End-stage liver disease Flashcards
What does the portal circulation in the liver look like?
Sources? 2
Liver receives blood supply from:
- Hepatic artery 25%: oxygenated
- Portal vein (75%) partially oxygenated blood collected from splanchnic circulation (vascular under stomach)
What is portal hypertension defined as?
What pressure is the strongest predictor of clinical decompensation?
Defined as hepatic venous pressure gradient (HVPG) over 5 mmHg
- reflects a pressure difference between portal & venous central system
- invasive (needs catheter to measure)
Clinical decompensation
- HVPG over 10 mmHg
What does Portal HTN result from? (2)
What does this cause (2)
- Increased intrahepatic vascular resistance AND
- architectural changes (fibrosis, nodules) and dynamic elements - Increased blood flow to the portal venous system
- established through splanchnic vasodilation (from excessive nitric oxide)
This will lead to hypovolemia & hypotension
- Triggers water retention
- Increases cardiac output
What happens to the veins as HVPG increases?
Varices: swollen veins in the esophagus or stomach
- Substances (toxins) - normally removed by liver, can bypass into circulation
- Collateral vessels develop at End of esophagus and proximal area of stomach
- Collateral vessels become enlarged & become full of “twists and turns”
- They can swell so much –> burst and cause bleeding
What does a HPVG of 10 mmHg suggest? (3)
- Variceal formation (bleeding at 12 mmHg)
- Clinical decompensation
- HCC & increased surgical risk
What is the treatment for pre-primary prophylaxis (pt with no varices)? (2)
- Screen EGD
- Follow up screening every 2-3 years or at time of decompensation
No benefits of NSBB (non-selective BB) use here
What are the 2 treatment options for primary prophylaxis (pt with varices)?
Which is more efficacious?
- NSSB
- Endoscopic variceal ligation (scope ties off varices with rubber bands)
Equivalent efficacy in both
What is the MOA of NSSB? (2)
Result?
Examples (2)
- Blocks B1 receptor = Reduction in cardiac output and heart rate
- Blocks B2 receptor = Reduces splenic blood flow = this allows for splanchnic vasoconstriction effect = reduces portal blood flow = reduces portal pressure (correlates with improvement in survival)
Propanolol, Nadolol
Why would a cardio selective BB not be effective in this ESLD?
B1 is blocked
B2 is not blocked so we will not get that splanchnic vasoconstriction
Carvedilol MOA
Efficacy?
Contraindication?
Non-selective BB with additional a-1 blocking properties
- Blocks a1: Additional vasodilating effects that further decreases portal hepatic resistance & portal pressure
- This is MORE effective than propranolol at lowering HVPG
Contraindication?
- NOT used for secondary prophylaxis (relates to intrinsic a1 adrenergic effect - may promote excessive hypotension & sodium retention)
What are the targets for propanolol and Nadolol (3)
- Resting heart rate 55-60 bp
- Avoid systolic pressure <90
- Final dose tolerated
Do you increase or decrease maximal dose of NSBB if ascites (inc fluid in liver) present?
Decrease
Target for Carvedilol (2)
- Avoid in systolic pressure <90
- Final dose tolerated
When is NSSB not recommended
In patients with SMALL varices in absence of risk factors (reg colour patches/cherry red spots/red whale markings)
What is the BB window hypothesis? When does it open and close
Open in early cirrhosis and decompensated cirrhosis with moderate-large varices with/without bleeding
Closes in end-stage cirrhosis with
- refractory ascites
- AKI
- Sepsis
etc..
What are the general recommendations of active bleeding of esophageal varices? (7)
Hemodynamic support
Maintain patent airway
Transfuse to maintain hemoglobin 7g/dL (80)
Pharmacologic therapy (somatostatin & analogs)
Endoscopic therapy (EVL, sclerotherapy)
Antibiotic prophylaxis
Shunt surgery or TIPS as salvage therapy
During active GI bleed, what do we stabilize blood volume to
Hgb
SBP
HR
- Hgb ~ 80 g/L
- SBP 90-100 mmHG
- HR < 100 bpm
What drug therapy do we start in active varices bleed? (2)
MOA
Duration of each
Vasoactive drug therapy
- control the bleeding episode by decreasing portal pressure & variceal blood flow
- Somatostatin (1st line) (up to 5 days)
- Vasopressin (not in canada) (24 hrs)
Octreotide (somatostatin)
Administration
Efficacy
Safety
IV bolus
Continuous infusion
Causes splanchnic vasoconstriction
Efficacy as a single therapy for variceal bleeding is controversial:
ADR
Few major side effects:
- hyperglycemia & abdominal discomfort
*Associated with tachyphylaxis
Vasopressin
Administration
Efficacy
Safety
Given as continuous IV infusion (no bolus dose)
Most potent splanchnic vasoconstrictor
* Decreases blood flow to all splanchnic organic (leads to a decrease in portal venous inflow & portal pressure)
Efficacy
- Sometimes given with nitroglycerin (to offset s/e profile & also help decrease portal pressure)
ADR
- Multiple side effects related to splanchnic vasoconstriction (bowel ischemia) and systemic vasoconstriction (HTN, MI) = LIMITS USE
What do trials say with endoscopic + octreotide vs endoscopic alone
combination improves initial control of bleeding & 5 day hemostasis AND it does not cause any difference in mortality or severe ADR
Benefits of starting short-term antibiotics during varices bleeding (3)
Infection is pathophysiologically linked with variceal bleeding
abx will
- reduce risk of infection
- reduce early re-bleeding
- reduce mortality)
Should you use PPI in variceal bleeding
No
What is the treatment for secondary prophylaxis of varices bleed? (4)
- NSBB + EVL (endoscopic variceal ligation)
- Variceal obliteration with EVL
- First surveillance EGD at 1-3 months –> then every 6-12 months thereafter
- Evaluate for liver transplant eligibility
