Ch35. Anesthesia for Patients with Liver Disease

1. Ch35. Anesthesia for Patients with Liver Disease R1 김용일

2. Liver has remarkable functional reserve • Hepatic disease에 의한 clinical manifestation은 extensive damage가 생길 때까지 나타나지 않을 수도 • 이처럼 little reserve를 지닌 marginal patient가 OR에 올 경우 마취와 수술에 의해 further hepatic decompensation 유발  overt hepatic failure 발생

3. HEPATITIS

4. ACUTE HEPATITIS • 대개 viral infection, drug reaction, exposure to hepatotoxin에 의함 • Acute hepatocellular injury with variable amounts of cell necrosis

5. Viral hepatitis • Transmission • Hepatitis A & E : oral-fecal route • Hepatitis B & C : percutaneously & by contact with body fluids • Hepatitis D : 전염되기 위해 host에 hepatitis B virus 필요 • Clinical manifestions • 1- to 2-week mild prodromal illness • Fatigue, malaise, low-grade fever, vausea, vomiting • Jaudice는 있을 수도, 없을 수도 있음 • 2-12 wks 지속, 완전히 회복되려면 4 mns 소요 • Hepatitis B & C : cholestasis, fulminant hepatic failure 생기기도 함 • Prognosis • Chronic active hepatitis : hepatitis B의 3-10%, C의 50% • Asymptomatic infectious carriers • HBsAg(+) Pt의 0.3-30%, hepatitis C의 0.5-1%에서(hepatitis C viral RNA 검출 시) • Immunization • Highly effective against hepatitis B infection • Postexposure prophylaxis with hyperimmune globulin is effective for hepatitis B • Hepatitis C는 vaccine, prophylaxis 모두 효과 없음

6. Drug-induced hepatitis • Cause • Direct dose-dependent toxicity of a drug • Idiosyncratic drug reaction • Alcoholic hepatitis • Chronic alcohol ingestion  fatty infiltration에 의한 hepatomegaly 발생 • Impaired fatty acid oxidation • Increased uptake & esterification of fatty acid • Diminished lipoprotein synthesis & secretion • Acetaminophen ingestion • Ingestion of 25G or more  fatal fulminant disease

7. Preoperative considerations • Elective surgery시 acute hepatitis는 resolve 되어야 • LFT의 normalization 필요 • Periop. Morbidity(12%), mortality(10% with laparotomy) 증가 • Acute alcohol toxicity : greatly complicated • 수술 동안의 alcohol withdrawal때문에 mortality rate 50%로 증가 • Lab. Evaluation • BUN, s-electrolyte, creatinine, glucose, transaminases, alkaline phosphatase, albumin, PT, platelet count 등 • Alcoholic hepatitis 외에는 대개 ALT가 AST보다 높음 • PT : best indicator of hepatic synthetic function • Vit. K 투여 후 PT 3 sec 이상 (INR >1.5) : severe hepatic dysfunction • 응급수술시에는 간기능 장애의 원인과 정도에 초점 맞출 것 • 최근 drug exposure, transfusion, prior enesthetics 확인 • Dehydration & electrolyte abNL 교정 • Coagulopathy 교정 위해 Vit. K, FFP 필요 • Premedi는 대개 하지 않음 • Acute withdrawal 있는 alcoholic Pt.에서는 benzodiazepine & thiamine 투여

8. Intraoperative considerations • Goal • Preserve existing hepatic function • Avoid factors that may be detrimental to the liver • Alcoholic Pt • Cross-tolerance to anesthetics • Close cardiovascular monitoring • Alcohol의 cardiac depression, alcoholic cardiomyopathy • IV 약제보다는 inhalation anesthetics가 선호 • Standard induction doses of IV agents는 사용 가능 • Metabolism or excretion 보다는 redistribution에 의해 제거되므로 • Isoflurane is the volatile agent of choice • Hepatic blood flow에 대한 영향이 가장 적음 • Hepatic blood flow 줄이는 인자 피할 것 • Hypotension, excessive sympathetic activation, high mean airway pr. • Coagulopathy 없을 경우 regional anesthetia 가능 • Hypotension 피할 것

9. CHRONIC HEPATITIS • Persistent hepatic inflammation for longer than 6 months • Evidenced by elevated serum aminotransferases • Liver biopsy에 의한 분류 • Chronic persistent hepatitis • 정상 cellular architecture는 유지되는 portal tract의 chronic inflammation • Chronic lobular hepatitis • Resolve 되는 acute hepatitis, but recurrent exacerbations • Hepatic lobule에 inflammation과 necrosis의 foci 존재 • Chronic active hepatitis • 정상세포구조가 파괴되는 chronic hepatic inflammation • LC : 20-50%에서 이미 보임 • 대개 hepatitic B or C의 sequelae로 발생 • Fatigue, recurrent jaundice • Only a mild elevation in serum aminotransferase activity • Often correlate poorly with disease severity • Chr. hepatitis B or C 외에서는 면역억제제에 반응 좋음 • Anesthetic management • Chronic persistent or lobular hepatitis는 acute hepatitis의 경우와 비슷 • Chronic active hepatitis에서는 이미 cirrhosis 있다고 가정할 것

10. CIRRHOSIS

11. Cirrhosis • m/c cause in US : alcohol • 그외 chronic active hepatitis, chronic biliary inflammation or obx., chronic Rt-sided CHF, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α1-antitrypsin deficiency, nonalcoholic steatohepatitis, cryptogenic cirrhosis 등 • Hepatocyte necrosis, fibrosis, nodular regeneration • 간의 정상 세포, 혈관 구조의 변형으로 portal venous flow가 막힘 • Signs Symptoms는 disease severity와 관련 적음 • Jaundice, ascites • Spider angiomas, palmar erythema, gynecomastia, splenomegaly • 3 Major complications • Variceal hemorrhage from portal hypertension • Intractable fluid retention in ascites, hepatorenal syndrome • Hepatic encephalopathy, coma • 10%에서 spontaneous bacterial peritonitis, 일부에서는 HCC 발생

12. Preoperative considerationsa. gastrointestinal manifestations • Portal-systemic venous collateral channels • Gastroesophageal • Massive bleeding from varices : Mj cause of morbidity & mortality • Blood loss, 장내 blood 분해로 인한 nitrogen load 증가로 hepatic encephalopathy 위험 • 치료 : IV fluid, blood product • Vasopressin, somatostatin, propranolol, balloon tamponade(Sengstaken-Blakemore tube), endoscopic sclerosis • IV NTG : vasopressin 고용량에 의한 CHF or MI 예방 • Percutaneous transjugular intrahepatic portosystemic shunts (TIPS) • Selective shunts(distal splenorenal) : varix 감압, 간혈류 저해 않으며 술후 encephalopathy 적음 • Hemorrhoidal • Periumbilical • retroperitoneal

13. Preoperative considerationsb. hematological manifestations • 원인 • Anemia • Blood loss, RBC destruction 증가, bone barrow suppression, nutritional deficiencies • Thrombocytopenia, leukopenia • Congestive splenomegaly (from portal HTN) • Coagulation factor deficiencies • Decreased hepatic synthesis • Preop. Blood transfusion • 지나치면 Nitrogen load 늘려 encephalopathy 유발 • 수술전 coagulopathy는 교정되어야 함 • FFP, cryoprecipitate • 수술전 platelet < 100,000/㎕시 platelet transfusion 고려

14. Preoperative considerationsc. circulatory manifestations • Cirrhosis : hyperdynamic circulatory state • Arteriovenous shunt • Systemic & pulm. circulation에서 발생 가능 • Anemia로 인한 blood viscosity 감소시 filling pr.는 증가하고 systemic vascular resistance는 감소하여 cardiac output이 증가하게 됨  cirrhotic cardiomyopathy

15. Preoperative considerationsd. respiratory manifestations • Hyperventilation 흔함 • Primary respiratory alkalosis 발생 • Hypoxemia 흔히 발생 • Rt-to-Lt shunting (up to 40% of cardiac output) 때문 • Shunt는 pulm. A-V communications, V-Q mismatching에 의해 발생 • Ascites로 인한 diaphragmatic elevation 때문에 lung volume 감소

16. Preoperative considerationse. renal manifestations and fluid balance • Ascites의 원인 • Portal HTN으로 hydrostatic pr. 증가되어 intestine에서 peritoneal cavity로 fluid transudation • Hypoalbuminemia로 plasma oncotic pr. 감소하여 fluid transudation • Protein-rich lymphatic fluid가 serosal surface of liver에서 삼출 • Renal sodium retention • “Underfilling” theory : effective plasma volume 감소로 인해 이차적으로 발생 • “Oveflow” theory : renal sodium retention으로 인해 transudation에 의해 ascites 발생 • Cirrhosis & ascites • Renal perfusion 감소, intrarenal hemodynamics 변화, proximal & distal sodium reabsorption 촉진, free water clearance 저해  hyponatremia (dilutional), hypokalemia (excessive urinary potassium losses)

17. Preoperative considerationse. renal manifestations and fluid balance • Hepatorenal syndrome • Progressive oliguria, avid sodium retention, azotemia, intrractable ascites • Very high mortality rate • Liver transplantation 필요 • Judicious periop. fluid management • 지나친 술전 diuresis 피할 것 • Acute intravascular fluid deficit은 colloid infusion으로 교정 • Ascites와 pph. Edema 함께 있을 때 diuresis 동안 체중이 1㎏/d 이상 줄지 않도록 • Loop diuretics • Bed rest, sodium restriction(<2gNaCl/d), spironolactone 효과 없을 때 • Hyponatremia (<120mEq/L)시 water restriction • Potassium deficit은 술전에 보충 • Prophylactic periop. Mannitol infusion may be effective in preventing renal failure

18. Preoperative considerationsf. central nervous system manifestations • Hepatic encephalopathy • Alterations in mental status • With fluctuating neurological signs • Asterixis, hyperreflexia, inverted plantar reflex) • 특징적 EEG changes • Symmetric high-voltage, slow-wave activity • 일부에서는 ICP 증가되기도 함 • Factors precipitate hepatic encephalopathy • G-I cleeding • Increased dietary protein intake • Hypokalemic alkalosis (from vomiting or diuresis) • Infections • Worsening liver function • 술전에 aggressive하게 치료 • Oral lactulose 30-50mL every 8h or neomycin 500mg every 6h  reduce intestinal ammonia absorption • Avoidance of sedatives

19. Intraoperative considerations • Hepatitis B or C carrier : blood & body fluid에 접촉하지 않도록 특히 주의할 것 • Drug responses • Unpredictable for response to anesthetic agents • NMBAs 등 highly ionized drug은 volume of distribution이 증가하여 증량 필요 • Hepatic elimination되는 약제(pancuronium, rocuronium, vecuronium)는 유지용량을 줄여야 함 • Anesthetic technique • Hepatic a. blood flow 유지할 것 • Regional anesthesia : thrombocytopenia, coagulopathy 없을 경우 가능 • Hypotension 주의 • General anesthesia • Induction : barbiturate or propofol induction • Maintenance : isoflurane in oxygen or oxygen-air mixture • Opioid supplementation : half-life 길어져 prolonged resp. depression 가능 • Cisatracurium : NMBA of choice (unique nonhepatic metabolism) • Preoxygenation & rapid-sequence induction with cricoid pressure • Unstable pt. & active bleeding 시에는 • Awake intubation • Rapid-sequence induction with cricoid pr., using ketamine (or etomidate) & succinylcholijne

20. Intraoperative considerations (2) • Monitoring • Vasopressin 사용시 5-lead ECG로 MI 관찰 • ABGA : acid-base status • Large Rt-to-Lt intrapulm. Shunt • Nitrous oxide 쓰지 말 것 • PEEP 필요 : V-Q mismatch, hypoxemia 치료 • Intraarterial pr. Monitoring • Intravascular volume status : CVP, pulm. a. pr. Monitoring • Urinary output • Fluid replacement • 술중 intravascular volume & urinary output 유지가 우선적 • Colloid iv fluid(albumin) 우선적으로 사용 • Sodium overload 막고, oncotic pressure 증가시킴 • Ascitic fluid 다량 제거시 iv colloid fluid replacement가 필수적 • Transfusion • 다량 수혈시 citrate toxicity 위험 • Hypocalcemia 유발

21. HEPATOBILIARY DISEASE

22. Hepatobiliary disease • Cholestasis • Progressive jaundice, dark urine with pale stool, pruritus • Extrahepatic obx of biliary tract : m/c cause • Gallstone, stricture, tumor in common hepatic duct • Intrahepatic cholestasis • Viral hepatitis, idiosyncratic drug reaction (phenothiazine, oral contraceptives) • Cholelithiasis • Cholecystitis : RUQ tenderness, fever, leukocytosis • Cholangitis : chill or high fever 동반 • Acute cholecystitis의 75%가 medical treatment로 2-7일 내에 호전됨 • 5-10%는 acalculous cholecystitis • Serious trauma, burns, prolonged labor, major surgery, critical illness

23. Hepatobiliary disease (2) • Preoperative considerations • Acute cholecystitis 환자 대부분이 수술전에 medically stabilized 된 후에 cholecystectomy 시행 (LC) • Nasogastric suction, iv fluids, antibiotics, opioid analgesics • Acalculous cholecystitis • 대개 critically ill pt.에서 발생  gangrene & perf. 위험 • 보통 응급수술 필요 • Extrahepatic biliary obx.시 vit.K deficiency 발생 가능 • Vit.K 투여 필요, PT 정상화되지 못하면 FFP 투여 • Generous preop. Hydration • Intraoperative considerations • Intraop. Cholangiogram 필요시 opioid 피할 것 • False-positive 유발 • Opioid-induced sphincter spasm 의심시 naloxone or glucagon 투여 • Renal elimination되는 약물 사용이 바람직함

24. HEPATIC SURGERY • Common hepatic procedures • Repair of lacerations, drainage of abscesses, resections for tumors • Hepatic surgery는 대량출혈 위험 • Multiple large-bore iv catheters • Fluid(blood) warmers • Arterial pr., CVP monitoring • Antifibrinolytics 투여로 출혈 줄일 수 있음 • Aprotinin, ε-aminocaproic acid, tranexamic acid • Postop Cx • Bleeding, sepsis, hepatic dysfunction