Principles of anesthesia in cirrhotic patients Jean Mantz, MD, PhD Professor of Anesthesia and Critical Care Chairman, Department of Anesthesia and Critical Care, Beaujon University Hospital INSERM U 676 University of Paris

Anesthesia and cirrhosis Principles of perioperative management Anesthesia and cirrhosis in: Liver transplantation Liver resection Endoscopic procedures Conclusion

Cirrhotic patients: Risk factors for perioperative morbi-mortality Ziser et al Anesthesiology 1999; 90: 42-53 Risk factors Morbidity (%) 30 day mortality (%) 6 month mortality (%) Child-Pugh score C vs AB     42 15 31 Ascite 48 20 39 Renal failure 21 36 COPD 41 18 29 Preoperative sepsis 74 49 60 GI bleeding 70 12 23 ASA status 4 or 5 68 32 52 Major surgery (thoracic, voies biliary, abodminal, septic) Intraoperative hypotension 45 26 Cause other than PBC 33 14 24

Cirrhotic patients: Risk factors for perioperative morbi-mortality Ziser et al Anesthesiology 1999; 90: 42-53 Risk factors Morbidity (%) 30 day mortality (%) 6 month mortality (%) Child-Pugh score C vs AB     42 15 31 Ascite 48 20 39 Renal failure 21 36 COPD 41 18 29 Preoperative sepsis 74 49 60 GI bleeding 70 12 23 ASA status 4 or 5 68 32 52 Major surgery (thoracic, voies biliary, abodminal, septic) Intraoperative hypotension 45 26 Cause other than PBC 33 14 24

Cirrhotic patients: Risk factors for perioperative morbi-mortality Ziser et al Anesthesiology 1999; 90: 42-53 Risk factors Morbidity (%) 30 day mortality (%) 6 month mortality (%) Child-Pugh score C vs AB     42 15 31 Ascite 48 20 39 Renal failure 21 36 COPD 41 18 29 Preoperative sepsis 74 49 60 GI bleeding 70 12 23 ASA status 4 or 5 68 32 52 Major surgery (thoracic, voies biliary, abodminal, septic) Intraoperative hypotension 45 26 Cause other than PBC 33 14 24

Venous compliance in cirrhosis Hadengue et al, Hepatology 1992 300 mL gélatine en 3 min

Fluid management Hypovolemia Fluid overload

Preoperative risk evaluation Circulatory (hyperkinetic profile with low SVR, high venous compliance, coronaropathy or cardiomoypathy, pulmonary hypertension) Ventilatory (Hypoxemia, intrapulmonary shunt, restrictive syndrome (ascite, pleural effusion)

Preoperative risk evaluation Circulatory (hyperkinetic profile with low SVR, high venous compliance, coronaropathy or cardiomoypathy, pulmonary hypertension) Ventilatory (Hypoxemia, intrapulmonary shunt, restrictive syndrome (ascite, pleural effusion) Renal (hypovolemia, hepatorenal syndrome) Cerebral (encephalopathy, cerebral edema) Coagulation (hypo-/ hypercoagulability, fibrinolysis) Pharmacokinetic/dynamic changes to drug effects

Choice of anesthetic agents/techniques Risks of regional anesthesia Use intravenous anesthetics with elimination independent from cytochrome P450 activity (Propofol AIVOC, ketamine, etomidate, fentanyl, sufentanil, remifentanil, atracurium/cisatracurium) Volatile anesthetics: desflurane/sevoflurane Maintain hemodynamic stability +++ MONITOR and TITRATE+++

Patient Risk/benefit balance of anesthesia and surgery Anesthesiologist Surgeon Hepatologist/ Gastroenterologist

Intraoperative period Short acting anesthetics Postoperative analgesia Prevention of PONV Reversal of muscle relaxants Maintenance of normovolemia, hemoglobin levels Prevention of awareness Maintenance of normothermia Maintain oxygenation Restrictive fluid therapy Avoid hyperglycemia Start postoperative rehabilitation

Intraoperative period Short acting anesthetics Postoperative analgesia Prevention of PONV Reversal of muscle relaxants Maintenance of normovolemia, hemoglobin levels Prevention of awareness Maintenance of normothermia Maintain oxygenation Restrictive fluid therapy Avoid hyperglycemia Start postoperative rehabilitation

Cirrhosis and coagulation abnormalities Antihemostatic Prohemostatic Thrombocytopenia Alteration of platelet functions  FvW and FVIII  Factors II, V, VII, IX, X, XI Abnormalities of fibrinogen  Protein C, protein S, protein Z, AT(III), heparin-CoFII, 2-macroglobulin  2-anti-plasmine, TAFI  t-PA  plasminogen  PAI-1 T. Lisman et al. J Hepatol 2002;37:280-7

Hepatology 2006,44:53-61

Coagulation abnormalities Cirrhosis Coagulation abnormalities Hemorrhage

Coagulation abnormalities Cirrhosis Coagulation abnormalities Portal hypertension ? Hemorrhage

Postoperative rehabilitation Multimodal analgesia Early extubation Early removal of tubes and catheters Early mobilization Thromboprophylaxis Early enteral nutrition Hydratation

Postoperative rehabilitation Multimodal analgesia Early extubation Early removal of tubes and catheters Early mobilization Thromboprophylaxis Early enteral nutrition Hydratation

Liver transplantation in Beaujon: recipients

2005-2007 (n=215) 1997-2000 (n=212) 2001-2004 (n=242) 1993-1996 (n=77) 1989-1992 (n=51)

Survival / indications Cirrhosis (n=416) Others (n=72) HCC (n=248) Fulminans (n=139)

Anesthesia for endoscopic procedures. High risk anesthesia +++ Outside the OR Inhalation of gastric content Obstructive hypoxemia Hemorrhage and perforation Pulmonary hypertension

Indications for endotracheal intubation Esophageal varices treatment (inhalation risk+++) Radiofrequency (painful procedures) Other indications: Long duration procedure (> 1h)) Comorbidities (obesity, major ascite, diabetic dysautonomia)

Conclusion Cirrhotic patients are at high risk of postoperative morbi-mortality Discuss the risk/benefit balance of surgery and anesthesia Maintain hemodynamic stability (monitor, titrate) There is no « minor » anesthesia

Thank you for your kind attention