RISK OF SURGERY IN THE RISK OF SURGERY IN THE PATIENT WITH LIVER PATIENT WITH LIVER

DISEASEDISEASE

Ajay JainAjay Jain

Gastroenterology FellowGastroenterology Fellow

January 16, 2002January 16, 2002

CASECASEID/CC:ID/CC: 57 F admitted Aug. 28 with L femur # 57 F admitted Aug. 28 with L femur #

PMHx: PMHx: HCV CirrhosisHCV Cirrhosis

» OGD (1998) Gr II varicesOGD (1998) Gr II varices» No GI bleed, encephalopathy, SBPNo GI bleed, encephalopathy, SBP

MEDS:MEDS: nadolol nadolol 40 mg OD40 mg ODspironolactone spironolactone 100mg OD100mg ODfurosemidefurosemide 40 mg OD40 mg OD

Other Hx:Other Hx:» no alcohol abuseno alcohol abuse

CASECASEO/E:O/E: 110/72,70, 18, afebrile110/72,70, 18, afebrileH&N:H&N: scleral icterus, jaundice, spider angiomatascleral icterus, jaundice, spider angiomata

CVS:CVS: JVP 3cm ASA, normal S1 S2, no S3 S4, no JVP 3cm ASA, normal S1 S2, no S3 S4, no murmurs, + SOAmurmurs, + SOA

PULM: clearPULM: clear

ABDO:distended, bulging flanks, + fluid wave, ABDO:distended, bulging flanks, + fluid wave, spleen tip palpable, liver span 8cm, non- spleen tip palpable, liver span 8cm, non-

tendertender

NEURO: no asterixisNEURO: no asterixis

CASECASELAB:LAB: HbHb 9797 (MCV 94) (MCV 94) NaNa++ 132132 WBCWBC 8.68.6 CrCr 36 36 PltsPlts 8484 UreaUrea 5.1 5.1 ALBALB 1818 ASTAST 8585 INRINR 2.12.1 ALTALT 6060 T.BILIT.BILI 180180 ALPALP 253253ABDO U/S:ABDO U/S: nodular liver 9cm c/w cirrhosisnodular liver 9cm c/w cirrhosis spleen 14cmspleen 14cm moderate ascitesmoderate ascites

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

IntroductionIntroduction

multiple functions of the livermultiple functions of the liver

» synthesis of most serum proteinssynthesis of most serum proteins

» metabolism of nutrients and drugsmetabolism of nutrients and drugs

» excretion and detoxification of endogenous toxins excretion and detoxification of endogenous toxins and exogenous agentsand exogenous agents

» filtering of portal venous bloodfiltering of portal venous blood

IntroductionIntroduction

any or all of the functions of the liver may be impaired in any or all of the functions of the liver may be impaired in patients with liver diseasepatients with liver disease

pharmacokinetic parameters of:pharmacokinetic parameters of:» anaestheticsanaesthetics» muscle relaxantsmuscle relaxants» analgesics, and sedatives analgesics, and sedatives

can be affected by changes in theircan be affected by changes in their» binding to plasma proteinsbinding to plasma proteins» detoxificationdetoxification» excretionexcretion

IntroductionIntroduction

bleeding risk may be increased due to coagulopathybleeding risk may be increased due to coagulopathy

susceptibility to infection may be increased due to:susceptibility to infection may be increased due to:» altered functioning of hepatic reticuloendothelial cellsaltered functioning of hepatic reticuloendothelial cells

» changes in the immune systemchanges in the immune system

» portal hypertensionportal hypertension

IntroductionIntroduction

in the vast majority of patients with liver disease in the vast majority of patients with liver disease in whom liver function is preserved, the operative in whom liver function is preserved, the operative risk is not likely to be increasedrisk is not likely to be increased

mild elevations of serum transaminases, alkaline mild elevations of serum transaminases, alkaline phosphatase, or bilirubin levels are frequent post-phosphatase, or bilirubin levels are frequent post-operativelyoperatively

» in pts without liver disease, these elevations are in pts without liver disease, these elevations are usually transient and of no clinical significance usually transient and of no clinical significance

IntroductionIntroduction

A diseased liver is particularly susceptible to A diseased liver is particularly susceptible to the hemodynamic changes that accompany the hemodynamic changes that accompany surgerysurgery

» altered hepatic flow may result in hepatic dysfunction altered hepatic flow may result in hepatic dysfunction in predisposed individualsin predisposed individuals

Med Clin North Am, 1987Med Clin North Am, 1987

Hepatology, 1991Hepatology, 1991

Effects of Anesthesia on the Effects of Anesthesia on the Diseased LiverDiseased Liver

anesthesia results in moderate reduction in hepatic anesthesia results in moderate reduction in hepatic arterial blood flow and hepatic oxygen uptakearterial blood flow and hepatic oxygen uptake

» no clinical significance of these changes seen in no clinical significance of these changes seen in healthy volunteershealthy volunteers

liver blood flow returns to baseline liver blood flow returns to baseline duringduring surgery surgery» initial hypoperfusion and/or reperfusion injury may initial hypoperfusion and/or reperfusion injury may

contribute to postoperative liver dysfunctioncontribute to postoperative liver dysfunction

Effects of Anesthesia on theEffects of Anesthesia on theDiseased LiverDiseased Liver

Volatile Anesthetics (Halothane & Enflurane)Volatile Anesthetics (Halothane & Enflurane)» reduce hepatic arterial (HA) blood flow (systemic reduce hepatic arterial (HA) blood flow (systemic

vasodilatation)vasodilatation)» small negative inotropic effectsmall negative inotropic effect» significant hepatic metabolism (halothane - 20%, significant hepatic metabolism (halothane - 20%,

enflurane - 3%)enflurane - 3%) IsofluraneIsoflurane

» may actually increase HA blood flowmay actually increase HA blood flow» preferred agent in patients with liver diseasepreferred agent in patients with liver disease» undergo less hepatic metabolism (0.2%) undergo less hepatic metabolism (0.2%)

(corresponds with lower risk of drug-induced hepatitis)(corresponds with lower risk of drug-induced hepatitis)

(risk of halothane hepatitis quite low: 1 in 35 000)(risk of halothane hepatitis quite low: 1 in 35 000)

Effects of Anesthesia on theEffects of Anesthesia on theDiseased LiverDiseased Liver

HypercarbiaHypercarbia» sympathetic stimulation of splanchnic vasculature, sympathetic stimulation of splanchnic vasculature,

thereby decreasing portal blood flowthereby decreasing portal blood flow

» pCOpCO22 should be maintained between 35-40 mmHg should be maintained between 35-40 mmHg

during surgeryduring surgery

Effects of Anesthesia on theEffects of Anesthesia on theDiseased LiverDiseased Liver

Neuromuscular Blocking AgentsNeuromuscular Blocking Agents» prolonged in patients with liver disease due to:prolonged in patients with liver disease due to:

reduced plasma pseudocholinesterase activityreduced plasma pseudocholinesterase activity decreased biliary excretiondecreased biliary excretion increased volume of distributionincreased volume of distribution

AtracuriumAtracurium» preferred agent in patients with liver diseasepreferred agent in patients with liver disease» metabolism independent of the livermetabolism independent of the liver

DoxacuriumDoxacurium» long-acting muscle relaxantlong-acting muscle relaxant» recommended for prolonged procedures including recommended for prolonged procedures including

hepatic transplantationhepatic transplantation

Effects of Anesthesia on theEffects of Anesthesia on theDiseased LiverDiseased Liver

NarcoticsNarcotics morphine and meperidinemorphine and meperidine

» reduces hepatic blood flowreduces hepatic blood flow fentanylfentanyl

» preferred narcotic agentpreferred narcotic agent

SedativesSedatives diazepamdiazepam

» prolonged metabolism in patients with liver diseaseprolonged metabolism in patients with liver disease lorazepamlorazepam

» eliminated by glucoronidation without hepatic metabolismeliminated by glucoronidation without hepatic metabolism» preferred agentpreferred agent

Effect of Type of Surgical Procedure Effect of Type of Surgical Procedure on the Diseased Liveron the Diseased Liver

important determinant of post-operative hepatic important determinant of post-operative hepatic dysfunctiondysfunction

risk: laparotomy > extra-abdominal surgeryrisk: laparotomy > extra-abdominal surgery» greater reduction in HA blood flowgreater reduction in HA blood flow

cholecystectomy, gastric surgery and colectomy cholecystectomy, gastric surgery and colectomy associated with high mortality rates in patients associated with high mortality rates in patients with decompensated cirrhosiswith decompensated cirrhosis

morbidity/mortality higher for emergent than morbidity/mortality higher for emergent than elective surgeryelective surgery

Effect of Type of Surgical Procedure Effect of Type of Surgical Procedure on the Diseased Liveron the Diseased Liver

Cardiac Surgery (limited experience)Cardiac Surgery (limited experience)

» 13 pts with alcoholic cirrhosis underwent emergent 13 pts with alcoholic cirrhosis underwent emergent CABG/valve replacementCABG/valve replacement

» post-operative mortality ratepost-operative mortality rate Child’s A:Child’s A: 0 % 0 % Child’s B:Child’s B: 80 %80 %

Ann Thorac Surg, 1998Ann Thorac Surg, 1998

Modified Child-Pugh ScoreModified Child-Pugh Score PointsPoints

ParameterParameter 11 22 33albuminalbumin >35 >35 28-35 28-35 <28 <28INRINR <1.7 <1.7 1.7-2.3 1.7-2.3 >2.3 >2.3bilirubin (mg/dL)bilirubin (mg/dL) <2.0 <2.0 2-32-3 >3.0 >3.0ascitesascites absent absent slight-mod tense slight-mod tenseencephalopathyencephalopathy none none Gr. I-II Gr. III-IV Gr. I-II Gr. III-IV

Class A:Class A: 5-65-6 pointspointsClass B:Class B: 7-9 7-9 pointspointsClass C:Class C: 10-1510-15 pointspoints

Estimating Operative Risk in Patients Estimating Operative Risk in Patients with Liver Diseasewith Liver Disease

minimal data on precise estimates of operative riskminimal data on precise estimates of operative risk

most data from small retrospective studies of most data from small retrospective studies of cirrhotic patients undergoing abdominal surgerycirrhotic patients undergoing abdominal surgery

pre-operative risk likely dependent on pre-operative risk likely dependent on typetype of of underlying liver diseaseunderlying liver disease

Contraindications to Elective Surgery Contraindications to Elective Surgery in Patients with Liver Diseasein Patients with Liver Disease

Acute viral hepatitisAcute viral hepatitis Acute alcoholic hepatitisAcute alcoholic hepatitis Fulminant hepatic failureFulminant hepatic failure Severe chronic hepatitisSevere chronic hepatitis Child’s class C cirrhosisChild’s class C cirrhosis Severe coagulopathy (PT > 3 sec vs control, Plt<50)Severe coagulopathy (PT > 3 sec vs control, Plt<50) Severe extrahepatic complicationsSevere extrahepatic complications

» hypoxemiahypoxemia

» cardiomyopathy, heart failurecardiomyopathy, heart failure

» acute renal failureacute renal failure

Acute HepatitisAcute Hepatitis

acute hepatitis contraindication to elective surgeryacute hepatitis contraindication to elective surgery

peri-operative mortality rates: 9.5 to 13%peri-operative mortality rates: 9.5 to 13%(in icteric patients)(in icteric patients)

surgery also contraindicated in patients with a surgery also contraindicated in patients with a histological diagnosis of alcoholic hepatitishistological diagnosis of alcoholic hepatitis

» mortality rates as high as 55% reported in patients mortality rates as high as 55% reported in patients undergoing open liver biopsy or portosystemic shunt undergoing open liver biopsy or portosystemic shunt surgerysurgery

JAMA, 1963JAMA, 1963Br J Surg, 1982Br J Surg, 1982

Chronic HepatitisChronic Hepatitis

surgical risk correlate with clinical, biochemical, surgical risk correlate with clinical, biochemical, and histological severity of diseaseand histological severity of disease

elective surgery reported to be safe in patients elective surgery reported to be safe in patients with asymptomatic mild chronic hepatitiswith asymptomatic mild chronic hepatitis

Fatty Liver and Non-Alcoholic Fatty Liver and Non-Alcoholic SteatohepatitisSteatohepatitis

alcoholic or non-alcoholic alcoholic or non-alcoholic fattyfatty liver is not a liver is not a contraindication to elective surgerycontraindication to elective surgery

trend toward increased mortality following hepatic trend toward increased mortality following hepatic resection in patients with moderate to severe steatosis resection in patients with moderate to severe steatosis (ie. >30% of hepatocytes containing fat)(ie. >30% of hepatocytes containing fat)

J Gastrointest Surg, 1998J Gastrointest Surg, 1998

period of abstinence from alcohol before surgery period of abstinence from alcohol before surgery advisableadvisable

Fatty Liver and Non-Alcoholic Fatty Liver and Non-Alcoholic SteatohepatitisSteatohepatitis

EFFECT OF PREOPERATIVE ABSTINENCE ON POOR EFFECT OF PREOPERATIVE ABSTINENCE ON POOR POSTOPERATIVE OUTCOME IN ALCOHOL MISUSERS: POSTOPERATIVE OUTCOME IN ALCOHOL MISUSERS: RANDOMIZED CONTROLLED TRIALRANDOMIZED CONTROLLED TRIAL

(BMJ, 1999)(BMJ, 1999) 41 alcoholic (>60g ethanol/d) patients without liver disease 41 alcoholic (>60g ethanol/d) patients without liver disease

undergoing elective colorectal surgeryundergoing elective colorectal surgery abstinence from alcohol (n=20) vs continuous drinking (n=21)abstinence from alcohol (n=20) vs continuous drinking (n=21)

AbstinenceAbstinence ContinuousContinuous post-op complicationspost-op complications 31% 31% 74% 74% post-op myocardial ischemia 23%post-op myocardial ischemia 23% 85% 85% post-op arrhythmiaspost-op arrhythmias 33% 33% 86% 86%

Other Causes of Liver DiseaseOther Causes of Liver Disease Autoimmune HepatitisAutoimmune Hepatitis

» if in remission, elective surgery well tolerated in if in remission, elective surgery well tolerated in patients with compensated liver diseasepatients with compensated liver disease

» perioperative administration of “stress” doses of perioperative administration of “stress” doses of hydrocortisone indicated in patients taking prednisonehydrocortisone indicated in patients taking prednisone

HemochromatosisHemochromatosis» monitoring of diabetes in perioperative periodmonitoring of diabetes in perioperative period

» assess for possibility of cardiomyopathyassess for possibility of cardiomyopathy

Wilson’s DiseaseWilson’s Disease» neuropsychiatric involvement - interferes with consentneuropsychiatric involvement - interferes with consent

» D-pencillamine can impair wound healing - decrease D-pencillamine can impair wound healing - decrease dose in first 1-2 postoperative weeksdose in first 1-2 postoperative weeks

CirrhosisCirrhosis retrospective studies have shown that perioperative mortality retrospective studies have shown that perioperative mortality

and morbidity rates correlate well with the Child-Turcotte-and morbidity rates correlate well with the Child-Turcotte-Pugh class of cirrhosisPugh class of cirrhosis

Alcoholic Cirrhosis (abdominal surgery): Mortality RatesAlcoholic Cirrhosis (abdominal surgery): Mortality Rates

19841984 19971997» Child’s AChild’s A 10% 10% 10% 10%

» Child’s BChild’s B 31 31 30 30

» Child’s CChild’s C 76 76 82 82

some studies have not confirmed predictive value of Child’s some studies have not confirmed predictive value of Child’s classification, mainly due to few Child’s C patientsclassification, mainly due to few Child’s C patients

APACHE III can predict survival in cirrhotic patients admitted APACHE III can predict survival in cirrhotic patients admitted to an ICU; yet to be studied in cirrhotics undergoing surgeryto an ICU; yet to be studied in cirrhotics undergoing surgery

Resection for Hepatocellular Resection for Hepatocellular Carcinoma (HCC)Carcinoma (HCC)

annual incidence of HCC 3 to 5%annual incidence of HCC 3 to 5% perioperative mortality rate for hepatic resection perioperative mortality rate for hepatic resection

3 to 16%3 to 16% postoperative morbidity rates as high as 60%postoperative morbidity rates as high as 60% 5 year recurrence rates are as high as 100%5 year recurrence rates are as high as 100% 5 year survival rates are no higher than 50%5 year survival rates are no higher than 50%

Preoperative EvaluationPreoperative Evaluation

1 in 700 otherwise healthy individuals will have abnormal 1 in 700 otherwise healthy individuals will have abnormal liver function testsliver function tests

any patient undergoing surgery:any patient undergoing surgery:» careful history to identify risk factors for liver diseasecareful history to identify risk factors for liver disease

» a history of jaundice or fever after anesthesiaa history of jaundice or fever after anesthesia

» alcohol history and complete review of medicationsalcohol history and complete review of medications

» sx or findings on physical examination suggestive of liver dzsx or findings on physical examination suggestive of liver dz

patients with known liver disease:patients with known liver disease:» identify presence of jaundice, ascites, or encephalopathyidentify presence of jaundice, ascites, or encephalopathy

» complete biochemical assessment of liver functioncomplete biochemical assessment of liver function

» correct coagulopathy, ascites and encephalopathycorrect coagulopathy, ascites and encephalopathy

Postoperative PeriodPostoperative Period

monitor for signs of liver decompensation monitor for signs of liver decompensation including worsening jaundice, encephalopathy and including worsening jaundice, encephalopathy and ascitesascites

bilirubin and prothrombin time best measures of bilirubin and prothrombin time best measures of hepatic functionhepatic function

renal function important to monitor because of the renal function important to monitor because of the risk of hepatorenal syndromerisk of hepatorenal syndrome

monitoring of serum glucose levels as monitoring of serum glucose levels as hypoglycemia often accompanies postoperative hypoglycemia often accompanies postoperative hepatic failurehepatic failure

CASE - Hospital CourseCASE - Hospital Course

Hospital Day 4Hospital Day 4 doubling of Cr and urea, small drop in Hbdoubling of Cr and urea, small drop in Hb diagnostic paracentesis c/w SBP ==> ceftriaxonediagnostic paracentesis c/w SBP ==> ceftriaxone

Hospital Day 6Hospital Day 6 asterixisasterixis bili 398, INR 1.90, increasing Crbili 398, INR 1.90, increasing Cr

Hospital Day 9Hospital Day 9 OGD - Gr III varix - no active bleedOGD - Gr III varix - no active bleed

CASE - Hospital CourseCASE - Hospital CourseHospital Day 12Hospital Day 12 NaNa++ 122, Cr 170, T.Bili 493, INR 2.2 122, Cr 170, T.Bili 493, INR 2.2 drowsydrowsy DNR status obtainedDNR status obtained

Hospital Day 13Hospital Day 13 hypotensive - Rx with IV fluidshypotensive - Rx with IV fluids comfort measurescomfort measures

Hospital Day 14Hospital Day 14 progressive obtundationprogressive obtundation glucometer 1.5glucometer 1.5 expiredexpired

DISCUSSIONDISCUSSION