Liver Disease in the ICU: Acute Liver Failure

Transcription

1 Liver Disease in the ICU: Acute Liver Failure Steven C Pugliese, MD Assistant Professor Division of Pulmonary Sciences and Cri@cal Care Medicine University of Colorado Denver 48 y/o male w/out prior liver disease admifed for 5 days of lethargy, abd pain, and confusion. 2-3 beers/day, oxycodone/apap for back pain, remote IV drug use. Exam: tender RUQ, grade III encephalopathy. AST 6000/ALT Bilirubin 3. INR 2. Utox: neg. Tylenol level: undetec. A. Admit to ICU B. ICU, transplant center referral C. ICU, transplant center referral, NAC D. ICU, transplant center referral, NAC, lactulose Learning objec@ves Understand appropriate triage of acute liver failure (ALF) with regard to ICU admission and referral to transplant center Role of N- acetylcysteine in ALF Role of lactulose in ALF

2 Acute Liver failure Coagulopathy (INR 1.5) Altered mental status (encephalopathy) No prior evidence of cirrhosis of illness less than 26 weeks *Lee et al AASLD paper: management of acute liver failure: update 2011 Who should be managed in ICU ALMOST EVERYONE! Usual MICU criteria Severe acidosis Hemodynamic instability Respiratory compromise Encephalopathy grade II (AASLD guideline) esp those with rapidly progressive or high grade HE (III or IV) Severe of transaminases* Probably >1000 Definitely > 5000 The role of the ICU Hospital survival of pts admi<ed with ALF N=2095 Mortality is dramajcally improving over Jme *Bernal et al J Hep :74-80

3 ICU care is improving mortality Hospital survival by ejology in pts not undergoing transplant N= 1733 Medical management alone has improved mortality Development of ICH *Bernal et al J Hep :74-80 Why is encephalopathy important? It s the single best predictor of mortality! Pa@ents at highest risk for complica@ons Aspira@on/Resp failure Hemodynamic compromise Intracranial hypertension Mul@organ failure Grades of encephalopathy: Survival based on HE grade: Grade I to II percent Grade III percent Grade IV <20 percent O grady et al Gastroenterology 1989;97(2):439 *Lee et al AASLD posi@on paper: management of acute liver failure: update 2011 Significance of high transaminases 1. Limited differen@al diagnosis (>1000 s) APAP, ischemic, Budd- Chiari, viral, autoimmune 2. High risk complica@ons (acute hepa@c necrosis) Hemodynamic HE Intracranial hypertension MODS 3. These pa@ents recover! *Stravitz, RT, CHEST 2008; 134:

4 When to call a transplant center? All pa@ents should be discussed (AALSD 2011) Ac@ve alcohol or drug abuse unlikely to be candidates Consider transfer of non- transplant candidates Size and resources of ICU Access to hepatologists Level of experience with ALF Nearly all transplant centers will provide triage assistance and emergent management advice at of day Lactulose in hepa@c encephalopathy NH3 Cytokines/Inflamma@on Altera@on in BBB Glutamate Glutamine Glutamine synthase Astrocyte swelling Hyponatremia Other neuro- inhibitory molecules Reac@ve Oxygen Species (via NH3) Lactulose impairs colonic absorpjon of ammonia: 1. Bacterial metabolism promotes gut acidifica@on driving NH3è NH4+ 2. Increased stool transit NH3 and bacteria Lactulose in chronic liver disease: European Journal of Gastroenterology & Hepatology : J Hepatol (3): BMJ (7447): Observa@onal Lactulose data is posi@ve the first choice for treatment of 2. RCT s too small to draw conclusions episodic OHE (GRADE II- 1, B, 1). 3. Large meta- analysis- no benefit

5 Worlds literature on lactulose in ALF: J Hepatol. 2002,36(suppl 1):33 (ABSTRACT) Findings: 1. Retrospec@ve registry data in those with ALF 1. Lactulose (n=70) 2. No lactulose (n=47) 2. No improvement in HE, dura@on of ICU stay, ammonia levels 3. Pt s receiving lactulose survived longer (15 versus 7 d) RISK/BENEFIT 1. Cheap 2. Non- toxic 3. Physiologic ra@onale 1. Aspira@on risk 2. Gaseous bowel disten@on- surgical field risk Current AASLD Guidelines in ALF: In early stages of encephalopathy, lactulose may be used either orally or rectally to effect a bowel purge, but should not be administered to the point of diarrhea, and may interfere with the surgical field by increasing bowel disten@on during liver transplanta@on (III). PracJcal approach from a crijcal care perspecjve: Consider: 1. Intubated 2. Low grade HE Avoid: 1. Non- Intubated high grade or rapidly progressive HE 2. Transplant candidate?

6 Role of N- acetylcysteine (NAC) in acute liver failure Acute Liver Failure Study Group Registry *Sidiqqui and Stravitz. Clin Liver Dis : pts with indeterminate ALF Assay detects APAP up to 12 days post 18% with APAP metabolites in toxic levels Survival trend in those receiving NAC *Khandelwal. Hepatology 2011;53: N- acetylcysteine can be given late in APAP induced ALF: APAP in fulminant failure (Harrison Lancet 1990) 100 pts admifed for ALF due to APAP NAC received median 17 hrs (10-36hrs) *Harrison PM et al. Lancet :

7 Gastroenterology 2009;137: pts randomized 1:1 NAC or IV dextrose in non- APAP ALF 52% vs 30% transplant free survival favoring NAC Benefit only in HE grade I/II pts No difference overall or III/IV pts Occult APAP use excluded by serum assay NAC may be useful early in non- APAP induced ALF Summary 1. ALF should be triaged to ICU 2. Early transplant in all ALF pts 3. Consider NAC in all pts with ALF 4. The role of lactulose remains unclear, need to weight risk/benefit 48 y/o male w/out prior liver disease admifed for 5 days of lethargy, abd pain, and confusion. 2-3 beers/day, oxycodone/apap for back pain, remote IV drug use. Exam: tender RUQ, grade III encephalopathy. AST 6000/ ALT Bilirubin 5. INR 8. Utox: neg. Tylenol level: undetec. A. Admit to ICU B. ICU, transplant center referral C. ICU, transplant center referral, NAC D. ICU, transplant center referral, NAC, lactulose E. Refrain from IV use of bath salts