Evaluate the change of some parameters in patients with multiple organ failure supported by continuous renal replacement therapy

Journal of military pharmaco-medicine no7-2018

EVALUATE THE CHANGE OF SOME PARAMETERS
IN PATIENTS WITH MULTIPLE ORGAN FAILURE SUPPORTED BY
CONTINUOUS RENAL REPLACEMENT THERAPY
Huynh Thi Ngoc Thuy*; Hoang Trung Vinh**; Do Quoc Huy*

SUMMARY
Objectives: Evaluating the changes of some clinical and subclinical parameters in patients
with multiple organ failure supported by continuous renal replacement therapy and comparing
some factors related to continuous renal replacement therapy and the outcome of the patients
supported by pre- and post-dilution to those by post-dilution only. Subjects and methods:
Prospective trial, compare before and after intervention in 77 patients diagnosed as multiple
organ failure according to SOFA score. The patients were divided into 2 groups: 41 patients in
group 1 - study group (supported by pre- and post-dilution), 36 patients in group 2 - control
group (supported by post-dilution). Data were received from clinical examination, diagnostic
tests during treatment. Results: Comparing with post-dilution, patients in group of pre- and postdilution had significant TNF-α clearance (p < 0.01), filter lifetime was longer (33.8 ± 11.8 h vs.
28.2 ± 11.7 h, p < 0.05), lower serum creatinine (1.6 ± 1.3 mg/dL vs. 2.4 ± 1.6 mg/dL, p < 0.05)
at the time of 72 h after intervention. Mechanical ventilation time, days in intensive care unit and
mortality rates of the two groups were similar (70.7% and 72.2%). Conclusion: Pre- and postdilution has many advantages in improving kidney function, purifying cytokines and prolonging
the filter lifetime.
* Keywords: Multiple organ failure; Continuous renal replacement therapy; Post-dilution; Pre-dilution.

INTRODUCTION
Multiple organ failure (MOF) is the
disease with severe progression and
make many patients stay at intensive care
unit (ICU) for a long time. In spite of
therapeutic progresses, the mortality rates
remained the highest in ICU. So that,
besides the intensive treatment methods,

the supportive assistance is always
focused to improve organ function and
reduce mortality rates. Continuous renal
replacement therapy (CRRT) can replace
the decreased kidney function and release

inflammatory cytokines. This technique
was supported for patients with MOF in
many researches, but there have not
been any trial comparing pre- and postdilution with post-dilution one. Therefore,
aims of this study are:
- Evaluating the changes of some
clinical and subclinical parameters in
patients with MOF supported by CRRT.
- Comparing some factors related to
CRRT and the outcome of the patients
supported by pre- and post-dilution to
those by post-dilution only.

* People’s Hospital 115
** 103 Military Hospital
Corresponding author: Huynh Thi Ngoc Thuy ()
Date received: 20/05/2018
Date accepted: 22/08/2018

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Journal of military pharmaco-medicine no7-2018
SUBJECTS AND METHODS

1. Subjects.
77 patients with MOF were appointed
for CRRT, including 2 groups: 41 patients
in group 1 supported by pre- and postdilution and 36 patients in group 2
supported by post-dilution were treated at
ICU of People's Hospital 115 from Feb,
2014 to Feb, 2016.
* Inclusion criteria:
- Patient age > 18 years diagnosed
with MOF according to the SOFA score
(table 1).
+ 6 organs: Cardiovascular, respiratory,
kidney, liver, coagulation, central nervous
system.
+ Criteria: SOFA score ≥ 2 or defined
by one of three approaches:
. As a single variable that reflects a
physiologic derangement.
. As a single variable that reflects a
therapeutic intervention in response to a
physiologic derangement.
. As a combination of variables that in
their own right define a syndrome.
+ Acute liver failure (ALF) with 1 in 2
following criteria: total bilirubin level >
1.9 mg/dL or having all of 3 criteria of ALF
by the AASLD (table 3).
+ MOF: At least 2 failured organ and
lasting more than 24 hours.
- Have the acute kidney injury identified

by RIFLE criteria (table 2): Serum creatinine
increased 2 times compared to baseline,
urine output < 0.5 mL/kg/h x at least 12 h.

- Causes of MOF were different: Sepsis,
shock, acute pancreatitis.
- With or without identified chronic
diseases.
- Receiving continuous veno-venous
hemofiltration (CVVH).
* Exclusion criteria:
- MOF without acute kidney injury.
- Died within 24 hours after admission
to ICU.
- Lack of test of kidney function after
intervention.
- Indicated for surgery without effective
treatment.
- The end-stage disease: Decompensated
cirrhosis, metastatic cancer.
- Pregnant or breast feeding.
2. Methods.
* Trial design: Prospective study, compare
before and after intervention.
* Trial content:
- Doing clinical examination and test
for evaluating organ injury, consists of
urea, creatinine, bilirubine, platelet, IL-6,
TNF-α, arterial blood gas.
- Critical care and treating basic diseases.

- Setting CRRT for two groups with the
parameters such as mode: CVVH; input:
femoral vein or internal jugularvein; filter:
AN69, if being clotted, change the new;
heparine dose: 10 - 20 UI/kg BW/h; blood
flow: 120 - 150 mL/min; replacement flow:
30 - 40 mL/kg/h; output flow: 0 - 200
mL/h, it was depended on body fluid
through by charateristics as edema,
weight, CVP, urine output, blood
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Journal of military pharmaco-medicine no7-2018
pressure; dilution: group 1 (pre- and postdilution), group 2 (post-dilution).
+ Criteria for stopping CRRT: Recovering
shock: heart rate < 110 bpm, MAP
≥ 70 mmHg, CVP < 12 cmH2O, blood
pressure is still stable after stopping

vasopressors ≥ 2 h, UO > 50 mL/h, serum
creatinine < 1.6 mg/dL. Patient died or too
heavy to cure.
+ Doing blood test: After 12 h (T12),
24 h (T24), 48 h (T48), end of CRRT (Tn).

* Criteria for diagnosis, classification in the study:
Table 1: SOFA score [4].
SOFA score

1

2

3

4

≤ 400

≤ 300

≤ 200 with respatory
support

≤ 100 with respatory
support

MAP < 70

Dopamin ≤ 5 or
dobutamin (any
dose)

Dopamin > 5 or
epinephrin ≤ 0.1
or NE ≤ 0.1

Dopamin > 15 or
epinephrin > 0.1 or

NE > 0.1

Kidney
Creatinine (mg/dL)
or urine output (mL/day)

1.2 - 1.9

2 - 3.4

3.5 - 4.9
< 500

>5
< 200

Liver
Total bilirubine (mg/dL)

1.2 - 1.9

2 - 5.9

6 - 11.9

> 12

≤ 150

≤ 100

≤ 50

≤ 20

13 - 14

10 -12

6-9

<6

Respiratory
PaO2/FiO2 (mmHg)
Cardiovascular
Hypotension*

Coagulation
3
3
Platelets x 10 /mm
Central nervous system
Glasgow Coma Score

(* Adrenergic agents administered for at least one hour (doses given are in µg/kg/min)).

Table 2: RIFLE criteria [5].
Creatinine criteria

Urine output criteria

Risk

Increased creatinine x 1.5

UO < 0.5 mL/kg/h x 6 h

Injury

Increased creatinine x 2

UO < 0.5 mL/kg/h x 12 h

Failure

Increased creatinine x 3
or creatinine ≥ 4 mg/dL
(acute rise of ≥ 0.5 mg/dL)

UO < 0.5 mL/kg/h x 24 h or
anuria x 12 h

Loss

Persistent ARF = complete loss of renal function > 4 weeks

End stage renal disease

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Journal of military pharmaco-medicine no7-2018
Table 3: Definition of acute liver failure by the AASLD (American Association for the
Study of Liver Diseases) [6].
Criteria
Acute liver disease

Characteristics
< 26 weeks without preexisting cirrhosis
Grade 1: Changes
level of consciousness

in

behavior

with

Grade
2:
Gross
disorientation,
asterixis, inappropriate behavior

minimal
drowsiness,

change

in

possible

Encephalopathy
Grade 3: Marked confusion, incoherent speech, sleeping most of the time
but arousable to vocal stimuli
Grade
4:
Comatose,
or decerebrate posturing
Coagulation abnormality

unresponsive

to

pain,

decorticate

INR ≥ 1.5

* Data analysis: Using SPSS 22 to analyze the percentage and the average values.
RESULTS
1. The common characteristics of patients.
Table 4: Compare some characteristics between 2 groups.
Injured organ

Group 1 (n = 41)

Group 2 (n = 36)

p

3.98 ± 0.88

3.94 ± 0.75

> 0.05

2 (n, %)

2 (100)

0

> 0.05

3 (n, %)

7 (41.2)

10 (58.8)

> 0.05

4 (n, %)

22 (52.4)

20 (47.6)

> 0.05

5 (n, %)

9 (64.3)

5 (35.7)

> 0.05

6 (n, %)

1 (50)

1 (50)

> 0.05

Kidney (n, %)

41 (53.2)

36 (46.8)

Respiratory (n, %)

40 (53.3)

35 (46.7)

> 0.05

Cardiovascular (n, %)

38 (55.1)

31 (44.9)

> 0.05

Central nervous system (n, %)

26 (53.1)

23 (46.9)

> 0.05

Coagulation (n, %)

10 (50)

10 (50)

> 0.05

Liver (n, %)

9 (60)

6 (40)

> 0.05

Mean
Number of injured organ

Type of injured organ

The number and type of injured organs had no differences between 2 groups.
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Journal of military pharmaco-medicine no7-2018
Table 5: Compare some subclinical characteristics.
Parameter
Glucose (mg/dL)
Urea (mg/dL)

Group 1 (n = 41)

Group 2 (n = 36)

p

183.3 ± 107.0

152.2 ± 75.9

> 0.05

95.8 ± 54.8

119.1 ± 65.4

> 0.05

Creatinine (mg/dL)

3.4 ± 2.2

3.6 ± 1.7

> 0.05

Total bilirubine (mg/dL)

1.9 ± 2.5

4.2 ± 5.8

> 0.05

135.8 ± 9.4

137.8 ± 8.5

> 0.05

Sodium (mmol/L)
Potassium (mmol/L)

4.2 ± 1.0

4.2 ± 1.1

> 0.05

Platelet count (K/µL)

200.3 ± 131.2

156.5 ± 81.6

> 0.05

CRP (mg/dL)

144.3 ± 100.6

160.2 ± 113.5

> 0.05

Lactate (mmol/L)

6.6 ± 5.9

5.1 ± 4.6

> 0.05

IL-6 (pg/mL)*

951.2

616.3

> 0.05

TNF-α (pg/mL)*

38.3

30.6

> 0.05

pH

7.26 ± 0.11

7.29 ± 0.13

> 0.05

PaCO2 (mmHg)

34.9 ± 15.0

32.7 ± 10.8

> 0.05

16.1 ± 5.1

16.3 ± 5.9

> 0.05

PaO2 (mmHg)

106.3 ± 57.2

107.7 ± 94.7

> 0.05

PaO2/FiO2

188.3 ± 132.8

174.2 ± 161.5

> 0.05

-

HCO3 (mmol/L)

(* IL-6 and TNF-α are not the normal distribution, using median and Mann-Whitney test)
The average values of subclinical parameters between 2 groups were similar.
2. Compare some results between two groups.
Table 5: Compare serum urea and creatinine at the evaluated times between 2 groups.
Parameters

Group 1 (n = 41)

Group 2 (n = 36)

p

Number

X ± SD

Number

X ± SD

T0

41

95.8 ± 54.8

36

119.1 ± 65.4

> 0.05

T24

41

66.9 ± 38.9

36

99.3 ± 76.2

< 0.05

T48

37

62.0 ± 37.1

31

77.8 ± 72.7

> 0.05

T72

31

51.6 ± 27.8

27

78.0 ± 44.2

< 0.05

T0

41

3.4 ± 2.2

36

3.6 ± 1.7

> 0.05

T24

41

2.1 ± 1.6

36

2.5 ± 1.8

> 0.05

T48

37

1.9 ± 1.2

31

2.0 ± 1.6

> 0.05

T72

31

1.3 ± 0.6

27

1.9 ± 1.2

< 0.05

Urea (mg/dL)

Creatinine (mg/dL)

- The average values of serum urea and creatinine in group 1 were lower statistically
than that in group 2 at 72 h after intervention.
- There were no differences between 2 groups at the other time.
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Journal of military pharmaco-medicine no7-2018
Table 6: Compare serum IL-6 và TNF-α between 2 groups.
Group 1 (n = 41)

Group 2 (n = 36)

p

Number

Median

Number

Median

Before CRRT

41

951.2

36

616.3

> 0.05

After CRRT

41

247.9

36

135.5

> 0.05

Before CRRT

24

38.3

24

30.6

> 0.05

After CRRT

24

31.7

24

37.9

> 0.05

IL-6 (pg/mL)

TNF-α (pg/mL)

(* Some blood samples were failed while transport, no full enough of TNF-α)
There were no differences between 2 groups about serum IL-6 and TNF-α before
and after CRRT.
Table 7: Compare the change of serum IL-6 and TNF-α before and after CRRT.
Group 1 (n = 41)

Group 2 (n = 36)

Parameters
Number

Median

Number

Median

∆ Before - after

41

703.3

36

480.8

p∆

41

< 0.001

36

< 0.001

∆ Before-After

24

6.6

24

(-) 7.3

p∆

24

< 0.01

24

> 0.05

IL6 (pg/mL)

TNFα (pg/mL)

(* Using Wilcoxin test for evaluating the difference between before and after CRRT)
- IL-6 concentrations were significantly reduced in both groups.
- TNF-α level was only statistically significant reduced in group 1.
Table 8: Mechanical ventilation time, days in ICU and mortality of 2 groups.
Parameters

Group 1 (n = 41)

Group 2 (n = 36)

p

Mechanical ventilation (days)

5.9 ± 5.3

9.1 ± 10.7

> 0.05

Days in ICU

8.2 ± 6.0

10.9 ± 10.9

> 0.05

Mortality (n, %)

29 (70.7)

26 (72.2)

> 0.05

There were no differences between 2 groups about above parameters.
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Journal of military pharmaco-medicine no7-2018
Table 9: Some factors related to CRRT.

Parameters

Group 1 (n = 41)

Group 2 (n = 36)

p

Time of starting CRRT (hour)

7.7 ± 6.8

11.7 ± 13.8

> 0.05

Numbers of CRRT

1.9 ± 1.3

1.5 ± 0.7

> 0.05

Average filter lifetime (hour)

33.8 ± 11.8

28.2 ± 11.7

< 0.05

Replacement volume (mL/kg/h)

36.7 ± 4.1

37.9 ± 5.1

> 0.05

- Average filter lifetime in group 1 was longer than that in group 2.
- The other parameters were similar in the 2 groups.
DISCUSSION
77 patients in this trial were treated
MOF with guidelines and recommendations.
They were also supported by CRRT with
two dilution modes. Patients in the research
were injured from 2 to 6 organs and the
ones with 4 organ failure had the highest
ratio. The study also showed that the
ratio of organ failure changed from high
to low as followed: kidney, respiratory,
cardiovascular, central nervous system,
coagulation and liver. The common
characteristics about injured organs and
subclinical parameters were similar in the
two groups. This similarity was the basis
for evaluating and comparing the effect of
pre- and post-dilution CRRT with postdilution CRRT in MOF patients.
Continuous renal replacement therapy

is one of mainly kidney replacement
methods in treating acute kidney injury
with oliguria/anuria. In this study, serum
urea and creatinine decreased gradually
after CRRT and there was no difference
between the two groups before intervention;
as well as at 24 h and 48 h. However, at
the time of 72 h after intervention, the
average value of serum urea and creatinine
in group used pre- and post-dilution was
136

lower statistically than those in group used
post-dilution. The ability to filter creatinine
effectively under unstable hemodynamic
conditions demonstrates the important role
of continuous dialysis in critical illness.
Olivier Joannes-Boyau et al in the IVOIRE
study showed the improvement of serum
creatinine level from 2.37 mg/dL (1.80 3.12) at baseline versus 0.99 mg/dL (0.7 1.4) at the 4th day after dialysis [4]. The
results from studies by T.N Hai and N.G Binh
also showed improvement in creatinine
concentration after filtration [1, 2].
About the inflammatory cytokine clearance,
the study showed that concentrations of
serum IL-6 and TNF-α decreased after
CRRT and there was no difference
between
two
groups.

Especially,
analyzing by Wilcoxin test, result showed
that CRRT could purify the inflammatory
cytokines clearly. IL-6 concentrations
were significantly reduced in both groups,
while TNF-α levels were only statistically
significantly reduced in group 1. The trial
results of H.V Quang also recorded that
CRRT reduced the concentrations of
cytokines [7]. However, Cole and Klouche
proved
that
although
prognosis
improved, CRRT did not change blood


Journal of military pharmaco-medicine no7-2018
cytokine level, this was explained to be
related
to
"immune
threshold
hypothesis", in which the removing
cytokines from the blood leads to
removing cytokines in the tissue due to
the balance of concentration [8].

supported with pre- and post-dilution
CRRT compared to the basal method

(post-dilution CRRT) proved that this
method can apply in clinical practice.

This study also recorded the parameters
such as mechanical ventilation, days in
ICU and mortality were no differences
between 2 groups. The mortality in our
study was higher than the others; such as
Elizabeth 56%, H.V Quang 55% and N.G Bình
67.7% [2, 3, 7]. The mortality was related
to the number of injured organs, this study
showed that the mean of organ failure
was 3.98 ± 0.88 in group supported with
pre- and post-dilution CRRT.

Studying MOF patients supported by
pre- and post-dilution CRRT and comparing
with those supported by post-dilution, we
had folowing results:

About the parameters of CRRT, this
research showed that the replacement
volume in 2 groups also had no differences,
with 36.7 ± 4.1 mL/kg/h in group 1 and
37.9 ± 5.1 mL/kg/h in group 2. This result
was similar to Joannes-Boyau's trial
(35 mL/kg/h) and Piccini's trial (45 mL/kg/h)
[4, 9]. The number and the time of starting
CRRT were not different between 2 groups,
but the average filter lifetime with pre- and

post-dilution was significantly longer than
that with post-dilution (33.8 ± 11.8 hours
versus 28.2 ± 11.7 hours). Van der Voort
and Uchino showed that post-dilution
shortened the filter lifetime compared with
pre-dilution [10, 11].
Thus, a combination of general
tendency in improving the kidney function
during treatment together with the higher
inflammatory cytokine clearance and the
longer filter lifetime when patients were

CONCLUSIONS

* Common results:
- At the time of 72 h after intervention;
serum urea and creatinine in group used
pre- and post-dilution were lower than
those in control group.
- IL-6 concentrations were significantly
reduced in both groups, but TNF-α level
was statistically significant reduced in
group 1.
* Some factors related to the CRRT
and outcomes:
- Average filter lifetime was longer while
using pre- and post-dilution CRRT.
- Mechanical ventilation time, days in
ICU and mortality rate were not statistically
significant between 2 groups.

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