01Approach to the Critical Patient/attcp80

Immediate priorities

›Airway and neurologic threats

›Grade 3 to 4 hepatic encephalopathy

›Loss of airway protection

›Impending cerebral edema

›If grade 3 to 4 encephalopathy, intubate for airway protection

›Avoid agitation and gag stimulation

›Head of bed elevation to 30 degrees

›Cerebral herniation signs

›Fixed dilated pupils

›Brainstem herniation may contraindicate transplant

›Metabolic and circulatory threats

›Hypoglycemia from loss of gluconeogenesis

›Glucose every 1 to 2 hours

›Continuous dextrose infusion D10W or D20W

›Vasodilatory shock

›SBP < 90 mmHg

›MAP < 65 mmHg

›If fluid-refractory hypotension, norepinephrine first line

›Balanced crystalloid resuscitation first

›Avoid hypervolemia and hypovolemia

›Etiology-directed early actions

›Suspected acetaminophen toxicity

›N-acetylcysteine without waiting for levels

›Activated charcoal if within 4 hours of ingestion

›Indeterminate etiology

›Empiric NAC for grade 1 to 2 encephalopathy

›Broad etiologic workup in parallel

02History/hx81

Timeline and presentation

›Onset and progression

›Jaundice timeline

›Hyperacute within 7 days

›Subacute over weeks

›Constitutional prodrome

›Malaise and fatigue

›Nausea and vomiting

›Abdominal symptoms

›Right upper quadrant pain

›Dark urine

›Encephalopathy history

›Confusion or somnolence

›Sleep-wake reversal

›Personality change

›Witnessed agitation or coma

›Collateral required

›Often unable to self-report

Etiologic history

›Medication and ingestion review

›Acetaminophen exposure

›Combination products included

›Sustained-release formulations

›Intentional vs unintentional overdose

›Time amount and co-ingestants

›Suicidal ideation history

›Herbal and dietary supplements

›CAM products

03Physical Exam/exam66

Vitals and general

›Hemodynamic snapshot

›Blood pressure

›Vasodilatory hypotension

›MAP < 65 mmHg

›Heart rate and respiratory rate

›Sinus tachycardia hyperdynamic state

›Tachypnea from respiratory alkalosis

›Temperature

›Fever absent in up to 30% of infected patients

›Hypothermia as severe marker

›General appearance

›Jaundice and icterus

›May be minimal in hyperacute

›Scleral icterus

›Excoriations

›Pruritus from cholestasis

›Skin findings

Neurologic exam

›Encephalopathy grading

›West-Haven grade 1 to 2

›Asterixis present in grade 2

›Mild confusion or somnolence

›West-Haven grade 3 to 4

›Marked confusion to coma

›Airway protection threatened

›Herniation screen

›Pupillary reflexes

04Differential Diagnosis/ddx37

Life threats and key categories

›Must-distinguish entities

›Acute-on-chronic liver failure

›ICD-10 K72.10

›Signs of chronic liver disease present

›Sepsis with hepatic dysfunction

›ICD-10 A41.9

›Coagulopathy and encephalopathy mimic

›Ischemic hepatitis shock liver

›AST and ALT often > 5000

›Rapid rise and fall after hypotension

›Vascular and infiltrative

›Budd-Chiari syndrome

›ICD-10 I82.0

›Ascites hepatomegaly abdominal pain

›Malignant infiltration

›Lymphoma or metastatic disease

›Can present as ALF

›Heat stroke

›Massive rhabdomyolysis

›Hepatic necrosis

Etiology-specific clues

›Metabolic and autoimmune

›Wilson disease

›Coombs-negative hemolytic anemia

›Bilirubin to ALP ratio > 2.0

›Autoimmune hepatitis

›Elevated ANA ASMA IgG

05Laboratory Tests/lt74

Hepatic and coagulation

›Hepatic panel

›AST ALT ALP GGT

›Pattern guides etiology

›Magnitude and trend

›Total and direct bilirubin

›Hyperbilirubinemia severity

›Trend over time

›Albumin

›Synthetic function marker

›May be normal in hyperacute

›Coagulation studies

›PT and INR

›INR >= 1.5 defines coagulopathy

›Does not predict bleeding risk

›aPTT and fibrinogen

›Rebalanced hemostasis

›Fibrinogen consumption

›Factor V level

›Clichy criteria input

›Prognostic marker

Metabolic and perfusion

›Metabolic panel

›Glucose

›Hypoglycemia from loss of gluconeogenesis

›Monitor every 1 to 2 hours

›Creatinine and electrolytes

›AKI in ~50% of ALF

06Diagnostic Tests/dt67

Scoring Systems

›King's College Criteria

›Acetaminophen ALF

›pH < 7.3 after resuscitation

›Or INR > 6.5 and creatinine > 3.4 mg equivalent and grade 3 to 4 HE

›Non-acetaminophen ALF

›INR > 6.5 alone

›Or any 3 of age < 10 or > 40 unfavorable etiology jaundice > 7 days INR > 3.5 bilirubin elevated

›Performance

›Specificity 93% for acetaminophen

›Sensitivity ~58% limited

›MELD and adjuncts

›MELD score

›More sensitive than KCC 77% vs 61%

›MELD >= 30.5 predicts transplant need

›Viscoelastic testing

›TEG or ROTEM for true bleeding risk

›SCCM recommends over INR

›Arterial ammonia as predictor

›Independent predictor of intracranial hypertension

›Threshold > 200 micromol/l

MRI

›MRI role

›Limited acute utility

›Availability constraints

›Unstable patient limitation

›Problem-solving indications

›MR venography for Budd-Chiari when Doppler equivocal

07Disposition/dispo31

Level of care

›ICU admission

›All ALF patients require ICU

›Grade 2 HE transfer to ICU

›Grade 3 to 4 HE intubation

›Monitoring needs

›Hourly neurologic checks

›Continuous glucose monitoring

›Transplant center transfer

›Early referral

›Within first few hours

›Before full criteria if deteriorating

›Transfer logistics

›Risk of deterioration in transit

›Secure airway before transfer if borderline

Transplant listing and prognosis

›UNOS Status 1a criteria

›ICU-level care plus one of

›Ventilator dependence

›Renal replacement therapy

›Coagulopathy criterion

›INR >= 2 with HE onset within 8 weeks

›Of initial symptoms

›Prognosis counseling

›Outcome thirds

›One-third recover spontaneously

›One-third transplant one-third die

›Post-transplant survival

08Treatment/t115

Initial stabilization

›Airway and breathing

›Intubate for grade 3 to 4 HE

›Airway protection

›Head of bed elevation 30 degrees

›Minimize stimulation

›Cluster care

›Avoid coughing and straining

›Circulation and metabolic

›Volume resuscitation

›Balanced crystalloids

›Avoid hypervolemia and hypovolemia

›Dextrose infusion

›D10W to prevent hypoglycemia

›Glucose every 1 to 2 hours

›If fluid-refractory hypotension, norepinephrine

›First-line vasopressor

›Class I supportive

N-acetylcysteine

›Acetaminophen ALF IV NAC

›Loading dose

›150 mg/kg IV over 15 to 60 minutes

›Telemetry during infusion

›Second phase

›50 mg/kg over 4 hours

›Equals 12.5 mg/kg/h

›Third phase

›100 mg/kg over 16 hours

›Equals 6.25 mg/kg/h

›Continuation

›6.25 mg/kg/h until ALT decreasing and INR < 2

›Do not stop arbitrarily at 21 hours

›Non-acetaminophen ALF NAC

›Indication

›Grade 1 to 2 encephalopathy

›Improves transplant-free survival 52% vs 30%

›Guideline support

›ACG recommended

›EASL recommended

›Adjunct decontamination

›Activated charcoal

›1 g/kg max 50 g

›If within 4 hours of acetaminophen ingestion

Etiology-specific therapy

›Toxin-mediated

›Mushroom Amanita poisoning

›Silibinin if available

›NAC and consider charcoal

›Wilson disease

›CRRT and consider plasma exchange

›Emergent transplant evaluation

›Immune and viral

›Autoimmune hepatitis

›Methylprednisolone 1 mg/kg

›Low threshold for transjugular biopsy

›HSV hepatitis

›IV acyclovir

›Empiric if HSV suspected

›Hepatitis B reactivation

›Entecavir or tenofovir

›Nucleos(t)ide analogue

Cerebral edema management

›Hyperammonemia and edema prophylaxis

›Hypertonic saline 3%

›Target Na 145 to 155 mEq/l

›Prophylactic in grade 3 to 4 HE

›CRRT

›First-line for hyperammonemia

›Used even without AKI

›High-volume plasma exchange

›Improved transplant-free survival in one RCT

›Consider in selected patients

›Acute ICP crisis

›Mannitol

›0.5 to 1 g/kg for acute ICP surges

›Higher rebound ICP and AKI risk vs hypertonic saline

›Temperature control

›Avoid hyperthermia

›Target normothermia

›Medications to avoid

›Vasopressin and terlipressin may raise ICP

›Use with caution

Coagulopathy and infection

›Coagulopathy management

›Do not prophylactically correct INR

›Hemostasis is rebalanced

›Overt bleeding uncommon ~5% of deaths

›Correct only for procedures or bleeding

›FFP cryoprecipitate platelets

›rFVIIa as needed

›Viscoelastic-guided transfusion

›TEG or ROTEM

›Avoid volume overload from FFP

›Infection management

›Surveillance cultures

›Blood urine sputum

›Regular intervals

›Empiric antimicrobials

›For SIRS clinical deterioration or worsening HE

›Antifungal coverage if deteriorating

›Prophylaxis caveat

›Routine prophylaxis not supported in well-resourced settings

›Reserve for clinical triggers

Supportive and avoid-list

›Supportive medications

›PPI for stress ulcer prophylaxis

›GI bleeding risk

›Standard ICU dosing

›Phosphate replacement

›Correct hypophosphatemia

›Supports regeneration

›Medications to avoid or limit

›Lactulose

›May use for grade 1 to 2 HE

›Discontinue grade 3 to 4 to avoid bowel distension

›Lactulose and rifaximin caveat

›No proven ALF benefit

›Unlike chronic liver disease

›Hepatotoxins and dosing

›Avoid additional hepatotoxic drugs

›Adjust for hepatic and renal impairment

09Special Populations/sp54

Pregnancy

›Pregnancy-specific etiologies

›Acute fatty liver of pregnancy

›Third trimester

›Hypoglycemia and coagulopathy

›HELLP syndrome

›Hemolysis elevated LFTs low platelets

›Overlaps with ALF

›Definitive management

›Expedited delivery

›Maternal-fetal medicine and transplant center

›Maternal supportive care

›Best spontaneous survival category

›Pregnancy-related etiology favorable

›NAC safe in pregnancy

›Monitoring

›Fetal monitoring when viable

›Maternal glucose and coagulation

Geriatric

›Older adult features

›Age as prognostic factor

›Age > 40 worsens non-acetaminophen King's criteria

›Reduced regenerative reserve

›Comorbidity burden

›Cardiac disease and ischemic hepatitis

›Polypharmacy and DILI risk

›Transplant candidacy

›Age and comorbidity affect eligibility

10Background/b57

Epidemiology

›Incidence and burden

›Rare condition

›1 to 6 cases per million per year

›Life-threatening emergency

›Etiology distribution

›Acetaminophen ~50% of US ALF

›Viral autoimmune Wilson indeterminate remainder

›Outcomes

›One-third recover one-third transplant one-third die

›AKI in ~50%

›Complications frequency

›Myocardial injury

›Troponin elevation in 74%

›OR 4.69 for death

›Intracranial hypertension

›55% with ammonia > 200 micromol/l

›Leading cause of death

Pathophysiology

›Mechanisms of injury

›Massive hepatocyte necrosis

›Loss of synthetic function

›Coagulopathy and hypoglycemia

›SIRS and multiorgan dysfunction

›Hallmark of ALF

›Drives cerebral edema

›Hyperammonemia

›Astrocyte swelling

11Patient Discharge Instructions/pdi30

copy discharge instructions

›Recovery home care

›Take only medicines approved by your liver team

›Avoid acetaminophen and over-the-counter painkillers

›Avoid alcohol completely

›Keep all follow-up appointments

›Hepatology within 1 to 2 weeks

›Blood tests as scheduled

›Mental health and substance support

›Attend psychiatric follow-up if overdose

›Substance use counseling if applicable

›Warning signs to return to ER

›Worsening yellow skin or eyes

›New or deepening jaundice

›Dark urine

›Confusion or extreme sleepiness

›Trouble waking

›New disorientation

›Bleeding or persistent vomiting

›Vomiting blood or black stools

›Cannot keep fluids down

›Abdominal swelling or fever

›New belly swelling

›Fever or chills

›Follow-up plan

›Serial liver and clotting blood tests

›Confirm normalization

›Repeat coagulation studies

12References/r24

Guidelines and key sources

›Guideline sources

›ACG Acute Liver Failure Guidelines 2023

›Shingina et al American Journal of Gastroenterology

›NAC and etiology-specific management

›AASLD position paper on acute liver failure

›Lee Stravitz Larson

›Transplant referral recommendations

›SCCM ICU management guidelines 2023

›Nanchal et al Critical Care Medicine

›Neurology and infectious disease considerations

›Landmark reviews and evidence

›Emergency physician review

›Montrief Koyfman Long AJEM 2019

›ED-focused approach

›Lancet and NEJM reviews

›Maiwall et al Lancet 2024

›Bernal Wendon NEJM 2013

›Troponin and myocardial injury data

›Parekh et al Hepatology 2007

›Subclinical injury and mortality

›Coding standards

›ICD-10 K72.00 acute hepatic failure without coma

›K72.01 with coma

›SNOMED CT acute liver failure disorder

Evidence & Review

Evidence & Review