2022 ESICM Hot Spot Express Phase I: From the perspective of clinical benefit, focus on the selection of resuscitation fluid for sepsis patients

Crystalloid: balanced saline solution versus normal saline

The 2021 Save Sepsis Campaign (SSC) International Guidelines: Management of Sepsis and Septic Shock are based on the evaluation of studies that suggest that balanced saline solutions improve patient outcomes compared with normal saline and are recommended for resuscitation in adults with sepsis ^[2].

。 However, in the same year, a large double-blind, factorial, randomized clinical trial of BaSICS showed that balanced saline solution did not reduce 90-day mortality compared with normal saline (27.
2 versus 26.
4%, p=0.
47) ^[3].

This seems to pose a challenge
to guideline recommendations.
At the 2022 ESICM Annual Meeting, F.
R.
from São Paulo, Brazil.
Professor Machado is the author of "What have we learnt about fluid replacement from the BaSICS trial?" This paper further analyzes the results of the study ^[4].

She first showed that the BaSICS study was not a resuscitation fluid study, but included all fluid treatments patients received during the ICU, and although the results were neutral, a subsequent systematic review and meta-analysis including the BaSICS study showed that balanced saline solutions were more likely to reduce the risk of
death compared with normal saline 。 Thirteen randomized controlled trials at low risk of bias totalling 35,884 patients, including 6,754 with sepsis, showed that balanced salt solutions reduced the risk of 90-day death in patients with sepsis by 14 percent to 1 percent higher [4,5^].

(Figure 1).

Figure 1.
Effect of balanced saline solution versus normal saline on patient mortality (excerpted from "What have we learnt about fluid replacement from the BaSICS trial?" ）

Secondary exploratory analysis of the BaSICS study showed that patients who were given balanced saline solution alone during both emergency department and ICU admission were more likely to reduce the risk of death at 90 days (OR 0.
78, 89% CI [0.
56 to 1.
03], probability of benefit 0.
92) ^[4,6].

(Figure 2)

Figure 2.
Conditional distribution of balanced saline solution versus normal saline OR before and after ICU entry (excerpt from "What have we learnt about fluid replacement from the BaSICS trial?" ）

In addition, the BaSICS study evaluated the effect of
different infusion rates on 90-day mortality.
Results showed that slow infusion (333 ml/h) did not reduce the risk of death compared with rapid infusion (999 ml/h) (P=0.
46) ^[7].

Rapid infusion is associated with a better prognosis in patients with sepsis, particularly in older patients ^[4].

(Figure 3).

Figure 3.
Revelations from the BaSICS study (excerpted from "What have we learnt about fluid replacement from the BaSICS trial?" ）

Colloidal solution:

Isocolloidal osmotic versus high colloidal osmotic pressure

The 2021 SSC guidelines oppose the use of artificial colloids for resuscitation, and for patients requiring high-dose crystalloid resuscitation, it is recommended to combine human albumin rather than crystalloid because it is more effective than crystalloid resuscitation alone at stabilizing hemodynamics and reducing the total amount of resuscitation fluid ^[2].

。 A systematic review and meta-analysis published in 2019 to assess the hemodynamic response of crystalloid and colloidal fluids in critically ill patients, including 55 RCTs, 18% of which were in patients with sepsis, showed that central venous pressure (CVP) and mean arterial pressure (MAP) were significantly higher in the human albumin group than in the crystalloid group (CVP:P<0.
001; MAP:P=0.
03)^{[ 8]}
。

Human blood albumin is available in two concentration dosage forms
: isocolloidal osmolality (5%) and high colloidal osmolality (20%-25%).
Professor Regenmortel from Belgium presented "Which fluid should we use in critically ill patients?" Two concentrations of human albumin were analyzed in combination with the latest study ^[9].

(Figure 5).

Figure 5.
Transfer effect of high colloidal osmotic albumin on liquids (excerpted from "Which fluid should we use in critically ill patients?" ）

In 2019, Hahn et al.
first developed a population dynamics model
after intravenous injection of 20% human albumin.
Fifteen healthy volunteers and 15 patients undergoing major abdominal surgery (day 1 after laparotomy) were given 3 mL/kg of 20% albumin intravenously within 30 minutes and blood samples and urine
were collected within 5 hours.
Mixed-effects modeling software was used to develop fluid volume dynamics models, using hemoglobin and urine output to estimate fluid changes
.
Excess amounts of human albumin have been shown to accelerate fluid flow inside and outside the plasma, resulting in long-lasting steady-state expansion, which is not seen after 5% human albumin transfusion ^[9,10].

This kinetic profile differs minimally between healthy subjects and patients undergoing major abdominal surgery, and has no effect on arterial pressure, inflammatory markers, and endothelial exfoliation products ^[10].

A prospective crossover study published in 2022 ^[11] involving 12 volunteers explored the expansion of 5% and 20% human albumin over time
.
The results showed that 20% of human albumin achieved maximum expansion effect after 10 minutes of infusion, and the maximum volume expansion could reach 200±66% of the infusion volume, while 5% of human albumin could only record the maximum expansion effect at the end of infusion, and the maximum expansion capacity was 66±12% of the infusion ^{volume [}9,11^].

。 At 6 hours, the effect of 5% human albumin transfusion on fluid balance was basically neutral (plasma expansion + urine output = infusion), but about 100 ml of extravascular fluid was still transferred to the plasma
.
However, 20% of human blood albumin has an early dehydration effect on the whole body (plasma expansion + urine output > 4 times the infusion amount), suggesting that 20% human blood albumin can prevent and treat peripheral fluid overload more effectively ^[11].

20% human albumin is more effective in improving hemodynamics, reducing the need for dialysis treatment, and improving microcirculation