Table 4 Large controlled, randomized human trials. This table summarizes large controlled, randomized human trials in terms of population, type of fluid, ratio of crystalloid (Cr)/colloid (Co) solutions, end points, outcomes, and conclusions

Finfer 2004 SAFE (n = 6933)

ICU patients hypovolemic instabilities

Albumin; saline

The clinicians decided the amount and rate of fluid.

The study treatment was to be used for all fluid resuscitation in the ICU until death or discharge or until 28 days following randomization.

28-day mortality, RRT, new organ failure

No significant difference in 28-day mortality rate or development of new organ failure.

Brunkhorst 2008 VISEP (n = 537)

Sever septic ICU patients

HES; Ringer’s lactate

CVP 8 mmHg

MAP 70 mmHg

ScvO₂ 70%

The treating physician decided on further measures to raise MAP and ScvO₂ into specified range.

Int he HES group: HES limit of 20 mL/kg/day

28-day mortality, RRT, new organ failure

HES was harmful, and its toxicity increased with accumulating doses.

Myburgh 2012 CHEST (n = 7000)

ICU patients

HES 130/0.4; Saline

Safety authority *6% HES (130/0.4) was administered to a maximum dose of 50 mL/kg/day

open-label 0.9% saline for the remainder of the 24-h period

90-day mortality, AKI, ICU, and hospital stay,

No significant difference in 90-day mortality rate; however, the HES group received more RRT.

Guidet 2012 CRYSTMAS (n = 174)

Hemodynamic stabilization in patients with severe sepsis

HES 130/0.4; Saline

MAP ≥ 65 mmHg and at least two of

the following parameters maintained for 4 h: CVP: 8–12 mmHg, urine output > 2 mL/kg, and ScvO₂ ≥ 70%

no increase in the infusion of vasopressors or inotropic therapy, and only additional study drug administration of ≤ 1 L were allowed within these 4 h

Required study fluid volume; ICU and hospital stay; SOFA score; AKI

Significantly less volume was required to achieve hemodynamic stabilization for HES vs. saline.

Perner 2012 6S (n = 798)

ICU patients with severe sepsis

HES 130/0.42; Ringer’s acetate

Resuscitation fluid used when ICU clinicians judged that volume expansion was needed (fluid challenge technique)

CVP (8–12 mmHg); MAP (> 65 mmHg); Urine output (> 0.5 mL/kg/h); ScvO₂ or SvO₂(> 70%)

maximum daily dose of trial fluid: 33 mL/kg of ideal body weight; maximum dose of HES: 50 mL/kg ideal BW/24 h

90-day mortality, RRT

Increased 90-day mortality with HES; increased use of RRT with HES.

Annane 2013 CRISTAL (n = 2857)

ICU patients with hypovolemic shock

Colloids (gelatins, dextrans, HES, 4% or 20% albumin);

Crystalloids (isotonic or hypertonic saline, Ringer’s lactate)

The amount of fluid and duration of treatment was left at the investigators with restrictions:

the daily maximal dose of HES 30 mL/kg of body weight

investigators were required to follow any local regulatory agency recommendations governing use.

28- and 90-day mortality; days alive without the need for RRT, MV, or vasopressors

No difference in 28-day mortality; 90-day mortality lower in colloid group.

Yates 2013 (n = 202)

Medium- to high-risk elective colorectal surgery patients

HES 130/0.4; Hartman’s solutions

Before induction of anesthesia: 250 mL bolus of fluid was administered and the SV response recorded. If the SV increased by more than 10%, the bolus was repeated.

After induction of anesthesia, further boluses of fluid were administered during surgery to maintain a SV < 10%.

Volulyte up to maximum of 50 mL/kg or 5000 mL

All patients received: i.v. infusion of Hartmann’s solution; rate of 1.5 mL/kg/h

from the start of the trial period and this continued for 24 h.

After surgery, if the urine output decreased below 0.5 mL/kg/h for 2 consecutive hours, a 250 mL bolus of fluid was administered. This continued for a 24 h period from the start of surgery.

Day 5 post-op GI morbidity; post-op complications, LOS, coagulation and inflammation

No difference in any of the measured outcomes

Caironi 2014 ALBIOS (n = 1810)

ICU patients with severe sepsis or septic shock

20% albumin with crystalloid; crystalloid

Albumin group: 300 mL of 20% albumin solution. From day 1 until day 28 or ICU discharge. 20% albumin was administered on a daily basis, to maintain a serum albumin level of 30 g per liter or more.

*Crystalloids were administered whenever it was clinically indicated by the attending physician.

28- and 90-day mortality; organ dysfunction, LOS

No difference in mortality or other outcomes

Lobo 2010 (n = 10)

Healthy male subjects

Gelofusine (4% succinylated gelatine) Voluven (6% HES); saline

Compare the blood volume- expanding capacity

Compare serum Na⁺, Cl⁻, HCO3⁻ concentrations

Na⁺ and water excretion

Plasma concentrations of hormones controlling H₂O and Na⁺ excretion.

Changes in body water, blood volume and extra vascular fluid volume

Colloid solutions four times greater increase in blood volume as compared to saline, and extravasation was significantly higher after saline infusion.