Printable list of all gastroenterology and hepatology SAQs

College Answer

The hepatorenal syndrome  is defmed as profound oliguria and avid sodium  retention in the setting of severe liver dysfunction.

{a) Causes: 
Can occur in the setting of both acute and acute-on-chronic liver disease of almost any cause 
eg. hepatitis, gestational liver failure, cirrl:tosis. 

(b) Mechanism: 
The  pathogenesis  appears  to be purely  functional  in  that  recovery:of :liver  function  or-· 
transplantation  of  the  failing  kidney  leads  to  recovery  of ·renal ·function.  Mechanisms··· implicated  include: hyperdynamic· circulation  with  lowering  of  renal  perfusion  pressure, activation   of   the  sympathetic   nervous   system   and   a  combination   of   precapillary vasoconstriction and past capillary dilatation  by vasoactive mediators leading to decreased glomerular  ultrafiltration  coefficient.  Hypovolaemia  and  raised  intra abdominal  pressure from ascites may also be factors. 

(c) Diagnosis: 
Is based on history (deteriorating renal function in the presence of severe liver disease) and the  combination   of  avid  sodiwn   retention  (UNa   <30mmolll),  oliguria,   unremarkable urinalysis and  sediment,  absence  of  obstruction and  exclusion  of  intravascular  volume depletion. 

(d) Treatment: 
Classic teaching is that. in the absence of liver function recovery or liver transplantation, 
there  is  no  treatment  other  than renal  replacement  therapy  for  established  hepatorenal 
syndrome. Other measures to be considered or experimental are: 
•  Volume expansion and albumin infusion 
•  Paracentesis 
•  Relief of portal hypertension (TIPS, shunt) 
•  Vasopressin analogs (omipressin), experimental 
•  Prostaglandin analogs -experimental

Discussion

Briefly, what is hepatorenal syndrome

Hepatorenal syndrome is kidney injury as the consequence of gradually reducing renal blood flow, in the context of gradually worsening liver failure.

Mechanism of hepatorenal syndrome

• Worsening hepatic function leads to worsening peripheral arterial vasodilation
• Vasodilation leads to increased cardiac output, renin-angiotensin-aldosterone overactivity, and sympathetic overactivity
• As a result, renal arterial vascular resistance increases in proportion to splanchnic and systemic arterial vasodilation
• This, there is progressive renal vasoconstriction and thus decreased glomerular filtration.
• In addition to this, worsening hepatic failure results in increasing ascites pressure (and thus decreasing renal perfusion pressure)

Causes of hepatorenal syndrome

• Sepsis of any origin
• Nephrotixic drugs in a patient with cirrhosis, particularly NSAIDs
• Rapid diuresis
• GI bleeding

Diagnosis

• This is a diagnosis of exclusion. The following criteria apply:
  • presence of liver disease and portal hypertension
  • increase in creatinine to over 133micromol/L
  • no other obvious cause of renal failure
  • no microscopic hematuria
  • no reponse to fluid challenge (i.e. no pre-renal failure)

Treatment of hepatorenal syndrome

• Albumin and fluid resuscitation
• Terlipressin
• Noradrenaline
• Octreotide

if all else fails, TIPS procedure may be appropriate.

References

UpToDate has an excellent synopsis of hepatorenal syndrome.

However, if you are cheap, you need free articles.

Salerno, Francesco, et al. "Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis." Postgraduate medical journal 84.998 (2008): 662-670.

Solà, Elsa, Mónica Guevara, and Pere Ginès. "Current treatment strategies for hepatorenal syndrome." Clinical Liver Disease 2.3 (2013): 136-139.

College Answer

Principles of management include resuscitation (of someone who may well have lost >25% of blood volume), establishing a diagnosis, and definitive treatment while avoiding therapies that might worsen his underlying condition.

Resuscitation includes assessment of airway protection and breathing adequacy, which combined with neurological impairment indicates need for emergency intubation.

Circulatory support requires adequate intravenous access, but may not need to be too aggressive (as excessive resuscitation may worsen portal hypertension), and could be guided by factors including usual blood pressure (? accept MAP of 60 mmHg), urine output, and other signs of circulatory compromise.

Temporary use of a Sengstaken Blakemore tube (or equivalent eg Minnesota) may be considered if blood loss is uncontrollable. Invasive monitoring may be useful, but is not necessary in the early phase of resuscitation.

Establishing  a  diagnosis  for  the  cause  of  bleeding  includes  immediate  examination  (signs suggesting non-GI haemorrhage, chronic liver disease), history (from family/observers) of immediate event and possible precipitants (drugs, retching etc). Differential diagnosis of causes for jaundice should be considered (including hepatitic and toxins). More detailed history and examination will need to be completed later.

Immediate commencement of therapy (eg. intravenous vasoconstrictor such as somatostatin or vasopressin) should be considered while organising urgent endoscopy (which will usually result in banding or sclerotherapy for varices, and injection for some other pathologies). Initial investigations should include cross match, coagulation tests, full blood count, urea & electrolytes, liver function tests, blood glucose and paracetamol level. An ascitic tap should be undertaken early for microscopy and culture (as infection may well be present). Some rationale should have been given for the investigations listed.

Candidates should be aware of therapies that may be specifically required (correction of coagulopathy [FFP &/or platelets], prophylactic antibiotics, laxatives eg. lactulose; beta-blockers once stable, proton pump inhibitors) or contraindicated (sedatives worsening hepatic encephalopathy).

Discussion

I have attempted to force the coherent college answer into a familiar system.

(a)       Outline the principles of, and rationale for, the initial management of this patient.

• Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history. History will focus on determining whether the source of the bleeding was indeed the gut (rather than a tracheal or bronchial source) and whether the vomiting preceded the hematemesis (which would be suspicious for a Mallory-Weiss tear or Boerhaave's syndrome)

• Airway:
  • This patient is likely to have hematemesis again; the airway needs to be protected
• Breathing/ventilation
  • Once he is intubated, ventilation settings will depend on the specifics of gas exchange and lung compliance
• Circulatory support
  • The inital stages of resuscitation will consist of replacement of blood and blood products
• Supportive management
  • Sedation should consist of anaesthetic agens with a short half-life and no long-lasting metabolites, such as propofol and remifentanyl
• Specific investigations
  • CXR to confirm ETT position and rule out GI perforation
  • FBC, G&H, coags, fibrinogen, EUC and CMP
  • Ultrasound of the abdomen to investigate the severity of portal hypertension
• Specific management
  • This patient requires urgent gastroscopy and banding or sclerotherapy of the varices
  • If a gastroscopy cannot be performed urgently, he will need to have a CT angiogram, with a view to proceed to angioembolisation of the bleeding vessels.
  • If blood loss is uncontrollable and gastroscopy/angioembolisation is delayed, a Sengstaken-Blakemore tube can be advanced and an attempt to tamponade the bleeding can be made.
  • Lactulose should be used to decrease the likelihood of hepatic encephalopathy

References

College Answer

Standard resuscitation goals and technique should be reiterated. Re-bleeding from varices requires repeat endoscopy for diagnosis and treatment. Additional treatments should be considered including vasoconstrictor infusions (eg. somatostatin or vasopressin with GTN), Trans-jugular Intra-hepatic Porto-systemic Shunt (TIPS), and surgical shunts (eg. spleno-renal). Balloon tamponade is being used less frequently because of a high incidence of complications (aspiration, oesophageal rupture, death).

Ongoing investigation and treatment of coagulopathy, and investigation of causes of jaundice should be undertaken. Treatment should include strategies to minimise hepatic encephalopathy.

Discussion

A systematic approach should be taken. I will not repeat the ABCs. Of course, one would ensure satisfactory maintenance of oxygenation and normotension. Certainly, one would replace the missing factors by transfusing blood products, as well as actual packed cells, and vitamin K.

Straight to the specific management:

• Hemostasis:
  • Re-bleeding from varices requires re-endoscopy. Sclerotherapy and/or banding would be the ideal way of managing this bleed, as it would have the fewest complications.
  • A Sengstaken-Blakemore tube is an option, but even when it was popular the experienced users noted that optimal pharmacological therapy is better than inexperienced use of balloon tamponade
• Reducing portal hypertension pharmacologically
  • Terlipressin is the drug of choice in decreasing portal venous congestion, and it has beenshown to decrease mortality in variceal bleeding
  • Octreotide is the next best choice
  • Non-selective beta blockade might be helpful to prevent further re-bleeding, but the jury is still out.
• Reducing portal hypertension invasively
  • TIPS decreases the chances of treatment failure in refractory variceal bleeding (in one study, the probability of remaining bleed-free was 97% in the TIPS group and 50% in the pharmacotherapy group)

References

Garcia-Tsao, Guadalupe, and Jaime Bosch. "Management of varices and variceal hemorrhage in cirrhosis." New England Journal of Medicine 362.9 (2010): 823-832.

García-Pagán, Juan Carlos, et al. "Early use of TIPS in patients with cirrhosis and variceal bleeding." New England Journal of Medicine 362.25 (2010): 2370-2379.

Vlavianos, P., et al. "Balloon tamponade in variceal bleeding: use and misuse."BMJ: British Medical Journal 298.6681 (1989): 1158.

Reverter, Enric, and Juan Carlos García‐Pagán. "Management of an acute variceal bleeding episode." Clinical Liver Disease 1.5 (2012): 151-154.

Ioannou, G. N., J. Doust, and D. C. Rockey. "Terlipressin in acute oesophageal variceal haemorrhage." Alimentary pharmacology & therapeutics 17.1 (2003): 53-64.

Corley, Douglas A., et al. "Octreotide for acute esophageal variceal bleeding: a meta-analysis." Gastroenterology 120.4 (2001): 946-954.

Reiberger, Thomas, et al. "Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol." Gut62.11 (2013): 1634-1641.

College Answer

Specific strategies to minimise hepatic encephalopathy should have been described if not already done so (including the use of lactulose). Precipitants must be minimised (treatment of infections, avoidance  of  sedatives,  correction  of  electrolyte  abnormalities/hypoxia, avoid  alkalosis,  limit dietary protein, consider unproven dietary supplements including BCAA etc.). Cautious volume expansion should be considered. Other reversible causes for renal dysfunction and coma should be sought and excluded. Management of ICP  may be necessary (and the CT does not exclude cerebral oedema). General supportive care should be considered (eg. physiotherapy, avoidance of line- related problems, family support etc.). Specific treatment may be required for ascites and its effects (drainage, colloid replacement etc).

Discussion

The college has given us a patient with a combination of several reasons to be encephalopathic; of these, the major one is liver failure -but we are also reminded that the creatinine has doubled.

Management of hepatic encephalopathy:

Specific management of hepatic encephalopathy

• Lactulose
• Rifaximin
• Avoidance of hyponatremia
• Nutritional management:
  • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
  • High fiber diet
  • Pro-biotics (though their benefit is unclear)

Management of the precipitating cause

• Stop GI bleeding (endoscopy, banding, etc)
• Antibiotics for SBP
• Correct dehydration
• Withdraw hepatotoxins

Supportive management of the encephalopathic patient

1. Support the airway.  If the patient is comatose or uncooperative, they may require intubation in order to correct disorders of gas exchange (as they may not be compliant with NIV and chest physiotherapy)
2. Wean ventilation to spontaneous mode as tolerated.​ Hypoxia and hpercapnea can be readily corrected if the patient is mechanically ventilated; otherwise, posture with chest physiotherapy and deep breathing exercises are crucial
   Avoid NIV; abdominal distension and a fluctuating level of consciousness will likely result in aspiration. HFNP is ok. 
3. Support haemodynamically;
   noradrenaline +/- terlipressin may be appropriate if hepatorenal syndrome is suspected
   Albumin (20%) is a reasonable resuscitation fluid
   Hepatic flow should be optimised by monitoring for abdominal compartment syndrome
4. Avoid sedation. As needed, use drugs which do not depend on hepatic metabolism (eg. remifentanyl).
   Cerebral oedema and the potential for intracranial catastrophe should be investigated with a CT brain
5. Correct electrolyte derangement
6. Monitor renal function (hepatorenal syndrome)
7. Ensure BSL is monitored and supplemental glucose is made available
   Ensure thiamine is co-administerd with glucose!
8. Correct clinically significant anaemia. 
   Address haematinic factor deficiencies.
9. Antibiotics as appropriate: ceftriaxone may be required if SBP is a real possibility.
   Blood cultures and inflammatory markers should be collected.

Pursuit of other explanations for decreased level of consciousness:

• Minimise sedation
• Optimise oxygenation and ventilation
• Screen for sepsis
• Observe for physical signs suggestive of raised intracranial pressure
• Manage uremia, and consider dialysis

References

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Riggio, Oliviero, et al. "Management of hepatic encephalopathy as an inpatient." Clinical Liver Disease 5.3 (2015): 79-82.

Bajaj, J. S. "Review article: the modern management of hepatic encephalopathy." Alimentary pharmacology & therapeutics 31.5 (2010): 537-547.

Amodio, Piero, et al. "The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus." Hepatology 58.1 (2013): 325-336.

Als-Nielsen, Bodil, Lise Lotte Gluud, and Christian Gluud. "Nonabsorbable disaccharides for hepatic encephalopathy." Cochrane Database Syst Rev 2 (2004).

Bass, Nathan M., et al. "Rifaximin treatment in hepatic encephalopathy." New England Journal of Medicine 362.12 (2010): 1071-1081.

College Answer

Prognosis of hepatic encephalopathy and associated organ dysfunction depends on whether the process is acute or chronic, and whether there are any reversible factors. The very high bilirubin level (350 mcgmol/L), and the fact that this man has rebled from his varices make his prognosis worse, but not unsalvageable. Shunting procedures may decrease his likelihood of further bleeding but are likely to worsen the encephalopathy.

Discussion

Severe hepatic encephalopathy in ICU seems to actually have a slightly better outcome than other sorts of organ system failures.

• The mortality at 1 year is about 54% according to one small study.
• Those patients who require nothing other than mechanical ventilation (i.e. ones who got intubated for low GCS and airway protection) tend to have better outcomes.
• The ones which have ascites, varices (which bleed) as well as sepsis - their 1-year mortalty tends to be as high as 60%.
• In spite of these grim numbers, the admission of cirrhosis patients to ICU is no longer viewed as a completely futile exercise, because there has been a gradual expansion of the treatment options available to them, and because their outcomes have improved with time.

Several things can be added, with regard to prognostication in chronic liver disease patients admitted to ICU:

• Childs-Pugh at admission is associated with survival at 12 months (Warren et al, 2015). Specifically:
  • Class A = 100% survival at 12 months
  • Class B = 50% survival at 12 months
  • Class C = 25% survival at 12 months
• The MELD score gives a 3- month  mortality prediction in patients awaiting a liver transplant:
  • 40 or more — 71.3% mortality
  • 30–39 — 52.6% mortality
  • 20–29 — 19.6% mortality
  • 10–19 — 6.0% mortality
  • <9 — 1.9% mortality
• In ICU, the liver scores have little influence because many other organ systems play are role in death or survival. Well-rounded models (SOFA, APACHE) are better at predicting ICU outcomes than liver-specific scoring systems (Levesque et al, 2012)

References

Fichet, Jérôme, et al. "Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy." Journal of critical care 24.3 (2009): 364-370.

García-Martínez, Rita, Macarena Simón-Talero, and Juan Córdoba. "Prognostic assessment in patients with hepatic encephalopathy." Disease markers 31.3 (2011): 171-179.

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Fichet, Jérôme, et al. "Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy." Journal of critical care 24.3 (2009): 364-370.

García-Martínez, Rita, Macarena Simón-Talero, and Juan Córdoba. "Prognostic assessment in patients with hepatic encephalopathy." Disease markers 31.3 (2011): 171-179.

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Pugh, R. N. H., et al. "Transection of the oesophagus for bleeding oesophageal varices." British Journal of Surgery 60.8 (1973): 646-649.

Forman, Lisa M., and Michael R. Lucey. "Predicting the prognosis of chronic liver disease: an evolution from Child to MELD." Hepatology 33.2 (2001): 473-475.

Child, CG_, and J. G. Turcotte. "Surgery and portal hypertension." Major problems in clinical surgery 1 (1964): 1.

Malinchoc, Michael, et al. "A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts." Hepatology 31.4 (2000): 864-871.

Zimmerman, Jack E., et al. "Intensive care unit admissions with cirrhosis: Risk‐stratifying patient groups and predicting individual survival." Hepatology 23.6 (1996): 1393-1401.

Cholongitas, E., et al. "Systematic review: the model for end‐stage liver disease–should it replace Child‐Pugh's classification for assessing prognosis in cirrhosis?." Alimentary pharmacology & therapeutics 22.11‐12 (2005): 1079-1089.

Ho, Yu-Pin, et al. "Outcome prediction for critically ill cirrhotic patients: a comparison of APACHE II and Child-Pugh scoring systems." Journal of intensive care medicine 19.2 (2004): 105-110.

Cholongitas, E., et al. "Risk factors, Sequential Organ Failure Assessment and Model for End‐stage Liver Disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit." Alimentary pharmacology & therapeutics 23.7 (2006): 883-893.

Levesque, Eric, et al. "Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit." Journal of hepatology 56.1 (2012): 95-102.

Yeoh, Sern Wei, et al. "Cirrhotics Treated In Intensive Care Unit Have High Short Term Survival in the Absence of Extrahepatic Organ Dysfunction." Journal of Gastroenterology and Hepatology Research 5.2 (2016): 1984-1988.

Wiesner, Russell, et al. "Model for end-stage liver disease (MELD) and allocation of donor livers." Gastroenterology 124.1 (2003): 91-96.

Saliba, Faouzi, et al. "Cirrhotic patients in the ICU: prognostic markers and outcome." Current opinion in critical care 19.2 (2013): 154-160.

Peng, Ying, Xingshun Qi, and Xiaozhong Guo. "Child–Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies." Medicine 95.8 (2016).

College Answer

Ascitic fluid analysis provides – Fluid for General appearance

Albumin / protein content

Red cell count White cell count Culture and sensitivity Cytology

Biochemistry - amylase

Indications for performing a tap include: any patient with ascites and PUO, critical illness or suspected malignancy.

Discussion

I would expand the college list:

Information which can be derived from an ascitic fluid analysis:

• Appearance - turbidity would be very suspicious for SBP
• Albumin - to calculate serum/ascites albumin gradient
• Amylase/lipase - to consider pancreatitis as the cause of ascites
• LDH (low indicates hepatic cause, whereas >500 suggests malignancy)
• Gram stain - for bacteria
• India ink stain - for hyphae
• ZN stain for acid-fast bacilli (tuberculosis)
• Culture/sensitivities
• Flow cytometry and cell count - RBC/WCC ratio would raise suspicion of SBP
• Cytology - presence of malignant cells
• alpha-foetoprotein - to investigate for HCC

Indications for ascitic fluid drainage:

• Diagnostic
  • see above
• Therapeutic
  • patient discomfort
  • respiratory compromise due to adominal pressure
  • abdominal compartment syndrome
  • infected ascitic fluid (i.e. as source control)
  • for peritoneal dialysis (this can be viewed as a therapeutic paracentesis

References

Bar-Meir, Simon, Emanuel Lerner, and Harold O. Conn. "Analysis of ascitic fluid in cirrhosis." Digestive diseases and sciences 24.2 (1979): 136-144.

Boyer, Thomas D., Arthur M. Kahn, and Telfer B. Reynolds. "Diagnostic value of ascitic fluid lactic dehydrogenase, protein, and WBC levels." Archives of internal medicine 138.7 (1978): 1103-1105.

Runyon, Bruce A., John C. Hoefs, and Timothy R. Morgan. "Ascitic fluid analysis in malignancy‐related ascites." Hepatology 8.5 (1988): 1104-1109.

College Answer

Cisapride: selectively enhances physiologic release of acetylcholine at level of myenteric plexus. Part  of  effect  via  activation  of  serotonin  (5-HT4)  receptors.  Enhances  oesophageal  peristaltic activity, gastric emptying, intestinal propulsive activity and colonic transit. Extensively metabolised via cytochrome P450 3A4 enzymes. Highly protein bound. Only administered orally. Significant adverse effects and interactions, especially prolonged QT interval (and arrhythmias) in particular when administered in patients at risk of arrhythmias or when administered concurrently with drugs that  prolong  QT  or  drugs  that  inhibit  P450  3A4  enzymes  (e.g.  azole  antifungals,  macrolide antibiotics, and protease inhibitors). Problems with limited availability, restrictions on prescribing, large number of documented interactions.

Metoclopramide: mode of action unclear (? via selective dopamine-2 receptor antagonist effects); sensitises tissues to the action of acetylcholine (motility effects abolished by anticholinergic drugs and  narcotic  analgesics).  Increases  tone  and  amplitude  of  gastric  contractions,  relaxes  pyloric sphincter and increases peristalsis of duodenum and jejunum. Administered orally, IV or IM. Conjugated by liver and renally excreted (reduced clearance with renal failure). Minimal protein binding. Dopamine agonist activity responsible for adverse effects (e.g. sedation, dystonic/extrapyramidal reactions).

Erythromycin: macrolide antibiotic that seems to stimulate motilin receptors, and enhances motilin release from enterochromaffin  cells of duodenum. Enhanced contractile effects on gastric antrum and duodenum. Administered orally or intravenously  ( probably IV more effective). Highly protein bound. Substantial hepatic metabolism. Prolonged QT and arrhythmias reported, as have hepatic dysfunction, overgrowth of non-susceptible organisms and colitis (Cl. difficile). Elevated levels of many other drugs (as a result of inhibition of metabolism) can lead to toxicity (e.g. theophylline, HMG-CoA reductase inhibitors, anti-epileptics, digoxin, warfarin etc).

Discussion

One study ran all of these drugs against each other to evaluate their comparative efficacy. The only useful finding was that metoclopramide worked faster than cisapride. And then cisapride was withdrawn from the market, following concerns of toxicity. The current Canadian Critical Care Nutrition Guidelines only mention metoclopramide and erythromycin (as well as enteral naloxone).

References

MacLaren, Robert, et al. "Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study." Critical care medicine 28.2 (2000): 438-444.

The best resource for all EBM in this topic is the Canadian Critical Care Nutrition Guidelineswebsite.

Society Of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition.Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. Crit Care Med 2009 Vol. 37, No. 5 , 2009

College Answer

Answers should address more than just prevention of gastric erosions/stress ulceration.

Consideration should be given to other causes including patients with known gastro-oesophageal varices (where sclerotherapy/banding, beta-blockers and techniques to lower venous pressure, and avoidance of local trauma should be considered).

With regard to stress ulceration many strategies have been employed, and should be considered in a broad answer.  General resuscitation of patients, correction of coagulopathy, early enteral feeding and avoidance of precipitants (eg. NSAIDs) in patients at risk are assumed to be beneficial (but not well studied).  Prospective randomised trials have generally compared drug regimens (antacids vs sucralfate vs H2-blockers vs proton pump inhibitors).  Other agents include prostaglandin analogs. Controversy surrounds the issues of widespread use of prophylactic agents, value of drugs vs placebo, nosocomial infection rates, and cost-benefit analyses.

Discussion

"Critically evaluate" demands a certain degree of structure. Contrary to the college answer, banding and sclerotherapy are not usually preventative techniques. If one were to dedicate any time during this ten minute answer to varices and leaking AVMs, one may wish to be very brief about it, as the meat is clearly in gastric ulceration.

Introduction

Gastrointestinal bleeding in the critically ill patient may be due to a variety of causes; these include bleeding from stress ulceration, oesophageal varices, and colonic polyps. Exacerbating causes include antiplatelet and anticoagulant medications, as well as poor perfusion of gastrointestinal mucosa in the context of shock. Given that in the ICU GI bleeding is combined with a series of other major organ dysfunction syndromes, it tends to have a castarophic mortality rate and it is important to be able to protect at-risk patients from this complication.

Rationale

Options:

• Proton pump inhibitors
• Histamine receptor antagonists
• non-pharmacological management - protective role of enteral feeding

Advantages

• Decreased risk of gastrointestinal bleeding
• Decreased exposure to blood products, and the attendent risks thereof

Disadvantages

• Decreased gastric acidity, thus increased risk of non-sterile aspiration
• Increased risk of gastrointestinal bacterial overgrowth and translocation
• Increased risk of Clostridium difficile infections
• Economic disadvantage (cost)

Evidence for the routine use of ulcer prophylaxis

• A recent meta-analysis suggests that the quality and quantity of the evidence is still poor, but on the weight of the available evidence there is neither a mortality improvement nor any increase in the risk of nosocomial pneumonia.
• There appears to be no benefit for stress ulcer prophylaxis in patients who are tolerating enteral feeding, and in these patients stress ulcer prophylaxis is not needed.
• There is insufficent evidence to recommend the mandatory use of stress ulcer prophylaxis in any specific patient group (again, 
• Obviously, correcting coagulopathy (and not triggering any new coagulopathy, nor disabling the platelets with NSAIDs) is a good way to prevent catsatropic bleeding in the ICU.

Evidence to support one drug class over another

• At the time of this paper having been written, there was insufficient evidence to recommend any specific medication (e.e H₂As vs PPIs); however the Danes recommended PPIs, because they are more effective at keeping the gastric pH at over 4.0.
• There is now lots of evidence, and it is still unclear whether PPIs or H₂As are more effective. Pro-PPI studies include a big 2016 meta-analysis by Alshamsi et al, which revealed them to be more effective at preventing clinically significant episodes of bleeding. However, it must be pointed out that many of the studies which met inclusion criteria didn't even specify what they meant by "bleeding". When other meta-analysis authors selected studies  limited to ones with a low risk of bias, the results they arrived at were not significant (Barletta et al, 2016).

Summary

PPIs are indicated in at-risk patient in ICU who are intolerant of eneteral feeding, and who are otherwise at risk of gastrointestinal bleeding. Further research is required to discriminated between different classes of drugs in terms of efficacy, and to identify the at-risk population.

References

Steinberg, Kenneth P. "Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit." Critical care medicine 30.6 (2002): S362-S364.

Marik, Paul E., et al. "Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis." Crit Care Med 38.11 (2010): 2222-2228.

Krag, Mette, et al. "Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients." Intensive care medicine 40.1 (2014): 11-22.

Madsen, Kristian Rørbæk, et al. "Guideline for Stress Ulcer Prophylaxis in the Intensive Care Unit." Danish medical journal 61.3 (2014): 1-4.

Alshamsi, Fayez, et al. "Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials." Critical Care 20.1 (2016): 120.

Barletta, Jeffrey F., et al. "Stress ulcer prophylaxis." Critical care medicine44.7 (2016): 1395-1405.

College Answer

Mental state could be severely depressed or patient may be agitated or confused.  

In general the potential aetiologies are the same, though some more likely in each type of state.   Consider: decreased oxygen delivery to braiin (hypoxaemia, low cardiac output, low blood pressure), effects of drugs (those administered or those withdrawing from), intracerebral pathology (thromboembolism, rarely bleed eg. into undetected secondaries), electrolyte disorders (especially glucose, Na and Calcium), infections (unlikely; eg. systemic/meningitis/encephalitis), postoperative confusional state (uncertain but probably multifactorial aetiology), post-ictal or psychiatric disorder.

Management involves exclusion of  reversible and  specific treatable causes considered likely/possible (eg. SpO2, vital signs, glucose, electrolytes, review drugs and history).  Appropriate treatment of any specific abnormalities detected. Protection of patient and staff with cautious use of restraint (chemical or physical) if absolutely necessary or specifically indicated.

Discussion

Potential aetiology for a severely altered mental status post hepatic resection:

• Hypoxia due to intrapulmonary portosystemic shunting, atelectasis or aspiration
• Hypercapnea due to right pleural effusion
• Hepatic encephalopathy due to high ammonia
• Cerebral oedema
• Diminished capacity to metabolise anaesthetic drugs and sedatives
• Intracranial haemorrhage in the context of coagulopathy
• Septic encephalopathy post-operatively

Management:

Specific management of hepatic encephalopathy

• Lactulose
• Rifaximin
• Avoidance of hyponatremia
• Nutritional management:
  • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
  • High fiber diet
  • Pro-biotics (though their benefit is unclear)

Management of the precipitating cause

• Stop GI bleeding (endoscopy, banding, etc)
• Antibiotics for SBP
• Correct dehydration
• Withdraw hepatotoxins

Supportive management of the encephalopathic patient

1. Support the airway.  If the patient is comatose or uncooperative, they may require intubation in order to correct disorders of gas exchange (as they may not be compliant with NIV and chest physiotherapy)
2. Wean ventilation to spontaneous mode as tolerated.​ Hypoxia and hpercapnea can be readily corrected if the patient is mechanically ventilated; otherwise, posture with chest physiotherapy and deep breathing exercises are crucial
   Avoid NIV; abdominal distension and a fluctuating level of consciousness will likely result in aspiration. HFNP is ok. 
3. Support haemodynamically;
   noradrenaline +/- terlipressin may be appropriate if hepatorenal syndrome is suspected
   Albumin (20%) is a reasonable resuscitation fluid
   Hepatic flow should be optimised by monitoring for abdominal compartment syndrome
4. Avoid sedation. As needed, use drugs which do not depend on hepatic metabolism (eg. remifentanyl).
   Cerebral oedema and the potential for intracranial catastrophe should be investigated with a CT brain
5. Correct electrolyte derangement
6. Monitor renal function (hepatorenal syndrome)
7. Ensure BSL is monitored and supplemental glucose is made available
   Ensure thiamine is co-administerd with glucose!
8. Correct clinically significant anaemia. 
   Address haematinic factor deficiencies.
9. Antibiotics as appropriate: ceftriaxone may be required if SBP is a real possibility.
   Blood cultures and inflammatory markers should be collected.

References

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Riggio, Oliviero, et al. "Management of hepatic encephalopathy as an inpatient." Clinical Liver Disease 5.3 (2015): 79-82.

Bajaj, J. S. "Review article: the modern management of hepatic encephalopathy." Alimentary pharmacology & therapeutics 31.5 (2010): 537-547.

Amodio, Piero, et al. "The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus." Hepatology 58.1 (2013): 325-336.

Als-Nielsen, Bodil, Lise Lotte Gluud, and Christian Gluud. "Nonabsorbable disaccharides for hepatic encephalopathy." Cochrane Database Syst Rev 2 (2004).

Bass, Nathan M., et al. "Rifaximin treatment in hepatic encephalopathy." New England Journal of Medicine 362.12 (2010): 1071-1081.

College Answer

The perioperative complications could be classified into (1) that of any major upper abdominal surgery and (2) specifically that of a hemi-hepatectomy for cholangiocarcinoma; or divided into various systems, ie.

(1) Respiratory:                     Inadequate  or  excessive  analgesia,  pulmonary oedema  from  fluid overload, R. haemothorax, R. pneumothorax, R diaphragmatic dysfunction, V/Q mismatch from hepatic failure, aspiration and possibly early pulmonary infection or thromboembolism. Very rarely, intraoperative air embolism ®ARDS.
(2) Cardiovascular:                Hypotension from bleeding, epidural block, perioperative myocardial ischaemia / infarction, Arrhythmias associated with electrolyte abnormalities.
(3) Gastro-intestinal failure:   Prolonged ileus, pseudo-obstruction, ascites, G I haemorrhage. (4) Renal:                                                Hepatorenal syndrome, acute tubular necrosis, oliguria.
(5) Hepatic:                             Cholangitis, hepatic failure, encephalopathy, coagulopathy, (6) CNS:                                                Encephalopathy.
(7) Metabolic:                        hyperlactataemia, iNa+, lK+, hypoglycaemia.
(8) Premorbid condition:        Possible ulcerative colitis/primary sclerosing cholangitis: Therefore, medication issues ie steroids, immune state, nutritional status etc.

Treatment is basically meticulous perioperative care with special regard to fluid and electrolyte balance, analgesia, coagulation control, and specific and supportive therapy for any individual complications that develop ie encephalopathy, hepatorenal syndrome etc.

Discussion

This question closely resembles Question 1 from the second paper of 2006. In the interest of simplified revision, the answer to that question is reproduced below:

References

Jarnagin, William R., et al. "Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade." Annals of surgery 236.4 (2002): 397-407.

Page, Andrew J., and David A. Kooby. "Perioperative management of hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 19-27.

Wrighton, Lindsay J., et al. "Postoperative management after hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 41-47.

Thorat, Ashok, and Wei-Chen Lee. Critical Care Issues After Major Hepatic Surgery. INTECH Open Access Publisher, 2013.

Pagano, Duilio, et al. "The unreliability of continuous postoperative lactate monitoring after extended hepatectomies: single center experience." Updates in surgery 67.1 (2015): 33-37.

Ciuni, Roberto, et al. "Nutritional aspects in patient undergoing liver resection." Updates in surgery 63.4 (2011): 249-252.

Hotta, Tsukasa, et al. "Evaluation of postoperative nutritional state after hepatectomy for hepatocellular carcinoma." Hepato-gastroenterology 50.53 (2002): 1511-1516.

Richter, B., et al. "Nutritional support after open liver resection: a systematic review." Digestive surgery 23.3 (2006): 139-145.

Marchesini, Giulio, et al. "Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial." Gastroenterology 124.7 (2003): 1792-1801.

Kim, Say-June, Dong-Goo Kim, and Myung Duk Lee. "Effects of branched-chain amino acid infusions on liver regeneration and plasma amino acid patterns in partially hepatectomized rats." Hepato-gastroenterology 58.109 (2010): 1280-1285.

Neelakanta, Gundappa, et al. "Early tracheal extubation after liver transplantation." Journal of cardiothoracic and vascular anesthesia 11.2 (1997): 165-167.

Narita, Masato, et al. "Noninvasive ventilation improves the outcome of pulmonary complications after liver resection." Internal Medicine 49.15 (2010): 1501-1507.

College Answer

This is a complex field with a large amount of literature to collate. Pancreatitis is usually presents with persistent upper abdominal pain, associated with nausea and vomiting, which can be associated with signs of local tenderness through to peritonism, and/or signs of a systemic inflammatory response  (e.g.  fever,  tachycardia) or  signs  of  associated  disorders  (e.g.  jaundice  with  biliary obstruction) or rarely signs of complications (e.g. ecchymotic discoloration in flank [Grey-Turner’s sign] or peri-umbilical [Cullen’s sign] regions). These signs may be difficult to elicit or masked in critically ill patients. Investigations that assist in the diagnosis include: serum amylase (usually > 3 times normal) (serum lipase does not improve diagnostic accuracy); liver function tests (looking for evidence of obstructive pattern with gall stone induced pancreatitis); plain abdominal radiograph (excludes other aetiologies, and may show localised ileus [“sentinel loop”]; abdominal ultrasound (enlarged hypo-echoic pancreas, and looking for gall stones); and abdominal CT scan with contrast (confirm diagnois and looking for areas of necrosis or pseudocysts). Ranson’s criteria (or more recently Glasgow criteria or Imrie score) are used to assess severity and predict outcome, and they include white cell count (>16,000/mm3), glucose (>11 mmol/L), AST > 250 IU/L, Ca < 2mmol/L, hypoxaemia (<8kPa), and a decrease in haematocrit (>10%) and an increase in urea (>1.8 mmol/L).

Complications include: those associated with a systemic inflammatory response (e.g. myocardial depression/shock,  ARDS,  renal  failure,  death);  respiratory  (including  pleural  effucsion  and atelectasis);  metabolic  (including  hypocalcaemia,  glucose  disturbances);  and   intrabdominal problems (including ileus, necrosis, pseudo-cysts, abscess formation, etc).

Treatment should include: aggressive fluid resuscitation to stabilise the haemodynamic state, treatment of underlying cause (e.g. ERCP if gall stones present, withdrawal of offending drug), treatment of pain (morphine controversial), surgical treatment of complications (e.g. aspiration/drainage of infected collections) and general support of the critically ill patient. More contentious issues that should be considered include: early prophylactic broad spectrum antibiotics (evidence that decrease complications), prophylactic anti-fungal therapy, jejunal feeding (safe, feasible, cheaper than TPN, possibly of benefit), the use of somatostatin, octreotide or protease inhibitors (none have sufficient evidence base to use routinely), and the timing and nature of surgical interventions.

Discussion

This question dates back to a time when there was a whole massive period during which one had plenty of thinking room, planning, and then the process of written communication could take place at a civilised pace, without rush. Now, of course, a question like this has the candidate trying to fit the last 30 years of pancreatitis literature into a ten minute answer.

One patently cannot do this.

The suggested answer below is one which could easily be produced over the course of ten minutes.

Diagnostic features

• Presentation with severe abdominal pain, nausea and vomiting on presentation
• Metabolic acidosis and shock; hypocalcemia
• Elevated pancreatic enzyme levels, of which lipase is the more pancreas-specific
• An abdominal CT may reveal that a widened common bile duct is present, potentially with an impacted stone in the bile duct.

Complications

• SIRS and hemodynamic compromise
• renal failure
• infection of pancreatic necrosis
• hepatic failure
• abdominal comaprtment syndrome
• ARDS
• hypocalcemia
• metabolic acidosis
• myocardial contractility depression
• ileus

Treatment

• Airway:
  • intubation may be required; aspiration may be a major risk
• Breathing:
  • mechanical ventilation with PEEP titrated to permit recruitment of collapsed lung bases
  • As ARDS develops, tidal volumes may nee to be reduced and lung-protective ventilation may need to be adopted, with permissive hypercapnea
• Circulation:
  • Initial stages of resuscitation will likely consist of fluids only
  • The SIRS response may lead to cardiovascular collapse; given that metabolic acidosis and SIRS-associated cardiomyopathy may also be present, inotropes as well as vasopressors will likely be required
• Pain control:
  • this will be vitally important in the non-intubated patient, in order to maintain VQ matching by continuing deep breathing
• Electrolytes- particularly calcium - must be carefully monitored
• Fluid balance management neesd to be careful, and dialysis may be required
• Feeds via the NG tube may be commenced; there does not appear to be any evidence that "pancreatic rest" is in any way beneficial. The necrotic pancreas is not going to be responsive to the normal secretory stimuli, and the
• Coagulation factors need to be corrected, and careful surveillance of the abdominal vessels must occur, as the splenic artery has a tendency to form aneurysms and bleed everywhere
• Antibiotics are probably not indicated
• ERCP to manage the cause of CBD obstruction should take place at the earliest opportunity, as indicated. if there is no ERCP-amenable cause, surgical drainage of the necrotic pseudocyst may take place as soonas the pseudocyst has formed a sufficiently distinct "wall".
• An alternative to surgical cyst drainage is endoscopic ultrasound-guided drainage, which may be a better option for the frail patient.

References

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

College Answer

(c)       Over the next 48 hours he develops increasing jaundice, with severe derangement of his Liver Function  Tests. What are the likely causes, and how are you going to manage this problem?

The potential causes of jaundice and abnormal LFTs within the first 72 hours are many. The pattern of elevation may help the diagnosis (eg. hepatocellular pattern [elevated transaminases, but minor elevation of Alkaline Phosphatase], cholestatic [minor elevation of transaminases]), and a systematic approach is helpful. Most likely causes include infection (systemic sepsis, mild hepatitic/intravascular cholestasis, liver abscess, acalculous cholecystitis), drug induced (cholestatic/hepatitic), haemodynamic/shock (ischaemic hepatitis) or haemolysis (sepsis, early destruction of transfused blood). Pre-existing intercurrent diseases (hepatitis, gall stones) could also be present.

Management depends on the specific/likely aetiology. A careful history (including drug history [eg. high dose of paracetamol before presentation]) and clinical examination (eg. signs of right heart failure, chronic liver disease, abdominal pain) followed by specific liver function tests to delineate the pattern of abnormality (including alkaline phosphatase [AP], gamma glutamyl transpeptidase [GGT] and/or conjugated/unconjugated bilirubin). More specific blood tests may be indicated (eg. haemolysis screen or viral serology). Imaging of right upper quadrant with ultrasound (to assess obstruction &/or stones) would usually be indicated (± other imaging eg. nuclear medicine or CT scan). After addressing the specific aetiology, further treatment would be largely supportive (with awareness of effects on drug metabolism).

Discussion

 The college has cheated the candidate by not presenting them with a list of LFTs to analyse. With no information, the differentials (and thus the manaement options) are distrubingly broad.

One can work though this systematically.

The following tests will need to be ordered, in order of escalating expense, invasiveness and esotericims:

• Albumin is a test of synthetic liver function, but is very nonspecific in critical illness.
• Coags: APTT, PT, fibrinogen and mixing studies. These test the synthetic liver function. PT will be raised if the liver has stopped storing fat-soluble vitamins, and APTT will be raised if the synthetic function is so poor that clotting factor synthesis is impaired. Mixing studies help to demonstrate that the addition of healthy plasma corrects the factor deficiency.
• Bilirubin differential (conjgated vs. unconjugated) helps discriminate biliary from nonbiliary causes of jaundice
• Amylase and lipase (to exclude pancreatitis)
• Ultrasound of the liver and biliary tree to rule out bile duct obstruction and any interruption of the hepatic vascular supply; and to look at the hepatic parenchymal texture (eg. fatty, cirrhotic, etc)
• Hepatitis virus tests  to rule out acute hepatitis
• Iron studies (to look for haemochromatosis)
• Ceruloplasmin (if Wilson's disease is a realistic possibility)
• Anti-smooth muscle antibodies (primary sclerosing cholangitis)
• Anti-liver microsomal antibodies (autoimmune hepatitis)
• Serum α-1 antitrypsin level (for deficiency)
• Liver biopsy (gold standard)

Differentials and their management

• Poor hepatic blood flow
  • decrease the PEEP to improve viscera
• Right heart failure
  • maintain cardiac output with inotropes and fluids
• Generalised shock state
  • maintain normotension with fluids and vasopressors
• Idiopathic drug reaction
  • change the offending drug to an analogue
• Hepatic vein thrombosis
  • anticoagulation
• Hepatic infarction
  • anticoagulation
• Infectious cause
  • viral serology
  • blood cultures

In addition, one would need to adjust drug doses and dosing intervals to allow for changes in hepatic clearance.

References

College Answer

Most likely cause is hepatic encephalopathy, but many other conditions would be excluded as part of her work up.  She has obvious liver dysfunction (GGT, ALT, bilirubin), supported by a low albumin and a very high ammonia level. Other results (eg. Na, Cr/urea, glucose) are not as extreme and less likely to contribute to her reduced conscious state.

An additional assessment of the synthetic function of the liver would support the diagnosis(eg. prothrombin time, which is a marker of severity and should be prolonged).

The high plasma creatinine probably reflects significant renal impairment (not rhabdomyolysis as CK only mildly elevated).   The urea value is probably a reflection of decreased production and a nutritional deficiency.  A normal value makes gastrointestinal bleeding and severe hypovolaemia unlikely as precipitants for the encephalopathy.

Discussion

This question closely resembles (but is not identical to) Question 29.2 from the second paper of 2011. The key difference is that in 2011, it was a 48 yr old male who escaped from the alcohol rehab camp. However, the bloods were identical.

In contrast to the 2011 question, this time the examiners are asking us for ONE diagnosis.

So, if the candidate were to put all their money on one pony, it would be hepatic encephalopathy. The ammonia, bilirubin, LFTs and background history all point to this. The one test which the college has not provided us with is the coags- coagulopathy would be informative as a part of the staging process for this condition, particularly the prothrombin time.

The significance of the creatitine and urea disparity is probably an issue of dehydration. The patient, haveing collapsed some time ago, has spent some hours/days slowly dehydrating. However, owing to the greatly diminished oral intake and muscle mass, the patient probably has a very slow rate of urea production. The absence of CK demonstrates the fact that rhabdomyolysis has no role to play in this process.

References

College Answer

The perioperative complications could be classified into (1) that of any major upper abdominal surgery and (2) specifically that of a hemi-hepatectomy for cholangiocarcinoma; or divided into various systems, i.e.

(1) Respiratory:                     Inadequate or excessive analgesia, pulmonary oedema from fluid overload, R. haemothorax, R. pneumothorax, R diaphragmatic dysfunction, V/Q mismatch from hepatic failure, aspiration and possibly early pulmonary infection or thromboembolism. Very rarely, intraoperative air embolism ®ARDS.

(2) Cardiovascular:                Hypotension   from   bleeding,   epidural   block,   perioperative myocardial ischaemia / infarction, Arrhythmias associated with electrolyte abnormalities.

(3) GI failure:                          Prolonged ileus, pseudo-obstruction, ascites, G I haemorrhage

(4) Renal:                                                Hepatorenal syndrome, acute tubular necrosis, oliguria.

(5) Hepatic:                             Cholangitis, hepatic failure, encephalopathy, coagulopathy,

(6) CNS:                                                Encephalopathy.

(7) Metabolic:                        hyperlactataemia, low Na+, high K+, hypoglycaemia.

(8) Premorbid condition possible ulcerative colitis/primary sclerosing cholangitis: Therefore, medication issues i.e. steroids, immune state, nutritional status etc.

Discussion

This is a question which benefits from a systematic approach. The college answer has already made this attempt.

Thus: a table of Problems and Solutions:

References

Jarnagin, William R., et al. "Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade." Annals of surgery 236.4 (2002): 397-407.

Page, Andrew J., and David A. Kooby. "Perioperative management of hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 19-27.

Wrighton, Lindsay J., et al. "Postoperative management after hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 41-47.

Thorat, Ashok, and Wei-Chen Lee. Critical Care Issues After Major Hepatic Surgery. INTECH Open Access Publisher, 2013.

Pagano, Duilio, et al. "The unreliability of continuous postoperative lactate monitoring after extended hepatectomies: single center experience." Updates in surgery 67.1 (2015): 33-37.

Ciuni, Roberto, et al. "Nutritional aspects in patient undergoing liver resection." Updates in surgery 63.4 (2011): 249-252.

Hotta, Tsukasa, et al. "Evaluation of postoperative nutritional state after hepatectomy for hepatocellular carcinoma." Hepato-gastroenterology 50.53 (2002): 1511-1516.

Richter, B., et al. "Nutritional support after open liver resection: a systematic review." Digestive surgery 23.3 (2006): 139-145.

Marchesini, Giulio, et al. "Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial." Gastroenterology 124.7 (2003): 1792-1801.

Kim, Say-June, Dong-Goo Kim, and Myung Duk Lee. "Effects of branched-chain amino acid infusions on liver regeneration and plasma amino acid patterns in partially hepatectomized rats." Hepato-gastroenterology 58.109 (2010): 1280-1285.

Neelakanta, Gundappa, et al. "Early tracheal extubation after liver transplantation." Journal of cardiothoracic and vascular anesthesia 11.2 (1997): 165-167.

Narita, Masato, et al. "Noninvasive ventilation improves the outcome of pulmonary complications after liver resection." Internal Medicine 49.15 (2010): 1501-1507.

College Answer

a)  What is the most likely cause of the renal deterioration? Give reasons.

Hepatorenal syndrome .
Reasons: Fulfils criteria for Type 1 HRS -(Acute deterioration, absent renal parenchymal disease, absent proteinuria, no shock and no history of nephrotoxic drugs)

List 4 important management measures specifically for the treatment of this patient's renal dysfunction.
Management of complications of renal dysfunction- hyperbilirubinaemia
Albumin administration
Terlipressin I Midodrine/ Octreotide
TIPS 
Consideration for liver transplantation

Discussion

Hepatorenal syndrome is discussed in greater detail in the answer to Question 13 from the first paper of 2001, and in a chapter or rambling digressions.

This case fits the criteria for diagnosis, which are as follows:

i.e. it is renal failure in a patient with coexisting liver failure and no other good reason to have renal failure. "Absence of proteinuria" promotes a view that this is a purely pre-renal disease, with no glomerular damage.

Type 1 hepatorenal syndrome is an acute episode, whereas Type 2 is gradual in onset.

As for "4 important management measures"...

• Albumin and fluid resuscitation:
  • On its own, the effect from this is minimal; mortality is ~ 70%
• Terlipressin
  • Improves mortality to from 70% to 50%
  • Thought to improve renal perfusion by decreasing the tension within the ascites compartment.
• Noradrenaline
  • The idea is to increase renal perfusion by increasing the MAP by about 10mmHg
• Octreotide
  • potent agent of splanchnic vasoconstriction
  • Mortality perhaps 60% 

If all else fails, TIPS procedure may be appropriate. As this disorder has an abysmal survival rate, those who qualify for transplant should be worked up for one.

The college examiners prescriptively asked for "management measures specifically for the treatment of this patient's renal dysfunction", but in their answer gave a generic support strategy ("Management of complications of renal dysfunction- hyperbilirubinaemia"). This answer is puzzling on several levels, and probably had no value in terms of marks for the actual trainees, revealing more information about the CICM quality control process than about hepatorenal syndrome.

References

UpToDate has an excellent synopsis of hepatorenal syndrome.

Salerno, Francesco, et al. "Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis." Postgraduate medical journal 84.998 (2008): 662-670.

Solà, Elsa, Mónica Guevara, and Pere Ginès. "Current treatment strategies for hepatorenal syndrome." Clinical Liver Disease 2.3 (2013): 136-139.

Arroyo, Vicente, et al. "Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis." Hepatology 23.1 (1996): 164-176.

Velez, Juan Carlos Q., and Paul J. Nietert. "Therapeutic response to vasoconstrictors in hepatorenal syndrome parallels increase in mean arterial pressure: a pooled analysis of clinical trials." American Journal of Kidney Diseases 58.6 (2011): 928-938.

Gluud, L. L., M. S. Kjaer, and E. Christensen. "Terlipressin for hepatorenal syndrome." Cochrane Database Syst Rev 4 (2006).

Kalambokis, Georgios, et al. "The effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics and function in nonazotemic cirrhotic patients with ascites."The American journal of gastroenterology 100.4 (2005): 879-885.

Rössle, Martin, and Alexander L. Gerbes. "TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update." Gut59.7 (2010): 988-1000.

Malinchoc, Michael, et al. "A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts." Hepatology 31.4 (2000): 864-871.

College Answer

.

Candidates listing 3 correct differentials for a fluid thrill (see a-c below) or providing 3 conditions which may result in massive ascites (see d-f below) were awarded  full marks.

a)  Massive ascites
b)  Massive ovarian cyst
c)  Pregnancy with hydramnios

d)  Severe liver disease
e)  Budd-Chiari syndrome
f)   Severe right heart failure or pericardial constriction

g)  Abdominal malignancy.

Discussion

This question asks for a fairly random detail from Talley and O'Connor.

The "fluid thrill" is one of the tests for ascites; however it will be positive in any condition where a major part of the abdomen is taken up by a big lake of sloshing fluid. Essentially, it consists of somebody (possibly the patient) pressing down on the middle of their abdomen, and the physician percussing one side while feeling for the percussion wave in the other side. A big sloshy lake of fluid will allow the percussion wave to transmit across, whereas bowel gas or stool will transmit nothing.

This generally held to be pretty unreliable sign of ascites, as it requires the ascites to be massive, and under tension.

In either case, the college was fairly non-specific in their expected answer. They would have been happy to hear several different explanations for abdominal fluid (cysts of all sorts, ascites or massive hydramnios are all valid causes). They were equally happy about three different reasons for massive ascites (which leaves the answer pretty well open to any suggestion.. Budd-Chiari? Liver cirrhosis? Severe right heart failure?).

References

A good description of the fluid thrill test can be found at the website of the University of California, San Diego.

College Answer

Hepatic failure
Inherited disorders of urea cycle
Drugs: Valproate, glycine, carbamezapine
Porta-systemic shunts
Increased protein load: GI bleed, TPN,
Infection with urease splitting organisms – proteus Gastric bypass, urinary diversion procedures Cancers – myeloma
Chemotherapy.

Discussion

This question closely resembles, though is not identical to, Question 14 from the second paper of 2012. There, one may find a discussion of the usefulness of the serum ammonia levels in critical illness.

Here, one is merely expected to regurgitate a series of differentials.

Using a familiar template, an easily remembered list would look like this:

• Hepatic vascular insufficiency, eg. hepatic necrosis due to ischaemia
• Hepatic failure
• Portosystemic shunts
• Infection with urea splitting organisms eg. Proteus mirabilis, H.pylori
• Multiple myeloma
• Drugs - eg. valproate, carbamazepine
• Congential disorders of urea cycle
• Increased protein catabolism, eg. chemotherapy, starvation, GI bleeding, or TPN

More detail, you beg? Impossibly large tables, useless for the purpose of rapid revision?

Another method of arranging the differentials, according to the physiological mechanism:

References

Conway, Edward Joseph, and Robert Cooke. "Blood ammonia." Biochemical Journal 33.4 (1939): 457.

Shambaugh, G. E. "Urea biosynthesis I. The urea cycle and relationships to the citric acid cycle." The American journal of clinical nutrition 30.12 (1977): 2083-2087.

McDermott Jr, William V., Raymond D. Adams, and Athol G. Riddell. "Ammonia metabolism in man." Annals of surgery 140.4 (1954): 539.

Vince, Angela, et al. "Ammonia production by intestinal bacteria." Gut 14.3 (1973): 171-177.

Vince, Angela J., and Sigrid M. Burridge. "Ammonia production by intestinal bacteria: the effects of lactose, lactulose and glucose." Journal of medical microbiology 13.2 (1980): 177-191.

Dohrenwend, Paul, and Richard D. Shih. "Glycine Induced Hyperammonemia After Bladder Rupture During Transurethral Resection of a Bladder Tumor." Journal of Medical Cases 4.4 (2013): 250-253.

Felipo, Vicente, and Roger F. Butterworth. "Neurobiology of ammonia." Progress in neurobiology 67.4 (2002): 259-279.

Hashim, Ibrahim A., and Jennifer A. Cuthbert. "Elevated ammonia concentrations: Potential for pre-analytical and analytical contributing factors." Clinical biochemistry 47.16 (2014): 233-236.

Clay, Alison S., and Bryan E. Hainline. "Hyperammonemia in the ICU." CHEST Journal 132.4 (2007): 1368-1378.

Weng, Te-I., Frank Fuh-Yuan Shih, and Wen-Jone Chen. "Unusual causes of hyperammonemia in the ED." The American journal of emergency medicine 22.2 (2004): 105-107.

Hawkes, N. D., et al. "Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy." Postgraduate medical journal 77.913 (2001): 717-722.

College Answer

23.1) What are the differential diagnoses of this patient’s  presentation?

1)  Pancreatitis
2)  Perf DU
3)  Intestinal obstruction
4)  Acute cholecystitis with sepsis
5)  Aspiration and sepsis
6)  Gut ischaemia

23.2) What are the causes of hypotension in acute pancreatitis?

a) sequestration (3rd spacing) of protein rich fluids in and around the pancreas and abbdominal cavity, retroperitoneum
b) compounded by pre existing fluid depletion.

c) direct myocardial depression
d) SIRS / sepsis
e) Intra-abd hypertension

f) Bleeding

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

Pulmonary dysfunction - Aspiration, pleural effusions, ARDS, atelectasis.

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

a) Antibiotic use in SAP without overt infection controversial and trial data are conflicting.

b) Antibiotics have been given either IV or IV plus orally/rectally via SDD.
c) Early trials - underpowered, mostly non blinded and included patients with differing disease severity suggested a reduction in both infections and improved outcome with early use of prophylactic antibiotics (Cefuroxime and imipenem) in necrotising SAP when compared with placebo. Subsequent meta analyses including a Cochrane review also suggested that antibiotics reduced infections and mortality and need for surgery in necrotic pancreatitis.
d) 2 recent RCTs (Isenmann 2004 and Dellinger 2007) have however demonstrated no effect on outcome or infection rate when prophylactic antibiotics were used in necrotic pancreatitis. The SCCM (2004) consensus conference on severe pancreatitis recommends against the use of routine prophylactic antibiotics.

Discussion

23.1) What are the differential diagnoses of this patient’s  presentation?

An obese hypoxic woman presents in a state of shock, febrile, and with this story of vomiting and abdominal pain. A systematic approach is called for, even though the lipase is high and the obvious single diagnosis is pancreatitis.

Vascular causes:

• acute mesenteric vasculitis
• mesenteric ischaemia, embolic or otherwise

Infectious causes: sepsis from any origin, but more likely the gut,

• biliary sepsis
• colitis

Neoplastic causes

• perforated colorectal mass
• SIRS due to a systemic cytokine release, due to lymphoma or leukaemia

Drug-induced causes

• Drug-induced pancreatitis or hepatitis

Autoimmune causes eg. inflammatory bowel disease with perforation

Traumatic causes eg. Boerhaave's syndrome due to excessive vomiting

Endocrinological cause of abdo pain and SIRS, eg. pacreatitis due to any number of causes

23.2) What are the causes of hypotension in acute pancreatitis?

Again, there are several mechanisms:

• "Third space losses" due to capillary leak, particularly sequestration in the abdomen
• Systemic inflammatory response due to cytokine release
• Gastrointestinal losses due to vomiting, diarrhoea, decreased oral intake, and gastric bleeding
• Retroperitoeal hematoma (maybe from a ruptured splenic artery aneurysm)
• Decreased preload due to abdominal compartment syndrome
• Cardiac ouput decrease due to acidosis and SIRS-associated cardiomyopathy

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

• ARDS due to systemic cytokine release
• Pleural effusions due to third space fluid mobilisation and aggressive fluid resuscitation
• Pulmonary oedema due to decreased cardiac contractility and depressed systolic function
• Aspiration pneumonia given that the patient has a decreased level of consciousness and presents with a history of vomiting

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

• Short answer: there is no role for antibiotics in acute pancreatitis.
• In the 1990s, authors were fond of using prophylactic antibiotics because small-scale trials demonstrated a benefit.
• These days the evidence does not support the use of antibiotics
• Cochrane has an even more recent review which agrees that there does not appear to be any benefit, even on the basis of studies which were not adequately powered to detect a subtle benefit
• For some reason, imipenem seems to stand out as an antibiotic which on its own prevents pancreatic necrosis infections. This, again, was the result of an inadequately powered trial.

Again, thank you to Rajkumar (you know who you are) for pointing out the error in this answer. There was a duplication of content from Question 22 of the same paper. Well spotted!

References

Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483.

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

Villatoro, Eduardo, Mubashir Mulla, and Mike Larvin. "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis."Cochrane Database Syst Rev 5.5 (2010).

College Answer

1. Splenomegaly
2. Ascites
3. Caput medusae
4. Haemorrhoids

Discussion

This question is identical to Question 5.1 from the second paper of 2010.

References

College Answer

List 4 clinical signs of portal hypertension.

•     Splenomegaly
•    Caput medusae
•     Ascites
•    Haemorrhoids on rectal examination
•    Haematemesis? Melaena

Discussion

This is fairly straightforward.

• Ascites
• Caput medusae
• Hepatomegaly and splenomegaly
• Haemorrhoids
• Oesophageal varices (and thus haematemesis)

References

Escorsell, Angels, Joan Carles García-Pagán, and Jaume Bosch. "Assessment of portal hypertension in humans." Clinics in liver disease 5.3 (2001): 575-589.

de Franchis, Roberto. "Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension." Journal of hepatology 53.4 (2010): 762-768.

College Answer

a)  Based on the above information, what do you think this woman is suffering from?

Acute liver failure (without more detail it is hard to say, hyperacute, acute, subacute or chronic)

b)  List 5 important aetiologies which could result in this presentation.

•     Sepsis
•    Viral hepatitis – Hep B/C/D, CMV/EBV
•    Drug induced
•     Poisoning
•    Miscellaneous  (wilson’s disease, acute fatty liver of pregnancy, ischaemic necrosis, Budd-Chiari, complications of hepatic surgery)
•     Idiopathic
•    Pregnancy related

c)  List 4 important complications (apart from respiratory failure) she is at risk of developing.

•    Cerebral oedema and herniation
•     Coagulopathy
•    GI bleed
•     Sepsis
•    Renal failure

d)  List 4 reasons why this woman might progress  to developing  respiratory failure.

•    Impaired ventilation because of coma
•    Pleural effusions
•    ARDS
•    Intra-pulmonary shunts
•    Aspiration pneumonia
•    Sepsis- pulmonary or extrapulmonary

Discussion

a)  Based on the above information, what do you think this woman is suffering from?

With the transaminases in their thousands, a raised bilirubin, coagulopathy and fever, one might assume that this lady has some sort of acute hepatitis. As the college rightly points out, "acute hepatic failure" is the only description one can make without any further history.

b)  List 5 important aetiologies which could result in this presentation.

• Vascular causes, eg. acute hepatic artery thrombosis or ischaemic hepatic injury
• Infectious causes, eg. acute viral hepatitis or liver abscess
• Neoplastic causes, eg. decompensation due to hepatocellular carcinoma
• Drug-induced hepatitis eg. paracetamol overdose
• Exacerbation of congenital disorder, eg. Wilson's disease
• Autummune hepatitis, eg. cryptogenic cirrhosis or idiopathic autoimmune hepatitis (IAIH)
• Traumatic hepatic injury

c)  List 4 important complications (apart from respiratory failure) she is at risk of developing.

There is a brilliant article on this subject which outlines all the possible and impossible complications of acute hepatic failure. I will summarise their Panel 1:

d)  List 4 reasons why this woman might progress  to developing  respiratory failure.

This answer calls for differentials of respiratory failure in a semiconscious shocked woman with fever.

• ARDS due to SIRS
• Aspiration pneumonia
• Decreased respiratory drive due to decreased level of consciousness
• Pleural effusions due to hypoalbuminaemia / ascites
• Intrapulmonary shunts - the so-called "hepatopulmonary syndrome" (very interesting to read about)

References

Bernal, William, et al. "Acute liver failure." The Lancet 376.9736 (2010): 190-201.

Fallon, Michael B., and Gary A. Abrams. "Pulmonary dysfunction in chronic liver disease." Hepatology 32.4 (2000): 859-865.

College Answer

a) What is a TIPS procedure and why is it used in patients with portal hypertension?

The hepatic vein is accessed via the internal jugular vein and IVC. A needle is then passed to connect the hepatic vein with the large portal vein near the centre of the liver, the needle tract  dilated  and  a stent  inserted  to maintain  the tract and form  the shunt  between  the higher pressure portal vein and the lower pressure hepatic vein.   This reduces portal hypertension.

b) What are 2 recognised indications for this procedure?

a)     Variceal bleeding that has failed endoscopic and pharmacological treatment. b)  Refractory ascites

c) Excluding mortality list 5 COMMON complications of TIPS procedure

•   thrombosis
•   occlusion of the stent
•   capsular puncture
•   bleeding
•   encephalopathy
•   stent migration

d) Describe  one  classification  system  used  in assessing  severity  of chronic  liver disease and outline its utility.

Either: Childs-Pugh score
Classified A,B or C by a composite of Total bilirubin, albumin, INR, ascites and hepatic encephalopathy.  Originally  used for prognostication  for surgery  – also used for prognostication  in  chronic  liver  disease  and  prediction  of  likelihood  of  complications  of cirrhosis

Or: MELD score severity scoring system for assessing severity of chronic liver that uses the serum  bilirubin,  creatinine  and INR. Initially developed  to predict  three month survival  in patients post TIPS. Now used for prognosis of liver disease and prioritizing liver transplant recipients

Discussion

The first 3 parts of this question are reasonably straightforward.

• TIPS is the transjugular intrahepatic portosystemic shunt, a conduit for portal venous blood to bypass the ineffective liver and thereby relieve portal hypertension.

Indications for TIPS:

• Refractory ascites
• Refractory rebleeding in variceal disease
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Hepatic vein thrombosis
• Hepatic veno-occlusive disease
• Portal vein thrombosis

Technical complications of TIPS:

• Vascular access complications
• Hepatic damage (through-and-through puncture): risk of intraperitoneal haemorrhage is 1-2%
• Haemobilia (damage to the biliary tree)
• Shunt stenosis or thrombosis (it happens in up to 70%)
• Shunt migration
• Hepatic vein stenosis (this can sabotage a future transplant)

Complications from portal venous shunting:

• Worsening hepatic encephalopathy
• Bilirubin rise: the diseased liver doesn't even get a chance to metabolise it
• Ischaemic hepatitis: the liver gets much of its oxygen from the portal vein, and even in spite of the hepatic arterial buffer response there is a risk of ischaemic hepatitis.
• Tricuspid endocarditis (organisms may now travel directly from the leaky gut into the systemic circulation)
• Haemolysis (due to the direct shearing effect of being in contact with the shunt)
• "Unmasked" cardiomyopathy: the TIPS returns splanchnic blood to the heart and acts as a volume challenge, and if there was pre-existing cardiomyopathy, it may be dramatically revealed in this manner.

The last part of the question is far from straightforward. How does one "briefly outline the utility" of something like the Childs-Pugh scoring system?

The system itself has existed since the 1970s, and it includes in its assessment the albumin level, the prothrombin time, the bilirubin, the presence of encephalopathy and the presence of ascites.

It seems the main point is prognosis. The utility of the scoring systems in general has been to estimate the expected lifespan of a cirrhosis patient, which has implications for liver transplantation. However, in the ICU, the overall mortality for cirrhosis patients is about 43%, irrespective of Childs-Pugh score. In general, SOFA and APACHE are better systems for predicting in-ICU mortality than the liver-specific scoring systems.

Thus, the answer to the "briefly outline utility" question should look like this:

Classification system:

• Childs-Pugh scoring system for cirrhosis
• Uses bilirubin, albumin, ascites, encephalopathy and INR to stratify the severity of cirrhosis according to risk of mortality and morbidity, particularly in the context of preoperative assessment

Its utility, briefly:

• Pre-transplant risk stratification
• Pre-TIPS risk stratification
• Helps estimate prognosis in untreated liver disease
• Does not discriminate survivors and non-survivors among cirrhosis patients admitted to ICU.

References

Ochs, Andreas, et al.New England Journal of Medicine 332.18 (1995): 1192-1197."The transjugular intrahepatic portosystemic stent–shunt procedure for refractory ascites." 

Guevara, Mónica, et al. "Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems."Hepatology 28.2 (1998): 416-422.

Papatheodoridis, George V., et al. "Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta‐analysis." Hepatology 30.3 (1999): 612-622.

Azoulay, D., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation." Bone marrow transplantation 25.9 (2000).

Ganger, Daniel R., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis." The American journal of gastroenterology 94.3 (1999): 603-608.

Freedman, A. M., et al. "Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review." Radiographics 13.6 (1993): 1185-1210.

Angermayr, B., et al. "Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt." Gut 52.6 (2003): 879-885.

Bazarah, Salem M., et al. "Utility of MELD and Child-Turcotte-Pugh scores and the Canadian waitlisting algorithm in predicting short-term survival after liver transplant." Clinical and investigative medicine 27 (2004): 162-167.

Singh, Nina, et al. "Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality." Journal of gastroenterology 33.1 (1998): 73-79.

Levesque, Eric, et al. "Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit." Journal of hepatology 56.1 (2012): 95-102.

College Answer

a)  Given this presentation, list 3 possible causes of his altered conscious state?

Alcohol intoxication

Hepatic encephalopathy 
Drug ingestion 
GI bleed

Sepsis 
Intracranial bleed

b)  Interpret the biochemical abnormalities

Liver dysfunction as demonstrated by elevated enzymes, reduced albumin, hypoglycaemia with decompensation indicated by marked elevation of ammonia. Hyponatraemia in keeping with cirrhosis. Raised lactate as a result of liver dysfunction / alcoholic ketoacidosis / sepsis / thiamine deficiency Raised creatinine indicates renal dysfunction and urea may be apparently “normal” because of decreased hepatic dysfunction and possible nutritional deficiencies. Urea:creatine ratio suggests that GI bleed and/or dehydration are unlikely

Discussion

a)

Ok, the college has given us an alcoholic and put 342 µmol/l of ammonia into him.

Thus one of the differentials would have to be hepatic encephalopathy.

Given the extent of the other liver function abnormalities, and of course the borderline BSL, one could surmise that hypoglycaemia is another valid differential.

Being a drunk, alcohol intoxication is not out of the question.

One might wish to use the VINDICATE acronym to come up with some differentials.

• V- Stroke
• I- Sepsis
• N- Seizures; hepatic encephalopathy
• D- Drug intoxication (including alcohol)
• I -
• C-
• A-
• T- Intracerebral bleed, GI bleed
• E- hyponatremia, hypoglycaemia

Fortunately, the college only asks for three answers. Hepatic encephalopathy, alcohol intoxication and sepsis seem the most likely, given the bloods.

b)  Interpret the biochemical abnormalities

• Sodium is low due to the hypervolemic hyponatremia of cirrhosis
• Creatinine is high potentially due to dehydration or hepatorenal syndrome.
• Urea is normal likely due to nutritional deficiency or failure of the urea cycle. (so its probably not a GI bleed)
• The LFTs are deranged in keeeping with a history of chronic liver disease, featuring a degree of synthetic failure (albumin of only 20) and hypoglycaemia.
• The CK is only slightly elevated, suggesting seziures were probably not taking place before the police arrived
• The lactate is raised, and there could be numerous reasons for this - but its likely either increased production due to sepsis or thiamine deficiency, combined with a decreased hepatic clearance.

There is some good material out there on the biochemical abnormalities of chronic liver disease, and their interpretation.

References

Chung, Raymond T., David L. Jaffe, and Lawrence S. Friedman. "Complications of chronic liver disease." Critical care clinics 11.2 (1995): 431-463.

Heidelbaugh, Joel J., and Michael Bruderly. "Cirrhosis and chronic liver failure: part II. Complications and treatment." American family physician 74.5 (2006).

College Answer

a) CT Scan:

• • Extensive hypodense areas in liver consistent with hepatic infarction
  • Splenomegaly
  • Hypodense areas in spleen consistent with splenic infarcts
  • Free fluid in abdomen

b) Cause:

•  Portal venous thrombosis

c) Causes of anti-thrombin III deficiency:

•   Hereditary

•   Acquired

o Post-operative state

o Liver disease

o Disseminated intravascular coagulation

o Nephrotic syndrome

o Vasculitis

• Further investigations:
  • Ultrasound of hepatic/abdominal vasculature.
  • ATIII activity on blood sample … Prothombotic screen also acceptable

e) Treatment:

• • Heparinisation
  • If there is heparin resistance or low ATIII activity, either antithrombin III concentrate or fresh frozen plasma.
  • Referral for advice regarding surgical (endovascular Vs open) options

Discussion

The CT scan I used was mined shamelessly from Google Images. It is not the one which appeared in the paper.

The first two parts of this question are straightforward.

The CT features of portal vein thrombosis are as follows:

• Direct visualisation of the clot:
  • Usually seen as a hypodense filling defect in the portal vein lumen
  • The decreased density inside the portal vessels is best seen in the contrast phase
  • Non-contract CT will not pick this up: you need portal venous phase contrast enhanced studies.
  • You can also sometimes see enhancement of the walls of the portal vein, which is either dilated vasa vasorum or a thin film of contrast flowing around the obstruction
  • The thrombus itself should not enhance with contrast. If there is enhancement, particularly in the arterial phase, the thrombus is probably malignant in origin (i.e a HCC has eroded into the lumen).
• Sequelae of portal vein obstruction:
  • Venous infarcts of the liver and spleen
  • Cavernous transformation of the portal vein (looks like a varicocele!)
  • Posrtosystemic collateral vessels and arterioportal shunts
  • Gut ischaemia
  • Ascites

The second half of the question requires detailed knowledge of AT-III deficiency. One can arrive at at least half of a sensible answer by logically asking why AT-III might not be present in sufficient quantities. Either you hereditarily fail to synthesise enough of it, or your liver is so damaged that it cannot produce enough. Or, it has been used up somehow, eg. in the context of DIC, MAHA, or in a bypass circuit. Lastly, it is possible that you are losing it along with other proteins via your leaky nephrotic kidneys.

The chapter which discusses thrombophilia screening tests contains within it this table, which lists the causes of AT-III deficiency with greater granularity.

The management of AT-III deficiency is, predictably, supplementation with AT-III. If the expensive purified factor is not available, FFP will suffice. Heparinisation for thrombosis actually will not work unless there is some antithrombin for the heparin to act upon.

Management options for PVT include the following:

• Do nothing:  If the patient is asymptomatic, or if significant risks are associated with anticoagulation (eg. bleeding varices), one may also rely on portal cavernous transformation to divert venous flow around the thrombus. However, rate of spontaneous resolution is low (~ 17%).
• Anticoagulate with heparin, LMWH or warfarin: Ideally, anticoagulation should be started in the first week (according to Basit et al, "Rate of recanalization is 69% if anticoagulation is started in the first week, but 25% if anticoagulation is started in second week").
• Control portal venous hypertension: 
  • ​β-blockers, eg. propanolol
  • Diuretics, eg. spironolactone
  • TIPS procedure
  • Intraportal thrombolysis
  • Surgical thrombectomy

References

UpToDate offers a good article about Antithrombin III deficiency, for a price.

Beresford, C. H. "Antithrombin III deficiency." Blood reviews 2.4 (1988): 239-250.

Mathieu, Didier, Norbert Vasile, and P. Grenier. "Portal thrombosis: dynamic CT features and course." Radiology 154.3 (1985): 737-741.

Lee, Hae-Kyung, et al. "Portal vein thrombosis: CT features." Abdominal imaging 33.1 (2008): 72-79.

Denninger, Marie‐Hélène, et al. "Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors." Hepatology31.3 (2000): 587-591.\

Valla, Dominique-Charles, and Bertrand Condat. "Portal vein thrombosis in adults: pathophysiology, pathogenesis and management." Journal of hepatology 32.5 (2000): 865-871.

Boyer, Thomas D. "Management of portal vein thrombosis."Gastroenterology & hepatology 4.10 (2008): 699.

Basit, Syed Abdul, Christian D. Stone, and Robert Gish. "Portal vein thrombosis." Clinics in liver disease 19.1 (2015): 199-221.

College Answer

a)

Haemodynamic stabilization – optimize cardiac output and tissue perfusion and avoid fluid overload as ventricular function may be impaired. Close haemodynamic monitoring. Vaso-active agents as indicated.

Correction of anaemia and coagulopathy – maintain haemocrit 0.25 – 0.3 to keep blood viscosity low. INR £2, APTT £50 secs, Fibrinogen above 0.5 g/L and Platelets above 30 x 109/L.

Fluid and electrolyte management – appropriate negative fluid balance day 1 decreases risk of pulmonary complications. Fluid overload may aggravate graft congestion and oedema caused by ischaemic-reperfusion. Electrolyte imbalances are common and need to be corrected.

Correction of metabolic abnormalities – hypoglycaemia is an ominous sign of compromised liver recovery, hyperglycaemia also may occur, acid-base abnormalities also occur

Early weaning from mechanical ventilation – associated with better outcome but not feasible in patients with respiratory failure, haemodynamic instability, pulmonary oedema, primary graft dysfunction, encephalopathy etc. Unsucessful early extubation may result in impaired oxygen delivery to transplanted liver

Monitoring of graft function LFTs, lactate, BSL, coagulation, hepatic artery doppler

Early detection of surgical complications - bleeding

Immunosuppressants

Infection prophylaxis

Housekeeping including analgesia (PCA) and appropriate nutrition plan

Other – ICP monitoring if decompensated CLD pre-op

b)

Delayed metabolism of sedative / anaesthetic drugs

Metabolic derangements – hypoglycaemia, hyponatraemia, hyperosmolar syndrome

Hepatic encephalopathy

Hypoxic-ischaemic cerebral injury

Seizures

Intracerebral haemorrhage

Discussion

This is a delicate topic for anybody who has not had the privilege of working in one of the sandstone centres of excellence, where liver transplants for the rich and famous serve as a constant source of private funding and media attention.

Thus, let there be a brief digression into the specifics of managing a post-op orthotopic liver transplant patient in the ICU.

(Incidentally, for those like me who were unsure precisely what the long words mean, "orthotopic" transplantation is the total removal of the old diseased liver, and the implantation of the donated organ into the same anatomical position).

The above link points to a scanned document from the Atlas of Organ Transplantation, which deals extensively with the pre-operative and peri-operative management of liver transplantation, detailing such interesting time intervals as "the Anhepatic stage". It however, is more aimed at the surgeons. Because the quality of the scanner leaves much to be desired, the gory pictures of open livers are just black-and-white blurs.

However, there is plenty of literature regarding the critical care management of liver transplant recipients.

Let us approach this answer systematically.

• Airway:
  • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
• Breathing:
  • In order for the graft to survive normoxia must be established
  • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
  • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
  • Thus, early weaning from invasive ventilation is one of the major goals
• Circulation
  • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
  • Hepatic oedema due to over-resuscitation should be avoided.
  • Arbitrarily, the CVP should remain within the range of 6-10.
  • Observe for reactive vasoconstriction
    • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
    • Now, with their new livers, normal vascular tone will return.
    • This might mean a sudden massive increase in the afterload.
    • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
    • Thus, GTN or nitroprusside infusions should be used liberally in these people.
  • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
• Neurology and sedation
  • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
• Fluids and electrolytes
  • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
  • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
  • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
  • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
• Graft function
  • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
  • Monitoring of the graft consist of several sequential assessments:
    • Hepatic arterial Doppler
    • BSL
    • Lactate
    • Bilirubin
  • Typically, 1-9% of liver transplants fail within hours of surgery.
• Surveillance for abdominal compartment syndrome
  • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
  • Abdominal girth values are required as sequential measurements.
• Nutritional support
  • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
• Hematological support
  • This consists of the replacement of missing blood products and blood cells.
  • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
  • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
• Immune suppression
  • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
• Antibiotics and sepsis surveillance
  • Many of these patients die from postoperative infectious complications
  • 48 hrs of IV antibiotics are typically administered
  • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
  • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

The second part of this question is far less interesting, and refers mainly to the candidate's ability to generate differentials for a decreased level of consciousness.

Using a usual template, one can arrive at a series of differential easily:

• Vascular causes, eg. stroke or hypoxic brain injury
• Infectious causes, eg. reactivated HSV or CMV encephalitis
• Drug-related causes, eg. slow metabolism of anaesthetic drugs reliant on hepatic clearance
• Hepatic encephalopathy
• Haematological, eg. intracranial bleeding due to coagulopathy
• Electrolyte disturbances, for instance cerebral oedema due to hyponatremia
• Endocrine disturbance eg. hypoglycaemia

References

The best, most comprehensive source is this article:

Feltracco, Paolo, et al. "Intensive care management of liver transplanted patients." World journal of hepatology 3.3 (2011): 61.

The rest are also helpful.

Stieber, Andrei C., R. D. Gordon, and J. R. Galloway. "Orthotopic liver transplantation." Hepatology. A text book of liver disease. WB Saunders, Philadelphia (1996): 1759-1780.

Mazariegos, George V., Ernesto P. Molmenti, and David J. Kramer. "Early complications after orthotopic liver transplantation." Surgical Clinics of North America 79.1 (1999): 109-129.

Razonable, Raymund R., et al. "Critical care issues in patients after liver transplantation." Liver Transplantation 17.5 (2011): 511.

Mandell, M. Susan, et al. "Reduced use of intensive care after liver transplantation: influence of early extubation." Liver Transplantation 8.8 (2002): 676-681.

College Answer

• Serum Ammonia
  • Used as an indicator of hepatic encephalopathy
  • Normal values do not rule out encephalopathy – therefore of limited utility in patients with known chronic liver disease
  • Not useful as a monitor during therapy
  • Very high levels may indicate cerebral herniation
  • May be useful to indicate undiagnosed cirrhosis in patients presenting with altered mental status
  • May also be elevated in: TPN, GI Bleed and steroid use, portosytemic shunts and inborn errors of metabolism.
• B-type natriuretic peptide (BNP)
  • Released from cardiac cells in response to ventricular wall distension
  • Elevated in heart failure
  • Can be used as a diagnostic marker in patients presenting with dyspnoea to emergency department, and can be useful prognostically and to guide therapy in heart failure
  • May be elevated in many other conditions in critical care, including sepsis, acute lung injury, PE and intracranial bleed
  • Interpretation of BNP in ICU patients is therefore complex and while it may have a role in prognosis and response to therapy in future its current place is unclear.

Discussion

This question was quite arbitrarily placed into the gastroenterology section, on no grounds other than the interesting association of ammonia with various metabolic disturbances, versus the rather boring association of BNP with heart failure.

The question asks us to "critically evaluate", which means a certain systematic approach. I note that this approach was not used in the college answer.

The use of ammonia levels in critical care:

• Introduction:
  • Ammonia is a metabolic byproduct of amino acid catabolism; there has been interest in measuring ammonia levels and making attempts to associate them with various forms of pathology.
• Rationale:
  • The most prolific site of production of ammonia ions is in the gut, where amino acids are converted into ammonia by gut microflora. The ammonia is then absorbed into the portal circulation and converted into urea in the hepatic urea cycle.
  • Hepatic damage and the failure of the urea cycle is therefore usually associated with a rise in the serum ammonia levels
  • The normal compensatory responses to raised serum ammonia (eg. conversion into glutamine) can give rise to cerebral oedema and thus is thought to play some role in the pathogenesis of hepatic encephalopathy
  • Other causes of raised ammonia levels include
    • Increased rates of protein catabolism, eg. extreme starvation or hematological malignancy
    • TPN
    • Inherited errors of metabolism
• Evidence:
  • Ammonia levels in the brain and in the venous circulation do not usually correlate in stable liver disease; however there is some degree of correlation in severe hepatic encephalopathy.
  • The severity of encephalopathy does not correlate with the magnitude of ammonia elevation. Severely encephalopathic patients may have normal levels of ammonia, and patients with mild and moderate hyperammonaemia may have reasonably intact sensorium.
  •  
• Summary:
  • The use of ammonia to assess the severity of hepatic encephalopathy is still controversial
  • a raised ammonia level may point to an undiagnosed error of metabolism in a patient with an otherwise unexplainable loss of consciousness

The use of BNP levels in critical care:

• Introduction:
  • BNP is a peptide released by stressed atria which has been a tempting target of laboratory analysis in determining the aetiology of breathlessness in the acutely distressed patient
• Rationale
  • BNP (brain natriuretic peptide) is a 32-amino acid peptide released by the human atria and ventricles in response to distending pressure. In spite of its name, its presence in the human brain is rather minimal- it was first identified in porcine brain tissue, where for some reason it is concentrated. BNP is a peptide which has natriuretic and diuretic actions in the renal tubule, and is though to be a part of the natural homeostatic mechanisms which work in defence of normal intravascular volume.
  • Thus, a raised BNP, suggesting increased atrial stretch, may be a serum marker which may differentiate cardiac failure and pulmonary oedema from respiratory infection in situations when both are equally likely on the basis of history and examination.
  • The classical patient for such serology would be the elderly lady or gentleman with severe COPD and CCF, who presents to the ED with shortness of breath, wheeze, fever, and clinical features of fluid overload.
  • It may also be a useful serum marker to guide the management of heart failure
• Evidence:
  • BNP is promoted by the college answer as if it helps emergency physicians identify heart failure, but actual emergency physicians and clinical trial evidence disagree with this statement.
  • BNP is not a very good indicator of head injury
  • There is no strong evidence supporting the use of BNP in discriminating between cardiac and non-cardiac causes of respiratory failure in the critically ill patients.
  • Though a 2007 study promoted BNP as a useful way to discriminate between cardiogenic pulmonary oedema and ARDS (its elevated in ARDS, but even more elevated in APO), a later 2008 study (Yardan et al) detrmined that its sensitivity is poor
  • BNP is also elevated in sepsis, acute lung injury of any cause,  and after cardiac surgery.
  • For pulmonary embolism, BNP may be useful to identify submassive PE (which would reveal right hear tstrain though a BNP leak)- something which has both management and prognostic implications
• Summary:
  • BNP is a non-specific marker of atrial and ventricular strain, and has limited diagnostic utility. Its role in treatment monitoring and risk stratification remains to be established.

References

Clay, Alison S., and Bryan E. Hainline. "Hyperammonemia in the ICU." CHEST Journal 132.4 (2007): 1368-1378.

Ong, Janus P., et al. "Correlation between ammonia levels and the severity of hepatic encephalopathy." The American journal of medicine 114.3 (2003): 188-193.

McKinney, A. M., et al. "Acute hepatic (or hyperammonemic) encephalopathy: diffuse cortical injury and the significance of ammonia." American Journal of Neuroradiology 32.7 (2011): E142-E142.

Richter, Derek, and Rex MC Dawson. "The ammonia and glutamine content of the brain." Journal of Biological Chemistry 176.3 (1948): 1199-1210.

Summar, Marshall L., et al. "Unmasked adult-onset urea cycle disorders in the critical care setting." Critical care clinics 21.4 (2005): S1-S8.

Troughton, Richard W., et al. "Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations." The Lancet355.9210 (2000): 1126-1130.

McCullough, Peter A., et al. "B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure analysis from Breathing Not Properly (BNP) multinational study."  Circulation 106.4 (2002): 416-422.

Hall, Christian. "Essential biochemistry and physiology of (NT-pro) BNP."European Journal of Heart Failure 6.3 (2004): 257-260.

Silver, Marc A., et al. "BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases." Congestive Heart Failure 10.s5 (2004): 1-30.

Jefic, Dane, et al. "Utility of B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in evaluation of respiratory failure in critically ill patients."CHEST Journal 128.1 (2005): 288-295.

Karmpaliotis, Dimitri, et al. "Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema." CHEST Journal 131.4 (2007): 964-971.

Demir, Ali, et al. "The value of Serum BNP for diagnosis of intracranial injury in minor head trauma." World journal of emergency surgery 9.1 (2014): 16.

Li, Nan, et al. "BNP and NT-proBNP levels in patients with sepsis." Ront Biosei18 (2013): 1237-1243.

Mitaka, Chieko, et al. "Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury." Journal of critical care 12.2 (1997): 66-71.

Kucher, Nils, Gert Printzen, and Samuel Z. Goldhaber. "Prognostic role of brain natriuretic peptide in acute pulmonary embolism." Circulation 107.20 (2003): 2545-2547.

Meyer, Brigitte, et al. "511: Nt-Pro-Bnp Is A Strong Predictor of Outcome in Critically Ill Patients Admitted to the Icu After Cardiac Surgery." Critical Care Medicine 39.12 (2011): 141.

Yardan, T., et al. "B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism." International journal of clinical practice 62.8 (2008): 1177-1182.

College Answer

a) Comment, with explanation, on each of the biochemical abnormalities.

Liver dysfunction as demonstrated by elevated enzymes, reduced albumin. Hypoglycaemia with decompensation indicated by marked elevation of ammonia. Hyponatraemia in keeping with cirrhosis.

Raised lactate as a result of liver dysfunction / alcoholic ketoacidosis / sepsis / thiamine deficiency
Raised creatinine indicates renal dysfunction and urea may be apparently “normal” because of
decreased hepatic dysfunction and possible nutritional deficiencies. Urea:creatinine ratio suggests
that GI bleed and/or dehydration are unlikely

b) List three possible causes of his altered conscious state.

• Alcohol intoxication
• Hepatic encephalopathy
• Drug ingestion
• Sepsis
• Intracranial bleed
• Wernickes encephalopathy

Discussion

This question is nearly identical to Question 29.2 from the second paper of 2011. The answer to that question is also duplicated here, to simplify revision

The following is a list of biochemical abnormalities and plausible explanations for them:

• Sodium is low due to the hypervolemic hyponatremia of cirrhosis
• Creatinine is high potentially due to dehydration or hepatorenal syndrome.
• Urea is normal likely due to nutritional deficiency or failure of the urea cycle. (so its probably not a GI bleed)
• The LFTs are deranged in keeeping with a history of chronic liver disease, featuring a degree of synthetic failure (albumin of only 20) and hypoglycaemia.
• Features of synthetic liver failure are present:
  • Ammonia is elevated.
  • Albumin is low.
  • Total protein is low.
  • Bilirubin is high
• The CK is only slightly elevated, suggesting seziures were probably not taking place before the police arrived
• The lactate is raised, and there could be numerous reasons for this - but its likely either increased production due to sepsis or thiamine deficiency, combined with a decreased hepatic clearance.

The college asks for three possible causes of unconsciousness in this comatose drunk. Three only. The most relevant ones would have to be

• Hepatic encephalopathy
• Alcohol intoxication
• Sepsis

A possible list of differentials would have to also include the following:

• V- Stroke
• I- Septic encephalopathy
• N- Seizures
• D- Drug intoxication
• I -
• C-
• A-
• T- Intracerebral bleed, GI bleed
• E- hyponatremia, hypoglycaemia

References

Johnston, David E. "Special considerations in interpreting liver function tests." American family physician 59 (1999): 2223-2232.

Limdi, J. K., and G. M. Hyde. "Evaluation of abnormal liver function tests." Postgraduate medical journal 79.932 (2003): 307-312.

Hoekstra, Lisette T., et al. "Physiological and biochemical basis of clinical liver function tests: a review." Annals of surgery 257.1 (2013): 27-36.

Giannini, Edoardo G., Roberto Testa, and Vincenzo Savarino. "Liver enzyme alteration: a guide for clinicians." Canadian medical association journal 172.3 (2005): 367-379.

Kim, W., et al. "Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease." Hepatology 47.4 (2008): 1363-1370.

Pratt, Daniel S., and Marshall M. Kaplan. "Evaluation of abnormal liver-enzyme results in asymptomatic patients." New England Journal of Medicine 342.17 (2000): 1266-1271.

Whitfield, J. B. "Gamma glutamyl transferase." Critical reviews in clinical laboratory sciences 38.4 (2001): 263-355.

Balistreri, William F., et al. "Intrahepatic cholestasis: Summary of an American Association for the Study of Liver Diseases single‐topic conference." Hepatology 42.1 (2005): 222-235.

Assy, N., et al. "Diagnostic approach to patients with cholestatic jaundice." World journal of gastroenterology 5.3 (1999): 252-262.

Stellpflug, Samuel J. "Transaminitis: The Lab Test That Has Inflammation…." Journal of Medical Toxicology 7.3 (2011): 252-253.

College Answer

a) What is the underlying diagnosis?

Hyperacute (fulminant) hepatic failure

b) List the possible causes in this patient.

Paracetamol
Idiosyncratic drug reaction
Other toxin e.g. Amanita phalloides
Viral (hepatitis A and E as hyperacute consider B, CMV, Epstein Barr)
Ischaemic hepatitis
Budd-Chiari

c) Outline your immediate management.

Concurrent resuscitation and institution of supportive care and monitoring with focussed assessment
to identify underlying cause and definitive management as indicated.

Airway management and oxygen – likely to need intubation and mechanical ventilation with
ARDSNet targets and PCO2 32-38 mmHg

Haemodynamic support for adequate MAP and CPP >60 and appropriate monitoring (A-line,
PAC/PiCCO, bedside echo etc.). Avoid fluid overload

Strategies to offset cerebral oedema (head-up, neutral position, sedation, PCO2 targets, Na 145-155
etc.) 

ICP monitoring controversial

Consider renal replacement therapy
Extracorporeal albumin dialysis therapies (SPAD, MARS and Prometheus) have limited evidence to
support use

Monitoring of coagulopathy using TEG/ROTEM to guide correction. Correction to cover invasive
procedures or if bleeding otherwise not.

Monitor blood glucose

Screening for infection and antibiotics as indicated +/- empiric broad spectrum cover including antifungal

Stress ulcer prophylaxis

Nutrition

Specific 
NAC
Lactulose / Neomycin / Rifaximin controversial and use varies from unit to unit

Investigations including liver USS, viral screen

Discussion with liver transplant team / transfer to ICU with liver unit (does not currently meet
transplantation criteria)

Discussion

The diagnosis is clearly liver failure. The college further qualify their description as "fulminant". That term is very 1990s. What makes a liver failure fulminate? Well, apparently that just means it is acute (see Sass et al, 2005). The term was originally applied to patients in whom encephalopathy developed within two weeks of the development of jaundice. These days, the terminology we use is hyparcute (0-7 days), acute (8-28 days) and subacute  (29 days to 8 weeks). The disorders were redefined by Williams et al in 1993, on the basis of the fact that they correlate better with survival statistics (paradoxically, the hyperacute ones do much better).

Possible categories of the causes:

Of these, the following short list is relevant. However, it must be added that the college did not specify how many differentials they wanted. You could have brought up your various azathiprine-induced hepatitis and Amanita phalloides mushrooms.

Thus:

• Hepatic ischaemia
• Acute viral hepatitis or liver abscess
• Acute right heart failure due to PE
• Drug-induced hepatitis eg. paracetamol overdose (or Amanita)
• Autummune hepatitis, eg. cryptogenic cirrhosis or idiopathic autoimmune hepatitis (IAIH)
• Traumatic hepatic injury due to fall

Management

As with most things, management falls into the category of specific management and supportive management. Specific management may be viewed as a series of antidotes or proven solutions tailored to specific causes of the liver failure.

A discussion of supportive management might take the following shape:

1.  Intubate the patient for airway protection, as they will be obtunded (and to control the CO₂)
2. Hyperventilation to low-normal PaCO2 (35 mmHg)
3. Maintain haemodynamic stability using noradrenaline preferentially.
4. Use propofol instead of benzodiazepines, and avoid long-acting opiates.
   Consider an ICP monitor
5. Hypothermia to a temperature of 32-33°
   Hypernatremia (to control ICP, with hypertonic saline) to achieve a sodium of 145-155 mmol/L
6. Haemodiafiltration - continuously - to remove ammonia
7. Anticipate hypoglycaemia.
8. Anticipate coagulopathy.
   Administer Vitamin K empirically.
   Consider blood products, but view complete correction as unobtainable.
9. Vigilant surveillance for sepsis: they are prone to it, and it makes the encephalopathy worse

References

​Sass, David A., and A. Obaid Shakil. "Fulminant hepatic failure." Liver Transplantation 11.6 (2005): 594-605.

Williams, R., S. W. Schalm, and J. G. O'Grady. "Acute liver failure: redefining the syndromes." The Lancet 342.8866 (1993): 273-275.

Chapter 44   (pp. 501) Liver  failure by Christopher  Willars  and  Julia  Wendon

Daly, Frank FS, et al. "Guidelines for the management of paracetamol poisoning in Australia and New Zealand-explanation and elaboration." Medical journal of Australia 188.5 (2008): 296.

Bailey, Benoit, René Blais, and Anne Letarte. "Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death." Annals of emergency medicine 44.4 (2004): 401-406.

Parsons-Smith, B. G., et al. "The electroencephalograph in liver disease." The Lancet 270.7001 (1957): 867-871.

Ramos, Juan Francisco Rivera, and Celina Rodríguez Leal. "Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy." Ann Hepatol 10 (2011): S36-S39.

Walsh, Timothy S., et al. "Energy expenditure in acetaminophen-induced fulminant hepatic failure." Critical care medicine 28.3 (2000): 649-654.

Ichai, Philippe, et al. "Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis." Liver transplantation 13.7 (2007): 996-1003.

O’Grady, John G., et al. "Early indicators of prognosis in fulminant hepatic failure." Gastroenterology 97.2 (1989): 439-445.

Dhiman, Radha K., et al. "Early indicators of prognosis in fulminant hepatic failure: An assessment of the Model for End‐Stage Liver Disease (MELD) and King's College Hospital Criteria." Liver transplantation 13.6 (2007): 814-821.

Yantorno, Silvina E., et al. "MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure." Liver transplantation13.6 (2007): 822-828.

Wiesner, Russell, et al. "Model for end-stage liver disease (MELD) and allocation of donor livers." Gastroenterology 124.1 (2003): 91-96.

Gleisner, Ana L., et al. "Survival benefit of liver transplantation and the effect of underlying liver disease." Surgery 147.3 (2010): 392-404.

Ding, G. K. A., and N. A. Buckley. "Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity." QJM101.9 (2008): 723-729.

Lee, William M., R. Todd Stravitz, and Anne M. Larson. "Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011." Hepatology 55.3 (2012): 965-967.

McPhail, Mark JW, Julia A. Wendon, and William Bernal. "Meta-analysis of performance of Kings’s College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure." Journal of hepatology 53.3 (2010): 492-499.

Stravitz, R. Todd, et al. "Intensive care of patients with acute liver failure: recommendations of the US Acute Liver Failure Study Group." Critical care medicine 35.11 (2007): 2498-2508.

Warrillow, S. J., and R. Bellomo. "Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy." Anaesthesia and intensive care 42.1 (2014): 78.

College Answer

a)    

• Acute liver failure

b)

• Toxins – paracetamol, alcohol, mushrooms. Viral hepatitis – hep A,B,C,D,E, EBV,CMV
• Idiosyncratic drug reaction
• Ischaemic hepatitis due to shock – cardiogenic, septic. Acute fatty liver of pregnancy.
• Congenital/genetic - Wilson’s disease. Hyperthermia - Heat stroke.
• Autoimmune hepatitis. Budd-chiari syndrome.
• Malignant hepatic infiltrations – breast cancer, lung cancer, melanoma, lymphoma, myeloma.

Discussion

Well, you can't call it "acute liver failure" or "hyper-acute" or subacute" because these have specific time intervals as definitions. All you can really say is that there is liver failure. The college gives malingant infiltration as a differential, which gives one the impression that they would be willing to consider the more insidious causes of liver damage.

Possible categories of the causes:

References

College Answer

a)

Haemodynamic stabilization – optimize cardiac output and tissue perfusion and avoid fluid overload as ventricular function may be impaired. Close haemodynamic monitoring. Vaso-active agents as indicated.

Correction of anaemia and coagulopathy – maintain haemocrit 0.25 – 0.3 to keep blood viscosity low. INR 2, APTT 50 secs, Fibrinogen above 0.5 g/L and Platelets above 30 x 10⁹/L.

Fluid and electrolyte management – appropriate negative fluid balance day 1 decreases risk of pulmonary complications. Fluid overload may aggravate graft congestion and oedema caused by ischaemic-reperfusion. Electrolyte imbalances are common and need to be corrected.

Correction of metabolic abnormalities – hypoglycaemia is an ominous sign of compromised liver recovery, hyperglycaemia also may occur, acid-base abnormalities also occur

Early weaning from mechanical ventilation – associated with better outcome but not feasible in patients with respiratory failure, haemodynamic instability, pulmonary oedema, primary graft dysfunction, encephalopathy etc. Unsuccessful early extubation may result in impaired oxygen delivery to transplanted liver

Monitoring of graft function LFTs, lactate, BSL, coagulation, hepatic artery doppler

Early detection of surgical complications - bleeding

Immunosuppressants

Infection prophylaxis

Housekeeping including analgesia (PCA) and appropriate nutrition plan

Other – ICP monitoring if decompensated CLD pre-op

b)

Delayed metabolism of sedative / anaesthetic drugs

Metabolic derangements – hypoglycaemia, hyponatraemia, hyperosmolar syndrome Hepatic encephalopathy

Hypoxic-ischaemic cerebral injury

Seizures

Intracerebral haemorrhage

Discussion

This question is essentially identical to Question 11 from the second paper of 2012. The answer has been reproduced below, in the face of goof SEO but in the interest of siplified revision.

There is also plenty of literature regarding the critical care management of liver transplant recipients.

Let us approach this answer systematically.
The following management steps may be followed in the first 24 hour period:

• Airway:
  • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
• Breathing:
  • In order for the graft to survive normoxia must be established
  • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
  • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
  • Thus, early weaning from invasive ventilation is one of the major goals
• Circulation
  • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
  • Hepatic oedema due to over-resuscitation should be avoided.
  • Arbitrarily, the CVP should remain within the range of 6-10.
  • Observe for reactive vasoconstriction
    • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
    • Now, with their new livers, normal vascular tone will return.
    • This might mean a sudden massive increase in the afterload.
    • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
    • Thus, GTN or nitroprusside infusions should be used liberally in these people.
  • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
• Neurology and sedation
  • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
• Fluids and electrolytes
  • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
  • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
  • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
  • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
• Graft function
  • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
  • Monitoring of the graft consist of several sequential assessments:
    • Hepatic arterial Doppler
    • BSL
    • Lactate
    • Bilirubin
  • Typically, 1-9% of liver transplants fail within hours of surgery.
• Surveillance for abdominal compartment syndrome
  • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
  • Abdominal girth values are required as sequential measurements.
• Nutritional support
  • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
• Hematological support
  • This consists of the replacement of missing blood products and blood cells.
  • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
  • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
• Immune suppression
  • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
• Antibiotics and sepsis surveillance
  • Many of these patients die from postoperative infectious complications
  • 48 hrs of IV antibiotics are typically administered
  • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
  • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

The second part of this question is far less interesting, and refers mainly to the candidate's ability to generate differentials for a decreased level of consciousness.

Using a usual template, one can arrive at a series of differential easily:

• Vascular causes, eg. stroke or hypoxic brain injury
• Infectious causes, eg. reactivated HSV or CMV encephalitis
• Drug-related causes, eg. slow metabolism of anaesthetic drugs reliant on hepatic clearance
• Hepatic encephalopathy
• Haematological, eg. intracranial bleeding due to coagulopathy
• Electrolyte disturbances, for instance cerebral oedema due to hyponatremia
• Endocrine disturbance eg. hypoglycaemia

References

The best, most comprehensive source is this article:

Feltracco, Paolo, et al. "Intensive care management of liver transplanted patients." World journal of hepatology 3.3 (2011): 61.

The rest are also helpful.

Stieber, Andrei C., R. D. Gordon, and J. R. Galloway. "Orthotopic liver transplantation." Hepatology. A text book of liver disease. WB Saunders, Philadelphia (1996): 1759-1780.

Mazariegos, George V., Ernesto P. Molmenti, and David J. Kramer. "Early complications after orthotopic liver transplantation." Surgical Clinics of North America 79.1 (1999): 109-129.

Razonable, Raymund R., et al. "Critical care issues in patients after liver transplantation." Liver Transplantation 17.5 (2011): 511.

Mandell, M. Susan, et al. "Reduced use of intensive care after liver transplantation: influence of early extubation." Liver Transplantation 8.8 (2002): 676-681.

College Answer

Increasing anion gap due to worsening renal impairment and possibly increasing lactate.

LFTs deranged with predominant finding of transaminitis. (This is likely to be associated with an increase in lactate).

Aetiologies

• Liver ischaemia due to hypoperfusion
• cardiac failure (poor output +/- liver congestion) severe sepsis with profound hypotension
• other shock states e.g. obstructive thrombo-embolic disease
• Drug related e.g. paracetamol (inadvertent or deliberate)
• (NB Acute alcoholic hepatitis is unlikely with such a high AST)

Discussion

The following biochemical abnormalities are present in the second set of results:

• High anion gap metabolic acidosis
• Renal impairment (raised urea and creatinine)
• Hypoalbuminaemia
• Borderline raised bilirubin
• Trivially elevated cholestatic liver enzymes
• Massively elevated hepatic transaminases
• A high AST to ALT ratio
• Trivially elevated inflammatory markers

The raised transaminases are described as a "transaminitis" by the college, a term which has been in use since 1977, in spite of some authors referring to it as "made up and improper" (Stellpflug, 2011). The previous set of results from Question 23.1 demonstrated a raised lactate and severe acidaemia wioth a normal glucose and normal haemoglobin. From the list of causes of elevated transaminases, the following are relevant diferentials, and parenthesised comments as to why they are relevant:

• Congestive heart failure (he has COPD: maybe the right heart?)
• Portal vein thrombosis (past history of cancer)
• Malignant infiltration (past history of cancer)
• Drug overdose (this is always an option)
• Viral hepatitis (this is always an option)
• Fatty liver or NASH
• Liver abscess (right lower lobe "infiltrate" may be sympathetic effusion)
• α1-antitrypsin deficiency (the college has given a history of COPD, implying emphysema, but no history of any actual smoking)
• Poor liver perfusion and ischaemia ("shock liver") - however, no history of profound hypotension

And then those things which this is not:

• Alcoholic hepatitis (unlikely: no history of drinking and GGT is not elevated)
• Pancreatitis (not a cholestatic picture)
• Traumatic causes (no history of trauma)
• Congenital issues, haemochromatosis, Wilson's disease (he's 70)

References

Stellpflug, Samuel J. "Transaminitis: The Lab Test That Has Inflammation…." Journal of Medical Toxicology 7.3 (2011): 252-253.

Johnston, David E. "Special considerations in interpreting liver function tests." American family physician 59 (1999): 2223-2232.

Limdi, J. K., and G. M. Hyde. "Evaluation of abnormal liver function tests." Postgraduate medical journal 79.932 (2003): 307-312.

Hoekstra, Lisette T., et al. "Physiological and biochemical basis of clinical liver function tests: a review." Annals of surgery 257.1 (2013): 27-36.

College Answer

Risk factors

• Constipation usually results from multiple interacting causative factors:
• Decreased gastrointestinal motility secondary to:  sepsis, 
• electrolyte abnormalities  drugs e.g. opiates
• spinal injury
• neuromuscular conditions such as Parkinsons long-term laxative abuse
• Immobility due to illness, injury or sedation. Bed rest or a period of immobility is thought to result in a weakening of the abdominal wall muscles leading to difficulty in raising the intraabdominal pressure sufficiently for defecation to occur.
• Stool quality, which may be affected by lack of fluid and fibre
• Lack of access to appropriate toilet facilities and lack of privacy
• Unconscious patients may not feel the need to defecate and cannot express this need
• Using a bedpan increases the likelihood of constipation. Intra-abdominal pressure needs to be raised for successful defecation and this is impaired while lying on a bedpan. 
• Increased incidence in the elderly and nursing home residents

Management Strategies

• May benefit from routine Bowel Management Protocol. 
• Routine laxatives for all, upgraded to stronger agents/enemas if no bowel action after 2 days.
• AXR if no successful bowel movements after 3-4 days.
• Consider surgical/mechanical cause for constipation and rule out with surgical review / AXR / CT.
• Consideration of neostigmine infusion if pseudo obstruction (rule out mechanical obstruction first – CT abdomen transition point).

Non-pharmacological Interventions:

• Sedation breaks to allow assessment of need
• Stop medications that cause constipation
• Normal enteral diet (high fibre feed)
• Availability of commodes/toilets near to patient area for ambulant patients
• Minimisation of opiate analgesia as able (consideration of Targin)
• Mobilisation / free patient from unnecessary lines/tubes etc.
• Adequate oral hydration
• Normalise electrolytes

Pharmacological Interventions:

• Bulk forming laxatives
• Osmotic laxatives
• Enemas
• Contact laxatives
• Prokinetics
• Neostigmine for pseudo-obstruction

Discussion

Risk factors for constipation in the critically ill:

Modifiable ICU-related risk factors

• Delayed enteral nutrition (delayed for longer than 24 hrs) - although early enteral nutrition has also been blamed, and in fact in ICU patients nasogastric nutritional formula is at least as likely to cause constipation as diarrhoea ( Montejo et al, 1999).
• Reduced mobility
• Deep sedation
• Heavy opiate use
• Anticholinergic drug side effects
• Calcium channel blockers
• The use of paralysing infusions
• Electrolyte disturbance, eg.hypokalemia hypercalcemia and hypomagnesemia
• Dehydration, inadequate fluid resuscitation (or excess diuresis)
• Hypotension (SBP under 90mmHg - Gacouin et al, 2010)
• Hypoxia (P/F ratio under 150 - also Gacouin et al)

Non-modifiable disease risk factors

• Abdominal surgery
• Severe illness
• Paralysis (eg. spinal cord injury) 
• Prior alcohol or cannabis use

Management strategies for constipation in the critically ill

Tier one therapies and investigations:

• Abdominal X-ray to exclude "true" bowel obstruction"
• Electrolytes and biochemistry to rule out and correct any electrolyte disturbance
• Fluid management review to ensure euvolaemia and adequate hydration
• Attention to primary pathology (eg. shock, hypoxic respiratory failure) - if this is being treated well and is getting better, patience may be all that is required.
• Drug chart audit to ensure exposure to opiates, anticholinergics and calcium channel blockers is minimised
• Mobility: physiotherapy for limbs, sit out of bed in a chair, etc
• Stool softeners, stimulants and bulk-forming laxatives:
  • Docusate
  • Sennocot
  • Soluble fibre

Tier two therapies and investigations: Assuming bowel obstruction and megacolon are ruled out

• Osmotic laxatives:
  • Lactulose
  • Polyethylene glycol
• PR examination:  this may have a therapeutic effect
• Enema
• Prokinetics, eg. erythromycin
• Opiate antagonists, eg. methylnaltrexone

Tier three therapies and investigations: assuming all of the above are ineffective, or mpossible to implement

• Abdominal CT  to investigate for possible abdominal pathology unseen on AXR
• Neostigmine infusion
• Manual disimpaction
• Surgical decompression

References

Mostafa, S. M., et al. "Constipation and its implications in the critically ill patient†." British journal of anaesthesia 91.6 (2003): 815-819.

Nassar, Antonio Paulo, Fernanda Maria Queiroz da Silva, and Roberto de Cleva. "Constipation in intensive care unit: incidence and risk factors." Journal of critical care 24.4 (2009): 630-e9.

Blaser, Annika Reintam, et al. "Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems." Intensive care medicine 38.3 (2012): 384-394.

Artinyan, Avo, et al. "Prolonged postoperative ileus—definition, risk factors, and predictors after surgery." World journal of surgery 32.7 (2008): 1495-1500.

Nadrowski, L. "Paralytic ileus: recent advances in pathophysiology and treatment." Current surgery 40.4 (1982): 260-273.

Smonig, Roland, et al. "Constipation is independently associated with delirium in critically ill ventilated patients." Intensive Care Medicine 42.1 (2016): 126-127.

Patanwala, Asad E., et al. "Pharmacologic management of constipation in the critically ill patient." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 26.7 (2006): 896-902.

Gacouin, Arnaud, et al. "Constipation in long-term ventilated patients: associated factors and impact on intensive care unit outcomes." Critical care medicine 38.10 (2010): 1933-1938.

Azevedo, Rodrigo Palácio de, and Flávia Ribeiro Machado. "Constipation in critically ill patients: much more than we imagine." Revista Brasileira de terapia intensiva 25.2 (2013): 73-74.

de Souza Guerra, Tatiana Lopes, Simone Sotero, and Norma Guimarães Marshall Mendonça. "Incidência de constipação intestinal em uma unidade de terapia intensiva." Rev Bras Ter Intensiva 25.2 (2013): 87-92.

College answer

a) Causes
• Gastric or duodenal ulcer with bleeding visible vessel
• Dieulafoy's lesion (large exposed arteriole within gastric wall)
• Tear at gastro-oesophageal junction (Mallory Weiss)
• Aorto-duodenal fistula
• Eroding cancer into vessel (short gastric artery, splenic artery)

b) Rebleed likely if:
• Advanced age
• Unable to band all varices
• Gastric > oesophageal varices
• Severe coagulopathy due to liver disease or massive transfusion
• Severity of portal hypertension or liver disease
• Size of varices – larger higher risk
• Presence of red signs (localised reddish spots on the mucosal surface of the varix)

c) Drugs to reduce risk of re-bleed
• Octreotide/somatostatin
• Vasopressin / terlipressin +/- venodilator
• Tranexamic acid
• Oral Sucralfate (local anti-fibrinolytic effect)
• PPI infusion if concomitant ulcer bleeding
• Beta blockers e.g. propranolol if haemodynamics permit
• Short-term prophylactic antibiotics

d) Options for re-bleeding:
• Measure and fix coagulation, ongoing resuscitation

• Repeat endoscopy
   o Can be done in ICU although may be more appropriate in the operating theatre
   o Requires airway protection
   o Allows endoscopic variceal obturation or endoscopic variceal ligation

• TIPS to reduce portal pressure; risks of encephalopathy
   o Strategy of choice with initial treatment failure
   o May be contra-indicated in high MELD score
   o Complications of shunting blood away from liver and increased hepatic encephalopathy

• Balloon tamponade (Sengstaken, Minnesota)
   o Only useful in varices in the oesophagus or GO junction; not useful for gastric
   o Requires airway protection
   o Mucosal injury and necrosis

• Surgery
   o Ligation and resection of gastric vessels
   o Oesophageal venous ligation
      ▪ Requires luminal incision; high risk of breakdown in context of liver disease
      ▪ May not be available depending on local resources

• Balloon-occluded retrograde transverse obliteration (BRTO)
   o New technique and still undergoing evaluation
   o Increases portal hepatic blood flow and may be alternative for patients who may not tolerate TIPS
   o Obliterates spontaneous porto-systemic shunts and may aggravate portal hypertension
• Activated factor 7
   o Questionable efficacy
   o Highly pro-coagulant
   o May have a role in buying time to allow retrieval to a more specialised centre

Discussion

a) Other causes of haematemesis could include a whole range of differentials. Owing to the author's shameful obsession with structured classifications, this range can be divided into "blood is coming from the gut" and "blood is not coming from the gut but somehow has ended up in the gut". This was generated with the use of Oh's Manual, but contains conditions which are not listed in the canonic Chapter 42  (pp. 487,  "Acute  gastrointestinal  bleeding"  by Joseph  JY  Sung).

Bleeding of gastrointestinal origin 

• Oesophageal sources:
  • Oesophageal varices (90% of varices)
  • Mallory-Weiss tears or Boerhaave's syndrome
  • Oesophagitis
• Gastric sources
  • Gastric varices (10% of varices)
  • Peptic ulcers (75% of bleeding ulcers)
  • Portal hypertensive gastropathy
  • Gastritis
• Duodenal sources
  • Duodenal ulcers (25% of bleeding ulcers)
  • Duodenitis
• Anywhere
  • Arterio-venous malformation
  • Dieulafoy lesion 
  • Trauma, eg. swallowed sharp object
  • Iatrogenic, eg. following sphincterotomy or duodenal polypectomy
  • Malignancy

Bleeding of non-gastrointestinal origin 

• Swallowed blood
  • Epistaxis
  • Haemoptysis
  • Blood swallowed during delivery (neonates)
  • Haemorrhage following dental surgery or facial trauma
• Exotic causes
  • Innomino-oesophageal fistula or aorto-duodenal fistula

b) The college have listed causes of rebleeding which seem fairly logical, eg. "unable band everything" and "still coagulopathic". To this list, one might also add gastroenterological lazyness (delayed endoscopy increases re-bleeding risk  according to Chen et al, 2012). From Augustine et al (2010), there are several features found to be strongly associated with "five-day failure", a composite endpoint consisting of re-bleeding and five-day mortality. All of these have been combined into this list:

• Uncontrolled bleeding
  • Ongoing acute bleeding, or failure to control bleeding at initial endoscopy ("unable to band all varices")
  • Delay in the procedure
  • Number of bands which were used - according to Xu et al (2011), more than 6 bands is a bad sign
• Severe liver disease
  • Severity of liver disease: Child-Pugh and MELD scores (even their individual components!)
  • A hepatic venous pressure gradient (HVPG) in excess of 20mmHg
  • Aetiology of cirrhosis (apparently some causes are associated with greater risk of rebleeding)
  • Portal vein thrombosis
• Severe initial haemorrhage
  • High transfusion needs
  • Shock state
• Endoscopic features
  • Red Colour Sign - "red wale markings, cherry red or hematocystic spots" (Kleber et al, 1991)
  • Gastric varices, as opposed to oesophageal ones (Park et al, 2015)
• Laboratory features
  • Haematocrit
  • Platelet count
  • Coagulopathy (prolonged PT)

c) Pharmacological agents which can decrease the risk of rebleeding:

• Terlipressin (has been shown to decrease mortality)
• Octreotide ( the next best choice after terlipressin)
• Propanolol (might be helpful but the jury is still out).
• Antibiotics - sepsis promotes the risk of variceal bleeding; literature demonstrates a benefit from antibiotics in this setting (the usual course is 7 days).
• Tranexamic acid - mentioned by the college in their answer, but Tavakoli et al published on this in 2017 and they did not find any difference in rebleeding rate, nor any other outcome variable for that matter. The whole thing is very 80s. However, as the college answers are definitive, the savvy candidate would need to include this potentially pointless therapy in their answer.
•  Proton pump inhibitors: but PPI infusion probably has no advantage over twice-daily dosing
• Sucralfate is also mentioned by the college in their answer. The "local anti-fibrinolytic effect" is seen more in patients who have had sclerotherapy and then go on to bleed from post-sclerotherapy ulcers (i.e. no longer varices, but still technically a rebleed). This was reported upon by Brooks (1995). The specific benefit seems to be the result of sucralfate counteracting the pro-fibrinolytic effect of ethanolamine oleate, the specific sclerosant agent widely used in the 1990s. 

d) Options for controlling a re-bleed: whenever the college ask for something with a list of advantages and disadvantages, it is usually better to put it in a table. Thus:

Factor VIIa is also mentioned by the college in their answer, though they themselves moderate their enthusiasm by pointing out that it has "questionable efficacy". If one reads the papers (eg. Bosch et al, 2008) this would certainly seem correct (there was no effect on any primary endpoints). The mention of this option in the college answer is itself questionable, as it is promoted as an option for controlling a re-bleed even when trial results "do not support the routine use of rFVIIa in this setting". In protest, I did not add it to my table.

References

College answer

• Liver failure
• Anti-epileptic drugs – Sodium valproate and Carbamazepine
• Other drugs / toxins eg paracetamol, salicylates, mushrooms
• Urosepsis with urea-splitting organisms e.g. Klebsiella, Proteus
• Urea-cycle disorders (Patients with high ammonia from drugs or urosepsis usually have undiagnosed mild disorders of urea-cycle metabolism)

Discussion

The patient; she is probably on valproate for her seizure disorder. Valproate overdose is a logical explanation for a decreased level of consciousness, myoclonus and high ammonia.

Causes of hyperammonaemia more broadly could be any of the following:

References

College answer

Mesenteric ischaemia occurs when blood flow is inadequate to meet the metabolic demands of the small bowel or colon.

Pathophysiology

• Occlusion of the arterial supply leads to ischaemia of the mucosa, before progressing to full thickness ischaemia and infarction with subsequent bacterial translocation leading to localised abscess formation, peritonitis and systemic sepsis depending of the extent of ischaemia.
• Arterial embolism – generally originates from atrial thrombi and therefore tends to occur with tachyarrhythmias, cardiac failure or rheumatic heart disease
• Arterial thrombosis – occlusion of atherosclerotic mesenteric vessel
  • Dissection of the aorta
  • Torsion
  • Closed loop bowel obstruction (intraluminal pressure > arterial pressure)
  • Surgical misadventure
• Venous thrombosis – venous occlusion generally in prothrombotic state e.g.: factor deficiency, malignancy, abdominal trauma, closed loop obstruction
• Mesenteric ischaemia may also occur as a near terminal event in low cardiac output states with poor global oxygen delivery
   

Diagnosis

• History:
  • Acute onset of central colicky or constant abdominal pain, often associated with nausea, vomiting, and constipation
  • May have history of pre-disposing condition e.g.
    • Atrial fibrillation
    • Mechanical cardiac valve
    • Predisposing conditions for atherosclerosis
    • Previous bowel surgery
• Examination:
  • General
    • Often look unwell, tachycardiac (?AF) tachypnoiec (related to metabolic acidosis), hypotensive
  • Abdomen
    • At first may be soft and non-tender in spite of quite severe pain (while only mucosa is ischaemic) progressing then to localised or generalised peritonism
• Investigations:
  • Laboratory
    • Lactate is often raised but may be normal
    • Non-specific markers of inflammation
  • Plain AXR -Riegler’s sign (gas on both sides of bowel wall), thickening of bowel wall
  • Ultrasound
    • May detect proximal vessel occlusion/narrowing
    • Images often inadequate due to pain, bowel gas, obesity etc.
  • CT
    • CT Angiography – information on vasculature as well indication of bowel injury (stranding, lack of enhancement, free air etc.)
    • Two phase imaging(contrast) for optimal venous images
    • Poor sensitivity
  • MRI
    • Good vascular images, but often unacceptable delay in image acquisition
  • Endoscopy
    • May identify ischaemic changes in bowel and rectum
  • Diagnostic surgery
    • May be only way to confirm diagnosis

Treatment

• General resuscitative
  • Fluid resuscitation and judicious vasoactive support
  • Anticoagulation – generally with heparin
  • Antibiotics – controversial but often given as gut translocation and perforation common
• Disease specific
  • Arterial thrombus/embolism
    • Reperfusion
    • Endovascular – mechanical thrombectomy, angioplasty and stenting or thrombolysis
      • Requires close monitoring and often require laparotomy for peritonitis and bowel resection
  • Open
    • Revascularisation – thrombectomy and or arterial bypass
    • Assessment of bowel viability
    • Resection of necrotic bowel
    • Often require “second look” operation
  • Venous thrombosis
    • Systemic anticoagulation
    • Consider percutaneous thrombectomy
    • Laparotomy for complications – peritonitis
  • Low output state
    • Optimise haemodynamic stability
    • Minimising vasoconstrictors controversial
    • Laparotomy for complications – peritonitis

Additional Examiners’ Comments:

The template above is only a guide to the expected answer.Important points sought by the Examiners were: the different categories of mesenteric ischaemia, comments about importance of history, examination and suspicion; it was essential to mention surgery as a diagnostic tool.

Discussion

The template below is also only a guide.

Pathophysiology

• Acute mesenteric ischaemia
  • Arterial embolism (40% of cases)
  • Arterial thrombosis from ruptured atheroma (20-35% of cases)
  • Arterial dissection (<5% of cases)
  • Non-occlusive mesenteric hypoperfusion (10-15% of cases)
  • Venous infarction (5-15% of cases)
• Chronic mesenteric ischaemia
  • Gradual onset of arterial insufficiency due to atherosclerosis

History

• History of atherosclerosis
• Hypercoagulable background
• AF
• Vasculitis
• Recent abdominal surgery
• Historical features associated with chornic mesenteri ischaemia, eg:
  • Postprandial pain ("mesenteric angina"), 30-60 minutes after eating
  • Weight loss
  • Diarrhoea or constipation
  • Early satiety

Examination

• Classic “pain out of proportion to examination”
• Epigastric bruit
• Peritonism
• Clinical features of shock

Biochemistry

• Features of organ system dysfunction, eg. rising creatinine
• Raised lactate
• Neutrophilia

Imaging

• Doppler ultrasound of the mesenteric vessels
• CT with IV contrast, two-phase to detect venous thrombosis
• Catheter angiography (also allows thrombolysis)
• Diagnostic laparotomy (the college felt this was an essential part of the answer)

Specific management

• Aggressive:
  • Endovascular repair
  • Open repair with or without vascular bypass
  • Catheter-directed clot aspiration or  thrombolysis
  • Stenting of dissected segments
• Conservative:
  • Heparin infusion (this is probably the only therapy required for venous mesenteric ischaemia)

Supportive management

• Airway protection may be required (high risk of aspiration)
• Mechnical ventilation (increased work of breathing due to acidosis)
• Circulatory support (vasodilated shock state)
• Analgesia and anaesthesia (opiates may actually be preferred, as they "rest the gut" by paralysing its motility)
• Neuromuscular junction blockers may help organ perfusion by their effect on abdominal compartment pressure
• Electrolyte correction (particularly correction of acdi-base balance)
• Fluid resuscitation (extensive third-space losses are to be expected)
• Abdominal compartment pressure - serial measurements 
• Parenteral nutrition (the patient should remain fasted)
• Antibiotics of a broad spectrum, eg. piperacillin/tazobactam or meropenem

References

College answer

    a.                                                         
•    Drug or alcohol effects 
•    Seizure disorder 
•    Traumatic injury 
•    Septic encephalopathy 
•    Hypoglycaemia and other electrolyte disorders 
•    Uraemia                                          
 
    b.                                                          
•    Asterixis 
•    Hypertonia 
•    Hyperreflexia 
•    Clonus           
•    Hippus 
•    Bradykinesia      
•    Nystagmus 
 

c.

c.                                                          
•    Basic principles of management include: 
 
Excluding other causes of altered mentation 
HE is a diagnosis of exclusion (part [a] of question 10). Serum ammonia levels should not be used as a diagnostic tool or to monitor response to treatment.
 
 
Identifying and treating precipitating cause 
•    Increased nitrogen load (GI bleed, excess protein intake, infection) 
•    Decreased toxin clearance (hypovolaemia, renal failure, constipation, port-systemic shunt, medication non-compliance, acute on chronic liver failure) 
•    Altered neurotransmission (sedating medications, alcohol, hypoxia, hypoglycaemia) 
 
Reducing nitrogen load in the gut/Ammonia formation 
First Line- 
•    Non-absorbable disaccharidases- Lactulose is metabolized by bacteria in the colon to acetic and lactic acid, which reduces colonic pH, decreases survival of urease producing bacteria in the gut, and facilitates conversion of ammonia (NH3) to ammonium (NH4+), which is less readily absorbed by the gut. The cathartic effect of these agents also increases faecal nitrogen waste.  
•    Antibiotics-Rifaximin is a minimally absorbed oral antibiotic with broad spectrum activity against gram-positive and gram-negative aerobic and anaerobic bacteria. Oral neomycin and metronidazole have been used to treat hepatic encephalopathy in the past but due to concerns of toxicity and side effects, rifaximin is now the preferred antibiotic.  
 
Second line- (all not required to score full marks) 
•    Probiotics- As gut bacteria play a central role in producing ammonia it has been theorized that altering gut flora using probiotics may be beneficial in HE.  
•    Polyethylene Glycol- Commonly used, safe and highly effective laxative that has recently been proposed as a possible agent for HE  
•    Flumazenil- benzodiazepine antagonist at GABA receptors. Can result in clinical improvement but no mortality benefit 
•    Ammonia scavengers- increase ammonia clearance and reduce systemic concentrations by providing an alternative pathway for renal ammonia clearance. 
•    L-ornithine l-aspartate (LOLA)- increases glutamine synthase and urea excretion. Similar clinical improvement when compared to lactulose. 
•    Zinc- Low zinc is associated with impairment of urea cycle enzymes leading to elevated ammonia levels.  
•    Porta-systemic shunts- Medically refractory HE should raise suspicion of a spontaneous splenorenal shunt and patients who have undergone TIPS should be considered for shunt reversal if severe HE persists 
 
Supportive care 
Management of cerebral oedema-Lactulose or rifaximin can be beneficial for the treatment of gradual-onset encephalopathy in patients with prior cirrhosis, but additional, aggressive treatment of brain edema with osmotic diuretics is required in new, fulminant forms to prevent secondary, permanent brain-stem damage and to sustain patients through liver transplantation.  
 
Nutrition - plays a key role in managing HE and preventing recurrence. Optimal daily energy intake should be 35 to 40 kcal/kg ideal body weight with daily protein intake of 1.2 to 1.5 g/kg ideal body weight.Multivitamin should be considered with the addition of specific treatments for clinically apparent vitamin deficiencies. 
 
Assessing the need for long term therapy and liver transplant evaluation 
Liver transplant evaluation should be considered in appropriate candidates once a diagnosis of overt hepatic encephalopathy is made 
 

Discussion

Possible causes of unconsciousness in the middle-aged alcoholic could be anything, considering also that we are not given any better description of it (i.e. it could represent merely confusion rather than coma). 

The top four would have to be:

• Hypoglycaemia
• Intracranial haemorrhage, eg. a subdural haematoma from a fall
• Intoxication - i.e. this patient may have access to alcohol while in hospital, or may have drunk something which is not exactly ethanol (eg. chlorhexidine-based hand wash)
• Seizures, eg. associated with withdrawal

Other possibilities include:

• Stroke, including cerebral venous sinus thrombosis
• CNS infection
• Septic encephalopathy
• Hyponatremia
• Space-occupying lesion

Clinical signs which might suggest HE can be extracted from this ancient grading system which was developed by Conn and Lieberthal (1979)

Specific steps in the management of hepatic encephalopathy should consist of specific therapies targeted at reducing the hepatic toxin load and management of the precipitating cause. The excellent college answer offers some detailed discussion, which is difficult to improve upon.

• Lactulose
• Rifaximin
• Avoidance of hyponatremia
• Nutritional management:
  • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
  • High fiber diet
  • Pro-biotics (though their benefit is unclear)
• Management of the precipitant:
  • Stop GI bleeding (endoscopy, banding, etc)
  • Antibiotics for SBP
  • Correct dehydration
  • Withdraw hepatotoxins

J.S. Bajaj (2010) offers a detailed exploration of the modern management of hepatic encephalopathy. Another excellent review is from Riggio et al (2015). From these, the following approach has been concocted, to easily recall and regurgitate in an exam setting:

References

College answer

(a) Method of delivery of nutrition                                                                                                  

• Mild pancreatitis – oral diet if tolerated. Commence at admission or within 24 hours.
  • No superiority of enteral over oral in this group (NEJM 2014)
• If unable to tolerate oral intake
  • Enteral preferred to TPN
  • Cochrane 2010 – reduced mortality and other end-points (including infective, MOF)

• Jejunal not shown to be superior to gastric feeding. Limited evidence (2 small metaanalyses). 
  • No evidence of benefit in delaying feeding awaiting jejunal tube placement – especially in light of apparent benefit of early feeding.
  • Gastric feeding succeeds in delivering nutritional targets in 90%
• Commence enteral feeds within 48 hours of admission, TPN >5 days

        (b) Use of antimicrobials                                                                                                            

• Prophylactic antibiotics not recommended o Not indicated for peripancreatic fluid collections or necrosis without clinical (or radiological) evidence of sepsis
  •  Number of meta-analyses – no improvement in mortality, rates of infected necrosis
• If clinical suspicion of infected necrosis or peripancreatic collection – FNA with culture (high sensitivity)
• Antibiotics if positive FNA result OR unstable and sepsis suspected while awaiting further investigation
• If used – choose appropriate antibiotic(s) with GP and Gn cover. Consider antifungal agents.
• Treatment of other infective complications – e.g. hospital-acquired pneumonia, line-related, urinary tract.

        (c) Role of ERCP                                                                                                                        

• Not routinely indicated
• May be cause
• Should be performed early (24-48 hrs.) in acute gallstone pancreatitis associated with persistent biliary obstruction or cholangitis
  • May not be tolerated / safe in critically unwell patient – consider percutaneous drainage as alternative

Discussion

Nutrition in acute pancreatitis:

• For mild or moderate pancreatitis:
  • Fast for the first 3-4 days? Oh's Manual suggests that these patients need no feeding whatsoever until the disease settles (i.e. for 5-7 days), but the 2017 college answer recommends immediate feeding. The college quote a study ("NEJM 2014") to support their answer, which presumably is the PYTHON trial by Bakker et al (2014). This was an RCT which compared immediate enteral feeding with oral diet initiated 72 hours after presentation, which is not exactly "commence at admission or within 24 hours" ​​​​​.​
  • Advance to normal oral diet before 72 hours. Bakker et al (2014) found that enteral nutrition is no better than oral.
  • No need to rush enteral nutrition. Only progress to enteral nutrition of the patient is not tolerating oral diet after 5-7 days
  • Avoid TPN. Only progress to TPN if enteral nutrition has been trialled and is clearly not tolerated. The college mention another study ("Cochrane 2010") to support their aversion to TPN,  presumably referring to the meta-analysis by Al-Omran et al (2010). After pruning the evidence tree the authors found only two trials to analyse, with a total of 70 patients. They were forced to conclude that the data were insufficient for any firm recommendation, but that the trend was in the direction of better outcomes with enteral nutrition. This vaguely reflects "reduced mortality and other end-points (including infective, MOF)" which is what the college examiners said about it.
• For severe pancreatitis:
  • EN is preferable to PN (ASPEN and ESPEN agree on this)
  • EN should be started early.
  • Tube position does not matter (gastric vs jejunal). The college refer to "2 small metaanalyses" in support of their assertion, presumably referring to Chang et al (2013)  with 157 patients and Petrov et al (2008) with 92 patients. A mor recent addition is Zhu et al (2016) who brought the numbers up to 237.  None of these ever found any benefit in jejunal feeding unless you've got clearly demonstrated impaired gastric emptying, i.e. a gastric outlet obstruction. 
  • Elemental feeds are preferred (ASPEN)
  • Nutritional requirements should be:
    • 25-35 kcal/kg of total body weight per day
    • 1.2 to 1.5g/kg of protein
    • 3-6g/kg of carbohydrate
    • go easy on the lipids (up to 2g/kg)
  • When to use parentral nutrition? These guidelines are much less prescriptive than previous statements. "when EN is contraindicated or not well tolerated", they say.

Antibiotics in pancreatitis:

• There is no role for prophylactic antibiotics in severe acute pancreatitis.
• Up to 20% of these patients go on to develop extrapancreatic infections which require antibiotics.
• Half of bacterial cultures of pancreatic necrosis are of non-enteric origin.
• Of course clinically significant extrapancreatic infections should still be treated with antibiotics

The role of ERCP in pancreatitis:

"May be cause", the college say economically, as if to type a "the" into their answer would incur an intolerable time cost. 

• ERCP specifically:
  • Diagnostic use:
    • To establish that there are gall stones in the common bile duct
    • To determine that the sphincter of Oddi is dysfunctional
    • To investigate pancreatic duct stenosis
    • To get biopsy samples of a neoplasm
    • To investigate any sort of anastomosis
    • To perform intra-ductal ultrasound
  • Therapeutic use:
    • Sphincterotomy, for stenosis or sphincter dysfunction
    • Stone extraction or fragmentation
    • Placement of a pancreatic duct or common bile duct stent
• Endoscopy more generally adds a few strategies:
  • Placement of nasojejunal tubes
  • Transgastric drainage of pancreatic pseudocysts

References

College answer

a)

Risk factors 

1. Coagulopathy, 
2. Mechanical ventilation for >48 hours
3. Renal failure
4. Traumatic brain injury, spinal cord injury, or burn injury
5. History of GI ulceration or bleeding within the past year
6. Shock 
7. An intensive care unit (ICU) stay more than one week, 
8. Occult GI bleeding for six or more days 
9. Glucocorticoid therapy.

b)

Strategies for prevention of GI bleeding resulting from stress ulcers among ICU patients. 

• Prevent gastric ischemia
  • Treat underlying problem responsible for gut Ischemia.
  • Supportive ICU care
• Reduce gastric acid injury
  • Decrease acid production (H2 Antagonist and PPI)
    • Advantages
      • Decreased risk of gastrointestinal bleeding
      • Decreased exposure to blood products, and associated risk related to transfusion
    • Disadvantages
      • Decreased gastric acidity, thus increased risk of non-sterile aspiration and development of nosocomial pneumonia.
      • Increased risk of gastrointestinal bacterial overgrowth and translocation
      • Increased risk of Clostridium difficile infections

H2 blockers: 

Inhibits histamine stimulated acid secretion and are better than placebo, antacid or sucralfate as stress ulcer prophylaxis. No evidence they are superior than PPI.

Tolerance, requires dose adjustment in renal failure; rarely causes thrombocytopenia. 

Proton pump inhibitors: 

Pantoprazole and omeprazole do seem to have some benefit in protecting patients from stress ulceration. In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. No clear evidence that one PPI is better than the other.

Meta-analysis of 13 RCTs; n = 1587 patients (H2 blockers versus PPI) Found less GI bleeding among those who received a PPI (1.3 versus 6.6 percent, odds ratio 0.30, 95% CI 0.17-0.54) no difference in mortality or the incidence of nosocomial pneumonia.  (Detail not required)

 Side effects include: Interstitial nephritis Clostridium difficile enterocolitis, GI upset and headaches. Long-term use associated with fractures, hypomagnesemia hypocalcemia.

Enteral feeding 

Observational studies data suggest that enteral nutrition may be adequate substitute for pharmacologic stress ulcer prophylaxis in ICU patients, however controlled trials are necessary for confirmation.  There appears to be no benefit for stress ulcer prophylaxis in patients who are tolerating enteral feeding, and in these patients stress ulcer prophylaxis may not be needed. However, it is still unclear if enteral feeding is alone sufficient in protection of stress ulcers in high risk patients. 

Examiners Comments:

 Generally, poorly answered. Superficial knowledge of pharmacology and evidence base. 

Discussion

a) 

According to Cook et al (1994), independent risk factors for stress ulceration are:

• Respiratory failure with mechanical ventilation for >48 hrs
• Coagulopathy or anticoagulant use
• Hypotension, shock states of any sort
• Liver failure
• Renal failure
• Fasting state (no enteral feeding)
• Steroid use (especially dexamethasone)

b)

To "include in your answer the available evidence for these", this answer to Question 1 from the first paper of 2003 was updated with contemporary data.

• Antacids - These were the mainstay of ulcer prophylaxis in the 1980s (see Gonzalez et al, 1985). They were given hourly, and required hourly gastric pH measurement to titrate (the usual goal was to aim for a gastric pH of > 5.0). The available agents tend to have nasty metallic ions eg. magnesium, aluminium, sodium. Also, one might develop some metabolic alkalosis, or worse yet a bowel obstruction.
• Sucralfate - an aluminium salt of sucrose octasulphate - coats ulcers and increases mucus production, but does absolutely nothing for gastric pH. This may be an advantage, as the low pH can continue killing pathogenic organisms, while the mucosa is protected by a thick coat of nicely viscous mucus. Again, constipation is a major side-effect. Sucralfate can form a bezoar, clogging the gastric outlet, and it can prevent the absorption of nutrients by binding to the components of enteral feeds. It is also thought to have a tendency to absorb or adsorb useful medications. The popularity of sucralfate decreased in the late 1990s when a trial compared it unfavorably to ranitidine (Cook et al, 1998); in fact ranitidine was twice as good.
• H2-receptor antagonists like ranitidine became popular in the wake of trials which favourable compared them to antacids and sucralfate. Unfortunately these drugs have a tendency towards tachyphylaxis after the first day of therapy. Their use has been largely superceded by PPIs; however their one major remaining advantage is cost. Wikipedia lists the wholesale price of one tablet as 0.01$ (US), making it attractive in the developing world
• Proton pump inhibitors eg. pantoprazole and omeprazole became available in the nineties and have subsequently superceded the H2 receptor antagonists. The college answer refers to a meta-analysis -if you can call that "refers", as they do not give a proper reference. That meta-analysis is Barkun et al (2012). A more recent publication (Alshamsi et al, 2016) included 19 trials (2117 patients) and found that overall there was a reduction in the risk of clinically significant bleeding when compared to H2 receptor antagonists, but with a NNT of 37. There was no mortality benefit. Also, thus far nobody can tell which patients are at sufficiently high risk to benefit from them. Fortunately, detail not required.
• Enteral nutrition buffers gastric pH and suppresses stress-induced vagal stimulation, while proving trophic and circulatory benefits to the gut mucosa, but is occasionally impractical (i.e. not always can you feed them). Furthermore, these benefits were demonstrated mainly in animal studies and retrospective audits (MacLaren, 2001). A more recent prospective RCT (El-Kersh, 2018) found no difference, but only 2 patients had GI bleeding in each group. Ultimately, the benefit of enteral nutrution as stress ulcer prophylaxis has been extrapolated from the finding that it is usually safe to withold PPIs from patients who are tolerating enteral nutrition, i.e. with no additional GI bleeding risk (Alhazzani et al, 2017).

References

College answer

Initial detailed assessment and resuscitation as indicated 
Particular care regarding volume status and identification of bleeding and early graft function Adequate analgesia and sedation 
Protocolised care; close liaison between ICU and other teams involved e.g. surgeons and transplant physicians 
Enteral nutrition 
DVT prophylaxis; usually mechanical Early mobilisation 
Lines and access management: need to rationalise multiple access when stability achieved and coagulation profile acceptable 
Assess suitability for stepdown if no complications 
 
Cardiovascular 
Vasodilated state often requiring pressor support for adequate MAP 
Careful management of volume status and early recognition of bleeding important; large fluid shifts; drain losses may be large and require ongoing volume administration. Avoid elevated CVP 
 
Graft 
Assessment of function via monitoring of coagulation profile, lactate, acid base and transaminases. 
(frequent blood tests/QID) 
Ultrasound assessment of graft particularly hepatic artery / vein / portal vein patency and flow characteristics 
Primary graft nonfunction may be indicated by conventional signs of liver failure i.e. worsening coagulopathy, acidosis, encephalopathy, AKI, hypoglycaemia 
 
Respiratory 
Early extubation when stability ensured 
Patients with hepatopulmonary syndrome or portopulmonary hypertension may need prolongation of ventilation.  pHT may require perioperative management with chronic therapies as well as acute therapies to reduce congestion of graft 
 
Coagulation / Transfusion 
Coagulopathy monitored and indicator of graft function, viscoelastic tests 
Not corrected unless bleeding or severe coagulopathy due to risks vascular thrombosis Hb target above 70 but consideration venesection if Hb > 100g/l 
 
Immunosuppression 
Should be protocoled e.g.  Methylprednisolone / Azathioprine OR MMF / Tacrolimus OR Cyclosporin Variations may be institution based or patient factors e.g. Basiliximab may be given if renal dysfunction preoperatively in lieu of Calcineurin inhibitor 
 
Infection 
Routine postoperative antibiotics not necessary but will depend upon institutional protocols / intraoperative events and preoperative patient status 
Postoperative IV antifungals often given in high risk cases (higher CP or MELD status) 
CMV prophylaxis if CMV pos graft in CMV neg recipient 
Hep B Ig and ongoing antivirals if Hep B patients 
Cytotoxic precautions
 

Renal 
Oliguria likely indicator of hypovolaemia; assess for bleeding 
Consider intraabdominal hypertension 
 
Examiner Comments: 
 
Generally, well answered. Candidates that did poorly made generic comments about post-operative care without specific issues related to liver transplantation or lacked detail in their answers. 
 

Discussion

This is another permutation of the liver transplant SAQ, which in its other incarnations has also included some questions about why the post-transplant patient might be still unconscious after 12 hours. This time,  the college asked about "specific management issues", which is ironically much less specific than the previous questions on this topic. The discussion section for the old SAQs (Question 9 from the second paper of 2015 and Question 11 from the second paper of 2012) was sufficiently detailed that it can also cover this question, and is therefore reproduced here with minimal modification. Furthermore it is worth pointing out that the college model answer to this SAQ is far better than the previous model answers.

The following management steps may be followed in the first 24 hour period:

• Airway:
  • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
• Breathing:
  • In order for the graft to survive normoxia must be established
  • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
  • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
  • Thus, early weaning from invasive ventilation is one of the major goals
• Circulation
  • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
  • Hepatic oedema due to over-resuscitation should be avoided.
  • Arbitrarily, the CVP should remain within the range of 6-10.
  • Observe for reactive vasoconstriction
    • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
    • Now, with their new livers, normal vascular tone will return.
    • This might mean a sudden massive increase in the afterload.
    • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
    • Thus, GTN or nitroprusside infusions should be used liberally in these people.
  • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
• Neurology and sedation
  • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
• Fluids and electrolytes
  • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
  • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
  • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
  • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
• Graft function
  • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
  • Monitoring of the graft consist of several sequential assessments:
    • Hepatic arterial Doppler
    • BSL
    • Lactate
    • Bilirubin
  • Typically, 1-9% of liver transplants fail within hours of surgery.
• Surveillance for abdominal compartment syndrome
  • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
  • Abdominal girth values are required as sequential measurements.
• Nutritional support
  • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
• Hematological support
  • This consists of the replacement of missing blood products and blood cells.
  • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
  • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
• Immune suppression
  • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
• Antibiotics and sepsis surveillance
  • Many of these patients die from postoperative infectious complications
  • 48 hrs of IV antibiotics are typically administered
  • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
  • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

References

College answer

Enterocutaneous fistula (ECF) with inadequate source control

Or ECF with undrained collection

Or ECF with septic shock

• Management
  • Fluid and electrolyte
    • Match losses with crystalloid replacement
    • High sodium loss in high output fistulae
    • Supplement magnesium, phosphate and potassium
  • Sepsis management
    • Source control
    • Target antibiotics, antifungal
• Surgical or percutaneous drainage of associated collections
• Definitive surgical management may be delayed 
• Rule out other sources of infection
   
• Nutrition
  • TPN often required particularly if proximal fistulae
  • Enteral intake may not be possible if < 75cm bowel remaining
  • Trial elemental feed if intolerant or increased output with polymeric feed
  • Role of zinc and vitamin supplement controversial
• Wound management and effluent control
  • Principle is effective drainage allowing wound healing
  • Ostomy appliance 
  • VAC dressing controversial as may cause harm, but can be very effective in effluent management of high output fistula
• Reducing fistulae output
  • Reduce enteral intake and/or consider elemental feed
  • Antidiarrheal – loperamide
  • Somatostatin analogues – octreotide
• Definition of fistulae anatomy
  • Often difficult to define single source
  • Define and/or exclude distal obstruction
  • CT, fistulography etc

Definitive surgery - may be much later

Examiner Comments:

Not well answered. Many candidates described a generic approach to intra-abdominal sepsis without considering the specific issues related to enterocutaneous fistulae.

Discussion

An approach more directly relevant to enterocutaneous fistulae is described by Cohen et al (2016),  Lundy & Fischer (2010) and Evenson (2016).

• Stabilisation where you resuscitate the septic shock
  • Fluid resuscitation should be conservative to prevent intestinal oedema
  • Vasopressor support should be careful to prevent intestinal ischaemia
• Diagnosis where you confirm the location and extent of the fistula, by:
  • Methylene blue dyed feeds
  • Contrast "fistulogram" using water-soluble contrast and plain films or fluoroscopy (contrsat both rectal and oral)
  • Contrast CT, which has largely surpassed the fistulogram
• Evaluation for spontaneous resolution where you decide whether this needs to go to theatre urgently, or whether you can sit on it for a month. Apart from imaging and historicla features, this includes
  • Nutritional assessment, incl. prealbumin, transferrin and clinical assessment
  • Attempted early surgery if you think you can't wait for it to get better on its own (and if the patient is likely to survive)
• Trial of non-operative management if the impression is that surgery can be delayed
• Management of infectious complications during conservative management:
  • Intra-abdominal faecal contamination initially - managed with broad-spectrum antibiotics (eg. peperacillin/tazobactam) as well as an antifungal if there are risk factors (malignancy, re-laparotomy, long term antibiotics)
  • Abdominal collections after a prolonged course of systemic antibiotics
• Management of non-infectious complications during conservative management: 
  • Fluid losses particularly of high-output fistulas: strategies to decrease output include
    • avoidance of vac dressings
    • TPN
    • Octreotide, l​​​​​operamide, opiates
    • Diverting proximal stoma
    • Relief of distal bowel obstruction
  • Malnutrition: TPN and vitamin supplementation
  • Gut atrophy: low volume enteral feeds, or enteral nutrition given via the fistula
  • Electrolyte disturbance resulting from high stoma output (management of this depends mainly on vigilant replacement)
  • Skin excoriation due to spills (management of this requires a dedicated stoma service, or plastic surgical input to deal with tissue loss)
• Definitive surgical management; or, when it becomes clear that this is not an option,
• Palliative care

References

College answer

Pre-op risk assessment 

• Respiratory system evaluation            
• Pulmonary hypertension
• Sleep apnoea
• Cardio-vascular evaluation and optimisation                    
• Functional capacity 
• Other considerations of relevance          
  • Diabetes, renal insufficiency, hiatus hernia, chronic pain and opioid tolerance issues, extreme weight

b)

Post-operative ICU Management 

• Monitored environment     
  • HDU, preferably in ICU with 1:1 nursing supervision 
  • Multi-specialty involvement with a shared mental model
• Respiratory management      
  • Head end elevation and guard against aspiration
  • High risk of post-operative atelectasis
  • Extubation to NIPPV if appropriate

• Fluid management       
  • Maintain intravascular volume fluid status while not causing edema of the anastomotic site due to excessive infusion, need for accurate monitoring of fluid status (invasive monitoring)
• Renal issues     
  • Prone to rhabdomyolysis (prolonged surgery, steep trendelenberg position, high BMI)
  • High index of clinical suspicion (particularly if complaining of pain in the buttocks, hips or shoulders)
• Hyper-coagulopathy and increased risk of venous thromboembolism    
• Close monitoring of glycaemic status and variability (insulin resistance); thyroid profile     
• Regular (rather than prn) anti emetics
• analgesia – avoid opioids if possible
• Early mobilisation and physiotherapy, close attention to ICU housekeeping issues (FASTHUGS etc.)     

Altered pharmacokinetic profile in morbidly obese patients needs careful consideration

Discussion

The phrase "multi-specialty involvement with a shared mental model" sounds like something the candidates should memorise and deploy alongside phrases like "therapeutic alliance" and "client-centered healthcare". It almost belongs on the glossy brochure of a private obesity clinic. Looking beyond nauseating corporate slogans, there is wisdom here: the involvement of multiple teams is required for these high-risk patients to thrive. The best single guideline statement to read for this answer was probably Mechanick et al (2013).

a)

Features of high-risk bariatric patients:  In discussing this, everybody seems to quote the 2010 study by Birkmeyer et al, who assessed the features associated with hospital complications of bariatric surgery among 15,275 Michigan residents. Another highly referenced publication is the LABS consortium paper in NEJM (2009). The following factors were found to be associated with an increased risk of serious complications:

• Patient factors:
  • Cardiovascular disease (eg. ischaemic herat disease)
  • Smoking
  • Sleep apnoea
  • Age over 70 (though LABS did not find this was the case)
  • BMI over 70
  • Cirrhosis
  • End-stage renal failure
  • Immunosuppression
  • Impaired functional status
  • History of DVT or PE
• Surgical factors:
  • Laparoscopic band patients are lower risk
  • Gastric bypass or sleeve gastrectomy patients were higher risk
    (all this may be because the laparoscopic surgery candidates had a lower BMI on average)

Pre-operative risk assessment for bariatric surgical patients should therefore consist of investigations which detect and (hopefully) modify some of these risks pre-operatively. Mechanick et al (2013) have an excellent preoperative checklist for this population (their Table 5), which is reproduced here with minimal modification:

• Bloods: BSL, lipids, kidney function, liver profile, urine analysis, FBC, coags
• Nutrient screening: iron studies, B12 and folic acid (RBC folate, homocysteine, methylmalonic acid optional), and 25‐vitamin D (vitamins A and E optional)
• Cardiac evaluation: ECG, CXR, echocardiography, lower limb Dopplers 
• GI evaluation: H.pylori screening, gallbladder evaluation, upper endoscopy if indicated
• Endocrine evaluation: HBA1c, TSH, androgens with PCOS suspicion, cortisol levels (for Cushing disease)
• Psychosocial‐behavioral evaluation: encourage patient to continue efforts for preoperative weight loss
• Diabetes educator: optimize glycemic control
• Smoking: cessation counseling
   

Post-operative management of bariatric surgery patients

An excellent article by Thornton et al (2017) is available for the paying customers of UpToDate. 

• Disposition
  • 1:1  nursing is reasonable because:
    • the patient may still be ventilated
    • there may be unstable BSL which requires constant adjustment
    • there may be haemodynamic instability which requires constant vigilance
• Extubation
  • ​​​​​​​One might summarise the extubation criteria for these patients as "crisp".  They need to be wide awake and completely cooperative, with full muscle power.
  • Re-intubation will be difficult due to what can be euphemistically be called "redundant oropharyngeal tissue". Approach to the cricothyroid membrane in an emergency may be impossible because of depth. 
• Ventilation
  • ​​​​​​​Dose your tidal volumes to ideal body weight
  • Oesophageal manometry would be ideal to help quantify the contributions of the chest wall to total compliance, but it is unlikely to be available, particularly as the upper GI surgeon may be somewhat reluctant to place any devices in the recently instrumented upper GI tract.
  • The guidelines recommend something they describe as "aggressive perioperative pulmonary toilet", which sounds terrible but probably just means "frequent tracheal suctioning".
  • After extubation, a period of NIV may be useful
• Vascular access and monitoring
  • PICC lines are usually suggested as a means of having convenient long-term IV access
  • Arterial lines are expected as a part of the management package, mainly because it is otherwise difficult to get blood from these people.
• Sedation
  • ​​​​​​​No specific recommendations are available, but people seem to trend towards the use of dexmedetomidine as a co-analgesic and sedative
• Analgesia
  • ​​​​​​​Because opiates are obviously bad for these people who are chronically at the brink of hypercapneic respiratory failure, generally regional techniques (such as thoracic epidural) are favoured
• Electrolytes and endocronology
  • ​​​​​​​One should pay careful attention the the BSL of all ICU patients, and there is really nothing about these diabetics that might discriminate them from other critically ill diabetics.
  • If the patient has hypothyroidism, it is important to negotiate some strategy with the surgeon regarding oral thyroxine replacement (i.e. how long would they want the patient to remain fasted after the anastomosis).
• Fluid management and renal monitoring
  • ​​​​​​​The college recommends caution with fluid resuscitation, so as to avoid making the anastomosis oedematous. This is of course completely at odds with the need to resuscitate them vigorously when you discover their rhabdomyolysis (Chakravartty et al, 2013). Older patients, those with long operations, high BMI, hypertension and those using statins are at higher risk. Apparently a CK rise over 1,000 IUs is relatively common, and is associated with an acute renal failure rate of 14%. If this develops, hospital mortality from this supposedly elective procedure increases to 25%. 
• Diet and nutrition
  • ​​​​​​​Mechanick et al (2013) recommend a "low‐sugar clear liquid meal program" to commence after 24 hours, but this is obviously going to depend on the type of surgery and how many inadvertent enterotomies there were.
  • Vitamin supplementation should take place in patients with risky premorbid nutrition (i.e. just because they are obese does not mean they are not suffering from poor nutrition)
• DVT prophylaxis
  • ​​​​​​​Low molecular weight heparin should probably be dosed to total body weight
• Antibiotics
  • ​​​​​​​Are not indicated, except to prevent or manage recalcitrant thiamine deficiency (apparently upper GI bacterial overgrowth in these people can result in thiamine deficiency)

References

College answer

a)

Plain films: - Identical to mechanical obstruction: dilated bowel loops: may have fluid levels CT demonstrates dilated large bowel without a clear transition point or obstructing lesion.

b)

Trauma, especially fractures 

Recent surgery, especially involving spinal anaesthesia 

Burns 

Diabetes Mellitus

Uraemia

Severe medical illness, such as pneumonia, myocardial infarction, or heart failure 

Neurologic conditions 

Chemotherapy (e.g., all-trans retinoic acid, methotrexate, vincristine) 

Retroperitoneal pathology, such as malignancy or haemorrhage 

Electrolyte disturbance 

Medication (e.g., narcotics, phenothiazine’s, calcium channel blockers, alpha-2-adrenergic agonists, epidural analgesics)  

c)

Initial management of acute colonic pseudo-obstruction consists of conservative therapy in patients without significant abdominal pain or signs of peritonitis and those who have one or more potential factors that are reversible.  

Treat underlying disease, stop aggravating drugs, avoid laxatives, and keep NPO. NG tube – encourage mobility. Consider opiate reversal agents e.g. GI naloxone or SC Naltrexone

If fail or progress consider neostigmine:  In patients with caecal diameter >12 cm (varies) or failure of 24 to 48 hours of conservative therapy. Up to 2 mg slow IV and repeat if needed. Lower doses may also be effective. Studies have shown high response rate with low rate of recurrence. Side effects include abdominal pain, hypersalivation, vomiting and bradycardia. Perforation may occur if there is unrecognised mechanical obstruction.

Colonoscopy decompression: Those patients who fail or who have contraindications to neostigmine. Technically difficult and perforation is a risk. No randomised trials.

Surgery: In the absence of a colonic perforation, cecostomy tube or a segmental or subtotal resection with primary anastomosis can be performed. In the patients with a colonic perforation, a total colectomy, ileostomy, and Hartmann procedure are performed to retain the option of future ileorectal anastomosis

Examiners Comments:

Management plan poorly structured in many cases. Overall reasonably well answered.

Discussion

a)

Radiological features of colonic pseudo-obstruction:

• Plain radiography: findings identical to mechanical obstruction, i.e. dilated bowel loops
• CT findings: gaseous dilatation of the colon with no stricture, mass or clear transition point. A "smooth transition" may be seen, which is a slight discrepancy in diameter between the proximal and distal bowel loops - less than 50% (Choi et al, 2008).

b)

The list of risk factors for colonic-pseudo-obstruction specifically is derived from Saunders et al (2005) and Wells et al (2017):

• Surgical: Cardiac surgery, solid organ transplantation, major orthopaedic surgery, spine surgery
• Cardiorespiratory    Shock, myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease
• Neurological    Dementia, Parkinson’s disease, Alzheimer’s disease, stroke, spinal cord injury
• Metabolic    Electrolyte imbalance, diabetes, renal failure, hepatic failure
• Medications    Opiates, anti-Parkinson agents, anticholinergics, antipsychotics, cytotoxic chemotherapy, clonidine
• Obstetric/gynaecological    Caesarean section, normal vaginal delivery, instrumental delivery, preeclampsia, normal pregnancy, pelvic surgery
• Infectious    Varicella-zoster virus, herpes virus, cytomegalovirus
• Miscellaneous    Major burns/trauma, severe sepsis, idiopathic

For ileus and constipation in general, you would expect the following risk factors:

Modifiable ICU-related risk factors

• Delayed enteral nutrition (delayed for longer than 24 hrs) - although early enteral nutrition has also been blamed, and in fact in ICU patients nasogastric nutritional formula is at least as likely to cause constipation as diarrhoea ( Montejo et al, 1999).
• Reduced mobility
• Deep sedation
• Heavy opiate use
• Anticholinergic drug side effects
• Calcium channel blockers
• The use of paralysing infusions
• Electrolyte disturbance, eg.hypokalemia hypercalcemia and hypomagnesemia
• Dehydration, inadequate fluid resuscitation (or excess diuresis)
• Hypotension (SBP under 90mmHg - Gacouin et al, 2010)
• Hypoxia (P/F ratio under 150 - also Gacouin et al)

Non-modifiable disease risk factors

• Abdominal surgery
• Severe illness
• Paralysis (eg. spinal cord injury) 
• Prior alcohol or cannabis use
• Nicotine withdrawal

c)

Most of this comes from Saunders et al (2005). Options for management of colonic pseudo-obstruction can be divided into categories:

Supportive

• Nil by mouth
• Correct electrolytes
• Ensure the patient is well-hydrated
• Nasogastric tube on free drrainage or low wall suction
• Rectal tube to gravity drainage
• Limit anti-motility medications, such as opiates and anticholinergic agents
• Mobilise the patient and sit them out ouf bed

Pharmacological (pro-motility) management

• Oral or nasogastric naloxone
• Methylnaltrexone
• Enema
• Erythromycin
• Neostigmine

Interventional (decompressive) management

• Sigmoidoscopy
• Colonoscopy 
• Surgical decompression
• Caecostomy 
• Colectomy, ileostomy, and Hartmann procedure

References

College answer

Mild hyponatraemia and hypokalemia may be secondary to fluid therapy or diuretic treatment. Mild acidosis may be secondary to initial ischaemic insult, or hyperchloraemic in the setting of fluid resuscitation. 
Low phosphate and protein may indicate pre-existing malnutrition: risk of refeeding. 
Features of liver impairment or failure with elevated total bilirubin, GGT, AST and ALT.  
High AST to ALT ratio is associated with cirrhosis. rhabdomyolysis (unlikely as CK normal). 
In this context both ischaemic liver damage (from out of hospital cardiac arrest) and alcoholic liver damage should be considered. However, the normal renal function may make ischaemic liver damage less likely. The high AST may reflect AMI as a precipitating factor for the arrest. 
 

Discussion

"Rationale for the results observed" appears to be a request for an unordered list of abnormalities, judging by the college answer. Thus, they are presented here in the format of abnormality(rationale)

• Trivial hyponatremia (liver disease, or fluids, or diuretics)
• Trivial hypokalemia (fluids or diuretics)
• Mild NAGMA -anion gap is 4.7 (saline resuscitation)
• Low albumin (liver disease or malnutrition)
• Raised bilirubin (liver disease)
• Trivially deranged LFTs (liver disease)
• Low phosphate (malnutrition)

It is unclear how this tests anything.

References

College answer

• Severe Right or congestive heart failure ( increases preload)
• Polycystic liver disease
• Caution in: portal vein thrombosis
• Pulmonary hypertension/tricuspid regurg
• Hepatopulmonary syndrome
• Active infection
• Tumor in shunt pathway

Complications:         (50% marks)

Peri-insertion:

• Technical failure
• Trauma to heart/liver
• Bleeding haemoperitoneum
• Bile leak
• Stent Migration

Post insertion:

• Encephalopathy
• Stenosis/obstruction of shunt (uncommon with modern stents)
• Portal or hepatic vein thrombosis
• Acute liver ischamia
• Infection: peritonitis, endotipsitis
• Heart failure
• Deterioration in hepatic function

Examiners Comments:

Candidates responses lacked specific details.

Discussion

In short, the rationale for a TIPS can be summarised as follows:

• Portal hypertension causes the majority of the morbidity from chronic liver disease
• This is due to raised portal pressure
• TIPS decompresses the portal circulation by allowing it to empty into the comparatively lower central venous circulation
• Ergo, TIPs should relieve the majority of the morbidity from chronic liver disease

Indications for TIPS include:

• Refractory ascites or hepatic hydrothorax
• Refractory rebleeding in variceal disease
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Bridge to liver transplant
• Hepatic vein thrombosis
• Hepatic veno-occlusive disease
• Portal vein thrombosis

Contraindications (from Boyer and Haskal, 2009) include

• Absolute contraindications:
  • Moderate to severe pulmonary hypertension
  • Congestive heart failure
  • Multiple hepatic cysts
  • Uncontrolled sepsis
  • Uncontrolled biliary obstruction
  • Total portal vein thrombosis (in the absence of any patent intrahepatic branches)
• Relative contraindications:
  • A MELD score above 18
  • Central hepatocellular carcinoma
  • Portal vein thrombosis (in the absence of an experienced operator)
  • Hepatic vein thrombosis
  • Severe coagulopathy or thrombocytopenia

Technical complications of TIPS procedure:

• Vascular access complications
• Hepatic damage (through-and-through puncture): risk of intraperitoneal haemorrhage is 1-2%
• Haemobilia (damage to the biliary tree)
• Shunt stenosis or thrombosis (it happens in up to 70%)
• Shunt migration
• Hepatic vein stenosis (this can sabotage a future transplant)

Complications from portal venous shunt:

• Worsening hepatic encephalopathy
• Shunt thrombosis or portal vein thrombosis (7-10%). If there is already a portal vein thrombosis, this risk appears to increase somewhat (Perarnau et al, 2010) - which probably reflects the overall prothrombotic diathesis.
• Bilirubin rise: the diseased liver doesn't even get a chance to metabolise it
• Ischaemic hepatitis: the liver gets much of its oxygen from the portal vein, and even in spite of the hepatic arterial buffer response there is a risk of ischaemic hepatitis.
• Haemolysis (due to the direct shearing effect of being in contact with the shunt)
• "Unmasked" cardiomyopathy: the TIPS returns splanchnic blood to the heart and acts as a volume challenge, and if there was pre-existing cardiomyopathy, it may be dramatically revealed in this manner.
• Tricuspid endocarditis (organisms may now travel directly from the leaky gut into the systemic circulation)
• Shunt infection may occur, where the shunt may become the source of infection. The term "edotipsitis" is supposed to reflect the fact that persistent bacteraemia resembles bacterial endocarditis. 

References

Ochs, Andreas, et al.New England Journal of Medicine 332.18 (1995): 1192-1197."The transjugular intrahepatic portosystemic stent–shunt procedure for refractory ascites." 

Guevara, Mónica, et al. "Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems."Hepatology 28.2 (1998): 416-422.

Papatheodoridis, George V., et al. "Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta‐analysis." Hepatology 30.3 (1999): 612-622.

Azoulay, D., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation." Bone marrow transplantation 25.9 (2000).

Ganger, Daniel R., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis." The American journal of gastroenterology 94.3 (1999): 603-608.

Freedman, A. M., et al. "Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review." Radiographics 13.6 (1993): 1185-1210.

Rösch, J., et al. "Transjugular intrahepatic portacaval shunt an experimental work." The American Journal of Surgery 121.5 (1971): 588-592.

Rössle, Martin. "TIPS: 25years later." Journal of hepatology 59.5 (2013): 1081-1093.

Colapinto, R. F., et al. "Creation of an intrahepatic portosystemic shunt with a Grüntzig balloon catheter." Canadian Medical Association Journal 126.3 (1982): 267.

Conn, Harold O. "Transjugular Intrahepatic Portal‐systemic Shunts: The State of the Art." Hepatology 17.1 (1993): 148-158.

Gülberg, Veit, et al. "Hepatic arterial buffer response in patients with advanced cirrhosis." Hepatology 35.3 (2002): 630-634.

Boyer, Thomas D., and Ziv J. Haskal. "The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: update 2009." Hepatology 51.1 (2010): 306-306.

Perarnau, Jean-Marc, et al. "Feasibility and long-term evolution of TIPS in cirrhotic patients with portal thrombosis." European journal of gastroenterology & hepatology 22.9 (2010): 1093-1098.

Orloff, Marshall J. "Emergency treatment of bleeding esophageal varices in cirrhosis." Current problems in surgery3.7 (1966): 13-28.

Unger, Lukas W., et al. "The role of TIPS in the management of liver transplant candidates." United European gastroenterology journal 5.8 (2017): 1100-1107.

DeSimone, J. A., et al. "Sustained bacteremia associated with transjugular intrahepatic portosystemic shunt (TIPS)." Clinical infectious diseases 30.2 (2000): 384-386.

Bouza, Emilio, et al. "Endotipsitis: an emerging prosthetic-related infection in patients with portal hypertension." Diagnostic microbiology and infectious disease 49.2 (2004): 77-82.

Sanyal, Arun J., and K. Rajender Reddy. "Vegetative infection of transjugular intrahepatic portosystemic shunts." Gastroenterology 115.1 (1998): 110-115.

College answer

References

UpToDate have a good article on acute diarrhoea for the paying customer.

Kelly, T. W. J., M. R. Patrick, and K. M. Hillman. "Study of diarrhea in critically ill patients." Critical care medicine 11.1 (1983): 7-9.

Wiesen, Patricia, Andre Van Gossum, and Jean-Charles Preiser. "Diarrhoea in the critically ill." Current opinion in critical care 12.2 (2006): 149-154.

Ferrie, Suzie, and Vivienne East. "Managing diarrhoea in intensive care."Australian Critical Care 20.1 (2007): 7-13.

Pawlowski, Sean W., Cirle Alcantara Warren, and Richard Guerrant. "Diagnosis and treatment of acute or persistent diarrhea." Gastroenterology 136.6 (2009): 1874-1886.

Schiller, Lawrence R. "Diarrhea." Medical Clinics of North America 84.5 (2000): 1259-1274.

Timothy A. Woods. "Diarrhea." Chapter 88 in: Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990.

Guerrant, Richard L., et al. "Practice guidelines for the management of infectious diarrhea." Clinical infectious diseases 32.3 (2001): 331-351.

Cox, George J., et al. "Etiology and outcome of diarrhea after marrow transplantation: a prospective study." Gastroenterology 107.5 (1994): 1398-1407.

Hamdeh, Shadi, et al. "Clinical approach to diarrheal disorders in allogeneic hematopoietic stem cell transplant recipients." World Journal of Hematology 5.1 (2016): 23-30.

College answer

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