Table 1.

Trials of goal-directed therapy [23,29-59]

Protocols				Fluids GDT versus control
Population	GDT endpoints	GDT therapy	Control protocol	Crystalloids	Colloids	Outcomes GDT versus control	Reference
Elective cardiac surgery	ΔSV < 10% (esophageal Doppler)	Bolus 200 ml colloid	Standard of care	Less	More	Reduction of gut mucosal hypoperfusion, less postoperative complications, shorter ICU stay, shorter HLOS	Mythen and Webb [29]
	ΔCVP < 3 mmHg
Proximal femoral fracture repair	FTc > 400 ms, ΔSV < 10% (esophageal Doppler)	Bolus 3 ml/kg colloid	Standard of care	Similar	More	Shorter HLOS	Sinclair et al. [30]
Transthoracic esophagectomy	CVP < 5 mmHg	Restrictive regimen	Standard of care	No data	No data	Less postoperative pulmonary complications	Kita et al. [31]
Major bowel surgery	FTc > 350 ms	Bolus 3 ml/kg colloid	Standard of care	No data	More	Less critical care admission	Conway et al. [32]
	ΔSV < 10% (Doppler)
Major elective surgery	FTc > 350 ms	Bolus 200 ml colloid	Standard of care (HR, CVP, MAP, UO)	Similar	More	Less PONV, earlier oral solid intake, shorter HLOS	Gan et al. [33]
	ΔSV < 10% (Doppler)
Proximal femoral fracture repair	Doppler - FTc > 400 ms,	Bolus 200 ml colloid	Standard of care (without CVP or Doppler)	Similar	More	Less intraoperative hypotension, sooner medically fit for discharge	Venn et al. [34]
	ΔSV < 10%
	CVP - ΔCVP < 5 mmHg
Elective colorectal resection	Maintaining preoperative body weight	Restrictive regimen	Standard of care	Less	Similar	Less postoperative complications (tissue healing, cardiopulmonary)	Brandstrup et al. [35]
High-risk surgical patients (≥60 years old)	DO2 = 550 to 600 ml/min/m2	Fluids, inotropes, vasodilators, vasopressors, RBC	Standard of care (without PAC)	No data	No data	More pulmonary embolism	Sandham et al. [36]
	CI = 3.5 to 4.5 l/min/m2
	MAP = 70 mmHg
	HR < 120 bpm, Ht ≥ 27%
Colorectal resection	ΔSV < 10% (Doppler)	Bolus 250 ml colloid	Routine monitoring (CVP = 12 to 15 mmHg)	Similar	More	Shorter recovery of gut function, less morbidity, shorter HLOS	Wakeling et al. [37]
	ΔCVP < 3 mmHg
Elective colorectal resection	FTc > 350 ms	7 ml/kg first bolus colloid, then bolus 3 ml/kg colloid	Standard of care (without bolus)	Similar	Similar	Less inotrope use, earlier diet, less days to medically fit, shorter HLOS	Noblett et al. [38]
	ΔSV < 10% (Doppler)
Low-risk patients off-pump coronary surgery	PAC	No data	Standard of care (CVP)	No data	No data	More use of inotropes	Resano et al. [39]
Major abdominal surgery	O2ER < 27%	Colloid bolus, RBC, dobutamine	Standard of care (MAP, UO)	No data	No data	Less organ failure, shorter HLOS	Donati et al. [40]
Cardiac bypass surgery	GEDVI = 640 ml/m2	Bolus 500 ml, vasopressors	Standard of care (CVP, MAP, clinical evaluation)	Similar	More	Shorter and reduced need for vasopressors, mechanical ventilation, and ICU therapy	Goepfert et al. [41]
	CI > 2.5 l/min/m2
	MAP = 70 mmHg
High-risk surgery	ΔPP < 10%	Bolus colloid	Standard of care	Similar	More	Less postoperative complications, shorter time of mechanical ventilation, ICU stay and HLOS	Lopes et al. [42]
Moderate to high-risk cardiac surgery	DO2 = 450 to 600 ml/min/m2	Bolus 100 ml colloid	CVP = 6 to 8 mmHg	Similar	More	Lower number of adjustments of inotropic agents	Kapoor et al. [43]
	CI = 2.5 to 4.2 l/min/m2		MAP = 90 to 105 mmHg
	SVI = 30 to 65 ml/beat/m2		UO > 1 ml/kg/h
	ScvO2 > 70%, SVV < 10%
Off-pump coronary surgery	ITBVI > 850 ml/m2	Bolus 500 ml colloid	Standard of care (MAP, CVP, HR)	Similar	More	Shorter HLOS	Smetkin et al. [44]
	ScvO2 > 60%
Laparoscopic segmental colectomy	2 GDT groups:	Bolus 200 ml colloid or 300 ml crystalloid	Standard of care	More (GDT crystalloid)	More (GDT colloid)	More postoperative complications on group GDT colloid	Senagore et al. [45]
	ΔSV < 10%
	Crystalloids versus colloids
Major abdominal surgery	PVI < 13%	Bolus 250 ml colloid (norepinephrine to MAP > 65 mmHg)	Standard of care (MAP, CVP)	Less	Similar	Lower lactate levels	Forget et al. [46]
Elective surgery for GI malignancy	Serum lactate < 1.6 mmol/l	Bolus 250 to 1,000 ml colloid (depending serum lactate)	Restrictive regimen	Similar	Similar	Less systemic complications in patients that need postoperative supplementary fluids	Wenkui et al., [47]
Major abdominal surgery	Peak aortic flow velocity < 13% (Doppler)	Bolus 250 ml, vasopressors, dobutamine, restrictive crystalloids	Standard of care (12 ml/kg/h crystalloids)	Less (patients with complication)	More (patients with complication)	More postoperative complications	Futier et al. [48]
Peripheral artery bypass grafting	CI > 2.5 l/min/m	Bolus 250 ml colloid, dobutamine	Standard of care (MAP, CVP)	No data	Similar	No difference between groups	Van der Linden et al. [49]
Major abdominal surgery	CI > 2.5 l/min/m2	Bolus 500 ml crystalloid, bolus 250 ml colloid, dobutamine, norepinephrine	Standard of care (MAP, CVP, UO)	Less	More	Less postoperative complications, shorter HLOS	Mayer et al. [50]
	SVI > 35 ml/beat/m2
	MAP > 65 mmHg
Elective intra-abdominal surgery in high-risk patients	SVV < 10%	Bolus 3 ml/kg colloid, dobutamine	Standard of care (MAP > 65 mmHg, HR < 100 bpm, CVP = 8 to 15 mmHg, UO > 0.5 ml/kg/h)	Similar	More	Better intraoperative hemodynamic stability, lower serum lactate, less postoperative complications	Benes et al. [51]
	CI > 2.5 l/min/m2
Elective total hip replacement	DO2 > 600 ml/min/m2	Bolus 250 ml colloid, dobutamine, RBC	Standard of care (MAP)	More	More	Less postoperative complications, (hypotension, cardiovascular)	Cecconi et al. [52]
	ΔSV < 10%, Hb > 10 g/dl
Elective colorectal surgery	ΔSV < 10%	Bolus 200 ml colloid	Zero balance intraoperative fluids (MAP > 60 mmHg)	Similar	More	No difference between groups	Brandstrup et al. [23]
Major abdominal surgery (cirrhotic patients)	2 GDT groups:	Bolus 250 ml LR followed by 3 ml/kg colloid	Same for both groups	Similar	Similar	No difference between groups	Abdullah et al. [53]
	PVI < 13%
	FTc > 350 ms
Major colorectal surgery	ΔSV < 10%	Bolus 200 ml colloid	Standard of care	Similar	More	More blood loss and need for transfusion in OR, longer HLOS	Challand et al. [54]
Noncardiac major surgery	FTc > 300 ms, ΔSV < 10%	Bolus 200 ml colloid	Bolus 200 ml crystalloid	Less	More	Less transfusion of FFP, better hemodynamic stability	Feldheiser et al. [55]
	MAP > 70 mmHg
	CI > 2.5 l/min/m2
Elective colectomy	FTc > 400 ms	7 ml/kg first bolus colloid, then bolus 3 ml/kg colloid	Restrictive regimen	Similar	More	No differences in outcomes	Srinivasa et al. [56]
	ΔSV < 10%		(HR, MAP, UO)
Cytoreductive surgery (ovarian cancer)	ΔSV < 10%	Bolus 200 ml	200 ml crystalloid	Less	More	Better hemodynamic stability, less FFP transfusion	Feldheiser et al. [57]
Major abdominal surgery	CI > 2.5 l/min/m2	Fluids, dobutamine, vasopressors	Standard of care	Similar	Similar	Less postoperative complications, lower infection rate	Salzwedel et al. [58]
	PPV < 10%
	MAP > 65 mmHg
Major abdominal surgery	CO SV	Bolus 250 ml colloid	Standard of care (CVP)	Less	More	No difference in outcomes	Pearse et al. [59]

Individual clinical trials and meta-analyses have shown that different fluid therapy regimens produce significantly different clinical outcomes and have resulted in considerable controversy as to the best approach. This table represents a summary of the known peer-reviewed GDT trials including their physiologic targets, fluids used, and outcomes measured.