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P (2004) Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Intensive Care Med 30:260–265CrossRefPubMed
9.
Zurück zum Zitat Kutsogiannis DJ, Gibney RT, Stollery D, Gao J (2005) Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 67:2361–2367CrossRefPubMed Kutsogiannis DJ, Gibney RT, Stollery D, Gao J (2005) Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 67:2361–2367CrossRefPubMed
10.
Zurück zum Zitat Brain MJ, Roodenburg OS, Adams N, McCracken P, Hockings L, Musgrave S, Butt W, Scheinkestel C (2014) Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the filter life in renal replacement therapy pilot trial. Crit Care Resusc 16:131–137PubMed Brain MJ, Roodenburg OS, Adams N, McCracken P, Hockings L, Musgrave S, Butt W, Scheinkestel C (2014) Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the filter life in renal replacement therapy pilot trial. Crit Care Resusc 16:131–137PubMed
11.
Zurück zum Zitat Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Inter 2:1–138CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Inter 2:1–138CrossRef
12.
Zurück zum Zitat Zhang Z, Hongying N (2012) Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med 38:20–28CrossRefPubMed Zhang Z, Hongying N (2012) Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med 38:20–28CrossRefPubMed
13.
Zurück zum Zitat Wu MY, Hsu YH, Bai CH, Lin YF, Wu CH, Tam KW (2012) Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials. Am J Kidney Dis 59:810–818CrossRefPubMed Wu MY, Hsu YH, Bai CH, Lin YF, Wu CH, Tam KW (2012) Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials. Am J Kidney Dis 59:810–818CrossRefPubMed
14.
Zurück zum Zitat James M, Bouchard J, Ho J, Klarenbach S, LaFrance JP, Rigatto C, Wald R, Zappitelli M, Pannu N (2013) Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 61:673–685CrossRefPubMed James M, Bouchard J, Ho J, Klarenbach S, LaFrance JP, Rigatto C, Wald R, Zappitelli M, Pannu N (2013) Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 61:673–685CrossRefPubMed
15.
Zurück zum Zitat Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R (2015) A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults. Crit Care Med 43:1622–1629CrossRefPubMed Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R (2015) A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults. Crit Care Med 43:1622–1629CrossRefPubMed
16.
Zurück zum Zitat Stucker F, Ponte B, Tataw J, Martin P, Wozniak H, Pugin J, Saudan P (2015) Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care 19:9CrossRef Stucker F, Ponte B, Tataw J, Martin P, Wozniak H, Pugin J, Saudan P (2015) Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care 19:9CrossRef
17.
Zurück zum Zitat Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, Vervloet MG, Beishuizen A, Girbes AR, Ter Wee PM, Groeneveld AB (2014) Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial. Crit Care 18:472PubMedCentralCrossRefPubMed Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, Vervloet MG, Beishuizen A, Girbes AR, Ter Wee PM, Groeneveld AB (2014) Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial. Crit Care 18:472PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat Tiranathanagul K, Jearnsujitwimol O, Susantitaphong P, Kijkriengkraikul N, Leelahavanichkul A, Srisawat N, Praditpornsilpa K, Eiam-Ong S (2011) Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration. Ther Apher Dial 15:556–564CrossRefPubMed Tiranathanagul K, Jearnsujitwimol O, Susantitaphong P, Kijkriengkraikul N, Leelahavanichkul A, Srisawat N, Praditpornsilpa K, Eiam-Ong S (2011) Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration. Ther Apher Dial 15:556–564CrossRefPubMed
19.
Zurück zum Zitat Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefPubMed Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefPubMed
20.
Zurück zum Zitat Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16PubMedCentralCrossRefPubMed Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16PubMedCentralCrossRefPubMed
21.
Zurück zum Zitat Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65–W94CrossRefPubMed Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65–W94CrossRefPubMed
22.
Zurück zum Zitat Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834CrossRefPubMed Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834CrossRefPubMed
23.
Zurück zum Zitat Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rucker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002CrossRefPubMed Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rucker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002CrossRefPubMed
24.
Zurück zum Zitat Hetzel GR, Schmitz M, Wissing H, Ries W, Schott G, Heering PJ, Isgro F, Kribben A, Himmele R, Grabensee B, Rump LC (2011) Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant 26:232–239CrossRefPubMed Hetzel GR, Schmitz M, Wissing H, Ries W, Schott G, Heering PJ, Isgro F, Kribben A, Himmele R, Grabensee B, Rump LC (2011) Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant 26:232–239CrossRefPubMed
25.
Zurück zum Zitat Betjes MG, van Oosterom D, van Agteren M, van de Wetering J (2007) Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding: similar hemofilter survival but significantly less bleeding. J Nephrol 20:602–608PubMed Betjes MG, van Oosterom D, van Agteren M, van de Wetering J (2007) Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding: similar hemofilter survival but significantly less bleeding. J Nephrol 20:602–608PubMed
26.
Zurück zum Zitat Fealy N, Baldwin I, Johnstone M, Egi M, Bellomo R (2007) A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration. Int J Artif Organs 30:301–307PubMed Fealy N, Baldwin I, Johnstone M, Egi M, Bellomo R (2007) A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration. Int J Artif Organs 30:301–307PubMed
27.
Zurück zum Zitat Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, Dijksman LM, Zandstra DF (2009) Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med 37:545–552CrossRefPubMed Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, Dijksman LM, Zandstra DF (2009) Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med 37:545–552CrossRefPubMed
28.
Zurück zum Zitat Calatzis A, Toepfer M, Schramm W, Spannagl M, Schiffl H (2001) Citrate anticoagulation for extracorporeal circuits: effects on whole blood coagulation activation and clot formation. Nephron 89:233–236CrossRefPubMed Calatzis A, Toepfer M, Schramm W, Spannagl M, Schiffl H (2001) Citrate anticoagulation for extracorporeal circuits: effects on whole blood coagulation activation and clot formation. Nephron 89:233–236CrossRefPubMed
29.
Zurück zum Zitat James MF, Roche AM (2004) Dose-response relationship between plasma ionized calcium concentration and thrombelastography. J Cardiothorac Vasc Anesth 18:581–586CrossRefPubMed James MF, Roche AM (2004) Dose-response relationship between plasma ionized calcium concentration and thrombelastography. J Cardiothorac Vasc Anesth 18:581–586CrossRefPubMed
30.
Zurück zum Zitat Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE (2001) Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 119:64S–94SCrossRefPubMed Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE (2001) Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 119:64S–94SCrossRefPubMed
31.
Zurück zum Zitat Cohen JR, Sarfati I, Birnbaum E, Benacquista T, Wise L (1990) The inactivation of antithrombin III by serum elastase in patients with surgical infections. Am Surg 56:665–667PubMed Cohen JR, Sarfati I, Birnbaum E, Benacquista T, Wise L (1990) The inactivation of antithrombin III by serum elastase in patients with surgical infections. Am Surg 56:665–667PubMed
32.
Zurück zum Zitat Martin PY, Chevrolet JC, Suter P, Favre H (1994) Anticoagulation in patients treated by continuous venovenous hemofiltration: a retrospective study. Am J Kidney Dis 24:806–812CrossRefPubMed Martin PY, Chevrolet JC, Suter P, Favre H (1994) Anticoagulation in patients treated by continuous venovenous hemofiltration: a retrospective study. Am J Kidney Dis 24:806–812CrossRefPubMed
33.
Zurück zum Zitat Oudemans-van Straaten HM, Kellum JA, Bellomo R (2011) Clinical review: anticoagulation for continuous renal replacement therapy – heparin or citrate? Crit Care 15:202PubMedCentralCrossRefPubMed Oudemans-van Straaten HM, Kellum JA, Bellomo R (2011) Clinical review: anticoagulation for continuous renal replacement therapy – heparin or citrate? Crit Care 15:202PubMedCentralCrossRefPubMed
34.
Zurück zum Zitat Jaichenko J, Schustack A, Abraham D, Gotloib L (1987) Regional heparinization facilitates safe hemodialysis and/or hemofiltration in the critically ill patient. Am J Clin Pathol 87:556–557PubMed Jaichenko J, Schustack A, Abraham D, Gotloib L (1987) Regional heparinization facilitates safe hemodialysis and/or hemofiltration in the critically ill patient. Am J Clin Pathol 87:556–557PubMed
35.
Zurück zum Zitat Gordon LA, Perkins HA, Richards V (1956) Studies in regional heparinization. I. The use of simultaneous neutralization with protamine; preliminary studies. N Engl J Med 255:1025–1029CrossRefPubMed Gordon LA, Perkins HA, Richards V (1956) Studies in regional heparinization. I. The use of simultaneous neutralization with protamine; preliminary studies. N Engl J Med 255:1025–1029CrossRefPubMed
36.
Zurück zum Zitat De Vico P, Messino V, Tartaglione A, Beccaris C, Buonomo C, Talarico D, Prati P, Sabato AF, Colella DF (2015) Safety and efficacy of citrate anti-coagulation continuous renal replacement therapies in post-cardiac surgery patients with liver dysfunction. Ther Apher Dial 19:272–278 De Vico P, Messino V, Tartaglione A, Beccaris C, Buonomo C, Talarico D, Prati P, Sabato AF, Colella DF (2015) Safety and efficacy of citrate anti-coagulation continuous renal replacement therapies in post-cardiac surgery patients with liver dysfunction. Ther Apher Dial 19:272–278
37.
Zurück zum Zitat Faybik P, Hetz H, Mitterer G, Krenn CG, Schiefer J, Funk GC, Bacher A (2011) Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system. Crit Care Med 39:273–279CrossRefPubMed Faybik P, Hetz H, Mitterer G, Krenn CG, Schiefer J, Funk GC, Bacher A (2011) Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system. Crit Care Med 39:273–279CrossRefPubMed
38.
Zurück zum Zitat Schultheiss C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, Haller B, Einwachter H, Schmid RM, Huber W (2012) Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care 16:R162PubMedCentralCrossRefPubMed Schultheiss C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, Haller B, Einwachter H, Schmid RM, Huber W (2012) Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care 16:R162PubMedCentralCrossRefPubMed
39.
Zurück zum Zitat Beyersmann J, Gastmeier P, Schumacher M (2014) Incidence in ICU populations: how to measure and report it? Intensive Care Med 40:871–876CrossRefPubMed Beyersmann J, Gastmeier P, Schumacher M (2014) Incidence in ICU populations: how to measure and report it? Intensive Care Med 40:871–876CrossRefPubMed
Metadaten
Titel
Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs
verfasst von
Ming Bai
Meilan Zhou
Lijie He
Feng Ma
Yangping Li
Yan Yu
Pengbo Wang
Li Li
Rui Jing
Lijuan Zhao
Shiren Sun
Publikationsdatum
01.12.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 12/2015
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-015-4099-0

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