A neglected topic for way too long, the interest in fluid therapy seems to be quickly rising as the medical community is making a shift from looking at fluids as a mere method of stabilization towards the appreciation of its relevant side effects. Many questions remain to be answered indeed: Is the upgrade from saline 0.9% to balanced crystalloids worth the extra cost? Does HES still have a place in the OR? Do we have to fill the gap left by HES on ICU with crystalloids, other colloids or even albumin? Is it really impossible to avoid fluid overload by using only crystalloids? Is there still a definitive place for human albumin? How do we treat and monitor specific patient populations, like patients with trauma, liver failure, brain edema and right heart failure among others? How do we avoid a one-size-fits-all regimen in perioperative goal-directed therapy? What with the fluids beyond resuscitation? And what do the authors of the big fluid trials do in real life themselves? The 9th International Fluid Academy Day will again be a 1 day concise meeting on all aspects of fluid managament and hemodynamic monitoring in the critically ill. Date: October 26th 2019, 8:00 - 18:00

1. Pietro Caironi, MD
Anestesia e Rianimazione,AOU S. Luigi Gonzaga
Università degli Studi di Torino
pietro.caironi@unito.it
What happened in the meantime?
(trials review)
9th IFAD
Valencia, Spain
October 26, 2019

2. DISCLOSURE
Lectures honoraria from
Grifols, De Mori, CSL Behring, Bbraun, Mitsubishi Chemicals,
Baxter, Ortho Diagnostic
Research support from
Mitsubishi Chemicals, Sphingotech, Grifols

3. Reiterer C, et al., Br J Anaesth 2019 Oct 15. [Epub ahead of print]
Van Regenmortel N, et al., Intensive Care Med. 2019 Oct;45(10):1422-1432
Brown RM, et al.Am J Respir Crit Care Med. 2019 Aug 27 [Epub ahead of print]
Park CHL, et al., Crit Care Med. 2019 Oct;47(10):e798-e805
Arslantas R, et al.Transplant Proc 2019 Sep;51(7):2262-2264
Levin M, et al., Lancet Respir Med. 2019 Jul;7(7):581-593
Bihari S, et al., J Appl Physiol (1985). 2019;126(6):1646-1660
Statkevicius S, et al., Crit Care. 2019 May 28;23(1):191
Kabon B, et al.,Anesthesiology 2019;130(5):728-744
Joosten A, et al.,Anesthesiology. 2019;130(2):227-236
Silversides JA, et al., Crit Care Med. 2018 Oct;46(10):1600-1607
Mårtensson J, et al., Intensive Care Med. 2018 Nov;44(11):1797-1806
Heming N, et al.,Anesthesiology 2018;129(6):1149-1158
Lewis SR, et al., Cochrane Database Syst Rev. 2018;8:CD000567
Van Regenmortel N, et al., Intensive Care Med. 2018 Apr;44(4):409-417
SelfWH, et al., N Engl J Med. 2018 Mar 1;378(9):819-828
Semler MW, et al., N Engl J Med. 2018 Mar 1;378(9):829-839
Joosten A, et al.,Anesthesiology. 2018;128(1):55-66
Several clinical trials and publications over the last year on fluids…
Cry vs. Coll
Maintenance fluid
BAL
ALB
BAL
Bolus vs. Slow ad.
ALB
ALB
Cry vs. Coll
Cry vs. Coll
Deresuscitation
ALB
Cry vs. Coll
Cry vs. Coll
Maintenance fluid
BAL
BAL
Cry vs. Coll

4. Update – Crystalloids vs. Colloids
Update –Type of fluids: Balanced Solutions / Normal Saline
Update –Type of fluids: 20% vs. 5% Albumin

5. Moderate- to high-risk pts during abdominal
surgery (n = 1057 pts)
Doppler-guided intra-op administration of
HES vs. RL
Crystalloids vs. Colloids (HES) in the perioperative period
No difference in post-operative serious complications
Any new evidence?
Incidence of serious post-operative complications

6. Kaboon B et al.,Anesthesiology – 2019 (Anesthesiology 2019;130:728-44)
Abdominal surgery in moderate- to high-risk patients (n = 1057 pts).
Doppler-guided intra-op volume replacement with 6% HES vs. RL.
No difference in post-operative serious complications (primary outcome). No evidence of renal toxicity.
Recent evidence on Crystalloids vs. Colloids (HES) trials – surgical patients
Heming N et al.,Anesthesiology – 2018 (Anesthesiology 2018;129:1149-58)
Pre-planned analysis of the CRYSTAL trial (n = 741 critically ill surgical patients
with hypovolemic shock). Crystalloids vs. Colloids (all types).
No difference in 28- and 90-mortality (primary outcomes). No difference in the use of RRT.
Joosten A et a.,Anesthesiology – 2018/2019
(Anesthesiology 2018;128:55-66;Anesthesiology 2019;130:227-36)
Major abdominal surgery (n = 160 pts) – 1-year follow-up (n= 129 pts).
Closed-loop system / predefined goal-directed administration of Plasmalyte vs. HES.
Fewer incidence of post-operative complications and higher long-term disability free survival higher
in the colloid group. No difference in long-term renal function.
No benefit No harm
No benefit No harm
Some benefit No harm
No solid evidence of benefit
No harm on surgical patients
(dose effects?)
(always tissue accumulation)

7. Take-Home Messages – 1
The use of HES in surgical patients does NOT appear to have a beneficial effects
as compared to the use of crystalloids, even in pre-defined goal-directed strategies
The use of HES in surgical patients does NOT appear to have a detrimental effects
on renal function (low dose – surgical patients)
The use of HES does NOT appear to be associated with a clear hemodynamic
and clinically relevant advantage, over the use of crystalloids
Further trials are necessary to elucidate possible clinical advantages on the use
of HES (colloids) observed in preliminary studies

8. Update – Crystalloids vs. Colloids
Update –Type of fluids: Balanced Solutions / Normal Saline
Update –Type of fluids: 20% vs. 5% Albumin

9. N Engl J Med 2018;378:829-39
Pragmatic, cluster-randomized,
multiple crossover trial in 5 ICUs
(single center)
N=15802 pts in ED and admitted to ICU
treated with iv fluids
0.9% NaCl vs.
Balanced Crystalloids
Primary composite endpoint
(major adverse kidney events) MAKE30: 14.3% vs. 15.4% (P=0.04)

10. Am J Respir Crit care Med 2019 Aug 27. doi 10.1164/rccm [Epub ahead of print]
In Sepsis
Several adjustments, secondary analyses, and sensitivity analyses…

11. Possible detrimental effects of BOLUS administration (volume / Cl– load)
Lancet Resp Med 2019;7:581-593
Re-analysis of the
FEAST trial
Children with severe febrile
Illness with hypoperfusion
(n = 3170)
ALB-bolus
NS-bolus
NS – no bolus
Elucidate possible mechanisms
of the detrimental effects
associated with bolus administration

12. Lancet Resp Med 2019;7:581-593
Specific alterations associated with bolus administration
Alterations in respiratory, neurological, and acid-base functions
associated with increased mortality risk of bolus administration

13. Lancet Resp Med 2019;7:581-593
Risk of volume and Cl– load – importance of the rapidity of fluid administration

14. Take-Home Messages – 2
The use of balanced solutions may be associated with a clinically relevant beneficial
effect (reduction of AKI, and possibly of mortality),
although the data are still inconclusive
Bolus administration may be associated, in specific pathological settings
(high permeability conditions), with potential detrimental effects, as compared to
no-bolus administration (volume load? Cl– load?)
Administration rate, especially during fluid resuscitation,
should be extensively investigated

15. Update – Crystalloids vs. Colloids
Update –Type of fluids: Balanced Solutions / Normal Saline
Update –Type of fluids: 20% vs. 5% Albumin

16. Martensson J et al., Intensive Care Med 2018;44:1797-1806
Comparison of
4-5% vs. 20%
Albumin
Resuscitation fluid requirements of ICU pts
resuscitated with 20% albumin vs. 4-5% albumin
Inclusion criteria
Adult pts hemodynamic unstable requiring
fluid bolus within 48 h of ICU admission
(hypotension, vasopressor need, PPV positive,
or CI, HR, UO, lactate, refill time) (n = 321)
Fluid resuscitation with 20% or 4-5% albumin
during the first 48 h for hemodynamic target
Primary outcome:
cumulative volume of resuscitation fluid

17. 4-5%
vs. 20%
Albumin
Martensson J et al., Intensive Care Med 2018;44:1797-1806
Small volume resuscitation with 20% albumin reduced resuscitation fluid requirement
and minimized fluid accumulation compared with resuscitation with 4-5% albumin
Small volume resuscitation with 20% albumin did not negatively impact kidney function
or other key clinical outcomes

18. De S. Mendes et al., Respiratory Research 2019;20:155
Experimental in-vivo model
of LPS-induced ALI
Hemodynamic resuscitation
With RL, 20%ALB, or 5%ALB
Iso-oncotic and hyper-oncotic ALB solutions
were associated with less lung injury compared to RL.
Hyper-oncotic ALB resulted in a greater AKI
than iso-oncotic ALB

19. Possible importance of infusion rate – Hypothesis…
Bihari S
(JAP 2019)
480 mL 20% ALB
in 20 min
60 mg/kg/min Yes No
ALBIOS
(NEJM 2014)
300 mL
20% ALB in 3h
4.7 mg/kg/min Yes No
RASP
(CCM 2019)
500 mL 4% ALB
in < 10 min
30 mg/kg/min No No
De S. Mendes
(RR 2019)
2 mL/kg 20% ALB
as bolus (flush)
420 mg/kg/min ~ Yes
Study Dosage and time Infusion rate
Intravascular
expansion
AKI Healthy?

20. Crit Care 2019;23:191
Pts with signs of hypoperfusion after major
abdominal surgery (n = 64)
10 ml/kg 5% albumin administration
rapidly (30 min) vs. slowly (180 min)
Measurement of plasma volume
using radiolabeled albumin
Slow albumin administration appears
less efficient for plasma volume expansion

21. Take-Home Messages – 3
The use of 20% albumin for volume resuscitation reduces fluid requirement
as compared to the use of 4-5% albumin
The use of hyper-oncotic 20% albumin is NOT associated with a risk of renal injury as
compared to 4-5% albumin
Administration rate of albumin-containing solutions should be further investigated,
both for its efficacy and safety profile
Thank you for your attention…!