Acute Care in Cirrhosis the First 24 Hours

Acute Care in Cirrhosis …the first 24 hours

Royal College Physicians GIM Training Day, Sheffield March 2018

Rebecca Jones Consultant Hepatologist Chronic Liver Disease

• Increasing prevalence of chronic liver disease – Rise in hospital admissions for complications • Decompensated cirrhosis • Acute on chronic liver failure – Large variation in in-hospital mortality rates across UK • E.g Dr Foster – 15% to 35% mortality for non-elective liver admissions – Rising mortality – 3rd commonest cause of premature mortality

• Commonest causes are – Alcohol – Obesity – Viral hepatitis – “Liver screen” – remember co-factors exist Liver Disease Mortality Trends

Atlas of Variation 2017 Decompensated Cirrhosis

• An acute deterioration in liver function in a patient with cirrhosis that can manifest with the following: – jaundice – increasing ascites – hepatic encephalopathy – renal impairment/ hypovolaemia – gastrointestinal (GI) bleeding – signs of sepsis • Overall risk of death during admission with decompensated cirrhosis is 10-20% • If there is organ failure then “acute on chronic liver failure” (ACLF) carries a 30% mortality rate at 28 days. • If alcohol related cirrhosis is diagnosed in hospital, the 1 year mortality is 30% and the 5 year mortality is 60%. Complications of Cirrhosis

HRS Ascites SBP

Varices Cirrhosis HCC

Encephalopathy Osteodystrophy Malnutrition Confused?

Scared? What leads to an acute admission?

And what causes people to die? Mortality

• Patients with cirrhosis die from – Bleeding – Sepsis – Renal Failure • They are admitted with these complications • They develop them during their admission

• Their care is often sub-optimal, with delays in appropriate diagnosis, prevention and management of complications of decompensation. 2013 NCEPOD Recommendation

• NCEPOD 2013 Measuring the Units – Only 47% of patients who died of alcohol related liver disease received “good” care – Identified avoidable deaths – Recommended a toolkit for acute management of patients admitted with decompensated ARLD • Principles are the same for all causes of decompensated liver disease – Cirrhosis Care Bundle – Effective, evidence based care for first 24hrs How did patients arrive in hospital?

11 Age – wholeAge population

66% (1584/2418) of the ARLD deaths were male

12 Presenting features

Complex patient group

Risk of death increased if (any of):

• Jaundice • Ascites • Encephalopathy • Renal failure • Acute alcoholic hepatitis

At least one of these features present in 438/512 patients (85%)

13 Principles of Acute Care

• Look for common precipitants and treat accordingly. • These include: – GI bleeding (variceal & non-variceal) – Sepsis (incl. look for SBP, chest, urine, cholangitis) – Alcoholic hepatitis – Portal vein thrombosis – Development of HCC – Drugs – opiates, NSAIDs, alcohol – Ischaemic liver injury (hypotension, any cause) – Dehydration – Constipation • Key words – Look – Treat – Prevent Varices Varices: endoscopy Varices Varices

• Varices occur when HVPG is >10 mmHg – Present in ~50 % of cirrhotic patients – Bleeding rate 5-15% per year – Mortality associated with variceal bleed is 20% at 6 weeks

• Will present acutely in a variety of ways – Shock – Not shocked – Haematemesis – Malaena – Anaemia

• And in a variety of circumstances – Patient known to have varices – Patient known to have cirrhosis – Patient with decompensated liver disease – Patient not known to have cirrhosis/liver disease Varices Varices General management

• Manage as for any GI bleed – ABC • Assess appropriate level of care – Transfuse as necessary • Support abnormal clotting or thrombocytopaenia – Request endoscopy • Assess urgency Varices Varices Specific medical management • If varices are known or strongly suspected – Care with transfusion • Aim Hb 8 • Caution in pushing up BP – aim for MAP of 65mmHg • Monitor urine output • Search for cause - AAH, PVT, Infection – Blood products • FFP (2) and platelets (50) – Actively seek out infection • Send blood cultures • CXR, urine, ascitic tap • Treat according to site – Actively prevent infection • Prophylactic antibiotics save lives – sepsis and rebleed risk • Broad spectrum IV – Use splanchnic vasoconstrictors • Terlipressin – 2mg qds • Caution in patients with history of ischaemic heart disease – They may be more shocked than you realise • Are they on beta-blockers? NICE Guideline on GI Bleeding (CG141; 2012)

• Risk assessment – Use the following formal risk assessment scores for all patients with acute upper gastrointestinal bleeding: • the Blatchford score at first assessment, and • the full Rockall score after endoscopy. • Timing of endoscopy – Offer endoscopy to unstable patients with severe acute upper gastrointestinal bleeding immediately after resuscitation. – Offer endoscopy within 24 hours of admission to all other patients with upper gastrointestinal bleeding. • Management of variceal bleeding – Offer prophylactic antibiotic therapy at presentation to patients with suspected or confirmed variceal bleeding. – Offer terlipressin to patients with suspected variceal bleeding at presentation. – Stop treatment after definitive haemostasis has been achieved, or after 5 days, unless there is another indication for its use – Band ligation for oesophageal varices; Glue for gastric varices • Consider transjugular intrahepatic portosystemic shunts (TIPS) if bleeding from oesophageal varices is not controlled by band ligation. • Offer TIPS if bleeding from gastric varices is not controlled by endoscopic injection of N-butyl-2-cyanoacrylate. Case study 12

A 32 year old with cirrhosis due to ARLD was admitted midweek in normal working hours with a GI bleed. They were hypothermic, hypotensive, acidotic and in renal failure. They had ascites and encephalopthy. Hb was 6g/dl. They were transfused and actively warmed. No attempt was made to obtain gastroenterology review. They were referred to ICU but denied admission. They remained oliguric, had a further massive haematemesis and had a cardiac arrest and died

The Advisors’ view was that more aggressive treatment of the bleed including endoscopy was indicated and that critical care admission was turned down inappropriately

20 Ascites Ascites

• Most common complication of cirrhosis • Advancing cirrhosis • Development of portal vein thrombosis • Development of Hepatocellular Carcinoma (HCC) • Prognostic indicator: 50% mortality at 2 years • Spectrum of severity • Grade 1 (radiologically present, not clinically) • Grade 2 (modest, clinically evident) • Grade 3 (large, very distended abdomen) – Uncomplicated • Diuretic controlled • Not infected, no renal failure – Refractory • Diuretic intolerant • Diuretic resistant • Spontaneous Bacterial Peritonitis • Renal failure ?Hepatorenal syndrome Diagnostic paracentesis • Diagnosis of aetiology • Diagnosis of infective complications • Left lower quadrant may be preferable – Abdominal wall is thinner • Complications – Abdominal wall haematoma 1% – Haemoperitoneum/bowel entry Epigastric arteries <0.1% • Aseptic technique Anterior superior iliac crest • Over 70% will have “coagulopathy” 3cm above • Cirrhosis is a pro-coagulant condition 3cm medial – No evidence of increased bleeding rates – No evidence to support routine use of platelets/FFP • BSG guidelines recommend informed consent

Runyon B. AASLD Guidelines 2009 Moore K, Aithal G. BSG Guidelines 2006 Interpreting ascitic cell counts

• Spontaneous bacterial peritonitis is an important infection to diagnose • Ascitic neutrophil count – 250 cells/cm3 is diagnostic (0.25 x 109/L) – In absence of perforated viscus etc • Ascitic culture from universal containers is not as good as aseptic inoculation into blood culture bottles – 40% vs 80% organism identification – Organisms in SBP usually gram –ve and single • Multiple organisms – think secondary peritonitis • Gram +ve – seen after hospitalisation, instrumentation, antibiotic prophylaxis Interpreting ascitic albumin and protein levels Serum ascites-albumin Ascitic total protein gradient • Very useful to establish group of • Useful to determine risk of causes spontaneous bacterial • SA-AG ≥11g/L peritonitis – Cirrhosis – Ascitic protein is >25g/L in – Cardiac failure 25% patients with cirrhosis – Nephrotic syndrome – SBP uncommon with ascitic protein >15g/L • SA-AG <11g/L – Risk of SBP increased with – Malignancy ascitic protein levels ≤ 10g/L – Tuberculosis – Pancreatitis Ascites Ascites: investigation

• Diagnostic tap – This is a mandatory urgent investigation for anyone admitted to hospital with ascites • For first presentations always send for – Cytology – Leucocyte count – Microbiology – Protein • In patients known to have cirrhosis, review previous results. It may not be necessary to repeat cytology if assessed recently but – Leucocyte count – Microbiology • Send ascitic fluid inoculated into blood culture bottles – Protein • Should always be done • And always looked up Ascites Management of ascites

• Review medication – Stop NSAIDS • Fluid status – Commence daily weight chart – If no renal impairment, commence diuretics • Usually spironolactone • If lots of peripheral oedema can consider furosemide/bumetanide – If there is renal impairment • Avoid starting diuretics, stop any already prescribed • Infection – If SBP is present • Ensure a sample of ascites has been inoculated into blood culture bottles to get best chance of identifying organism. • Treat with appropriate antibiotics and adjust according to culture results • Treat for 5 days – if concerned about response then repeat tap Ascites Management of ascites

• Paracentesis – Consider if ascites tense, causing respiratory compromise, or where diuretic therapy cannot be used – Imperative to carefully assess intravascular volume beforehand, and to counterbalance fluid shifts and potential for renal failure with albumin infusion – local protocol.

• Nutrition – Protein energy malnutrition – Salt-to-tolerance diet

• Imaging – What is the cause? – Why now? Has the portal vein gone? Has an HCC developed? SBP Spontaneous bacterial peritonitis

• A life-threatening complication of cirrhosis • 30 day mortality is 30% • Recurrence rates are 70% within 1st year • 20% of hospitalised patients with cirrhosis and ascites • Usually a mono-culture • Usually in low protein ascites (<15) • Fever, pain, peritonism may be absent • Death from • Decompensation secondary to sepsis • GI bleeding (varices) exacerbated by sepsis • Renal failure (Hepato-renal syndrome) • Prompt diagnosis • Ascitic neutrophil count ≥ 250/mm3 (0.25 x 109/L) • Send fluid in blood culture bottles • Send blood cultures • Prompt treatment • 3rd generation cephalosporin for 5 days or trust protocol • Prevent renal failure • Albumin IVI • Seek local protocols Sort et al. NEJM, 1999 HRS Diagnostic Criteria for HRS

• Chronic liver disease

• Low GFR with creat >1.5mg/dL (133M) and Cr. Clear. < 40ml/min

• Absence of known causes of renal failure (e.g. shock, renal disease, ongoing sepsis, nephrotoxic drugs)

• Proteinuria <0.5g/day and normal renal USS

• No sustained improvement of renal function with fluid challenge International Ascites Club Diagnostic Criteria HRS

Murray Epstein 1969 HRS Main Features of HRS

• Functional renal failure caused by • intra-renal vasoconstriction in patients with • end-stage liver disease and circulatory dysfunction. • Circulatory dysfunction is caused by • splanchnic vasodilatation and • insufficient cardiac output, • leading to effective hypovolemia. • Occurs spontaneously with deteriorating liver function or secondary to a precipitating event such as bacterial infection. • Recommendation for albumin as part of SBP treatment – improved survival due to lower incidence of HRS

International Ascites Club: Gut 2007 HRS Hepatorenal syndrome

• Ascites is the first part of a spectrum of renal impairment severity in cirrhosis

• Onset of hepatorenal syndrome is a poor prognostic sign – Rapid deterioration – very poor short term prognosis • presentation acutely is often with acute renal failure – Slower deterioration poor medium term prognosis • presentation acutely is usually with ascites and mild to moderate renal impairment – This helps decisions re urgency of action and decision making HRS HRS: more specific management

Effect of terlipressin Terlipressin+albumin more effective than volume expansion alone

100 5

3 75 2

Pl. Creatinine(mg/dl) 50 0

Mean Arterial Pressure Mean (mmHg) Baseline Treated Baseline Treated

J. Uriz et al J. Hepatol. 2000 HRS NSAID’s cause renal failure in Ascites

120 100 80

60 40 20

Creat. Clear (ml/min) Clear Creat. 0 Baseline Indomethacin

Boyer et al 1979 HRS HRS: basic management

• Assessment of renal perfusion • Is patient shocked/hypotensive? • Stop anti-hypertensives/propanolol • Review of medication • Stop diuretics • Check not on NSAIDS • Careful assessment of intravascular volume • If patient is obviously dry – give fluid - colloid • Monitor carefully – risk of pulmonary oedema • Start to give IV fluids • Albumin – volume will depend on intravascular fluid status • Salt-poor if lots of ascites/peripheral oedema • Monitor carefully – risk of pulmonary oedema • Exclude +/or treat sepsis • Including ascitic tap • Assess need for catherisation • Any suggestion of oliguria or not responding to treatment • Fluid balance and weight Encephalo -pathy Hepatic encephalopathy

• Brain dysfunction caused by liver insufficiency and/or PSS • it manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. • Overt encephalopathy – Present in about 10% of patients with cirrhosis at diagnosis – Will appear in about 40% at some point – Often recurs • Minimal encephalopathy hard to detect clinically – Psychometric tests orientated at attention – Visuospatial awareness • Overt much more obvious – Personality changes – Sleep-wake reversal – Motor system abnormalities and extra-pyramidal symptoms – “Flap” – Stupor – Coma • Precipitating factors are common when HE is due to cirrhosis – Look, Treat, Prevent Encephalo -pathy Precipitants

Wide differential diagnosis, which must also consider and treat if present. If risk factors eg for subdurals – CT scan head. It is a diagnosis of exclusion. AASLD Practice Guideline 2014 Case study 13

A 56 year old with cirrhosis due to alcohol had undergone endoscopy for variceal banding a year previously. They had been abstinent since. A few days after review in outpatients they were admitted having become encephalopathic, not maintaining airway and hypoxic. An early decision was made by the admitting consultant on the PTWR not to escalate care and the patient died 36hrs later

The Advisors’ view was that a greater attempt should have been made to exclude reversible causes of the patient’s illness, and that escalation would have been appropriate while doing this. There was little documented evidence to justify the decision that was made and they were surprised that this decision had not been questioned

38 Approach to treatment

• Initiate care for unconscious patients – protect airway • Seek and treat other causes of altered mental status • Identify and treat precipitants • Commence empirical HE treatment Treatment

• Lactulose – Start at 20-30mls tds-qds – Aim for 2-3 soft bowel motions a day – Not more – unpleasant, undignified, and doesn’t benefit! • There are effective add-on therapies – e.g. rifaximin, especially useful to reduce subsequent episode severity and hospitalisation • Nutritional support Ascites in cirrhosis: Nutrition

• Abdominal pain & discomfort • Difficulty breathing & pleural effusions • Limited mobility • SBP incidence • Early satiety • Repeated drains and hospital admissions • Vomiting • Inappropriate salt restrictions Early nutritional support: top tips

• Protein energy malnutrition • MUST score not effective

• For all patients – Assess sarcopaenia (beware the NAFLD patient) – Give nutritional supplements eg Fresubin protein energy drinks – Give calories – Give snacks incl. late-night • If ascites or oedema – Salt reduce – no added salt

• Further down the line more specialist advice from dieticians • Have to consider socio-economic factors and culinary skill Food for thought

• Male patient aged 55 • Alcohol related liver disease • Advanced stage with poor prognosis – Ascites, peripheral oedema, hyponatraemia – Listed for liver transplantation – Untransplantable and removed from waiting list – Hospice care • 6 months later – Admin error – arrives in OPA • 8 years later – Reassessed for transplantation! Investigation of decompensation

• Sepsis common cause of decompensation

• Inflammatory indices often not elevated

• Spontaneous bacterial peritonitis in 15% with decompensation and ascites

• Cultures of blood and ascites important first line investigations

44 Were the right investigations done?

1 in 5 patients, investigations not done: • Ascitic tap (25 cases) • Blood cultures (12 cases)

• Ultrasound (13 cases) 45 Management of deterioration

Main theme renal deterioration: • Delayed / inadequate fluids (23 patients) • Delay stopping diuretics • Reluctance to consider renal replacement • Terlipressin indicated but not administered (7 cases)

46 Recording of alcohol history

Final admission Previous admissions

• Very limited in 116 • Not recorded in 21

47 Recommendations – initial management

• All patients presenting with decompensated ARLD should have blood cultures included in their initial investigations on admission to hospital

• If ascites is present in patients presenting with decompensated ARLD, a diagnostic ascitic tap should be performed as part of their initial assessment. Coagulopathy is not a contraindication to this procedure

• A toolkit for the management of patients admitted with decompensated ARLD should be developed and made widely available to all physicians / doctors involved in the care of patients admitted to acute hospitals

48 Nutritional assessment

• NICE recommends nutritional assessment within 48 hours of admission • Malnutrition common in this group of patients

• Nutritional assessment in only 129/368 (35%)

• Appropriate nutritional plan documented in 184/351 (52%) cases

49 NCEPOD Recommendation

Dyson JK et al. APT 2016;44:1030-1038 Care Bundle Implementation

Dyson JK et al. APT 2016;44:1030-1038 Care Bundle Improved Quality of Crae

Dyson JK et al. APT 2016;44:1030-1038 Find it! Use it!

• https://www.basl.org.uk/uploaded_files/Deco mpCirrhosisCareBundle_BSG_BASL_24-9- 14.docx

• Search “BASL Cirrhosis Care Bundle”