This study evaluated the efficacy of perioperative intravenous N-acetylcysteine (NAC) in reducing acute kidney injury (AKI) and improving liver graft function in patients undergoing living donor orthotopic liver transplantation. 100 patients undergoing transplantation were randomly assigned to receive either intravenous NAC or saline as control. The results showed NAC decreased the incidence of postoperative AKI, primary graft non-function, and reduced hospital and ICU stay compared to the control group. However, NAC had no effect on the number of ventilator days or mortality.

1. Ain-Shams Journal of Anesthesiology
2015.08:483-490
Department of Anesthesiology, Intensive Care and Pain Management,
Faculty of Medicine, Ain-Shams University, Cairo, Egypt
Perioperative N-acetylcysteine for patients undergoing living
donor orthotopic liver transplantation

2. Disclosure
We have no financial relationships with any commercial
interest related to the content of this presentation

3. Background
N-acetylcysteine (NAC) plays a role in the treatment of acetaminophen toxicity and
the prevention of acute kidney injury (AKI) in radiocontrast exposure ,
cardiac surgery and sepsis . NAC is a rich source of sulfhydryl (SH) groups, which
replenish glutathione (GSH) stores .
GSH as a free radical scavenger, decreases toxic free radical-induced damage that
may contribute to impaired liver graft function and AKI after orthotropic liver
transplant .
Furthermore, findings of experimental studies evaluating NAC in liver
transplantation showed improvement of liver function in rat liver , a better
survival rate and reduction of graft non function in pigs with liver ischemia.

4. Evaluate the efficacy of perioperative intravenous use of NAC
as a pharmaco-protective agent in liver transplant recipients
for decreasing post-LDLT AKI and improving liver graft
function.
Aim of the work

5. Group C = 50
received an equal volume of 0.9% saline continuous
intravenous infusion at the same rate and volume for 3
days
Group N = 50
received NAC 150 mg/kg infusion intravenously over
15 min before surgery, followed by 12.5 mg/kg/h NAC
for 4 h after the induction of general anesthesia and a
subsequent dose of 6.25 mg/kg/h continuous infusion
for 3 days postoperatively
108 patients were assessed for randomization. 5 surgical
interventions were aborted , and 3 individuals refused to
participate in the study
Methods
Exclusion criteria
Allergy to NAC, history of asthma, fulminate hepatic
failure, or re-do LT, moderate to severe renal impairment
(creatinine clearance < 60 ml/min) or pre-existing renal
failure requiring hemodialysis or continuous
hemofiltration.
Inclusion criteria
Adults more than 18 years of age, baseline serum
creatinine less than 1–1.2 mg/dl or
creatinine clearance 97–140 ml/min and patients with
mild renal dysfunction with serum creatinine 2–2.5
mg/dl or creatinine clearance 85–125 ml/min
Primary outcome,include postoperative acute kidney injury (POAKI) assessed using RIFLE criteria on admission,
day 7 and day 14. Secondary outcomes include severity of the post reperfusion syndrome (PRS) and the incidence
of primary graft non-function (PGNF), renal functions test, total dose of loop diuretics and dopamine, adverse
events, survival, as well as the length of ICU and hospital stays

6. Demographic data Group C
(n=50)
Group N
(n=50)
Significance
Age (years) 47(7) 49(6) P=0.09
Sex Male/Female 36/14 32/18 P=0.4
Weight (Kg) 79(10) 81(8) P=0.6
MELD Score (median) 11 12 P=0.8
Pretransplant S cr (mg/dl) 1.2(0.4) 1.3(0.4) P=0.2
Etiology
Hepatitis C
Hepatitis B
Hepatitis B and C
HCC
Others
16(32%)
12(24%)
12(24%)
6(12%)
4(8%)
18(36%)
14(28%)
8(16%)
8(16%)
2(4%)
P=0.7
P=0.7
P=0.3
P=0.6
P=0.4
Graft weight to recipient
weight ratio (GWRWR)
mean (SD)
1(0.2) 0.9(0.3) P=0.9
Graft weight (g) 752(236) 699(180) P=0.2
Results
Patients characteristic data.
Data are presented as mean (SD), median or numbers

7. Intraoperative data Group C
(n=50)
Group N
(n=50)
Significance
Platelets (units) 7(5) 8(4) P=0.1
Cold ischemia time (min) 46(7) 48(7) P=0.3
Warm ischemia time (min) 29(5) 31(4) P=0.08
Duration of surgery (min) 872(188) 824(110) P=0.1
MAP during preanhepatic phase (mmHg) 73(5) 71(8) P=0.08
MAP during anehepatic phase (mmHg) 70 (8) 67(10) P=0.09
MAP during neohepatic phase(mmHg) 68(7) 71(9)
Intraoperative norepinephrine dose (µg/Kg/min) 0.5(0.2) 0.3(0.2)
lactate level preanhepatic phase (mmol/L) 3.3(1.2) 3.6(1.2) P=0.1
lactate level anehepatic phase(mmol/L) 7.1(2.3) 6.7(2.1) P=0.3
lactate level neohepatic phase (mmol/L) 9.3(2.6) 7.8 (2.4)
Need for epinephrine(n) 13(26%) 6(12%) P=0.08
Need for dopamine(n) 7(14%) 3(6%) P=0.2
Post reperfusion injury(n) 13(26%) 6(12%) P=0.08
Severity of post reperfusion injury (n)
Mild
Severe
6
7
5
1
P=0. 8
UOP preanhepatic phase (ml/Kg/h) 1.6(1.1) 1.9(1.2) P=0.3
UOP anehepatic phase (ml/kg/h) 1.9(1.1) 2.2(1.1) P=0.3
UOP neohepatic phase (ml/kg/h) 2.4(1.2) 2.6(1.3) P=0.5
Intraoperative data
P=0.04*
P=0.001*
P=0.03*
P=0.03*
Data are presented as mean (SD), median or numbers.
*P ˂ 0.05 indicates significant difference between groups.

8. Postoperative on admission data Group C
(n=50)
Group N
(n=50)
Significance
Liver function test
AST
ALT
S. bilirubin
S.albumin
PT
INR
435(381)
543(418)
2.5(1.4)
3.2(0.5)
18(2)
2.4(1)
396(391)
498(363)
2.2(1.2)
3.4(0.6)
17(2)
2.1(1)
P=0.6
P=0.6
P=0.3
P=0.08
P=0.2
P=0.1
S. creatinine (mg/dl) 0.9(0.4) 0.7(0.3)
MAP (mmHg) 85(10) 87(10) P=0.3
HR (beat/min) 79(10) 82(10) P=0.08
CVP(cmH2O) 9(1) 8(2) P=0.06
Serum lactate level (mmol/L) 7(2) 6(2)
PRBC (units ) 3(2) 2(1) P=0.07
Fresh frozen plasma (units) 2(1) 2(1) P=0.5
Postoperative data on ICU admission
P=0.03*
P=0.03*
Data are presented as mean (SD), median or numbers.
*P ˂ 0.05 indicates significant difference between groups.

9. Bar chart presenting number of patients classified using RIFEL classification on ICU admission in
Group N and Group C.*p<0.05 was Significantly different between Group C and Group N.

10. RIFEL Classification on day 7
FailureInjuryRiskNo AKI
Numberofpatients
50
48
46
44
42
40
38
36
34
32
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
0
Group N
Group C
group
Bar chart presenting number of patients classified using RIFEL classification by day 7 in Group
N and Group C. *p< 0.05was significantly different Group C and Group N.

11. RIFEL Classification on day 14
FailureInjuryRiskNo Aki
Numberofpatients
50
48
46
44
42
40
38
36
34
32
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
0
Group N
Group C
group
Bar chart presenting number of patients classified using RIFEL classification by day 14 in Group
N and Group C. *p< 0.05was significantly different Group C and Group N.

12. Primary graft function (PGF)
PGNFPGF
Numberofpatients
50
40
30
20
10
0
Group N
Group C
group
Bar chart presenting Primary graft function (PGF) as assessed by Nanashima's classification within
72 hrs. *p<0.05 was significantly different between Group C and GroupN.

13. Postoperative data during first 7 days Group C
(n=50)
Group N
(n=50)
Significance
Liver function test
AST
ALT
S. bilirubin
S.albumin
PT
INR
77(19)
81(10)
1.2(0.8)
3.9(0.5)
15(3)
1.5(0.5)
71(16)
77(13)
0.9(0.6)
4.0(0.6)
14(3)
1.3(0.3)
P=0.07
P=0.08
P=0.08
P=0.2
P=0.06
P=0.06
S.creatinine ( mean) 1.2(0.8) 0.9(0.5)
Serum lactate level (mmol/L) 1.8(1.2) 1.2(0.9)
UOP ml/Kg/h 1.6(0.6) 1.3(0.6)
Postoperative data during first 7 days
P=0.048*
P=0.01*
P=0.005*
Data are presented as mean (SD), median or numbers.
*P ˂ 0.05 indicates significant difference between groups.

14. Postoperative data during second 7 days Group C
(n=50)
Group N
(n=50)
Significance
Liver function test
AST
ALT
S. bilirubin
S.albumin
PT
INR
54(9)
46(9)
1.1(0.6)
4.0(0.5)
14(3)
1.3(0.4)
51(10)
42(10)
0.8(0.5)
4.2(0.6)
13(3)
1.2(0.3)
P=0.06
P=0.06
P=0.06
P=0.06
P=0.09
P=0.2
S.creatinine ( mg/dl ) 0.9(0.6) 0.7(0.3)
Serum lactate level (mmol/L) 1.2(0.6) 0.9(0.6)
UOP ml/Kg/h 1.5(0.6) 1.2(0.6)
Postoperative data during second 7 days
P=0.02*
P=0.01*
P=0.48*
Data are presented as mean (SD), median or numbers.
*P ˂ 0.05 indicates significant difference between groups.

15. Postoperative data during 14 days Group C
(n=50)
Group N
(n=50)
significance
Ventilator days 3(2) 2(2) P=0.06
Total dose of loop diuretics (mg) mean 56(33) 44(24)
Need for dopamine dose(n) 12 4
Patient survival/mortality(n) 49/1 50/0 P=0.3
Hospital duration 26(7) 24(5)
ICU stay 6(2) 5(2)
Renal replacement therapy 8 2
Postoperative bleeding 2 1 P=0.6
Graft rejection 2 0 P=0.2
Vascular thrombosis (hepatic artery stenosis) 1 0 P=0.3
Cardiovascular event 0 0
Hypotensive episode 4 1 P=0.2
Infection 5 3 P=0.5
Postoperative data during 14 days
P=0.04*
P=0.03*
P=0.04*
P=0.02*
P=0.46*
Data are presented as mean (SD), median or numbers.
*P ˂ 0.05 indicates significant difference between groups.

16. The current study has potential limitations including, lack of
measurement of the serum GSH level, the use of longer therapy with
a high dose of NAC infusion and multicenter trials are warranted.
Limitations of the study

17. Conclusion
Perioperative intravenous NAC in patients undergoing right-lobe
LDLT was safe as there was a decreased incidence of POAKI , PGNF
and a decrease in the hospital duration and the ICU stay, but no
effect on the number of ventilator days and mortality.

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