LIVER DYSFUNCTION AND ITS CLINICAL IMPLICATIONS IN CARDIAC SURGERY PATIENTS

By

Khaled M. Helmy*, Mohamed E. Abdel Shafi*, Hala Abd El Sadik El Attar*,

Alaa Brik** and Amira Shokry***

Anesthesiology*, Cardiothoracic Surgery** and Internal Medicine*** Departments,

Faculty of Medicine, Zagazig University

 

ABSTRACT

Background: Patients with preoperative hepatic dysfunction who undergo Cardiac Surgery and Cardiopulmonary bypass are at high risk of postoperative complications, so cardiac surgery was infrequently performed in patients with liver dysfunction. Objective: The aim of this study is to assist the feasibility to perform cardiac surgery in patients with liver dysfunction. Patients and methods: Between April 2005 and April 2006, 27 patients with cirrhosis who underwent cardiac surgery in Zagazig University Hospital were identified. Their preoperative status and postoperative clinical results were assessed. Results: 10 patients were classified as having Modified-Pugh class A cirrhosis, 16 were class B, and 1 was class C. Eighteen patients underwent cardiac surgery with the use of cardiopulmonary bypass, and 9 patients underwent off-pump coronary artery bypass surgery. The overall in-hospital mortality rate was 10%, 31%, 100% for class A, B and C, respectively. No mortality occurred in patients who had revascularization without the use of cardiopulmonary bypass (n=5). Preoperative serum total bilirubin (TB), platelet count, and CPB time were defined as predictors to differentiate survivors and non survivors. Postoperative major complications, included bleeding, hepatic, renal, infection, neurological and pulmonary complications. Conclusion: Our results suggest that cardiac surgery can be performed safely in patients with Modified-Pugh class A and selected patients with class B. Cardiac surgery (whether valvular or coronary artery surgery), for patients with chronic liver dysfunction should be carried out with a short duration of CPB or should be done on the beating heart, if possible, in the case of coronary artery surgery.

 Key words: Cardiac Surgery, liver disease, Modified-Pugh classification, Postoperative complications, Cardiopulmonary bypass.

 

INTRODUCTION

            Patients with preoperative hepatic dysfunction who undergo cardiac surgery and cardiopulmonary bypass are at high risk of postoperative complications^(1-3). The reported in-hospital mortality rate in cirrhotic patients of Pugh class B and C is high^(4-6). This prospective study was designed to examine postoperative morbidity and mortality rates and to find predictors of outcome in patients with liver cirrhosis (LC) undergoing cardiac surgery^(7-9).

 

PATIENTS AND METHODS

            The data were recorded prospectively on all patients with liver dysfunction who underwent cardiac surgery inZagazig University Hospital between April 2005 and April 2006. Data of 27 patients were recorded. The preoperative data were recorded for age, sex, diagnosis of cirrhosis, type and severity of surgery, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) and presence of ascites, encephalopathy, malnutrition and malignancy. Biochemical measurements included complete blood picture, blood sugar, liver functions (enzyms, albumin, bilirubin), renal functions (blood urea nitrogen, serum creatinine), electrolytes (serum sodium and potassium) and coagulation parameters including bleeding time and prothrombin time (PT). Arterial blood gases (ABGs) were measured to calculate arterial/alveolar oxygen tension ratio [P(a/A)O₂] using alveolar gas equation⁽¹⁰⁾.

            Diagnosis of cirrhosis was established with liver biopsy or a history of liver disease (bilharizial or viral) with impaired liver function tests added to liver ultrasound or computer tomography and magnetic resonance imaging.

            A modified-Pugh scoring system has been recently introduced by Moemen et al.⁽¹¹⁾ to categorize surgical patients with chronic liver disease (Table 1) which included 5 parameters (serum bilirubin, serum albumin, PT, ascites and encephalopathy) and adds other 4 parameters; serum Na, serum creatinine, white blood count (WBC) and arterial/alveolar oxygen tension ratio [P(a/A)O₂].

Table (1): Grading of the Modified-Pugh scoring system.

Variable	Scoring point (class)
	1(A)	2(B)	3(C)
Encephalopathy (grade)	0	I, II	III, IV
Ascites	0	Mild	Moderate, severe
Bilirubin (mg/dl)	<4.0	4.0-5.0	>5.0
Serum albumin (g/dl)	>3.5	3.5-2.8	<2.8
Prothrombin time, prolonged (S)	0	1-4	>4
Serum sodium (mEq/L)	>130	130-120	<120
Serum creratinine (mg/dl)	<1.5	1.5-2.5	>2.5
White blood count (103/mm3)	<10	10-12	>12
Arterial/alveolar oxygen tension ratio	³0.75	0.74-0.55	<0.55

Grade; mild: 9-10 points, moderate: 11-14 points, severe; 15-27 points.

 

Anesthetic management:

            Preoperatively patients were prepared to optimize their organ functions, and to try to improve their risk factors. Broad spectrum antibiotics were administered preoperatively for all patients and just before the initiation of CBP.

            Anesthesia was induced with fentanyl (40-100 mg/kg), propofol (1.5-2.5 mg/kg), 2 mg of midazolam and tracheal intubation was facilitated with atracurium 0.5 mg/kg. Anesthesia was maintained with propofol infusion (50-150mg/kg/min), fentanyl (2-3 mg/kg/h), and midazolam, 1 mg, as judged by the anesthiologist to maintain cardio-vascular stability.

 

 Surgical procedures:

            A standard surgical technique was used in all patients through a median sternotomy incision. Before CPB, 300 U/kg heparin and additional boluses of 50 U/kg were given if necessary to maintain an activated clotting time at least 400 second. For CPB, as non-pulsatile roller-pump was used for all patients, containing a flat sheet membrane oxygenator. Surgery was performed with a core temperature of 28-32°C. Mean pump flow was 3.0 L/min/m². The mean arterial pressure (MAP) was kept between 50 and 80 mmHg with adrenaline, nitoglycerine or nitropruside. Routine CPB priming consisted of lactated Ringer's solution (1500 ml heparin 2000 U/L). Haematocrit level was kept at 25% during CPB. Fresh whole blood, packed red cells, fresh frozen plasma and when necessary, platelet transfusions were administered. Heparin was reversed with 4-5 mg/kg protamine, immediately after separation of CPB in all patients.

            Cardiac procedures without the use of CPB were performed in randomly patients. These included patients referred for pericardiectomy and patients undergoing off-pump coronary artery bypass grafting (CABG) with good target vessels and preserved left ventricular function. In patients undergoing off-pump CABG, heparin was administered to achieve an activated clotting time of 300 seconds. Following the completion of the procedure, activated clotting time (ACT) was maintained between 100 and 120 seconds (using titrated doses of protamine). Intravenous heparin was not administered in patients undergoing pericariectomy.

            The priority of procedures were classified as follows: emergent procedures were defined as immediate surgery under life threatening conditions; elective procedures were defined as surgery in patients discharged after diagnosis and readmitted for surgery on an elective base.

            The data of postoperative course in intensive care unit were recorded and all patients were submitted to the same routine management in ICU and blood components were given whenever needed.

            The major complications were classified as: bleeding, infection, hepatic, renal, pulmonary and neurological complications.

            Mortality was noted either in-hospital mortality or after discharging the patients from hospital.

Statistical analysis:

            Statistical calculations were performed by using SPSS (the statistical packet for social sciences) version 10.0 (SPSS Inc., Chicago, IL). Data are expressed as means ±standard deviations. Non parametric tests (Mann-Whitney test and Fisher's exact test) were used for comparison between survivors and non survivors. Values of P less than 0.05 were considered significant.

 

RESULTS

            Perioperative data were summarized in Table 2 and 3. In the first 24 h after operation, the mean chest tube output was 1100±330 ml (range 350-1700 ml), mean duration of mechanical ventilation was 30±20 h (range 14-130 h).

            Overall mean durations of intensive care unit (ICU) stay and hospitalization were 5.2±4.05 days and 10.5±7.82 day, respectively. Postoperative bleeding and requirements for blood and blood products were three times the standard amounts.

Surgical procedures:

            Table 4 summarizes the operative procedures among the entire patient population. Table 5 depicts the distribution of operative procedures in regard to the underlying Modified-Pugh class.

Overall mortality and morbidities:

            The hospital mortality was 26% (n=7). Mortality for modified-Pugh class A, B, C was 10% (n = 1/10), 31% (n = 5/16) and 100% (n = 1/1), respectively. One patient with modified-Pugh class A cirrhosis died of serious sternal wound infection and sepsis. The causes of death in patients with class B cirrhosis were characterized by multisystem organ failure (three patients) and hemorrhagic gastrointestinal complications (Two patients). The non survivor with class C, cirrhosis was weaned from CPB with difficulty and died of multisystem organ failure. Postoperative morbidities included hemorrhagic gastrointenstinal complication 15% (n= 4), renal failure requiring dialysis 1% (n = 3), respiratory failure 22% (n = 6), sternal infection 8% (n=2) and reoperation for bleeding 8% (n = 2). Table 6 shows mortality and morbidities.

            Postoperative morbidity and mortality were more closely related to the modified-Pugh scoring system class (table 1).

            Anaylsis of possible risk factors for mortality of cirrhotic patients undergoing cardiac surgery was shown in table 7.

Table (2): Patient characteristics (mean±SD or numbers and percentage).

	N = 27
Gender (femal/male)	7/20
Age (yr)	52 ± 8.5
Body surface area (m2)	1.85 ± 0.22
Ejection fraction	58 ± 145
Bilirubin (mg/dL)	1.8 ± 2.0
Albumin (gm/dL)	2.8 ± 0.5
Prothrombin time (seconds)	16.4 ± 2.6
Preoperative platelet (x 109/dL)	16.2 ± 7.5
Serum sodium (m Eq/L)	130.2 ± 4.2
Serum creatinine (mg/dL)	1.6 ± 0.43
Leucocytic count (103/mm3)	9.1 ± 2.34
Arterial/ alveolar oxygen tension ratio	0.69 ± 0.1
Modified-Pugh classification
A	10 (37%)
B	16 (60%)
C	1 (3%)
Etiology
Hepatitis B and or C	15 (55%)
Schistosomiasis	8 (30%)
Cardiac	4 (15%)
Urgency of operation
Elective	23 (58% )
Emergency	4 (15%)

 

Table (3): Preoperative characteristics

	N = 27	%
Diabetic mellitus	7	26
Hypertension	20	74
Previous myocardial infarction	6	22
New York Heart Association NYHA class III and IV	20	74
Previous cardiac surgery	4	15
Malignant ventricular arrhythmias	2	7
Previous stroke	4	15
Renal failure	2	7

 

Table (4): Operative procedures:

	N	(%)
CABG	8	(30)
On-pump	3	(11)
Off-pump	5	(19)
Isolated valve replacement
Aortic	4	(15)
Mitral	5	(19)
Tricuspid	1	(3)
Double valve replacement	5	(19)
Pericardiectomy	4	(15)
Mean cross clamp time (minutes)	92±44
Mean cardiopulmonary bypass time (minutes)	157±50

 

Table (5): Operative procedures by modified Pugh class

Procedure	Class A	Class B	Class C	Total
Isolated CABG	4	3	1	8
Isolated valve replacement	3	7	-	10
Double valve replacement	2	3	-	5
Pericardiectomy replacement	1	3	-	4
Total	10	16	1	27

 

 Table (6): In-Hospital mortality and morbidity.

	N	(%)
Overall hospital mortality	7	(26)
Modified Pugh-class A	1	(10)
Modified Pugh-class B	5	(31)
Modified Pugh-class C	1	(100)
Hemorrhagic gastrointenstinal complications	4	(15)
Renal failure requiring dialysis	3	(11)
Respiratory failure	6	(22)
Sepsis	3	(11)
Sternal infection	2	(8)
Bleeding requiring reoperative interference	2	(8)

 

 

Table (7):  Analysis of possible risk factors for mortality for cirrhotic patients undergoing open heart surgery

Possible risk factor	Survivor (n=20)	Non survivor (n=7)	P-value
Age (year)	50 ± 1.8	56 ± 8	0.6
Preoperative TB (mg/dL)	2.00 ± 2.05	5.14 ± 3.53	0.008
Preoperative creatinine (mg /dL)	1.64± 0.45	1.81± 0.42	0.4
Preoperative Leucocytic count (103/ mm3)	10.000±1.80	11.000±1.82	0.2
Preoperative albumin (g/dL)	4.1 ± 0.8	4.0 ± 0.8	0.3
Preoperative platelet (x 109/dL)	16.2 ± 6.8	10.6 ± 2.4	0.04
Preoperative serum sodium (m Eq/L)	130.2± 3.1	127.1± 5.2	0.08
Blood transfusion requirement (u)	5.55 ± 2.5	5.74 ± 1.9	0.2
CPB time (min)	145 ± 42	220 ± 58	0.03
Aortic cross-clamp time (min)	94 ± 29	110 ± 38	0.07
Preoperative prothrombin time (seconds)	1.55± 1.60	2.85± 1.86	0.09
Preoperative [P/(a/A)O2] ratio	0.73± 6.29	0.71± 7.97	0.4
Postoperative bleeding (ml)	1004 ± 800	1316 ± 550	0.06

 

TB:  Total bilirubin;                               CPB: cardiopulmonary bypass.

DISCUSSION

            In patients with cirrhosis, cardiac surgery that requires cardiopulmonary bypass has an increased perioperative risk⁽⁴⁾. The overall hospital mortality was 26%. The mortality rate increased significantly according to the modified-Pugh classification (class A, 10%, B; 31% and C, 100%). The increased morbidity and mortality were caused by an elevated incidence of bleeding and sepsis and were felt to be unrelated to cardiac complications. Hayashida et al.⁽¹⁾reported an operative mortality of 28% patients with class B. Similarly, Lin et al.⁽⁹⁾ reported an operative mortality of 0% in 5 patients with class B (n=4) and C (n=1) undergoing cardiac surgery. Our data confirm these improved results in patients with class B (n =16) with a hospital mortality of 31%.

            The present study has been designed to apply a new scoring system to categorize surgical risk in cirrhotic patients in the field of cardiac surgery. The suggested score is a Pugh-modification based on its 5 parameters, but, in addition including other 4 parameters, serum Na, creatinine, wbc and P (a/A) O₂. The score as modified by Moemen et al.⁽¹¹⁾proved to be a more accurate and specific predictor of mortality, in agreement with Webster⁽¹²⁾.   

            In class A; there was no limitation of liver function that would inhibit an operation, and regeneration capability was normal. In class B, there were certain limitations of liver functions and there was a variable response in all operations. Although regeneration capability of the liver was limited in class B, a good tolerance was observed following a thorough preoperative preparation. There were advanced limitations of liver functions in class C. The regeneration capability of the liver was either minimal or absent. Outcome of operations for this class were unfavorable regardless of the adequacy of preoperative preparation^(2,5). This improvement in outcome is probably related to multiple factors, including the advances in the perioperative management of cardiac surgery patients and the introduction of new surgical procedures such as CABG without cardiopulmonary bypass (off-pump CABG). These data suggest that CPB triggers the production and release of numerous vasoactive substances and cytotoxic mediators that affect coagulopathy, immune system, vascular resistance, fluid balance, and major organ function⁽¹³⁾. Other contributing factors, such as hypothermia, hemodilution, and hypoperfusion during CPB, also may be responsible for the morbidity and mortality after operation⁽¹⁴⁾.

            Our study also showed that preoperative serum TB, platelet count and CPB time were identified as predictors to differentiate between survivors and non survivors.

 

Serum total bilirubin (TB):

Non survivors presented with significantly higher preoperative bilirubin levels. This is in full agreement with the findings of other authors^{(11,15,16,17)}.

 

Serum platelet count:

The association between preoperative platelet count and hospital mortality was statistically significant. The severity of cirrhosis as determined by the modified Pugh class. There were no hospital deaths among patients with normal platelet count. Finally, the study shows, for the first time, the association between preoperative platelet count and in-hospital mortality. This correlation persisted after stratifying patients based on Modified-Pugh classification.

 

Cardiopulmonary bypass (CBP) time:

In this study, patients with longer CPB durations had high chest tube output, extended duration of intubation, gastrointenstinal system bleeding, sepsis and less chance for survival. This agrees with the study by Kaplan et al.⁽⁶⁾.

            The postoperative complication rate is increased for patients with chronic liver disease^(18,19). We observed the following categories of complications postoperatively: hepatic, infectious, respiratory, renal, and gastrointestinal bleeding.

            In order to improve preoperative status and to decrease postoperative complications in these patients, assurance of good nutritional status (particularly when infectious complications are concerned) is important. Good nutritional status also provides hemostatic stability⁽⁶⁾.

Conclusion:

            Our results suggest that cardiac surgery can be performed with low operative mortality and good survival in patients with modified-Pugh class A. In a selected group of patients with class B acceptable operative results can be achieved particularly in patients undergoing off-pump coronary revascularization. Operative mortality remains very high in class C patients knowing that most of these patients undergo an emergent procedure in the setting of a life threatening condition. Careful patient selection is critical in order to improve surgical outcome in patients with liver cirrhosis. 

 

Acknowledgement: The authors would like to express their deep thanks and gratitude to Prof. Dr. Mohamed Ezzat Moemen, for his great contributions in this research paper.

 

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