Cirrhosis, Alcohol and the ITUCirrhosis, Alcohol and the ITU

Dr Allister J GrantConsultant HepatologistLeicester Royal Infirmary

http://hepatologist.eu

The 4 Stages of Life

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

Alcohol Related Deaths in E&W 1991-2004

http://www.statistics.gov.uk/cci/nugget.asp?id=1091

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

Leicester City

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

ANARP 2004

Cirrhosis and the ITU-BackgroundCirrhosis 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”

Survival of Cirrhotic Patients Survival of Cirrhotic Patients Admitted to ITUAdmitted to ITU

Author NumberSurvival

ITU Hospital

Cholongitas et al 2006 (UK)

312 - 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%

Rabe et al 2004 (Germany)

76 41% -

Predictors of Outcome Predictors of Outcome

• Liver specific Scoring SystemsoMeld/Peldo Child Pugho Glasgow acute alcoholic hepatitis score

• Critical Care scoring Systemso Apache II/IIIo SOFA

Meld ScoreMeld 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

Meld ScoreMeld Score• MELD Score Listing Status Comments

• <24 3 CPT score = 7 to 9; too early for transplantation

• 24 – 29 2b CPT score ≥10; end-stage chronic liver disease; severely ill pt, not requiring hospitalization

• ≥30 2a CPT 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).

Child-Pugh classification of liver failureChild-Pugh classification of liver failure

• No of points 1 2 3

• Bilirubin (µmol/l) <34 34-51 >51• Albumin (g/l) >35 28-35 <28• Prothrombin time <3 3-10 >10• Ascites None Slight Moderate to severe• Encephalopathy None Slight Moderate to severe

• Grade A=5-6 points, grade B=7-9 points, grade C=10-15 points.

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 1st day of ITU stay

• Scores only valid when applied to a cohort

Sequential Organ Failure Assessment (SOFA) ScoreSequential Organ Failure Assessment (SOFA) Score

Vincent et al ICM 1996;22:707-710

Predictors of OutcomePredictors 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 (>133mol/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

A comparison of Child-Pugh, APACHE II and APACHE A comparison of Child-Pugh, APACHE II and APACHE III scoring systems in predicting hospital mortality III scoring systems in predicting hospital mortality of patients with liver cirrhosisof patients with liver cirrhosis

Constantinos Chatzicostas, Maria Roussomoustakaki, Georgios Notas, Ioannis G Vlachonikolis, Demetrios Samonakis, John Romanos, Emmanouel Vardas, and Elias A Kouroumalis

ConclusionThe 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.

Survival After Admission to ICU 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

Comparison of APACHE II, Child-Pugh Score and SOFA Comparison of APACHE II, Child-Pugh Score and SOFA in assessing prognosis after 24 hours in ITUin assessing prognosis after 24 hours in ITU

HepatologyHepatology 2001 34:225-261 2001 34:225-261

• 143 medical ICU patients

• Assessed with the above prognostic indices

• Readmissions excluded

• Cirrhotics with known cancer were excluded

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 Mortality Rates in Cirrhotic Patients Depending on the Number of Failing OrgansNumber of Failing Organs

Sequential Organ Failure Assessment (SOFA) ScoreSequential Organ Failure Assessment (SOFA) Score

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

Defining the impact of organ Defining the impact of organ dysfunction in cirrhosis: dysfunction in cirrhosis:

Survival at a cost?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 StudiesBSG Presentation 2008

MethodsMethods

• 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

ResultsResults

• 763 patient admission episodes– 105 excluded due to being elective admissions– Further 95 were re-admission episodes

• 563 first admission episodes analysed

Number 563

Age 50 (16-87)

Male 348 (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 admissionPatient characteristics on ITU admission

Organ SupportOrgan Support

Organ Support Day 1 At any time

Number Requiring Ventilation

349/563 (62%)

405/563 (72%)

Number Requiring Vasopressors

202/563 (36%)

229/563 (41%)

Number Requiring RRT 102/563 (18%)

273/563 (49%)

ITU Survival/Non SurvivalITU Survival/Non Survival

Survivors Non-survivors

p value

Number 307 (55%) 256 (45%) -

Age 49 (30-68) 51 (34-68) ns

Male : Female 196:111 152:104 ns

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

ITU Survival/Non SurvivalITU 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

SOFA 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

ConclusionConclusion• 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

EXAMPLESEXAMPLES

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)

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

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