acute liver failure in pediatric
DESCRIPTION
acute liver failureTRANSCRIPT
Defenition
Etiology
Pathology
Clinical symptoms
LABs
Management
Defenition
Etiology
Pathology
Clinical symptoms
LABs
Management
Definition Definition
1. Biochemical evidence of acute liver injury
(< 8 wks duration)
2. No evidence of chronic liver disease
3.Coagulopathy ( PT>15sec, INR > 1.5 not corrected by vit K, or PT > 20 sec or INR >2)
1. Biochemical evidence of acute liver injury
(< 8 wks duration)
2. No evidence of chronic liver disease
3.Coagulopathy ( PT>15sec, INR > 1.5 not corrected by vit K, or PT > 20 sec or INR >2)
Acute Hepatic Failure-CharacteristicsAcute Hepatic Failure-Characteristics
Impairment of liver functions, jaundiceImpairment of liver functions, jaundice
Encephalopathy
Coagulopathy
Impairment of liver functions, jaundiceImpairment of liver functions, jaundice
Encephalopathy
Coagulopathy
FHFFHF
According to time-length between first signs According to time-length between first signs of liver disease and development of of liver disease and development of encephalopathyencephalopathy
Fulminant = acute liver disease with encephalopathy within 8 weeks of first sign of liver disease.
Acute = up to 28 days
Subacute = 5-12 weeks
According to time-length between first signs According to time-length between first signs of liver disease and development of of liver disease and development of encephalopathyencephalopathy
Fulminant = acute liver disease with encephalopathy within 8 weeks of first sign of liver disease.
Acute = up to 28 days
Subacute = 5-12 weeks
Chronic hepatic failure
Acute on chronic hepatocellular failure
Chronic hepatic failure
Acute on chronic hepatocellular failure
Etiology - CauseEtiology - Cause
Neonate
Infectious - Herpesvirus, echovirus, adenovirus, HBV
Metabolic - Galactosemia, tyrosenemia, neonatal hemochromatosis, mitrochondrial disease, alpha-antitrypsin deficiency
Neonate
Infectious - Herpesvirus, echovirus, adenovirus, HBV
Metabolic - Galactosemia, tyrosenemia, neonatal hemochromatosis, mitrochondrial disease, alpha-antitrypsin deficiency
Older children Older children
Infection - HAV, HBV, Hep D and E, Herpes virus, sepsis, Dengue virus, Leptosirosis
Drugs - valproate, alcohol, isoniazid, acetaminophen, carbamazepine, halothane, ketoconazole and herbal supplement
Infection - HAV, HBV, Hep D and E, Herpes virus, sepsis, Dengue virus, Leptosirosis
Drugs - valproate, alcohol, isoniazid, acetaminophen, carbamazepine, halothane, ketoconazole and herbal supplement
Toxin - Amanita phalloides, carbon tetrachloride, phosphorus
Metabolic - Hereditary fructose intolerance, Wilson’s disease
Autoimmune - Autoimmune hepatitis, Reye’s syndrome
Hepatic ischemia - hepatic vascular occlusion, congenital heart failure, circulatory shock,
Toxin - Amanita phalloides, carbon tetrachloride, phosphorus
Metabolic - Hereditary fructose intolerance, Wilson’s disease
Autoimmune - Autoimmune hepatitis, Reye’s syndrome
Hepatic ischemia - hepatic vascular occlusion, congenital heart failure, circulatory shock,
CURRENT Diagnosis & Treatment: Pediatrics http://accessmedicine.com/content.aspx?aID=6584425 CURRENT Diagnosis & Treatment: Pediatrics http://accessmedicine.com/content.aspx?aID=6584425
Indications for Liver Transplantation in ChildrenIndications for Liver Transplantation in Children
50% Biliary Atresia50% Biliary Atresia
20% Metabolic Diseases (Wilson, Tyrosinemia)
10-15% cirrhosis secondary to viral’ metabolic disease
13% fulminant hepatic failure
2% acetaminophen overdose
50% Biliary Atresia50% Biliary Atresia
20% Metabolic Diseases (Wilson, Tyrosinemia)
10-15% cirrhosis secondary to viral’ metabolic disease
13% fulminant hepatic failure
2% acetaminophen overdose
PathologyPathology
Liver biopsy reveals patchy or confluent massive necrosis of hepatocytes
Multilobuar or bridging necrosis -> collapse of reticulin framework
Zonal pattern necrosis ->acetaminophen, circulatory shock
Microvesiculat fatty infiltrate of hepatocyte ->Reye syndrome, B-oxydance defects, tetracycline toxicity
Liver biopsy reveals patchy or confluent massive necrosis of hepatocytes
Multilobuar or bridging necrosis -> collapse of reticulin framework
Zonal pattern necrosis ->acetaminophen, circulatory shock
Microvesiculat fatty infiltrate of hepatocyte ->Reye syndrome, B-oxydance defects, tetracycline toxicity
Signs that Predict Development of FHFSigns that Predict Development of FHF
Bilirubin> 20 mg%Bilirubin> 20 mg%
Changes in consciousness
Hyperventilation
Hypoglycemia
Decrease in albumin
INR prolongation, decrease in coagulation factors 5,7
Decrease in liver span along with decline in transaminases and increase of bilirubin
Bilirubin> 20 mg%Bilirubin> 20 mg%
Changes in consciousness
Hyperventilation
Hypoglycemia
Decrease in albumin
INR prolongation, decrease in coagulation factors 5,7
Decrease in liver span along with decline in transaminases and increase of bilirubin
Ascitis
AST>3000 u/L
Increase of PMN
Decrease of BUN but increasing of serum Ammonia
Respiratory alkalosis
Marked jaundice
Ascitis
AST>3000 u/L
Increase of PMN
Decrease of BUN but increasing of serum Ammonia
Respiratory alkalosis
Marked jaundice
Stages of Hepatic EncephalopathyStages of Hepatic EncephalopathyII IIII IIIIII IV
SymptomSymptomss
Periods of lethargy, Periods of lethargy, euphoria: reversible of euphoria: reversible of day-night sleeping: day-night sleeping: may be alertmay be alert
Drowsiness, Drowsiness, inappropriate inappropriate
behavior, behavior, agitation, wide agitation, wide mood swings, mood swings, disorientationdisorientation
Stupor but Stupor but arousal, confused, arousal, confused,
incoherent incoherent speechspeech
ComaIVa : response to noxious stimuliIVb: no response
SignsSignsTrouble drawing Trouble drawing
figures, performing figures, performing mental tasksmental tasks
Asterixis, fetor Asterixis, fetor hepaticus, hepaticus,
incontinenceincontinence
Asterixis, Asterixis, hyperreflexia, hyperreflexia,
extensor reflexs, extensor reflexs, rigidityrigidity
Areflexia, no asterixis, flaccidity
ElectroencepElectroencephalogramhalogram NormalNormal
Generalized Generalized slowing alpha slowing alpha
wavewave
Markedly Markedly abnormal, abnormal,
triphasic wavestriphasic waves
Markedly abnormal, Markedly abnormal, bilateral slowing bilateral slowing
delta waves electric-delta waves electric-cortical silencecortical silence
Ref: Nelson textbook of pediatric Ref: Nelson textbook of pediatric 18th edition Page. 170418th edition Page. 1704
Classification of Hepatic Encephalopathy Infants/ChildrenRef: Lippincort and wilkin 2007
Classification of Hepatic Encephalopathy Infants/ChildrenRef: Lippincort and wilkin 2007
Grade 1: confused, mood changes
Grade 2: drowsy, inappropriate behavior
Grade 3: stuporous but obeys simple commands or sleepy but arousable
Grade 4A: comatose but arousable with painful stimuli
Grade 4B: deep coma, not arousable with any stimuli
Grade 1: confused, mood changes
Grade 2: drowsy, inappropriate behavior
Grade 3: stuporous but obeys simple commands or sleepy but arousable
Grade 4A: comatose but arousable with painful stimuli
Grade 4B: deep coma, not arousable with any stimuli
Encephalopathy- Mechanisms Encephalopathy- Mechanisms Accumulation of nitrous metabolitesAccumulation of nitrous metabolites
Accumulation of toxic substances
Hypoglycemia
Brain edema
False neurotransmitters
Electrolyte changes
Acidosis
Accumulation of nitrous metabolitesAccumulation of nitrous metabolites
Accumulation of toxic substances
Hypoglycemia
Brain edema
False neurotransmitters
Electrolyte changes
Acidosis
LaboratoryLaboratory
Coagulation factor - PT
CBC
UA
BUN, Cr
Blood glucose
LFT
Coagulation factor - PT
CBC
UA
BUN, Cr
Blood glucose
LFT
CoagulopathyCoagulopathy
Used to be the leading cause of death Used to be the leading cause of death before liver transplantationbefore liver transplantation
Low levels of coagulation factors 2,7,9,10
High levels of factor 8
Milder coagulopathy may be caused by disturbance of vitamin K absorption (cholestasis).
Associated and aggravated by thrombocytopenia/pathy
Used to be the leading cause of death Used to be the leading cause of death before liver transplantationbefore liver transplantation
Low levels of coagulation factors 2,7,9,10
High levels of factor 8
Milder coagulopathy may be caused by disturbance of vitamin K absorption (cholestasis).
Associated and aggravated by thrombocytopenia/pathy
Other Complications of FHFOther Complications of FHF
Cerebral EdemaCerebral Edema
= In up to 80% of patients
The leading cause of death
NO PAPILLEDEMA
CT is useful for identification in only 30-60% of patients; rules out bleeding
Cerebral EdemaCerebral Edema
= In up to 80% of patients
The leading cause of death
NO PAPILLEDEMA
CT is useful for identification in only 30-60% of patients; rules out bleeding
Hepatorenal SyndromeHepatorenal Syndrome
Cause unknownCause unknown
Characterized by oliguria, anuria in later stages
ATN or functional renal failure may occur.
Essential to correct hypovolemia to maintain renal perfusion
Hemodialysis
Cause unknownCause unknown
Characterized by oliguria, anuria in later stages
ATN or functional renal failure may occur.
Essential to correct hypovolemia to maintain renal perfusion
Hemodialysis
Complications- InfectionComplications- Infection
Increased susceptibility to infection, due to defect Increased susceptibility to infection, due to defect of opsonization, low complement, impaired PMN of opsonization, low complement, impaired PMN function, need for invasive monitoringfunction, need for invasive monitoring
May not be associated with fever
May aggravate encephalopathy
Endotoxemia may increase liver injury
Gram negative organisms or Staph Aureus
Remember: the only sign of infection may be deterioration of liver function of encephalopathy
Increased susceptibility to infection, due to defect Increased susceptibility to infection, due to defect of opsonization, low complement, impaired PMN of opsonization, low complement, impaired PMN function, need for invasive monitoringfunction, need for invasive monitoring
May not be associated with fever
May aggravate encephalopathy
Endotoxemia may increase liver injury
Gram negative organisms or Staph Aureus
Remember: the only sign of infection may be deterioration of liver function of encephalopathy
Other ComplicationsOther Complications
Hemodynamic instabilityHemodynamic instability
Hypoxia
Acid-base and electrolyte disturbances (=respiratory and metabolic alkalosis)
Hemodynamic instabilityHemodynamic instability
Hypoxia
Acid-base and electrolyte disturbances (=respiratory and metabolic alkalosis)
ManagementManagement
The essentials of management are:The essentials of management are:
1. Diagnosis of cause of liver injury and encephalopathy
2. “skilled intensive care to minimize aggravating factors and complications until liver function recovers or transplantation can be performed”
3. Liver transplantation
The essentials of management are:The essentials of management are:
1. Diagnosis of cause of liver injury and encephalopathy
2. “skilled intensive care to minimize aggravating factors and complications until liver function recovers or transplantation can be performed”
3. Liver transplantation
On ET tube to prevent aspiration
Reduce cerebral edema by hyperventilation
Supplemental oxygen
Avoid sedative drugs unless on mechanical ventilator
Prophylactic use of antacid, H2 blockers
Lactulose should be given every 2-4 hours
Lactulose syr dilute with 1-3 ml water can be given as a retention enema q 6 hr
On ET tube to prevent aspiration
Reduce cerebral edema by hyperventilation
Supplemental oxygen
Avoid sedative drugs unless on mechanical ventilator
Prophylactic use of antacid, H2 blockers
Lactulose should be given every 2-4 hours
Lactulose syr dilute with 1-3 ml water can be given as a retention enema q 6 hr
Blood sugar checked every 3-6 hoursBlood sugar checked every 3-6 hours
Limit fluids to 60% maintenance unless dehydrated
Maintain normal BP, CVP
Fluids D10-20% - adequate dextrose should be infused (6–8 mg/kg/min) to maintain normal blood glucose and cellular metabolism
3mmol/kg/24h of potassium
Infusion of fresh frozen plasma and platelets to treat clinically significant bleeding
Monitor urine output
Blood sugar checked every 3-6 hoursBlood sugar checked every 3-6 hours
Limit fluids to 60% maintenance unless dehydrated
Maintain normal BP, CVP
Fluids D10-20% - adequate dextrose should be infused (6–8 mg/kg/min) to maintain normal blood glucose and cellular metabolism
3mmol/kg/24h of potassium
Infusion of fresh frozen plasma and platelets to treat clinically significant bleeding
Monitor urine output
Oral antibiotic may be more effective than Oral antibiotic may be more effective than lactulose in lowering serum ammonia levellactulose in lowering serum ammonia level- nonabsorbable antibiotic such as - nonabsorbable antibiotic such as neomycin, metronidazole, gentamycinneomycin, metronidazole, gentamycin
Paracetamol poisoning- N-acetyl cycteine. Paracetamol poisoning- N-acetyl cycteine. Monitor PT/PTT every 12 hours Monitor PT/PTT every 12 hours
Mechanical ventilation: agitation, hypoxia, coma grade 3-4
Oral antibiotic may be more effective than Oral antibiotic may be more effective than lactulose in lowering serum ammonia levellactulose in lowering serum ammonia level- nonabsorbable antibiotic such as - nonabsorbable antibiotic such as neomycin, metronidazole, gentamycinneomycin, metronidazole, gentamycin
Paracetamol poisoning- N-acetyl cycteine. Paracetamol poisoning- N-acetyl cycteine. Monitor PT/PTT every 12 hours Monitor PT/PTT every 12 hours
Mechanical ventilation: agitation, hypoxia, coma grade 3-4