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Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair

Authors: Duane J. Funk, Kent T. HayGlass, Joshua Koulack, Greg Harding, April Boyd, Ryan Brinkman

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Goal-directed therapy (GDT) has been shown in numerous studies to decrease perioperative morbidity and mortality. The mechanism of benefit of GDT, however, has not been clearly elucidated. Targeted resuscitation of the vascular endothelium with GDT might alter the postoperative inflammatory response and be responsible for the decreased complications with this therapy.

Methods

This trial was registered at ClinicalTrials.gov as NCT01681251. Forty patients undergoing elective open repair of their abdominal aortic aneurysm, 18 years of age and older, were randomized to an interventional arm with GDT targeting stroke volume variation with an arterial pulse contour cardiac output monitor, or control, where fluid therapy was administered at the discretion of the attending anesthesiologist. We measured levels of several inflammatory cytokines (C-reactive protein, Pentraxin 3, suppressor of tumorgenicity--2, interleukin-1 receptor antagonist, and tumor necrosis factor receptor-III) preoperatively and at several postoperative time points to determine if there was a difference in inflammatory response. We also assessed each group for a composite of postoperative complications.

Results

Twenty patients were randomized to GDT and twenty were randomized to control. Length of stay was not different between groups. Intervention patients received less crystalloid and more colloid. At the end of the study, intervention patients had a higher cardiac index (3.4 ± 0.5 vs. 2.5 ± 0.7 l/minute per m2, p < 0.01) and stroke volume index (50.1 ± 7.4 vs. 38.1 ± 9.8 ml/m2, p < 0.01) than controls. There were significantly fewer complications in the intervention than control group (28 vs. 12, p = 0.02). The length of hospital and ICU stay did not differ between groups. There was no difference in the levels of inflammatory cytokines between groups.

Conclusions

Despite being associated with fewer complications and improved hemodynamics, there was no difference in the inflammatory response of patients treated with GDT. This suggests that the clinical benefit of GDT occurs in spite of a similar inflammatory burden. Further work needs to be performed to delineate the mechanism of benefit of GDT.

Trial registration

ClinicalTrials.gov Identifier: NCT01681251. Registered 18 May 2011.
Literature
1.
go back to reference Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003;238:641–8.PubMedPubMedCentral Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003;238:641–8.PubMedPubMedCentral
2.
go back to reference Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–40.PubMed Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–40.PubMed
3.
4.
go back to reference Shires T, Williams J, Brown F. Acute change in extracellular fluids associated with major surgical procedures. Ann Surg. 1961;154:803–10.PubMedPubMedCentral Shires T, Williams J, Brown F. Acute change in extracellular fluids associated with major surgical procedures. Ann Surg. 1961;154:803–10.PubMedPubMedCentral
5.
go back to reference Funk DJ, Moretti EW, Gan TJ. Minimally invasive cardiac output monitoring in the perioperative setting. Anesth Analg. 2009;108:887–97.PubMed Funk DJ, Moretti EW, Gan TJ. Minimally invasive cardiac output monitoring in the perioperative setting. Anesth Analg. 2009;108:887–97.PubMed
6.
go back to reference Moretti EW, Robertson KM, El-Moalem H, Gan TJ. Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration. Anesth Analg. 2003;96:611–7.PubMed Moretti EW, Robertson KM, El-Moalem H, Gan TJ. Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration. Anesth Analg. 2003;96:611–7.PubMed
7.
go back to reference Conway DH, Mayall R, Abdul-Latif MS, Gilligan S, Tackaberry C. Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery. Anaesthesia. 2002;57:845–9.PubMed Conway DH, Mayall R, Abdul-Latif MS, Gilligan S, Tackaberry C. Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery. Anaesthesia. 2002;57:845–9.PubMed
8.
go back to reference Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]. Crit Care. 2005;9:R687–93.PubMedPubMedCentral Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]. Crit Care. 2005;9:R687–93.PubMedPubMedCentral
9.
go back to reference Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg. 2006;93:1069–76.PubMed Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg. 2006;93:1069–76.PubMed
10.
go back to reference Venn R, Steele A, Richardson P, Poloniecki J, Grounds M, Newman P. Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth. 2002;88:65–71.PubMed Venn R, Steele A, Richardson P, Poloniecki J, Grounds M, Newman P. Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth. 2002;88:65–71.PubMed
11.
go back to reference Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR, et al. Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth. 2005;95:634–42.PubMed Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR, et al. Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth. 2005;95:634–42.PubMed
12.
go back to reference Bonazzi M, Gentile F, Biasi GM, Migliavacca S, Esposti D, Cipolla M, et al. Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. Eur J Vasc Endovasc Surg. 2002;23:445–51.PubMed Bonazzi M, Gentile F, Biasi GM, Migliavacca S, Esposti D, Cipolla M, et al. Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. Eur J Vasc Endovasc Surg. 2002;23:445–51.PubMed
13.
go back to reference Valentine RJ, Duke ML, Inman MH, Grayburn PA, Hagino RT, Kakish HB, et al. Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. J Vasc Surg. 1998;27:203–11. discussion 211–2.PubMed Valentine RJ, Duke ML, Inman MH, Grayburn PA, Hagino RT, Kakish HB, et al. Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. J Vasc Surg. 1998;27:203–11. discussion 211–2.PubMed
14.
go back to reference Ackland GL, Iqbal S, Paredes LG, Toner A, Lyness C, Jenkins N, et al. Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial. Lancet Respir Med. 2015;3:33–41.PubMed Ackland GL, Iqbal S, Paredes LG, Toner A, Lyness C, Jenkins N, et al. Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial. Lancet Respir Med. 2015;3:33–41.PubMed
15.
go back to reference Bangash MN, Patel NS, Benetti E, Collino M, Hinds CJ, Thiemermann C, et al. Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow. Crit Care. 2013;17:R57.PubMedPubMedCentral Bangash MN, Patel NS, Benetti E, Collino M, Hinds CJ, Thiemermann C, et al. Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow. Crit Care. 2013;17:R57.PubMedPubMedCentral
16.
go back to reference Jhanji S, Vivian-Smith A, Lucena-Amaro S, Watson D, Hinds CJ, Pearse RM. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Crit Care. 2010;14:R151.PubMedPubMedCentral Jhanji S, Vivian-Smith A, Lucena-Amaro S, Watson D, Hinds CJ, Pearse RM. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Crit Care. 2010;14:R151.PubMedPubMedCentral
17.
go back to reference Jakob SM, Takala J. Gut perfusion in the critically ill. Intensive Care Med. 2000;26:813–5.PubMed Jakob SM, Takala J. Gut perfusion in the critically ill. Intensive Care Med. 2000;26:813–5.PubMed
18.
go back to reference Takala J, Jakob SM. Splanchnic perfusion in intensive care patients. Minerva Anestesiol. 2000;66:333–6.PubMed Takala J, Jakob SM. Splanchnic perfusion in intensive care patients. Minerva Anestesiol. 2000;66:333–6.PubMed
19.
go back to reference Lee WL, Slutsky AS. Sepsis and endothelial permeability. N Engl J Med. 2010;363:689–91.PubMed Lee WL, Slutsky AS. Sepsis and endothelial permeability. N Engl J Med. 2010;363:689–91.PubMed
20.
go back to reference Stefura WP, Campbell JD, Douville R, Stinson MJ, Simons FE, Becker AB, et al. Ultrasensitive ELISA for measurement of human cytokine responses in primary culture. Methods Mol Med. 2008;138:107–19.PubMed Stefura WP, Campbell JD, Douville R, Stinson MJ, Simons FE, Becker AB, et al. Ultrasensitive ELISA for measurement of human cytokine responses in primary culture. Methods Mol Med. 2008;138:107–19.PubMed
21.
go back to reference Stinson M, Douville R, Lissitsyn Y, Blanchard M, Stefura W, Simons E, et al. Quantification of human chemokine production in TLR-stimulated and antigen-specific recall responses. Methods Mol Med. 2008;138:121–31.PubMed Stinson M, Douville R, Lissitsyn Y, Blanchard M, Stefura W, Simons E, et al. Quantification of human chemokine production in TLR-stimulated and antigen-specific recall responses. Methods Mol Med. 2008;138:121–31.PubMed
22.
go back to reference Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e179–347.PubMed Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e179–347.PubMed
23.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.PubMed Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.PubMed
24.
go back to reference Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.PubMedPubMedCentral Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.PubMedPubMedCentral
25.
go back to reference American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416.CrossRef American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416.CrossRef
26.
go back to reference Daly C, Rollins BJ. Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies. Microcirculation. 2003;10:247–57.PubMed Daly C, Rollins BJ. Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies. Microcirculation. 2003;10:247–57.PubMed
27.
go back to reference Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol. 2008;294:F697–701.PubMed Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol. 2008;294:F697–701.PubMed
28.
go back to reference Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013;62:1541–51.PubMed Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013;62:1541–51.PubMed
29.
go back to reference Gonzalez-Quesada C, Frangogiannis NG. Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr Atheroscler Rep. 2009;11:131–8.PubMedPubMedCentral Gonzalez-Quesada C, Frangogiannis NG. Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr Atheroscler Rep. 2009;11:131–8.PubMedPubMedCentral
30.
go back to reference Gan TJ, Soppitt A, Maroof M, El-Moalem H, Robertson KM, Moretti E, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology. 2002;97:820–6.PubMed Gan TJ, Soppitt A, Maroof M, El-Moalem H, Robertson KM, Moretti E, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology. 2002;97:820–6.PubMed
31.
go back to reference Biffl WL, Moore EE, Moore FA, Peterson VM. Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg. 1996;224:647–64.PubMedPubMedCentral Biffl WL, Moore EE, Moore FA, Peterson VM. Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg. 1996;224:647–64.PubMedPubMedCentral
32.
go back to reference Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci. 1990;79:161–5. Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci. 1990;79:161–5.
33.
go back to reference Mythen MG, Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg. 1995;130:423–9.PubMed Mythen MG, Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg. 1995;130:423–9.PubMed
34.
go back to reference Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, et al. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med. 2007;35:2016–24.PubMed Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, et al. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med. 2007;35:2016–24.PubMed
35.
go back to reference Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.PubMed Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.PubMed
36.
go back to reference Jones CA, London NR, Chen H, Park KW, Sauvaget D, Stockton RA, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat Med. 2008;14:448–53.PubMedPubMedCentral Jones CA, London NR, Chen H, Park KW, Sauvaget D, Stockton RA, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat Med. 2008;14:448–53.PubMedPubMedCentral
37.
go back to reference London NR, Zhu W, Bozza FA, Smith MC, Greif DM, Sorensen LK, et al. Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci Transl Med. 2010;2:23ra19.PubMedPubMedCentral London NR, Zhu W, Bozza FA, Smith MC, Greif DM, Sorensen LK, et al. Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci Transl Med. 2010;2:23ra19.PubMedPubMedCentral
38.
go back to reference Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH. Physiologic patterns in surviving and nonsurviving shock patients. Use of sequential cardiorespiratory variables in defining criteria for therapeutic goals and early warning of death. Arch Surg. 1973;106:630–6.PubMed Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH. Physiologic patterns in surviving and nonsurviving shock patients. Use of sequential cardiorespiratory variables in defining criteria for therapeutic goals and early warning of death. Arch Surg. 1973;106:630–6.PubMed
39.
go back to reference Shoemaker WC, Appel PL, Kram HB. Hemodynamic and oxygen transport responses in survivors and nonsurvivors of high-risk surgery. Crit Care Med. 1993;21:977–90.PubMed Shoemaker WC, Appel PL, Kram HB. Hemodynamic and oxygen transport responses in survivors and nonsurvivors of high-risk surgery. Crit Care Med. 1993;21:977–90.PubMed
40.
go back to reference Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest. 1988;94:1176–86.PubMed Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest. 1988;94:1176–86.PubMed
41.
go back to reference Yu M, Takanishi D, Myers SA, Takiguchi SA, Severino R, Hasaniya N, et al. Frequency of mortality and myocardial infarction during maximizing oxygen delivery: a prospective, randomized trial. Crit Care Med. 1995;23:1025–32.PubMed Yu M, Takanishi D, Myers SA, Takiguchi SA, Severino R, Hasaniya N, et al. Frequency of mortality and myocardial infarction during maximizing oxygen delivery: a prospective, randomized trial. Crit Care Med. 1995;23:1025–32.PubMed
42.
go back to reference Donati A, Loggi S, Preiser JC, Orsetti G, Munch C, Gabbanelli V, et al. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest. 2007;132:1817–24.PubMed Donati A, Loggi S, Preiser JC, Orsetti G, Munch C, Gabbanelli V, et al. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest. 2007;132:1817–24.PubMed
43.
go back to reference Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med. 1995;333:1025–32.PubMed Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med. 1995;333:1025–32.PubMed
44.
go back to reference Hayes MA, Timmins AC, Yau E, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330:1717–22.PubMed Hayes MA, Timmins AC, Yau E, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330:1717–22.PubMed
45.
go back to reference Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;348:5–14.PubMed Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;348:5–14.PubMed
46.
go back to reference Cannesson M, Le Manach Y, Hofer CK, Goarin JP, Lehot JJ, Vallet B, et al. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a “gray zone” approach. Anesthesiology. 2011;115:231–41.PubMed Cannesson M, Le Manach Y, Hofer CK, Goarin JP, Lehot JJ, Vallet B, et al. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a “gray zone” approach. Anesthesiology. 2011;115:231–41.PubMed
Metadata
Title
A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair
Authors
Duane J. Funk
Kent T. HayGlass
Joshua Koulack
Greg Harding
April Boyd
Ryan Brinkman
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0974-x

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