Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature

Jonathan E Sevransky, Seema Nour, Gregory M Susla, Dale M Needham, Steven Hollenberg, Peter Pronovost, Jonathan E Sevransky, Seema Nour, Gregory M Susla, Dale M Needham, Steven Hollenberg, Peter Pronovost

Abstract

Introduction: Patients with sepsis suffer high morbidity and mortality. We sought to conduct a systematic review of the literature to evaluate the association between hemodynamic goals of therapy and patient outcomes.

Methods: We conducted a comprehensive search of the literature to systematically review hemodynamic goals used in clinical trials in patients with sepsis. We searched the literature using the Pubmed (1965-June 2006), Embase (1974-June 2006), CINAHL (1982-June 2006), pre-CINAHL, and Cochrane Library (2006, issue 3) electronic databases on 1 August 2006 for the following terms: sepsis, septic shock, severe sepsis, human clinical trials. We also hand-searched references and our personal files. Studies were selected if they met all of the following criteria: randomized, controlled trial study design; enrollment of adult patients with sepsis; presence of a hemodynamic goal for patient management; > 24-hour follow-up; and survival included as an outcome. Studies were independently selected and reviewed by two investigators.

Results: A total of 6,006 citations were retrieved, and 13 eligible articles were reviewed. Mean arterial pressure was a treatment goal in nine studies, and systolic blood pressure was a treatment goal in three studies. A goal for pulmonary artery occlusion pressure, central venous pressure, and cardiac index was given in four, three, and five studies, respectively. The range of hemodynamic goals used in the trials were: mean arterial pressure 60-100 mmHg, central venous pressure 6-13 mmHg, pulmonary artery occlusion pressure 13-17 mmHg, and cardiac index 3-6 l/min/m2. All trials that used a systolic blood pressure goal used 90 mmHg as the aim.

Conclusion: For those trials that specify hemodynamic goals, the wide range of treatment targets suggest a lack of agreement on blood pressure and filling pressure goals for management of patients with sepsis. There was also inconsistency between trials in which measures were targeted. Further research is necessary to determine whether this lack of consistency in hemodynamic goals may contribute to heterogeneity in treatment effects for clinical trials of novel sepsis therapies.

Figures

Figure 1
Figure 1
Study flow diagram. RCT, randomized controlled trial.
Figure 2
Figure 2
Hemodynamic goals in sepsis trials. (a) Mean arterial pressure (MAP) goals in sepsis trials. (b) Central venous pressure (CVP) goals in sepsis trials. (c) Pulmonary artery occlusion pressure (PAOP) goals in sepsis trials. (d) Cardiac index in sepsis trials. For studies that provided an interval goal range, the mean of the range is graphed. One study provided a separate CI for the treatment and control groups; these are graphed separately.

References

    1. Laupland KB, Zygun DA, Doig CJ, Bagshaw SM, Svenson LW, Fick GH. One-year mortality of bloodstream infection-associated sepsis and septic shock among patients presenting to a regional critical care system. Intensive Care Med. 2005;31(2):213–9. doi: 10.1007/s00134-004-2544-6.
    1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the united states from 1979 through 2000. N Engl J Med. 2003;348:1546–1554. doi: 10.1056/NEJMoa022139.
    1. Annane D, Aegerter P, Jars-Guincestre MC, Guidet B, for the CUB-Rea Network Current epidemiology of septic shock: the CUB-rea network. Am J Respir Crit Care Med. 2003;168:165–172. doi: 10.1164/rccm.2201087.
    1. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, for the Surviving Sepsis Campaign Management Guidelines Committee et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–873. doi: 10.1097/01.CCM.0000117317.18092.E4.
    1. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;25:1095–1100. doi: 10.1097/00003246-199707000-00001.
    1. Hollenberg SM. For every complex problem, there is a solution that is simple ... and wrong. Crit Care Med. 2000;28:3088–3089. doi: 10.1097/00003246-200008000-00074.
    1. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. 1999;340:207–214. doi: 10.1056/NEJM199901213400307.
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–1655.
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4.
    1. Peake SL, Moran JL, Leppard PI. N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock. Crit Care Med. 1996;24:1302–1310. doi: 10.1097/00003246-199608000-00006.
    1. Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26:645–650. doi: 10.1097/00003246-199804000-00010.
    1. Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest. 1992;102:216–220.
    1. Cole L, Bellomo R, Hart G, Journois D, Davenport P, Tipping P, Ronco C. A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med. 2002;30:100–106. doi: 10.1097/00003246-200201000-00016.
    1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377. doi: 10.1056/NEJMoa010307.
    1. Boldt J, Papsdorf M, Piper SN, Rothe A, Hempelmann G. Continuous heparinization and circulating adhesion molecules in the critically ill. Shock. 1999;11:13–18.
    1. Emet S, Memis D, Pamukcu Z. The influence of N-acetyl-L-cystein infusion on cytokine levels and gastric intramucosal pH during severe sepsis. Crit Care. 2004;8:R172–R179. doi: 10.1186/cc2866.
    1. Briegel J, Forst H, Hallar M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single center study. Crit Care Med. 1999;27:723–732. doi: 10.1097/00003246-199904000-00025.
    1. Alia I, Esteban A, Gordo F, Lorente JA, Diaz C, Rodriguez JA, Frutos F. A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock. Chest. 1999;115:453–461. doi: 10.1378/chest.115.2.453.
    1. Spapen H, Zhang H, Demanet C, Vleminckx W, Vincent JL, Huyghens L. Does N-acetyl-L-cysteine influence cytokine response during early human septic shock? Chest. 1998;113:1616–1624.
    1. Bakker J, Grover R, McLuckie A, Holzapfel L, Andersson J, Lodato R, Watson D, Grossman S, Donaldson J, Takala J. Administration of the nitric oxide synthase inhibitor N G-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002) Crit Care Med. 2004;32:1–12. doi: 10.1097/01.CCM.0000105118.66983.19.
    1. Lopez A, Lorente JA, Steingrub J, Bakker J, McLuckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med. 2004;32:21–30. doi: 10.1097/01.CCM.0000105581.01815.C6.
    1. Hollenberg SM, Ahrens TS, Annane D, Astiz ME, Chalfin DB, Dasta JF, Heard SO, Martin C, Napolitano LM, Susla GM, Totaro R, Vincent J-L, Zanotti-Cavazzoni S. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med. 2004;32:1928–1948. doi: 10.1097/01.CCM.0000139761.05492.D6.
    1. Clark M, Plank L, Connolly A, Streat SJ, Hill AA, Gupta R, Monk DN, Shenkin A, Hill GL. Effect of a chimeric antibody to tumor necrosis factor alpha on cytokine and physiologic responses in patients with severe sepsis. A randomized clinical trial. Crit Care Med. 1998;26:1650–1659. doi: 10.1097/00003246-199810000-00016.
    1. Kumar A, Anel R, Bunnell E, Zanotti S, Habet K, Haery C, Marshall S, Cheang M, Neumann A, Ali A, Kavinsky C, Parrillo JE. Preload-independent mechanisms contribute to increased stroke volume following large volume saline infusion in normal volunteers: a prospective interventional study. Crit Care. 2004;8:R128–R136. doi: 10.1186/cc2844.
    1. Fowler RA, Cook DJ. The arc of the pulmonary artery catheter. JAMA. 2003;290:2732–2734. doi: 10.1001/jama.290.20.2732.
    1. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med. 1995;333:1025–1032. doi: 10.1056/NEJM199510193331601.
    1. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: A randomized controlled trial. JAMA. 2003;290:238–247. doi: 10.1001/jama.290.2.238.
    1. Abraham E, Laterre P, Garg R, Levy H, Talwar D, Trzaskoma BL, Francois B, Guy JS, Bruckmann M, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med. 2005;353:1332–1341. doi: 10.1056/NEJMoa050935.
    1. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, et al. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001:1869–1878. doi: 10.1001/jama.286.15.1869.
    1. Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, Dal Nogare A, Nasraway S, Berman S, Cooney R, et al. Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II study group. Lancet. 1998;351:929–933.
    1. Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C, Teboul JL. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med. 2007;35:64–68. doi: 10.1097/01.CCM.0000249851.94101.4F.
    1. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335:1864–1869. doi: 10.1056/NEJM199612193352502.
    1. Wheeler AP, Bernard GR, Thompson BT, Schoenfeld D, Wiedemann HP, deBoisblanc B, Connors AF, Jr, Hite RD, Harabin AL, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006;354:2213–2224. doi: 10.1056/NEJMoa061895.
    1. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF, Jr, Hite RD, Harabin AL, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564–2575. doi: 10.1056/NEJMoa062200.
    1. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–461. doi: 10.1056/NEJMoa052521.
    1. Taylor BE, Schallom ME, Sona CS, Buchman TG, Boyle WA, Mazuski JE, Schuerer DE, Thomas JM, Kaiser C, Huey WY, Ward MR, et al. Efficacy and safety of an insulin infusion protocol in a surgical ICU. J Am Coll Surg. 2006;202:1–9. doi: 10.1016/j.jamcollsurg.2005.09.015.

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