Liver Disease: Management of Cirrhosis Flashcards
Ascites defn
§ Accumulation of fluid in the peritoneal cavity.
§ Several contributing factors including:
–Splanchnic vasodilation
–Increased capillary filtration pressure
–Activation of the renin-angiotensin-aldosterone-system (RAAS)
–Decreased albumin
Lymphatic system is overwhelmed
Symptoms of Ascites
§ Abdominal distension
§ Shortness of breath
§ Weight gain
§ Early satiety
goals for ascites tx
§ Eliminate symptoms
§ Reduce the volume in fluid in abdomen, but need to very careful not to cause intravascular volume depletion
§ Prevent recurrence
treatment for Ascites approaches
§ Sodium and fluid restriction § Diuretics § Albumin § Invasive procedures: –Paracentesis –TIPS (Transjugular intrahepatic portosystemic shunt)
Diuretics (3)
Dont need to know dosing for exam
Furosemide:
§ Dose: 40 – 160 mg/day
§ Start 40 mg day, increase 20 –
40 mg/day up to 160 mg
Spironolactone: § Onset of action 2 – 5 days § Dose: 100 - 400 mg/day § Start 100 – 200 mg/day, increase every 5 – 7 days up to 400 mg Aldosterone antagonist Longer to work
Metolazone:
§ Dose: 2.5 – 10 mg/day
§ Start 2.5 mg day, increase up to
10 mg/day as tolerated
Titrate to response!
Measure abdominal girth
Urine output, what is taken in
Target a certain amount of loss per day
Diuretics monitoring for efficacy
Weight, abdominal girth, ins and outs
Roughly 500 ml/day or 0.5 kg/day
Urine output, what is taken in
Target a certain amount of loss per day
titrating dose based on that
Diuretics monitoring for toxicity
Electrolytes, serum creatinine, BUN, hypotension
furosemide, metolazone – uric acid, hyperglycemia, volume depletion
spironolactone – hyperkalemia, gynecomastia/mastalgia, muscle cramps
ascites non-pharm
rescit dietary Na+
restrict fluids to 1.5L/day
bedrest if severe or refractory
ascities parecentesis
flowchart
tap 3-4 L + nonpharm –> improvement = no med
no improvement –> spironolactone
improve –> continue spir
no improvement –? furosemide
improve –? continue spir + furos
no improvement –? metolazone
improve –? continue spir + furos + metolazone
if no improvement, continue 3 diuretics and perform weekly large vol paracentesis
if >5L is removed, infuse 6-8g/L albumin
consider TIPS
what is TIPS
transjugular intrahepatic portosystemic shunt
Metallic shunt connects portal vein t hepatic vein, bypasses the liver
Preventing backup and ascities
Spontaneous Bacterial Peritonitis (SBP)
§ Occurs in 10 – 25 % of patients with ascites § Infection of pre-existing ascitic fluid in peritoneal cavity § Pathogens: E. coli, enterococcus, S. pneumonia § Exact mechanism for inoculation unknown
SBP Treatment:
prevention?
§ Empiric antibiotics: 3rd generation cephalosporins (cefotaxime, ceftriaxone) § Adjust therapy based on culture results of ascites fluid.
Prevention:
§ Trimethoprim/sulfamethoxazole or ciprofloxacin
§ May need long term if previous SBP
Watch for aby resistance, reserve for highest risk pt
Esophageal Varices
what is it
§ Dilated and weakened blood vessels caused
by portal hypertension
§ Alternate routes of blood flow from the portal
to systemic circulation
§ Low pressure vessels handling high pressure
loads
§ Presence is correlated to disease severity
Portal HTN
Dilated blood vessels as pressure goes out to collateral channels
Dilation of rectal veins
Normally low pressure vessels that become engourged, can burst and blee
what are collaterals?
- Esophageal varices
- Umbilical vein to abdominal wall (caput medusa)
- Rectal veins (internal mhemorrhoids
Esophageal Varices
how is it diagnosed?
§ Diagnosed by endoscopy
§ About 20% mortality risk per episode
§ Risk of bleeding dependent on: severity
of liver disease, property of varix (size,
thickness of wall), previous history of
bleeding
§ Variceal bleeding can occur once portal
venous pressure exceeds 12 mmHg
(normal is around 4 mmHg)
Esophageal Varices: Goals
§ Primary Prevention: prevent the first bleeding episode
§ Acute Treatment: stabilize patient with an acute variceal hemorrhage
§ Secondary Prevention: prevent recurrence in someone who has already had a variceal bleed
Primary Prophylaxis of Esophageal Varices
no varix
Varix < 5mm
Varix > 5mm
diagnosis of cirrhosis –> Screen patients for esophageal varices with endoscopy
No varix
Observe patient
Varix < 5mm
Prevention: Beta-blockers
Varix > 5mm
Beta-blockers/EVL (combination)
Beta Blockers
B1 vs B2 blocking action
§ Reduce portal blood flow
§ Non-selective beta blockers preferred
–ie propranolol 10 – 20 mg po bid, nadolol 20 – 40 mg daily
§ Titrate dose to decrease resting heart rate by 25% or 55 – 60 bpm or development of adverse effects.
Beta1 block action – decrease CO, leads
to decrease portal perfusion
Beta2 block action – unopposed alphaadrenergic vasoconstriction, leads to decrease splanchnic perfusion
bb monitoring
–Efficacy: decrease heart rate, lack of bleeding
–Toxicity: hypotension, bradycardia, fatigue, depression, nightmares
Endoscopic Approaches
EVL
EIS
§ EVL: Endoscopic Variceal Ligation
–Placement of rubber bands around the varix
–Placed using a clear plastic channel attached to an endoscope
–Varix sloughs off after 2 – 3 days
§ EIS: Endoscopic injection sclerotherapy
–not as effective as beta-blockers/EVL, not used much
Treatment of Acute Varices
agents used
§ Acute Variceal Bleeding is a medical emergency
§ Accounts of one-third of all deaths
§ Agents used include:
–Vasopressin – helps splanchnic vasoconstriction (quick vasoconstcition)
–Octreotide – synthetic analogue of somatostatin, inhibits the release of vasodilatory hormone (causes splanchnic vasoconstriction)
–Both are given as continuous IV infusions
Treatment of Acute Varices supportive pharm endoscopic surgical
Supportive:Fluids +/- blood
Vitamin K/fresh frozen
plasma/platelets
Prophylactic antibiotics
Pharmacologic Options: Vasopressin, Octreotide
Endoscopic techniques: Sclerotherapy, Band ligation
Surgical: Sclerotherapy, Band ligation, TIPS
Secondary Prevention of Varices
§ Risk of rebleeding is close to 80% (high)
§ Secondary prophylaxis includes:
–Non-selective beta blockers
–EVL
–Combination of both (most of the time)
–TIPS or shunt surgery for failed therapy
Hepatic Encephalopathy (HE)
§ Metabolically induced disturbance on the brain, potentially reversible.
§ Accumulation of substances that are normally removed in the liver.
–Accumulation of gut derived nitrogenous substances such as ammonia (most common reason), another possible cause is decreased clearance
of GABA
§ Must distinguish HE from other causes associated with changes in cognition
major risk factors of hepatic encephalopathy
TIPS, protal vein thrombosis infections (SBP) AKI, electrolyte derangements (dec K_) GI bleed hypoxemia, hyercapnia
Treatment of HE
Lactulose
mechansim
monitoring
§ Mechanism: acidifies the GI tract (NH3 + H+ = NH4+)
§ Increased GI transit through osmotic effect.
§ Dose: 30 – 60 ml TID to QID, adjust dose to produce 2 – 3 soft stools per day, can be given oral, feeding tube, rectally avail
monitoring
Efficacy: number of bowel movements, neurological status
Toxicity: GI discomfort, diarrhea, dehydration
Treatment of HE
Rifaximin
§ Mechanism: Reduces urease producing bacteria in
the gut = decrease in blood ammonia
§ Dose: 550 mg bid
§ Expensive, requires special authorization for ABC
would be long term use (more than 2 wks)
monitoring:
Efficacy: neurological status
Toxicity: GI discomfort, nausea, headache, dizziness, edema
Treatment of HE
flowchart see slide 31
Give lactulose if HE
check improvement in 24-48 hours
Reoccur, give rifaximin
Futher recurrence, look at other thins, consider liver transplant )dont need to know this part)
Treatment of HE
flowchart see slide 31
Give lactulose if HE
check improvement in 24-48 hours
Reoccur, give rifaximin
Futher recurrence, look at other thins, consider liver transplant (dont need to know this part)
Pharmacokinetic Considerations in Liver Disease
Patient factors:
§ Does the patient require this drug? At this dose? Is there an alternative?
§ How severe is the patient? What is the clinical status of the patient?
§ Is the patient liver function stable or changing?
§ What is the expected length of therapy?
Drug factors:
§ Is the drug eliminated via Phase I or Phase II?
§ Is there active metabolites?
§ How much (%) of the drug is eliminated by the hepatic route?
§ What are the consequences of not adjusting the dose?
§ Decrease clearance § Decrease in first pass effect § Decrease albumin § Increase volume of distribution in patients with ascites (esp polar drugs) § Increase half-life (T1/2 = Vd/Cl)
anticipate drug accumulation, enhanced effect
Start seeing effects on phase I earlier
If severely affected, will see both Phase I and II impacts
low E drugs dependent on intrisnic metabolism
high E dependent on blood flow
- both bloodflow and intrinsic metabolism is affected in pts with ESRD or severe disease
