RISK OF SURGERY IN THE PATIENT WITH LIVER DISEASE Ajay Jain Gastroenterology Fellow January 16, 2002

CASE ID/CC: 57 F admitted Aug. 28 with L femur # PMHx: HCV Cirrhosis OGD (1998) Gr II varices No GI bleed, encephalopathy, SBP MEDS: nadolol 40 mg OD spironolactone 100mg OD furosemide 40 mg OD Other Hx: no alcohol abuse

CASE O/E: 110/72,70, 18, afebrile H&N: scleral icterus, jaundice, spider angiomata CVS: JVP 3cm ASA, normal S1 S2, no S3 S4, no murmurs, + SOA PULM: clear ABDO:distended, bulging flanks, + fluid wave, spleen tip palpable, liver span 8cm, non-tender NEURO: no asterixis

CASE LAB: Hb 97 (MCV 94) Na+ 132 WBC 8.6 Cr 36 Plts 84 Urea 5.1 ALB 18 AST 85 INR 2.1 ALT 60 T.BILI 180 ALP 253 ABDO U/S: nodular liver 9cm c/w cirrhosis spleen 14cm moderate ascites

What recommendations would you provide to the orthopedic surgeon and the patient?

Introduction multiple functions of the liver synthesis of most serum proteins metabolism of nutrients and drugs excretion and detoxification of endogenous toxins and exogenous agents filtering of portal venous blood

Introduction any or all of the functions of the liver may be impaired in patients with liver disease pharmacokinetic parameters of: anaesthetics muscle relaxants analgesics, and sedatives can be affected by changes in their binding to plasma proteins detoxification excretion

Introduction bleeding risk may be increased due to coagulopathy susceptibility to infection may be increased due to: altered functioning of hepatic reticuloendothelial cells changes in the immune system portal hypertension

Introduction in the vast majority of patients with liver disease in whom liver function is preserved, the operative risk is not likely to be increased mild elevations of serum transaminases, alkaline phosphatase, or bilirubin levels are frequent post-operatively in pts without liver disease, these elevations are usually transient and of no clinical significance

Introduction A diseased liver is particularly susceptible to the hemodynamic changes that accompany surgery altered hepatic flow may result in hepatic dysfunction in predisposed individuals Med Clin North Am, 1987 Hepatology, 1991

Effects of Anesthesia on the Diseased Liver anesthesia results in moderate reduction in hepatic arterial blood flow and hepatic oxygen uptake no clinical significance of these changes seen in healthy volunteers liver blood flow returns to baseline during surgery initial hypoperfusion and/or reperfusion injury may contribute to postoperative liver dysfunction

Effects of Anesthesia on the Diseased Liver Volatile Anesthetics (Halothane & Enflurane) reduce hepatic arterial (HA) blood flow (systemic vasodilatation) small negative inotropic effect significant hepatic metabolism (halothane - 20%, enflurane - 3%) Isoflurane may actually increase HA blood flow preferred agent in patients with liver disease undergo less hepatic metabolism (0.2%) (corresponds with lower risk of drug-induced hepatitis) (risk of halothane hepatitis quite low: 1 in 35 000)

Effects of Anesthesia on the Diseased Liver Hypercarbia sympathetic stimulation of splanchnic vasculature, thereby decreasing portal blood flow pCO2 should be maintained between 35-40 mmHg during surgery

Effects of Anesthesia on the Diseased Liver Neuromuscular Blocking Agents prolonged in patients with liver disease due to: reduced plasma pseudocholinesterase activity decreased biliary excretion increased volume of distribution Atracurium preferred agent in patients with liver disease metabolism independent of the liver Doxacurium long-acting muscle relaxant recommended for prolonged procedures including hepatic transplantation

Effects of Anesthesia on the Diseased Liver Narcotics morphine and meperidine reduces hepatic blood flow fentanyl preferred narcotic agent Sedatives diazepam prolonged metabolism in patients with liver disease lorazepam eliminated by glucoronidation without hepatic metabolism preferred agent

Effect of Type of Surgical Procedure on the Diseased Liver important determinant of post-operative hepatic dysfunction risk: laparotomy > extra-abdominal surgery greater reduction in HA blood flow cholecystectomy, gastric surgery and colectomy associated with high mortality rates in patients with decompensated cirrhosis morbidity/mortality higher for emergent than elective surgery

Effect of Type of Surgical Procedure on the Diseased Liver Cardiac Surgery (limited experience) 13 pts with alcoholic cirrhosis underwent emergent CABG/valve replacement post-operative mortality rate Child’s A: 0 % Child’s B: 80 % Ann Thorac Surg, 1998

Modified Child-Pugh Score Points Parameter 1 2 3 albumin >35 28-35 <28 INR <1.7 1.7-2.3 >2.3 bilirubin (mg/dL) <2.0 2-3 >3.0 ascites absent slight-mod tense encephalopathy none Gr. I-II Gr. III-IV Class A: 5-6 points Class B: 7-9 points Class C: 10-15 points

Estimating Operative Risk in Patients with Liver Disease minimal data on precise estimates of operative risk most data from small retrospective studies of cirrhotic patients undergoing abdominal surgery pre-operative risk likely dependent on type of underlying liver disease

Contraindications to Elective Surgery in Patients with Liver Disease Acute viral hepatitis Acute alcoholic hepatitis Fulminant hepatic failure Severe chronic hepatitis Child’s class C cirrhosis Severe coagulopathy (PT > 3 sec vs control, Plt<50) Severe extrahepatic complications hypoxemia cardiomyopathy, heart failure acute renal failure

Acute Hepatitis acute hepatitis contraindication to elective surgery peri-operative mortality rates: 9.5 to 13% (in icteric patients) surgery also contraindicated in patients with a histological diagnosis of alcoholic hepatitis mortality rates as high as 55% reported in patients undergoing open liver biopsy or portosystemic shunt surgery JAMA, 1963 Br J Surg, 1982

Chronic Hepatitis surgical risk correlate with clinical, biochemical, and histological severity of disease elective surgery reported to be safe in patients with asymptomatic mild chronic hepatitis

Fatty Liver and Non-Alcoholic Steatohepatitis alcoholic or non-alcoholic fatty liver is not a contraindication to elective surgery trend toward increased mortality following hepatic resection in patients with moderate to severe steatosis (ie. >30% of hepatocytes containing fat) J Gastrointest Surg, 1998 period of abstinence from alcohol before surgery advisable

Fatty Liver and Non-Alcoholic Steatohepatitis EFFECT OF PREOPERATIVE ABSTINENCE ON POOR POSTOPERATIVE OUTCOME IN ALCOHOL MISUSERS: RANDOMIZED CONTROLLED TRIAL (BMJ, 1999) 41 alcoholic (>60g ethanol/d) patients without liver disease undergoing elective colorectal surgery abstinence from alcohol (n=20) vs continuous drinking (n=21) Abstinence Continuous post-op complications 31% 74% post-op myocardial ischemia 23% 85% post-op arrhythmias 33% 86%

Other Causes of Liver Disease Autoimmune Hepatitis if in remission, elective surgery well tolerated in patients with compensated liver disease perioperative administration of “stress” doses of hydrocortisone indicated in patients taking prednisone Hemochromatosis monitoring of diabetes in perioperative period assess for possibility of cardiomyopathy Wilson’s Disease neuropsychiatric involvement - interferes with consent D-pencillamine can impair wound healing - decrease dose in first 1-2 postoperative weeks

Cirrhosis retrospective studies have shown that perioperative mortality and morbidity rates correlate well with the Child-Turcotte-Pugh class of cirrhosis Alcoholic Cirrhosis (abdominal surgery): Mortality Rates 1984 1997 Child’s A 10% 10% Child’s B 31 30 Child’s C 76 82 some studies have not confirmed predictive value of Child’s classification, mainly due to few Child’s C patients APACHE III can predict survival in cirrhotic patients admitted to an ICU; yet to be studied in cirrhotics undergoing surgery

Resection for Hepatocellular Carcinoma (HCC) annual incidence of HCC 3 to 5% perioperative mortality rate for hepatic resection 3 to 16% postoperative morbidity rates as high as 60% 5 year recurrence rates are as high as 100% 5 year survival rates are no higher than 50%

Preoperative Evaluation 1 in 700 otherwise healthy individuals will have abnormal liver function tests any patient undergoing surgery: careful history to identify risk factors for liver disease a history of jaundice or fever after anesthesia alcohol history and complete review of medications sx or findings on physical examination suggestive of liver dz patients with known liver disease: identify presence of jaundice, ascites, or encephalopathy complete biochemical assessment of liver function correct coagulopathy, ascites and encephalopathy

Postoperative Period monitor for signs of liver decompensation including worsening jaundice, encephalopathy and ascites bilirubin and prothrombin time best measures of hepatic function renal function important to monitor because of the risk of hepatorenal syndrome monitoring of serum glucose levels as hypoglycemia often accompanies postoperative hepatic failure

CASE - Hospital Course Hospital Day 4 doubling of Cr and urea, small drop in Hb diagnostic paracentesis c/w SBP ==> ceftriaxone Hospital Day 6 asterixis bili 398, INR 1.90, increasing Cr Hospital Day 9 OGD - Gr III varix - no active bleed

CASE - Hospital Course Hospital Day 12 Na+ 122, Cr 170, T.Bili 493, INR 2.2 drowsy DNR status obtained Hospital Day 13 hypotensive - Rx with IV fluids comfort measures Hospital Day 14 progressive obtundation glucometer 1.5 expired

DISCUSSION