Introduction: The prevalence of coronary artery diseases in India is increasing, hence to assess associated risk factors for coronary artery bypass graft (CABG) surgeries shall contribute in minimizing in hospital deaths. Acute liver ischemia-related complication is a rare complication of on-pump CABG surgery, but with high mortality. AIM: To evaluate changes in liver function tests and incidence of acute liver injury after on-pump CABG surgery. Methods: 150 patients were serially enrolled and data collected were ALT, AST, ALP, total and direct bilirubin level preoperatively and at 24, 48, 72 hours after the surgery as well as at discharge. Furthermore, those with abnormal liver function tests or suffering viral hepatitis were excluded. Results: 15% female and 85% male patients, primarily aged between 56 to 65 (with ages ranging from 35 to 85). 67.82% had previously suffered a heart attack, 68.56% were diabetic, 28.50% had hyperlipidemia and 68.56% were hypertensives. Further, 74.78% were either smokers or tobacco chewers. 63.5% patients suffered from obesity. The average cardiac ejection fraction was 30-45%. The mean cardiopulmonary time duration was 125.50 minutes and aortic cross clamp time was 76.50 minutes. For 100% of patients, inotropic drugs were used and for 1.5% patients, an intraaortic balloon pump was used after separation from cardiopulmonary bypass. The pre-operative total bilirubin level had a mean of 0.69 ± 0.35 mg/dL, peaking upto 2.45 on first post operative day. The direct bilirubin levels peaked at 1.56 mg/dL in this same period (Table 3). Age, gender, and BMI were evaluated. Significant correlation between age and AST levels POD from pre-operative levels (t:3.12, p<.05). Age had negative significant correlation with ALP elevation on 3rd (t: -1.89 , p<.05). Male gender had significant elevation on ALP levels 1st POD(t: 1.98 , p<.05). Female gender had significant correlation with total bilirubin changes at discharge time from pre-operative levels(t: 3.05, p<.05). BMI showed negative correlation with total bilirubin changes on 2nd POD(t: -3.89 , p<.05). According to regression analysis results, with the exception of a direct and significant correlation between prior myocardial infarction (MI) and changes in total bilirubin levels within the first 48 hours post-surgery (t:-2.704 , p<.05), there was no other significant effect by cardiovascular risk factors such as HTN, HLP or DM. A negative correlation was found between Ejection fraction and AST levels on 1st POD (t:-3.4, p<.05). A negative correlation was found between Ejection fraction and bilirubin levels on 2nd POD (t:-2.4, p<.05). 3rd POD (t: -2.67, p<.05). A negative correlation was found between Ejection fraction and total bilirubin levels 3rd POD (t: -1.9, p<.05). Smoking history significantly correlated with elevation in AST levels POD 2&3 and bilirubin levels on 3rd POD. Conclusion: In the majority of cases, the LFT return close to normal levels at the time of discharge from hospital. Cardiopulmonary bypass time and aortic cross clamp time and inserting IABP contributed maximum to acute liver injury in on-pump CABG surgery. We recommend surgeons should evolve strategies based on competency to reduce pump and clamp time. A patient's biochemical liver tests levels may elevate after surgery if the patient is elderly, history of MI, has a low cardiac ejection fraction reserve, and smokes cigarettes.
The prevalence of coronary artery diseases in India is increasing, hence to assess associated risk factors for coronary artery bypass graft (CABG) surgeries shall contribute in minimizing in hospital deaths [1,2]. Acute liver ischemia-related complication is a rare complication of on-pump CABG surgery, but with high mortality [3]. On Cardiopulmonary bypass pump CABG (ONCAB) carries a greater risk of tissue malperfusion and organ dysfunction. Malperfusion throughout CPB results in hypoperfusion, oxidative stress and catecholamine surge during the procedure which may lead to post-CABG side effects [4-6].
Incidence of gastrointestinal complications after cardiac surgery is 0.41%-3.7%, with resultant mortality rates 13.9-52%. 10% of patients undergoing ONCAB suffer hepatocellular dysfunction. Even with advances the gastrointestinal complications and the subsequent mortality rates have remain undiminshed. So strategies need to be evolved to reduce morbidity and mortality by predicting the degree of liver hepatic dysfunction during open-heart surgery (7).
The present study was designed to find incidence of acute liver injury with changes in liver function tests after ONCAB surgery. Acute liver injury is defined as a rise in serum alanine amino transferase levels of more than 500 IU/L within 48 hours of surgery (7).
The present study aims were to determine the impact of various risk factors on hepatocellular health during on pump cardiac surgeries.
This prospective descriptive study included 150 serially chosen patients admitted under surgeon authors who had undergone on-pump CABG surgery at IMS, BHU (Varanasi) between 2020 and 2025. Information regarding patient including diabetes mellitus, hypertension, hyperlipidemia, history of myocardial infarction, any hepatobiliary, hematologic disorders and use of cigarette were noted.
The standard similar surgical and anesthetic protocols were followed for all patients. Meanwhile, emergency CABG or CABG long with valvular surgeries were excluded from the study.
All patients were kept at a temperature of 28 - 32 °C (mild to moderate hypothermia), and their mean arterial pressure was kept above 70 mmHg with Inotropic drugs (epinephrine, norepinephrine, or dobutamine) on as per requirement basis
150 patients were serially enrolled and data collected were ALT, AST, ALP, total and direct bilirubin level preoperatively and at 24, 48, 72 hours after the surgery as well as at discharge. Furthermore, those with abnormal liver function tests or suffering viral hepatitis were excluded. Statistical analysis was performed using SPSS software. The sample size was calculated based on previous studies.
A regression model was developed to demonstrate the independent variables effect on the dependent variables. Microsoft office excel and SPSS software were used for data analysis and model estimation, respectively.
An analysis was conducted on a population of 150 who fulfilled the inclusion criteria, with a gender split of 15% female and 85% male, primarily aged between 56 to 65 (with ages ranging from 35 to 85). 67.82% had previously suffered a heart attack, 68.56% were diabetic, 28.50% had hyperlipidemia and 68.56% were hypertensives. Further, 74.78% were either smokers or tobacco chewers. 63.5% patients suffered from obesity. (table 1).
Table 1. Base line patient characteristics
VARIABLE PERCENTAGE
|
Sex |
Male |
85 |
|
|
Female |
15 |
|
Age |
35-45 |
4.57 |
|
|
46-55 |
15.78 |
|
|
56-65 |
45.96 |
|
|
66-75 |
22.65 |
|
|
76-85 |
11.04 |
|
BMI |
< 18.5 |
5.89 |
|
|
18.5-24.9 |
30.78 |
|
|
25-29.9 |
46.88 |
|
|
> 30 |
16.45 |
|
Previous myocardial infarction |
|
67.82 |
|
Diabetes mellitus |
|
68.56 |
|
Hyperlipidemia |
|
28.50 |
|
Hypertension |
|
68.56 |
|
Cigarette smoker/ tobacco chewer |
|
74.78 |
|
|
||
The average cardiac ejection fraction was 30-45%. The mean cardiopulmonary time duration was 125.50 minutes and aortic cross clamp time was 76.50 minutes. For 100% of patients, inotropic drugs were used and for 1.5% patients, an intraaortic balloon pump was used after separation from cardiopulmonary bypass. (TABLE 2)
Table 2.Frequency distribution of factors related to the surgical condition
|
VARIABLE |
PERCENTAGE |
|
Use of Inotrope drugs |
100 |
|
Insertion of intraaortic balloon pump |
1.5 |
|
Pump time (mean + SD ) |
125.5 + 43.25 |
|
Clamp time (mean + SD ) |
76.50 +22.50 |
The pre-operative total bilirubin level had a mean of 0.69 ± 0.35 mg/dL, peaking upto 2.45 on first post operative day. The direct bilirubin levels peaked at 1.56 mg/dL in this same period (Table 3).
|
|
Pre-operative day |
1st post op day |
2nd post op day |
3rd post op day |
Discharge time |
|
AST |
26.05±5.28 |
55.31±35.38 |
67.27±23.10 |
62.08±46.78 |
29±34.67 |
|
ALT |
24.50±7.78 |
34.84±36.90 |
45.17±12.89 |
47.45±78.37 |
22.89±78.23 |
|
ALP |
145.67±67.37 |
178.67±34.87 |
169.78±67.98 |
189.89±79.08 |
195.78±101.90 |
|
Total Bilirubin |
0.69±0.35 |
2.45±0.62 |
1.89±0.34 |
1.40±0.23 |
0.76±0.45 |
|
Direct bilirubin |
0.22±0.17 |
1.56±0.47 |
1.26±0.22 |
0.89±0.45 |
0.56±0.23 |
Regression analysis technique; with univariate linear regression model was used to ascertain causal impact of dependent and independent variable on LFT parameters while accounting for autocorrelation between the independent variables. We considered any relationships as significant at 95% confidence if p≤0.05, and following results were derived.
Evaluation of the effects of Surgical independent variables on LFT:
Cardiopulmonary bypass pump time, aortic cross clamp time, use of inotropic drugs and insertion of intra-aortic balloon pump show significant relationship with AST level on first and second POD and direct bilirubin levels on 3rd POD.
Clamp time duration had significant causal correlation with AST level increase on 1st and 2 nd POD. ALT levels increase on 2 nd POD, and total bilirubin levels on 1st POD. Since inotropes were required in all cases making it an essential component of on pump CABG so its differential independent impact couldn’t be ascertained. Intra-aortic balloon pump use caused AST/ALT increase on POD 1-3, and bilirubin levels on 3rd pOD.
Evaluation of the effects of Patient specific independent variables on LFT :
Age, gender, and BMI were evaluated. Significant correlation between age and AST levels POD from pre-operative levels (t:3.12, p<.05). Age had negative significant correlation with ALP elevation on 3rd (t: -1.89 , p<.05). Male gender had significant elevation on ALP levels 1st POD(t: 1.98 , p<.05). Female gender had significant correlation with total bilirubin changes at discharge time from pre-operative levels(t: 3.05, p<.05). BMI showed negative correlation with total bilirubin changes on 2nd POD(t: -3.89 , p<.05).
Effect of patients underlying disease risk factor variables:
According to regression analysis results, with the exception of a direct and significant correlation between prior myocardial infarction (MI) and changes in total bilirubin levels within the first 48 hours post-surgery (t:-2.704 , p<.05), there was no other significant effect by cardiovascular risk factors such as HTN, HLP or DM. A negative correlation was found between Ejection fraction and AST levels on 1st POD (t:-3.4, p<.05). A negative correlation was found between Ejection fraction and bilirubin levels on 2nd POD (t:-2.4, p<.05). 3rd POD (t: -2.67, p<.05). A negative correlation was found between Ejection fraction and total bilirubin levels 3rd POD (t: -1.9, p<.05). Smoking history significantly correlated with elevation in AST levels POD 2&3 and bilirubin levels on 3rd POD
Altered liver perfusion during cardiopulmonary bypass causes liver dysfunction due to the arrest of systemic circulation and hypoperfusion resulting in oxidative stress and ischemia. About 10% of patients undergoing surgery requiring CPB resulted in hepatic dysfunction (8).
However, Raman et al. found incidence of ischemic liver injury after heart surgery only 1.1% (7). In present study, 12.9% of patients had AST/ALT higher than threefold the normal upper limit; however, the incidence of acute ischemic liver injury (transient increase in aminotransferases to over 500 IU/L within POD 1-3 was merely 0.77%. Total and direct bilirubin, AST, ALP, ALT had elevation during POD 1-3 reverted back to near normal by discharge time due to CPB.
Our study also revealed comparable outcomes. AST showed the greatest fluctuation (POD 2) sequestered from non-hepatic organs too. ALT which is more liver specific, showed maximum elevation on POD 3. The time sequence of aminotransferase growth was similar to that seen in ischemic liver injury (9). Total and direct bilirubin increased by 30-40% on POD 2. The results suggest aminotransferases are good indicators for detecting liver injuries; particularly 24 hours after heart surgery, where changes are more obvious.
The prolonged cardiopulmonary pump time during CABG as a result of non-pulsatile perfusion, low blood flow, and free radical injury disturbs oxygenation to tissues and organs.
During POD 1-3, the present syudy demonstrated a significant correlation between pump time and AST and direct bilirubin changes. Aortic cross clamp time was directly correlated with AST, ALT, and total bilirubin.
Holmes et al. (2005) warned that inotropes may diminish total tissue perfusion because of an increased peripheral vascular resistance (10). Although inotropes infusion during surgery was sine qua non so any differential effect on liver function couldn’t be found.
Application of IABP is seen as a sign of a critical hemodynamics. Ascione et al. (2006) proposed that the use of IABP during cardiac surgery may affect the liver (11). In present study use of IABP caused LFT alterations.
Previous studies showed female gender as a risk factor for lower cardiac output after surgery and increased risk of ischemic liver injury (12). In present study, females had elevated total bilirubin levels at discharge post-surgery.
BMI has been identified as an independent prognostic factor for complications and mortality after CABG surgery in prior research, showing a U-shaped correlation between the two (13). In this study, BMI level had reverse correlations to total and direct bilirubin levels post-surgery, which suggests lower postoperative bilirubin values with higher BMIs. Finally, low EF and myocardial infarction history are acknowledged as effective independent factors in gastrointestinal complications after cardiac surgery (14). Interestingly, our study also found that EF was significantly correlated with AST on the second/third days and direct bilirubin changes on the third day, implying that decreased cardiac ejection fraction can lead to some degree of liver injury following CPB.
There was a significant relationship between myocardial infarction and elevated total bilirubin increase post-surgery. Smoking was related to increased AST and direct bilirubin levels post-surgery.
In the majority of cases, the LFT return close to normal levels at the time of discharge from hospital. Cardiopulmonary bypass time and aortic cross clamp time and inserting IABP contributed maximum to acute liver injury in on-pump CABG surgery. We recommend surgeons should evolve strategies based on competency to reduce pump and clamp time.
A patient's biochemical liver tests levels may elevate after surgery if the patient is elderly, history of MI, has a low cardiac ejection fraction reserve, and smokes cigarettes.
More studies are required with a larger sample size of patients.