1. Cirrhosis, Alcohol and the ITU Dr Allister J Grant Consultant Hepatologist Leicester Royal Infirmary http://hepatologist.eu

2. The 4 Stages of Life

4. Mortality from Cirrhosis Total recorded alcohol consumption doubled between 1960 and 2002 104% increase in Scotland between 1987- 1991 and 1997-2001 in men Mortality in women increased 46% in Scotland and 44% in England Lancet 2006; 367: 52-6

6. Alcohol Related Deaths in E&W 1991-2004 http://www.statistics.gov.uk/cci/nugget.asp?id=1091

7. Alcohol in the East Midlands In 2004 the General Household Survey found that 23% of men and 11% of women in the East Midlands reported binge drinking on at least one day in the previous week. Although knowledge of alcohol units is increasing only 13% of those who had heard of units used them to keep a check on how many units they drank. There were approximately 30,000 alcohol-related hospital admissions during 2004/05 in the East Midlands. Alcohol is a factor in an estimated 2,000 deaths annually in the East Midlands. The mortality rate due to alcohol related diseases varies throughout the region with more than a two fold difference across local authorities. Mortality rates from chronic liver disease have more than doubled in the last ten years. www.empho.org.uk

9. Leicester City Local alcohol profiles for England –NWPHO 2006 http://www.nwph.net/alcohol/lape/

10. ANARP 2004

11. Cirrhosis and the ITU-Background 4000 patients died in UK from complications of cirrhosis in the year 2000 – Incidence of cirrhosis is rising dramatically – Increasing numbers of patients will present with cirrhosis and organ dysfunction Patients are frequently denied access to ITU on basis of presumed futility – “Prognostic pessimism”

12. Survival of Cirrhotic Patients Admitted to ITU Author Number Survival ITUHospital Cholongitas et al 2006 (UK)312-35% Aggarwal A et al 2001 (USA)24063%51% Wehler et al 2001 (Germany)14364%54% Arabi et al 2004 (Saudi Arabia)129-26% Zimmerman et al 1996 (USA)117-37% Tsai et al 2003 (Taiwan)111-35% Rabe et al 2004 (Germany)7641%-

13. Predictors of Outcome Liver specific Scoring Systems o Meld/Peld o Child Pugh o Glasgow acute alcoholic hepatitis score Critical Care scoring Systems o Apache II/III o SOFA

14. Meld Score MELD Score = 10 {0.957 Ln(Scr) + 0.378 Ln(Tbil) + 1.12 Ln(INR) + 0.643} Used in organ allocation on the transplant list in USA/UK

15. Meld Score MELD Score Listing StatusComments <243CPT score = 7 to 9; too early for transplantation 24 – 292bCPT score ≥10; end-stage chronic liver disease; severely ill pt, not requiring hospitalization ≥302aCPT score ≥10; end-stage chronic liver disease; severely ill pt, hospitalized in an ICU *Notes: Assuming pts meet listing criteria (appropriate cadidates for liver transplantation) Criteria for status 1 remain unchanges; acute liver failure/disease with estimated survival of <7 days (highest priority for liver transplantation).

16. Child-Pugh classification of liver failure No of points 1 2 3 Bilirubin (µmol/l) 51 Albumin (g/l)>3528-35<28 Prothrombin time 10 AscitesNoneSlightModerate to severe EncephalopathyNoneSlightModerate to severe Grade A=5-6 points, grade B=7-9 points, grade C=10-15 points.

17. Apache Scores Used to estimate group mortality and severity of illness for ITU patients Combination of acute physiological scores and chronic health evaluation points Apache II used as national standard but lacks bilirubin and albumin found in Apache III ?Applicable to ward environment as all studies use APACHE on 1 st day of ITU stay Scores only valid when applied to a cohort

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

20. Predictors of Outcome 54 consecutive patients, overall mortality 43% – Apache II score significant predictor of outcome – Child Pugh scores not predictive Univariate analysis significant predictors: – Requirement and length of mechanical ventilation – Pulmonary infiltrates – GI haemorrhages – Serum creatinine > 1.5 mg/dl (>133  mol/L) – Infections Mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Singh N et al. Outcome of patients with cirrhosis requiring intensive care unit support ; prospective assessment of predictors of mortality. J Gastroenterology 1998; 33:73-79

21. A comparison of Child-Pugh, APACHE II and APACHE III scoring systems in predicting hospital mortality of patients with liver cirrhosis Constantinos Chatzicostas, Maria Roussomoustakaki, Georgios Notas, Ioannis G Vlachonikolis, Demetrios Samonakis, John Romanos, Emmanouel Vardas, and Elias A Kouroumalis

22. Conclusion The results indicate that, of the three models, Child- Pugh score had the least statistically significant discrepancy between predicted and observed mortality across the strata of increasing predicting mortality. This supports the hypothesis that APACHE scores do not work accurately outside ICU settings.

23. Survival After Admission to ICU 420 patients – non transplant candidates admitted to a medical ICU Mortality with 3 risk factors – Vasopressors – Jaundice (clinical) – Apache III score >90 92% one month mortality vs 11% with no risk factors Chest 2004 Vol. 126, 5;1598-1603

25. Comparison of APACHE II, Child-Pugh Score and SOFA in assessing prognosis after 24 hours in ITU Hepatology 2001 34:225-261 143 medical ICU patients Assessed with the above prognostic indices Readmissions excluded Cirrhotics with known cancer were excluded

27. Organ failure defined as a SOFA score of 3 or more for each respective organ Hepatology. 2001, 34,2: 255-261 Mortality Rates in Cirrhotic Patients Depending on the Number of Failing Organs

28. Sequential Organ Failure Assessment (SOFA) Score

29. Predicted Hospital Mortality in 143 Cirrhotic Patients on their First Day in ICU

30. Defining the impact of organ dysfunction in cirrhosis: Survival at a cost? DL Shawcross, MJ Austin, RD Abeles, M McPhail, A Yeoman, N Taylor, AJ Portal, W Bernal, G Auzinger, E Sizer, JA Wendon. Institute of Liver Studies BSG Presentation 2008

31. Methods Critical Illness scoring systems : – SOFA, APACHE II Liver specific scores : – MELD, Child-Pugh Use of vasopressors, invasive ventilation and renal replacement therapy (RRT) recorded Therapeutic Intervention Scoring System (TISS) points calculated for each admission – 1 TISS point = £48

32. Results 763 patient admission episodes – 105 excluded due to being elective admissions – Further 95 were re-admission episodes 563 first admission episodes analysed

33. Number563 Age50 (16-87) Male348 (62%) Aetiology Alcohol Viral hepatitis Autoimmune Cryptogenic Other 263 (47%) 98 (17%) 73 (13%) 48 (9%) 81 (14%) Reason for admission Variceal Bleed Non Variceal Bleed 196 (35%) 367 (65%) Scoring System Child-Pugh MELD APACHE II SOFA 12 (11-13) 25 (14-34) 22 (16-28) 11 (8-13) Patient characteristics on ITU admission

34. Organ Support Day 1At any time Number Requiring Ventilation349/563 (62%)405/563 (72%) Number Requiring Vasopressors202/563 (36%)229/563 (41%) Number Requiring RRT102/563 (18%)273/563 (49%)

35. ITU Survival/Non Survival SurvivorsNon-survivorsp value Number307 (55%)256 (45%)- Age49 (30-68)51 (34-68)ns Male : Female196:111152:104ns Aetiology Alcohol Other 146/263 (56%) 161/300 (54%) 117/263 (44%) 139/300 (46%) ns Reason for Variceal Bleed Admission Non Variceal 139/196 (71%) 168/367 (46%) 57/196 (29%) 199/367 (54%) <0.0001

36. ITU Survival/Non Survival SurvivorsNon Survivorsp value Child-Pugh score11 (10-12)13 (11-13)<0.0001 MELD17 (10-28)31 (23-37)<0.0001 APACHE II17 (14-23)27 (21-31)<0.0001 SOFA9 (7-11)13 (10-16)<0.0001 Requirement for RRT27%73%<0.0001 Requirement for Vasopressors20%80%<0.0001 Requirement for Ventilation44 %56%<0.0001

37. Conclusion ITU admission not futile in cirrhotic patients with organ dysfunction – 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? Admit early and assess response

38. EXAMPLES

39. Which patients will not benefit? Established multi-organ failure (3 organ) Chronic inexorable decline “end stage disease” Patients with high Apache III scores Patients where there is no hope of long term survival (transplantation not being an option)

40. What about High Dependency Care? Limited resource Outreach teams for critical care to support ward staff and junior medical staff Targeted at those who will benefit most Early plan needs to made by Consultant Hepatologist/Gastroenterologist and Intensivists

41. Difficult decisions No compulsion to treat if futile Communication gap with relatives Clear plans at early stage of treatment Realistic assessment of prognosis