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Table 2 Observational controlled trials of bundled goal-directed therapy

From: Conservative fluid therapy in septic shock: an example of targeted therapeutic minimization

Study and country Sign score Goal-directed therapy (goals)   Time and fluid quantification (L)a
     Control Bundled GDT
Cardoso et al. 2010, Portugal [42] (−) 500 ml to 1000 ml crystalloid bolus, or 300 ml to 500 ml colloid bolus to achieve CVP ≥12 mmHg   Quantified but not reported.
Castellanos-Ortega et al. 2010, Spain [35] (−) 500-1000 ml crystalloid bolus, additional fluid to achieve CVP ≥8 mmHg   Quantified but not reported.
El Solh et al. 2008, USA [31] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg 6 h: 2.5 ± 1.0 3.9 ± 2.0
24 h: 3.2 ± 1.3 4.9 ± 2.5
Ferrer et al. 2008, Spain [33] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg   Quantified but not reported
Gao et al. 2005, UK [36] (−) Immediate fluid bolus of 0.5 L   Quantified but not reported
Girardis et al. 2009, Italy [34] (−) Fluids targeting CVP >6 mmHg or a global end-diastolic volume by trans-pulmonary thermodilution >700 ml/m2   Quantified but not reported
Heppner et al. 2012, Germany [39] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg   Quantified but not reported.
Jones et al. 2007, USA [30] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg 6 h: 2.5 ± 2.4 4.7 ± 1.8
Kortgen et al. 2006, Germany [27] (−) CVP 8–12 mmHg or intrathoracic blood volume index 850–1000 ml/m2 6 h: 2.8 [1.8,3.8] 2.5 [1.6,3.9]
Lefrant et al. 2010, France [41] (−) ≥20 ml/kg crystalloids or colloids within 6 hours 6 h crystalloid: 1.0 [0.5,2.0] 1.5 [0.5,2.0]
6 h colloid: 0.5 [0.5,1.0] 1.0 [0.5,1.1]
Micek et al. 2006, USA [25] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg In ED: 2.8 ± 1.6 3.8 ± 1.7
Miller et al. 2013, USA [38] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg   Quantified but not reported.
Na et al. 2012, Asia [40]b (−) Fluid bolus to achieve CVP >8 mmHg by 6 hours In ED: 1.5 [1.0,2.5] 1.5 [0.9,2.7]
In ICU: 7.8 [5.2,11.6] 5.6 [3.3,9.2]
Nguyen et al. 2007, USA [29] (−) CVP ≥8 mmHg In ED: 2.8 ± 1.5 2.8 ± 2.1
72 h: 7.8 ± 5.2 7.9 ± 6.1
Pestaña et al. 2010, Spain [37] (−) Crystalloid within 6 hours to achieve CVP ≥8 mmHg or global end-diastolic volume index ≥680 ml/m2   Quantified but not reported.
Sebat et al. 2005, USA [32] (−) 1000 ml crystalloid in ED, 600 ml increments per MAP & UO protocol   Quantified but not reported.
Shapiro et al. 2006, USA [28] (−) 500 ml crystalloid bolus, repeat until CVP 8–12 mmHg 6 h: 2.9 ± 1.8 4.1 ± 2.6
24 h: 6.5 ± 4.5 7.6 ± 3.9
Trzeciak et al. 2006, USA [26] (−) 250-1000 ml crystalloid bolus until CVP ≥8 mmHg ED: 3.5 ± 2.3 5.7 ± 3.0
ICU 24 h: 5.5 ± 4.9 2.8 ± 1.7
ED and ICU 24 h: 9.1 ± 5.1 7.9 ± 3.4
  1. Double plus signs (++) indicate studies with very unlikely bias, a plus sign (+) indicates studies with unlikely bias, and a minus sign (−) indicates studies with high risk of bias. aValues expressed as mean ± standard deviation or median [interquartile range]. bChina, India, Taiwan, Singapore, Korea. CVP, central venous pressure; ED, emergency department; GDT, goal-directed therapy; MAP, mean arterial pressure; UO, urine output.