Thread by @gretchemaben

At the request of several people, here is a thread on acute liver failure and decompensated cirrhosis in the ICU. Disclaimer: This is a broad overview of some key issues, but I am not a hepatologist. 1/

Let's start with a definition of acute liver failure (different from decompensated cirrhosis): It is characterized by acute liver injury, hepatic encephalopathy, and an elevated INR in a patient without cirrhosis or preexisting liver disease. 2/

Let's talk about variceal hemorrhage. It has a 15-20% 30 day mortality. Note that portal hypertensive gastropathy is common, but is uncommonly a cause of significant bleeding. EGD for PHG shows friable mucosa with diffuse mucosal oozing. 3/

Goals of therapy for variceal hemorrhage:
- Restore hemodynamic stability (IV access and fluid resuscitation, pRBC transfusion for hgb <7)
- Restore adequate oxygenation (Supplemental O2 if needed, Airway protection) 4/

- Control bleeding (Octreotide bolus and infusion (50 mcg IV per hour) or Terlipressin if available. If ongoing hematemesis consider NGT and Erythromycin. Urgent endoscopy within 12 hours; can do endoscopic variceal ligation or endoscopic sclerotherapy. 5/

Self-expanding metal stents have been used for refractory bleeding. If bleeding cannot be controlled endoscopically can consider TIPS or surgical shunting. Balloon tamponade for short-term hemostasis if severe bleeding.) 6/

- Prevent complications (SBP prophylaxis with Ceftriaxone or Cipro (when taking oral) for 7 days.) 7/

Let's talk about ascites, the most common complication of cirrhosis. It is typically treated with diuretics and sodium restriction, but some patients need repeated paracentesis or TIPS. 8/

For patients with diuretic-resistant ascites you should stop medications that decrease systemic blood pressure (BBs, ACEIs, and ARBs), as well as NSAIDs (cause renal vasoconstriction). Oral Midodrine may be helpful. 9/

For paracenteses >5 L give Albumin (6-8 g/L of fluid removed). Typically give 25% if hypervolemic and 5% if the patient is dehydrated. Both are isotonic. 10/

What about hepatic hydrothorax? It is a pleural effusion in a patient with cirrhosis and no underlying cardiopulmonary disease. Usually right-sided, but can be bilateral and rarely left-sided. 11/

Treated with diuretics and sodium restriction. Some cases require repeated thoracentesis or TIPS. Do not place a chest tube as it can result in protein and electrolyte depletion, infection, renal failure, and bleeding. 12/

Refractory hydrothorax can be managed with repeated thoracentesis, TIPS, pleurodesis, surgical repair of diaphragm defects, or liver transplantation. 13/

Initial thoracentesis needs diagnostic testing (cell count with diff, gram stain and culture, protein, albumin, LDH, bilirubin, and pH). Don’t forget to send serum labs! Can also check TG level, PCR for TB, amylase level, and cytology depending on suspicion. 14/

You can also find spontaneous bacterial empyema (SBEM):
Diagnostic Criteria:
-Positive pleural fluid culture & PMN > 250.
-Negative pleural fluid culture & PMN >500.
-No evidence of pneumonia on imaging.
-Treatment: 3rd generation cephalosporin or IV Levofloxacin if allergic. 15/

Now let's talk about spontaneous bacterial peritonitis (SBP). It is a infection of preexisting ascitic fluid without evidence for an intra-abdominal secondary source.

Clinical manifestations include fever, abdominal pain, and altered mental status. 16/

Diagnosis with positive ascitic fluid culture and/or ascetic PMN count of >/=250 cells/mm3.

Treatment: Cefotaxime and can narrow based on culture results.
17/

Treat for 5 days then reassess. Unusual/resistant/endocarditis organisms may need longer treatment. If fever or pain persist after 5 days repeat paracentesis. 18/

If PMN <250, stop. If PMN > pretreatment look for surgical source of infection. If PMN >250 but less than pretreatment, continue abx for 28 hours and repeat paracentesis. 19/

Risk of renal failure may be decreased with IV Albumin 1.5 gm/kg within 6 hours of diagnosis then 1 g/kg on day 3. Give albumin if creatinine >1, BUN >30, total bilirubin >4. 20/

Start empiric treatment in any patient with ascites who has one or more of:
Temperature > 100.0 F
Abdominal pain
Change in mental status
Ascitic PMN >250.
21/

Discontinue non-selective BBs (increased mortality, risk of HRS, and hospital LOS).

If bacterascities (bacteria present with PMN <250), treat if symptomatic, but if asymptomatic repeat paracentesis in 48 hours.
22/

Everyone's favorite: Hepatic encephalopathy (HE)!

Grades:
I: Changes in behavior, mild confusion, slurred speech, disordered sleep
II: Lethargy, moderate confusion
III: Stupor, incoherent speech, sleeping but wakes with stimulation
IV: Coma, Unresponsive to pain
23/

Treatment:
- Correct precipitating causes: GIB, infection, hypokalemia, metabolic alkalosis, renal failure, hypovolemia, hypoxia, sedative use, hypoglycemia, or constipation.
24/

- Lower blood ammonia:
Lactulose 30-45 mL 2-4 times/day (titrate to stools).

Rifaximin 400 mg po TID or 550 mg BID (generally added to Lactulose rather than used as a replacement).
25/

Note that protein restriction is not ideal for ICU patients who need adequate nutrition.

Albumin dialysis (extracorporeal nonbiologic liver support system) has been shown to improve HE, but did not have an effect on survival.
26/

Cerebral edema is uncommon in grade 1 or II HE, but is present in 25-35% of patients with grade III HE and in 75% of patients with grade IV HE.

Pupillary changes are a sign of increased ICP.

Seizure activity is common, but may be difficult to detect.
27/

Some suggest ICP monitoring to guide management, but infection and bleeding are potential complications. You should at least be screening for cerebral edema in patients with grades 3 and 4 HE.
28/

Treatment:
Hyperosmotic agents like Mannitol 0.5-1 g/kg.
Hyperventilation to a PaCO2 of 25-30 (only a temporary treatment).
Barbituates if severe ICP elevation.
29/

Let's talk about portal vein thromboses (PVT). They can contribute to the development of portal HTN.

Acute PVT: May be clinically silent, but may have abdominal pain (sudden or progressive). May have EV bleeding. Consider septic PVT if fever, chills, and painful liver. 30/

Chronic PVT: Often asymptomatic but may have symptoms related to portal hypertension or portal cholangiopathy.

Diagnosis: Doppler ultrasound initially if low suspicion. Abdominal CT with contrast to confirm or if high suspicion.
31/

Treatment of acute PVT is anticoagulation with LMWH bridge to Warfarin or possibly a DOAC. Treat for at least 3-6 months, but long-term is recommended if uncorrectable thrombotic risk factors.
32/

Treatment of chronic PVT is less clear because those patients are at risk for recurrent thrombosis, but also for variceal bleeding, so decisions regarding anticoagulation are made on a case-to-case basis.
33/

Another sticky situation (or less sticky if thrombocytopenia): Coagulopathy!

Patients with liver disease can have both impaired hemostasis (coagulation factor defects, thrombocytopenia and platelet dysfunction, altered fibrinolytic system) and prothrombotic changes.
34/

Do not assume that these patients are anticoagulated as standard coagulation testing does not accurately assess bleeding or clotting risk in patients w/ cirrhosis. It is better to use thromboelastography (TEG) or thromboelastometry (ROTEM) to assess hemostasis.
35/

Abnormal hemostasis labs do not require treatment if the patient is asymptomatic. 36/

If the patient is bleeding:
- Vitamin K if possible deficiency (suspected poor nutrition, cholestatic disease, diarrhea, antibiotic use). Give 10 mg IV, but can give 10 mg po for 3 days if minor bleeding.
37/

- Consider cryoprecipitate (one bag per 10 kg) if poorly controlled bleeding or if fibrinogen is <100-120 mg/dL.
- If hyperfibrinolysis consider an antifibrinolytic agent like tranexamic acid or aminocaproic acid.
38/

- Ideally avoid other therapies like PCCs, FFP, and rFVIIa, but may be used on a case-by-case basis.
39/

Thrombocytopenia is common. Transfusion is only needed if there is an invasive procedure planned. Aim for platelets of >50K for moderate-risk procedures and 100K in high-risk situations or if active bleeding.
40/

Thrombopoietin receptor agonists can increase the platelet count over several days.

Partial splenic embolization has also been used for thrombocytopenia.
41/

Society of Interventional Radiology Consensus Guidelines recommend:
- INR N/A for low risk and <2.5 for high risk procedure.
- Platelets >20 for low risk and >30 for high risk.
- Fibrinogen >100.
42/

There is a condition called accelerated intravascular coagulation and fibrinolysis (AICF) which looks very similar to DIC. It is caused by ongoing intravascular thrombin generation with coagulation factor consumption.
43/

- Factor VIII levels are generally increased or normal in liver disease, but decreased in DIC.
- D-dimer levels are generally normal or mildly elevated in liver disease, but are often dramatically increased in DIC.
- Note that DIC can also occur in liver disease.
44/

Now for the dreaded complication: Hepatorenal syndrome (HRS).

NOT ALL ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS IS HRS!
45/

Clinical presentation: Progressively rising serum creatinine, normal urine sediment, minimal proteinuria (or none), and very low urine sodium. Can be oliguric or nonoliguric.
46/

Types:
- Type 1: More serious. At least a 2 fold increase in serum creatinine to >2,5 mg/dL over <2 weeks.
- Type 2: Less severe impairment.
47/

Diagnostic criteria:
- Chronic or acute liver disease with advanced hepatic failure and portal hypertension.
- AKI with increase in serum creatinine of 0.3 mg/dL or more over 48 ours or an increase in baseline of 50% within 7 days.
Cont...
48/

- Absence of other apparent causes for AKI (shock, nephrotoxins, obstruction, etc).
* Urine RBC <50 cells
* Proteinuria <500 mg/day
* Lack of improvement with IV Albumin 1 g/kg for at least 2 days and diuretic cessation.
49/

Treatment:

Critically ill: Norepinephrine with goal increase of MAP by 10 mmHg to at least >82 mmHg with Albumin 1 gm/kg (up to 100 gm) daily IV for at least 2 days.
50/

Not critically ill: Terlipressin is available. In the US, try a combination of Midodrine, Octreotide (infusion or subQ), and Albumin 1 gm/kg (up to 100 gm) IV daily for two days then 25-50 gm daily until cessation of Midodrine and Octreotide.
51/

For patients treated with norepinephrine, terlipressin, or octreotide treat for 2 weeks (although some use longer durations).

Some patients who fail to respond to therapy may benefit from a TIPS.
52/

Patients who are liver transplant candidates or have a reversible form of liver injury may be candidates for dialysis. 53/

Let's differentiate between hepatopulmonary syndrome and portopulmonary hypertension for all of you budding pulmonologists.

Hepatopulmonary syndrome is a triad of liver disease, increased A-a gradient on room air, and evidence of intrapulmonary vascular abnormalities.
54/

There are no effective medical therapies and liver transplantation is the best treatment. Oxygen supplementation is warranted for patients with severe hypoxemia. 55/

Portopulmonary hypertension is the presence of pulmonary hypertension in a patient with portal hypertension.

Patients may present with fatigue, dyspnea, peripheral edema, chest pain, and syncope.

Diagnose with right heart catheterization.
56/

Treatment:
- Treat portal hypertension (Diuretics. Avoid BBs. Liver transplantation.)
- Avoid TIPS as can increase RV preload and worsen heart failure.
- May also be candidates for PAH-directed therapy based on WHO functional class.
57/

So if these patients are coagulopathic do they need DVT prophylaxis? Patients with cirrhosis are at risk for VTE.
58/

VTE prophylaxis is appropriate for high-risk hospitalized patients with liver disease. Exceptions include ambulatory patients, platelets <50K, active bleeding, and high-risk varices. 59/

We give a lot of NAC to patients with Tylenol ODs, but when else can it be used? Consider NAC for patients who are not liver transplant candidates, in those where Tylenol toxicity may be a contributing factor, & to those with an indeterminate cause for their liver failure. 60/

What about hypotension in patients with cirrhosis?
- Norepinephrine is still recommended as a first-line vasopressor in these patients.
- A goal MAP of >60 mmHg is appropriate for most patients.
61/

What to do with that pesky lactate?
Impaired liver function may lead to decreased lactate clearance, so trends in lactate are more important than absolute numbers.
62/

When should you add antifungal therapy to patients with cirrhosis?

Add antifungal therapy to intubated patients with yeast in their sputum/BAL and an additional positive fungal culture from another sterile site.
63/

Add antifungal therapy to ICU patients without clinical improvement after 48 hours in high prevalence regions (>5%) or with risk factors for development of invasive fungal infections. 64/

Other Tips:
- Get procedures done early in ALF because the coagulopathy will get worse.
65/

- Social EtOH use is not necessarily a contraindication for liver transplantation. Even for patients with alcoholic liver disease there are some programs who have transplanted patients who were unlikely to survive for 6 months of abstinence and short-term data are promising. 66/

- Acute-on-chronic liver failure (ACLF) is when an acute insult leads to a significant worsening of previously compensated liver disease. Note that this has a significantly higher mortality than a traditional acute decompensation of liver failure. 67/

-Patients with decompensated cirrhosis are very sick and have high mortality rates. Median survival is <6 months for patients with a MELD score of >/=21 or >/=18 and a hospitalization for an acute liver-related illness. 68/

Other markers of poor survival include:
- MAP <82 mmHg
- Presence of relative adrenal insufficiency
- Hepatopulmonary syndrome
- Rapidly progressive HRS
- ICU admission for complications of liver disease (with pressor requirement, serum creatinine >1.5, or jaundice).
69/

REFERENCES! 70/

Thanks for joining me for this tweetucation! And remember: Be nice to your liver, because it sure won't be nice to you if you're not! 71/71

*48 hours