Intensive Care management of Acute Liver Failure Ian

Overview n n n 1: Acute/Fulminant Hepatic Failure 2: Decompensated Chronic Liver Disease Organ

Approach to the patient with liver failure ? Liver failure Diagnosis Are there specific

ALF -diagnosis and assessment n n ALF is a clinical syndrome rather than a

Causes of ALF Aetiology of Acute Liver Failure FRH 1994 -2005 Paracetamol NANB Drugs

Pop Quiz n Mimics of ALF? This work is licensed under a Creative Commons

Differential Diagnosis n Sepsis – similar haemodynamic pictures: low SVR & high CO n

Management of specific causes n Identify and treat the cause: – Paracetamol OD; n

Acute Liver Failure n Support – – – – CNS Respiration Circulation CRRT/? MARS

ALF- general management n FFP is only given if actively bleeding n Quantitative and

Pop Quiz n How much benefit does NAC give in ALF? This work is

N-Acetylcysteine in paracetamol induced ALF - Keays et al, NEJM 1991 Prospective study, NAC

Infection n Infection is common - cause of death in 11% n Gram-positive organisms

Management - Haemodynamics n Similar picture to SIRS/sepsis n Reduced OER despite increased DO

Renal management n Renal failure occurs in up to 70% FHF n Multifactorial n

Coagulopathy management – PPI (Prophylaxis against GI Bleed) – FFP & Vitamin K (Avoid

CNS dysfunction in Acute Liver Failure n n n Cerebral oedema in 50 -

Cerebral management n Preserve cerebral perfusion pressure n effective airway protection & ventilation n

Summary of General Management Provide Multi-organ support n Treat Hypoglycaemia n Avoid Infection n

Liver assist devices This work is licensed under a Creative Commons Attribution-Non. Commercial 3.

Chronic Liver Disease in ICU n “Patients with cirrhosis are frequently denied access to

Survival of cirrhotics admitted to ITU Author Survival Number ITU Hospital Cholongitas et al

Freeman Outcomes Jan 2007 -Dec 2008: 119 patients; 61% Male. Score Predicted Mortality %

ITU Survival/Non Survival Survivors Non-survivors p value Number 307 (55%) 256 (45%) - Age

ITU Survival/Non Survival Survivors Non Survivors p value Child-Pugh score 11 (10 -12) 13

Sequential Organ Failure Assessment (SOFA) Score Vincent et al ICM 1996; 22: 707 -710

AUC 0. 88 >10: 93% Mortality This work is licensed under a Creative Commons

Summary Multiple generic organ support n Reassessment 48 hrs+ n – SOFA n Underlying

Questions? This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported

Conclusions n ITU admission not futile in cirrhotic patients with organ dysfunction – –

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Intensive Care management of (Acute) Liver Failure Ian Nesbitt Consultant in Anaesthesia & Critical Care Freeman Hospital Newcastle upon Tyne This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Overview n n n 1: Acute/Fulminant Hepatic Failure 2: Decompensated Chronic Liver Disease Organ specific support Decision making Questions This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Approach to the patient with liver failure ? Liver failure Diagnosis Are there specific curative treatments? ALF supportive therapy FHF improves definitive therapy Patient does not recover from FHF Liver gets better or get a better liver Death This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

ALF -diagnosis and assessment n n ALF is a clinical syndrome rather than a specific disease Classical triad is: – jaundice – coagulopathy – encephalopathy This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Causes of ALF Aetiology of Acute Liver Failure FRH 1994 -2005 Paracetamol NANB Drugs Other This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Pop Quiz n Mimics of ALF? This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Differential Diagnosis n Sepsis – similar haemodynamic pictures: low SVR & high CO n Pre-eclampsia/Eclampsia – Rx same whether due to eclampsia or ALF secondary to fatty liver of pregnancy n Acute on Chronic Liver Failure This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Management of specific causes n Identify and treat the cause: – Paracetamol OD; n N-Acetylcystine – Herpes induced ALF; n Acyclovir – ALF & pregnancy induced fatty liver; n Urgent delivery of the foetus. – Budd-Chiari (rapid ascites/abdo pain); n thrombolysis/anticoagulation This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Acute Liver Failure n Support – – – – CNS Respiration Circulation CRRT/? MARS Coagulation Infection Metabolism This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

ALF- general management n FFP is only given if actively bleeding n Quantitative and qualitative platelet deficiency n GI bleeding relatively rare n Feeding – enteral – low protein, low sodium NOT appropriate This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Pop Quiz n How much benefit does NAC give in ALF? This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

N-Acetylcysteine in paracetamol induced ALF - Keays et al, NEJM 1991 Prospective study, NAC v Placebo This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Infection n Infection is common - cause of death in 11% n Gram-positive organisms in the first week n Fungal infections after 2 weeks. – usual signs may be absent – rigorous infection surveillance – ? prophylactic Cefuroxime associated with improved outcome. – Prophylactic fluconazole, 100 mg/day Selective Gut Decontamination The only sign of infection may be deterioration of liver function or encephalopathy This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Management - Haemodynamics n Similar picture to SIRS/sepsis n Reduced OER despite increased DO 2 n Relative hypovolaemia secondary to vasodilation n Colloid loading n PAFC? n Vasopressors n NAdr improves BP, but CI and DO 2 may be reduced This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Renal management n Renal failure occurs in up to 70% FHF n Multifactorial n Hypovolaemia and sepsis important precipitators n altered levels of vasodilators and constrictors n Paracetamol may cause direct renal toxicity n Early CRRT aids fluid management This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Coagulopathy management – PPI (Prophylaxis against GI Bleed) – FFP & Vitamin K (Avoid correction unless active bleeding- PT<20 sec) – Thrombocytopenia (keep > 50 x 109/L) – NG Tube (Early nutrition) This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

CNS dysfunction in Acute Liver Failure n n n Cerebral oedema in 50 - 80 % at autopsy. ICP > 30 mm. Hg in 50 % of pts with ALF Clinical signs often late n Remember also: n Fitting n Hypoglycaemia n Electrolytes n Acid - Base n Sepsis n Renal failure n Hypoxia This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Cerebral management n Preserve cerebral perfusion pressure n effective airway protection & ventilation n nurse 10 o to 20 o head up – minimize stimulation – Sedation, suctioning n Thiopentone n 50 mg bolus (infusion 50 mg/hr for up to 6 hrs) n Hypothermia (33 -35 OC) n risks v benefits of ICP n RICP- mannitol (if osmolarity <320) This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Summary of General Management Provide Multi-organ support n Treat Hypoglycaemia n Avoid Infection n Appropriately treat Coagulopathy n Avoid Brain Injury n n Easy-peasy…. . This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Liver assist devices This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Chronic Liver Disease in ICU n “Patients with cirrhosis are frequently denied access to ITU” n Grounds of futility n “Prognostic pessimism” n Is this pessimism justified ? This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Survival of cirrhotics admitted to ITU Author Survival Number ITU Hospital Cholongitas et al 2006 (UK) 348 - 35% Aggarwal A et al 2001 (USA) 240 63% 51% Wehler et al 2001 (Germany) 143 64% 54% Arabi et al 2004 (Saudi Arabia) 129 - 26% Zimmerman et al 1996 (USA) 117 - 37% Tsai et al 2003 (Taiwan) 111 - 35% This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Freeman Outcomes Jan 2007 -Dec 2008: 119 patients; 61% Male. Score Predicted Mortality % Actual ICU/Hospital Mortality % SMR APACHE II 23. 8 47 39/45 0. 8 ICNARC 25. 4 42 39/45 0. 95 This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

ITU Survival/Non Survival Survivors Non-survivors p value Number 307 (55%) 256 (45%) - Age 49 (30 -68) 51 (34 -68) ns 196: 111 152: 104 ns Alcohol 146/263 (56%) 117/263 (44%) ns Other 161/300 (54%) 139/300 (46%) Variceal Bleed 139/196 (71%) 57/196 (29%) Non Variceal 168/367 (46%) 199/367 (54%) Male : Female Aetiology Reason for Admission <0. 0001 This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

ITU Survival/Non Survival Survivors Non Survivors p value Child-Pugh score 11 (10 -12) 13 (11 -13) <0. 0001 MELD 17 (10 -28) 31 (23 -37) <0. 0001 APACHE II 17 (14 -23) 27 (21 -31) <0. 0001 9 (7 -11) 13 (10 -16) <0. 0001 Requirement for RRT 27% 73% <0. 0001 Requirement for Vasopressors 20% 80% <0. 0001 Requirement for Ventilation 44 % 56% <0. 0001 SOFA This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Sequential Organ Failure Assessment (SOFA) Score Vincent et al ICM 1996; 22: 707 -710 This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

AUC 0. 88 >10: 93% Mortality This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Summary Multiple generic organ support n Reassessment 48 hrs+ n – SOFA n Underlying diagnosis important – Variceal bleed – Others n Liver gets better or you get a better liver This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Questions? This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.

Conclusions n ITU admission not futile in cirrhotic patients with organ dysfunction – – n 55% survive ITU, 41% to hospital discharge Aetiology not related to outcome Variceal bleeders have better survival Requirement for renal replacement therapy and/or vasopressors strongly linked with mortality Outcomes Improving – Earlier admission? – Early intubation? n Admit early and assess response This work is licensed under a Creative Commons Attribution-Non. Commercial 3. 0 Unported License.