Introduction: Sepsis is a life-threatening condition characterized by dysregulated inflammatory responses, often leading to multiple organ dysfunction and high mortality rates. Continuous renal replacement therapy (CRRT) and extracorporeal blood purification therapies have emerged as vital adjuncts to manage fluid overload and modulate immune responses in septic shock. This study evaluates the impact of daily fluid balance variation on 90-day mortality and hospital length of stay in ICU patients undergoing CRRT for septic shock with endotoxin activity. Methods: A post hoc analysis of the EUPHAS 2 project was conducted on 61 ICU patients with nonresponsive endotoxin shock at San Bortolo Hospital (2016–2021). Bayesian joint models assessed the relationship between fluid balance and mortality. Mediation analysis explored the impact of CRRT on mechanical ventilation duration and hospital stay. Results: Fluid overload and excessive ultrafiltration were associated with prolonged mechanical ventilation and extended hospital stays. Targeted fluid balance management reduced 90-day mortality risk by 50%. CRRT reduced hospital length of stay directly by 5.31 days but indirectly extended it by 11.78 days due to mechanical ventilation. Optimal fluid balance was critical for minimizing mortality and complications. Conclusions: Careful and tailored fluid management in CRRT is essential for improving survival rates and clinical outcomes in septic shock patients. Continuous monitoring of fluid dynamics is necessary to optimize hemodynamic stability and avoid complications. Future multicenter studies are needed to validate these findings and refine fluid management protocols.

1.
Singer
M
,
Deutschman
CS
,
Seymour
CW
,
Shankar-Hari
M
,
Annane
D
,
Bauer
M
, et al
.
The third international consensus definitions for sepsis and septic shock (Sepsis-3)
.
JAMA
.
2016
;
315
(
8
):
801
10
.
2.
Eubank
TA
,
Long
SW
,
Perez
KK
.
Role of rapid diagnostics in diagnosis and management of patients with sepsis
.
J Infect Dis
.
2020
;
222
(
Suppl 2
):
S103
9
.
3.
Lakomy
M
,
Kaleczyc
J
,
Całka
J
.
The effect of oestradiolum benzoicum and progesterone on AChE activity in the nerves of the female reproductive system of immature pigs
.
Gegenbaurs Morphol Jahrb
.
1986
;
132
(
3
):
333
48
.
4.
Zarbock
A
,
Koyner
JL
,
Gomez
H
,
Pickkers
P
,
Forni
L
;
Acute Disease Quality Initiative group
.
Sepsis-associated acute kidney injury: treatment standard
.
Nephrol Dial Transplant
.
2023
;
39
(
1
):
26
35
.
5.
Dellinger
RP
,
Bagshaw
SM
,
Antonelli
M
,
Foster
DM
,
Klein
DJ
,
Marshall
JC
, et al
.
Effect of targeted Polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES randomized clinical trial
.
JAMA
.
2018
;
320
(
14
):
1455
63
.
6.
Ronco
C
,
Chawla
L
,
Husain-Syed
F
,
Kellum
JA
.
Rationale for Sequential Extracorporeal Therapy (SET) in sepsis
.
Crit Care
.
2023
;
27
(
1
):
50
.
7.
Wu
S
,
Xu
T
,
Wu
C
,
Lei
X
,
Tian
X
.
Continuous renal replacement therapy in sepsis-associated acute kidney injury: effects on inflammatory mediators and coagulation function
.
Asian J Surg
.
2021
;
44
(
10
):
1254
9
.
8.
White
K
,
Laupland
KB
,
Bellomo
R
,
Serpa-Neto
A
.
The interaction of net ultrafiltration rate with urine output and fluid balance after continuous renal replacement therapy initiation: a multi-Centre study
.
J Crit Care
.
2024
;
83
:
154835
.
9.
Hyun
DG
,
Ahn
JH
,
Huh
JW
,
Hong
SB
,
Koh
Y
,
Oh
DK
, et al
.
Impact of a cumulative positive fluid balance during the first three ICU days in patients with sepsis: a propensity score-matched cohort study
.
Ann Intensive Care
.
2023
;
13
(
1
):
105
.
10.
Moschopoulos
CD
,
Dimopoulou
D
,
Dimopoulou
A
,
Dimopoulou
K
,
Protopapas
K
,
Zavras
N
, et al
.
New insights into the fluid management in patients with septic shock
.
Medicina
.
2023
;
59
(
6
):
1047
.
11.
von Elm
E
,
Altman
DG
,
Egger
M
,
Pocock
SJ
,
Gøtzsche
PC
,
Vandenbroucke
JP
, et al
.
The Strengthening The Reporting of Observational studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies
.
Int J Surg
.
2014
;
12
(
12
):
1495
9
.
12.
Capuzzo
M
,
Valpondi
V
,
Sgarbi
A
,
Bortolazzi
S
,
Pavoni
V
,
Gilli
G
, et al
.
Validation of severity scoring systems SAPS II and Apache II in a single-center population
.
Intensive Care Med
.
2000
;
26
(
12
):
1779
85
.
13.
Khwaja
A
.
KDIGO clinical practice guidelines for acute kidney injury
.
Nephron Clin Pract
.
2012
;
120
(
4
):
c179
84
.
14.
Jones
GRD
,
Imam
SK
.
Validation of the revised MDRD formula and the original Cockcroft and Gault formula for estimation of the glomerular filtration rate using Australian data
.
Pathology
.
2009
;
41
(
4
):
379
82
.
15.
VanderWeele
TJ
.
A unification of mediation and interaction: a 4-way decomposition
.
Epidemiology
.
2014
;
25
(
5
):
749
61
.
16.
Neyra
JA
,
Mehta
RL
,
Murugan
R
.
Fluid management during continuous renal replacement therapy: a case-based approach
.
Nephron
.
2023
;
147
(
12
):
782
7
.
17.
Prowle
J
,
Mehta
R
.
Fluid balance management during continuous renal replacement therapy
.
Semin Dial
.
2021
;
34
(
6
):
440
8
.
18.
Messmer
AS
,
Zingg
C
,
Müller
M
,
Gerber
JL
,
Schefold
JC
,
Pfortmueller
CA
.
Fluid overload and mortality in adult critical care patients: a systematic review and meta-analysis of observational studies
.
Crit Care Med
.
2020
;
48
(
12
):
1862
70
.
19.
Garzotto
F
,
Ostermann
M
,
Martín-Langerwerf
D
,
Sánchez-Sánchez
M
,
Teng
J
,
Robert
R
, et al
.
The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients
.
Crit Care
.
2016
;
20
(
1
):
196
.
20.
Balakumar
V
,
Murugan
R
,
Sileanu
FE
,
Palevsky
P
,
Clermont
G
,
Kellum
JA
.
Both positive and negative fluid balance may Be associated with reduced long-term survival in the critically ill
.
Crit Care Med
.
2017
;
45
(
8
):
e749
57
.
21.
Shen
Y
,
Huang
X
,
Zhang
W
.
Association between fluid intake and mortality in critically ill patients with negative fluid balance: a retrospective cohort study
.
Crit Care
.
2017
;
21
(
1
):
104
.
22.
Bitker
L
,
Dupuis
C
,
Pradat
P
,
Deniel
G
,
Klouche
K
,
Mezidi
M
, et al
.
Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial
.
Intensive Care Med
.
2024
;
50
(
12
):
2061
72
.
23.
Daugirdas
JT
.
Pathophysiology of dialysis hypotension: an update
.
Am J Kidney Dis
.
2001
;
38
(
4 Suppl 4
):
S11
7
.
24.
Murugan
R
,
Hoste
E
,
Mehta
RL
,
Samoni
S
,
Ding
X
,
Rosner
MH
, et al
.
Precision fluid management in continuous renal replacement therapy
.
Blood Purif
.
2016
;
42
(
3
):
266
78
.
25.
Opgenorth
D
,
Reil
E
,
Lau
V
,
Fraser
N
,
Zuege
D
,
Wang
X
, et al
.
Improving the quality of the performance and delivery of Continuous Renal Replacement Therapy (CRRT) to critically ill patients across a healthcare system: quality CRRT: a study protocol
.
BMJ Open
.
2022
;
12
(
2
):
e054583
.
26.
Murugan
R
,
Bellomo
R
,
Palevsky
PM
,
Kellum
JA
.
Ultrafiltration in critically ill patients treated with kidney replacement therapy
.
Nat Rev Nephrol
.
2021
;
17
(
4
):
262
76
.
27.
Davies
A
,
Srivastava
S
,
Seligman
W
,
Motuel
L
,
Deogan
V
,
Ahmed
S
, et al
.
Prevention of acute kidney injury through accurate fluid balance monitoring
.
BMJ Open Qual
.
2017
;
6
(
2
):
e000006
.
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