acute liver failure
Post on 16-Jul-2015
96 Views
Preview:
TRANSCRIPT
ACUTE LIVER FAILURE IN CHILDREN
DR.VIDEESH GUIDED BY
DNB TRAINEE DR.ANITA
M.D (PAEDS)
INTRODUCTION
Acute liver failure (ALF) is a clinical syndrome resultingfrom massive necrosis or from severe functionalimpairment of hepatocytes.
Functions including:
Synthetic
Excretory
Detoxification
all are severely impaired.
DEFINITIONThe original definition of fulminant hepatic failure as coined by Trey and Davidson in 1970 stipulated an onset of hepatic encephalopathy within 8 weeks of the first symptoms of illness, in patients without pre-existing liver disease.
The recognition that different clinical patterns of acute liver failure related to aetiology and prognosis, has led to revision of this definition and the development of differerent classifications.
O`GRADY et al proposed three subcategories of ALF
TYPE INTERVAL CEREBRAL
EDEMA
PROGNOSIS CAUSES
HYPERACUTE <7 days common moderate Hep A,B
Acetaminoph
en
ACUTE 8-28 days common poor Non-A/B/C,
drugs
SUBACUTE 29days-24
wks
rare poor Non-A/B/C,
drugs
• Biochemical evidence of acute liver injury of <8wksduration
• No evidenvce of chronic liver disease
• PT>15sec or INR>1.5 not corrected by Vit K in thepresence of clinical hepatic encephalopathy
• PT>20sec or INR>2 regardless of encephalopathy.
The currently accepted definition includes:
EPIDEMIOLOGY
The true incidence of ALF in children is not known
It is estimated that 0.2%-1% of all acute hepatitis can progress to liver failure.
ETIOLOGY :In about half to two-third of patients with ALF
etiology is unknown.
INFECTIVE
• Hepatitis virus A, B, C, D, E
• Herpes simplex
• Epstein Barr virus
• Parvovirus B19
• Varicella zoster
• CMV
• Adenovirus
• Echovirus
• Coxsackie virus
ADRUG REACTIONS AND TOXINS
• Acetaminophen (paracetamol) overdose
• Halothane
• Isoniazid
• Sodium Valproate
• Phenytoin
• Herbal remedies
• Ecstasy(Methylene Dioxymetamphetamine)
AMETABOLIC
• Wilson’s diseaseA
• Neonatal hemochromatosis
• Tyrosinemia type 1
• Mitochondrial disorders
• Hereditary fructose intolerance
• Alpha-1 antitrypsin deficiency
• Niemann-pick disease
• Indian childhood cirrhosis
• Glycogen storage disease type 4
• Urea cycle defect
ISCHAEMIC
• Budd–Chiari syndrome
• Venoocclusive disease
• Right sided congestive heart failure
• Cardiogenic shock
MISCELLANEOUS
• Massive malignant infiltration
• Severe bacterial sepsis
• Heat stroke
• Autoimmune hepatitis
• Viral infection on underlying chronic liver disease.
In India, the etiological proportions are seen as HAV infection(35%),HEV(15%), Mixed HAV,HEV (15%) and HBV(10%),non A to E(15%) and Drug induced (5%).
If appropriate testing is not done hepatitis B may not be diagnosed since one-third to one-half of acute liver failure become seronegative for hepatitis B surface antigen (HBsAg) after a few days.
Superinfection of hepatitis B with delta virus causes ALF in 50% of cases.
Reactivation of hepatitis B or C virus may lead to ALF following antitumour chemotherapy or cessation of immunosuppressive therapy.
Massive infiltration of the liver as in a lymphoma can lead to ALF
Wilson’s disease must always be excluded in any patient who is less than 35 years old, particularly if haemolysis is associated.ALF can be due to superimposed acute viral infection.
PATHOLOGY
Patchy or confluent massive necrosis of hepatocytes is
seen on liver biopsy.
Multilobular or bridging necrosis with collapse of the
reticulin framework of the liver occurs.
There may be little or no regeneration of hepatocytes
Centrilobular pattern of necrosis :
• Acetaminophen hepatotoxicity
• Circulatory shock
Microvesicular fatty infiltrate of
hepatocytes :
• Reye’s syndrome,
• β-oxidation defects,
• Tetracycline toxicity
NECROSIS OF HEPATOCYTES
PATHOGENESIS
About 1-2% of patients with viral hepatitis experience ALF.
Massive destruction of hepatocytes is due to:
• Cytotoxic effect of the virus,
• Immune response to the viral antigen.
Hepatotoxic metabolites bonding covalently to macromolecular cell constituents occurs in:
• Acetaminophen,
• Isoniazid.
Fulminant hepatic failure may follow depletion of intracellular substrates involved in detoxification, particularly glutathione.
Factors contributing to the pathogenesis include :
• Impaired hepatocyte regeneration,
• Altered parenchymal perfusion,
• Endotoxemia,
• Decreased hepatic reticuloendothelial function.
The pathogenesis of hepatic encephalopathy relates to:
• Increased serum levels of ammonia
• False neurotransmitters, amines
• Increased γ-aminobutyric acid receptor activity
• Increased circulating levels of endogenous benzodiazepine-like compounds
CLINICAL FEATURESInitially prodromal symptoms include:
• Low grade fever
• Abdominal pain
• Anorexia
• Vomiting
These symptoms are followed by
• Progressive jaundice
• Fetor hepaticus
A rapid decrease in liver size without clinical improvement is an ominous sign.
A hemorrhagic diathesis and ascites can also develop
Patients with hepatic encephalopathy initially have minor disturbances of consciousness or motor function.
Irritability, poor feeding, and a change in sleep rhythm may be the only findings in infants.
Asterixis may be demonstrable in older children.
Patients are often somnolent or confused or combative on arousal and eventually may become responsive only to painful stimuli.
Patients may rapidly progress to deeper stages of coma that include:
• Extensor responses
• Decerebrate
• Decorticate posturing
Respirations are usually increased early, but respiratory failure may occur in stage IV coma
STAGES I II III IV
Symptoms Periods of lethargy,
euphoria, reversal
of day-night
sleeping, may be
alert
Drowsiness,
inappropriate
behaviour,
agitation, wide
mood
swings,
disorientation
Stupor but
arousable,
confused,
incoherent
speech
Coma
IVa responds to
noxious stimuli
IVb no
response
Signs Trouble drawing
figures, performing
mental tasks
Asterixis, fetor
hepaticus,
Incontinence
Asterixis,
hyperreflexia,
extensor
reflexes,
rigidity
Areflexia, no
asterixis,
flaccidity
Electroencep
halogramNormal Generalized
slowing, q
waves
Markedly
abnormal,
triphasic
waves
Markedly
abnormal
bilateral
slowing,
d waves,
electric-cortical
silence
STAGES OF HEPATIC ENCEPHALOPATHY
ACUTE LIVER FAILURE :
MANAGEMENT
Acute liver failure is a medical emergency , often associated with unpredictable and sometimes fatal outcome.
Recovery occurs if liver gets adequate time to regenerate with supportive therapy.
Every child with ALF must be treated in ICU setting preferably with liver transplant facility.
AIMS OF THE THERAPY
To prevent & manage complications,
To access the etiology & treat accordingly,
Preparing the patient for liver transplantation if lack of spontaneous recovery by intensive supportive care.
INITIAL WORKUP &
INVESTIGATIONS
GENERAL :• Complete blood count• Liver function tests• Ammonia levels• PT , INR• Blood sugar level• Electrolytes• RFT• Urine analysis• Blood culture• Blood gas and acid-base parameters• Blood grouping-cross match• X-ray chest
VIRAL HEPATITIS MARKERS :
• HAV IgM Antibody
• HEV IgM Antibody
• HBsAg
• Anti HBc IgM Antibody
• HBV DNA
Store sera prior to administration of any blood products for further investigations if needed
IN PRESENCE OF SEVERE
HEMOLYSIS OR SEVERE ANEMIA
• Malaria parasite, malaria antigen
• G6PD level estimation
• Ceruloplasmin, urine copper
• Leptospira antibody
Liver biopsy has no role in ALF
IN SELECTED PATIENTS :
• Autoimmune markers (Coombs test, antinuclear
antibody, liver kidney microsomal antibody (LKM), smooth muscle antibody)
• Ceruloplasmin, urinary copper
• Paracetamol level, Sodium valproate level
• Urine succinylacetone
GENERAL PRINCIPLES OF CARE AND
MONITORING PROTOCOL
• Ensure complete asepsis
• Establish adequate IV access (CVP line)
• Continous monitoring of vital signs
• Pulse oximetry
• Neurological/ coma grading every two hrly
• Blood sugar estimation 2-6 hrly as needed
• Electrolytes, ABG, PT, LFT, RFT 12-24 hrly
• CBC, Blood culture, ESR, urine culture,
CRP, x-ray chest 24-72 hrly
• Nasogastric tube for feeding/ drainage
• Urinary cathetre
• Care of bowel, bladder, back, skin, eyes
STANDARD PROTOCOL FOR
MANAGEMENT OF ALF
• Raise head end (30°-45°) and maintain head in neutral position
• Inj. Cefotaxim and Cloxacillin
• IV Fluids N/5 saline in 10% dextrose at 2/3rd of maintenance after initial fluid resuscitation
• KCl to be added as per serum potassium level.
• Lactulose through NG Tube.
• Mannitol 20% 3-5ml/kg/dose IV slow bolus 4-6 hrly for 6-8 doses (In grade 3-4 coma).
• Ranitidine IV 12 hrly.
• Inj. Vit K.
• Hepatic coma feeds.
CONDITIONS WITH SPECIFIC
THERAPYNo. Condition Therapy
01. Acetaminophen toxicity N-acetyl cysteine
02. Amanita poisoning Penicillin & silibinin
03. Herpes simplex Acyclovir
04. Malaria Antimalarials
05. Enteric encephalopathy Cefotaxim/ceftriaxone
06. Wilsons disease d-penicillamine
07. Tyrosinemia Nitisinone
08. Leptospirosis Penicillin, doxycycline,
tetracyclines
There is increasing evidence for use of N-acetyl cysteine(NAC) infusion in all cases of ALF irrespective of the etiology
Dose : 100 mg/kg/day.
NUTRITION • Catabolic stage characterised by increased negative
nitrogen balance & increased resting energy expenditure.
• Enteral nutrition with higher caloric density feeds to avoid excessive free water and hypo-osmolality.
• Normal protein intake in stage ii & iii encephalopathy.
• Afterwards restriction of proteins.
FLUID AND ELECTROLYTE
DISTURBANCES
HYPOTENSION :
• Volume replacement with NS, RL, plasma or blood.• Give 2/3rd maintenance fluid - N/5 saline in 10% dextrose.• Avoid overloading.• If MAP (DBP+1/3PP) is <60mmHg – Start Inotropes.
METABOLIC ACIDOSIS :
• Suspect fluid deficit.• Look for sepsis (if no fluid deficit).
HYPOKALAEMIA :
• Can precipitate & worsen the severity of hepatic encephalopathy.
• Associated with metabolic alkalosis.• Give KCL infusion.
METABOLIC ALKALOSIS :
• Increase IV KCL to next step.
HYPONATREMIA :
• Restrict fluids to 2/3-3/4 maitenance.• Restrict sodium infusion to <2mEq/kg/day.
HYPERNATREMIA :
• May be precipitated with lactulose administration :reduce/stop lactulose.
• Give N/5 fluids including correction fluid.
HYPOGLYCEMIA :
• Infuse 50 % Dextrose @ 1ml/kg.• Maintain blood sugar between 100-200mg/dl.
ANTIBIOTICS
Empirical administration of antibiotics is recommended whereInfection or impending risk of sepsis is high
• Surveillance cultures reveal significant isolates
• Progression of or advanced stage hepatic encephalopathy
• Refractory hypotension
• Presence of SIRS components
• Patients listed for OLT ( immunosupression )
PREVENTION OF GI HEMORRHAGE
• Secondary to gastritis, stress ulcers, coagulopathy
• Inj. Vit K <1 yr -2.5mg/day >1 yr -5mg/day>5 yr -10mg/day
• IV ranitidine
• IV proton pump inhibitor
HEPATIC ENCEPHALOPATHY
• Reduce or stop protein in grade iii /iv
• Prefer vegetable proteins-BCAA
• Lactulose-0.5ml/kg/dose every 6 hrs orally
• Nonabsorbable oral antibiotics- Rifaximin
• Analgesia and judicious sedation- Propofol, benzodiazepines
COMPLICATIONS OF MANAGEMENT
01.RAISED INTRACRANIAL PRESSURE
Sustained rise of ICP >20 mmHg
C/F - Abnormally reacting pupils- Increased muscular tone- Decerebrate posturing- Abnormal reflexes- Focal seizures- Loss of brainstem reflexes- Bradycardia- Increased B.P.
CEREBRAL EDEMA(B/W STAGE II&III ) HAS VERY POOR PROGNOSIS
& ALL EFFORTS SHOULD BE TAKEN TO PREVENT IT.
STRATEGIES TO PREVENT CEREBRAL
EDEMA
• Avoid excessive handling, suctioning, stimulation
• Prevent coughing, vomiting, frequent movements, neck veins compression, fever, hypertension, hypoxia
• Raise head end 30°. Avoid neck flexion
• Fluid restriction to 60-75% of maintenence with good cerebral perfusion pressure
• Mannitol 20% 0.5gm/kg over 10-15min repeated 4-6hrly for max 72hr in mild to moderate ICP(<60mmHg).
• In anuric or ARF patient dialysis with mannitol
• Elective ventilation- hyperventilate to maintain pCO2 bw 30-35mmHg
• Mannitol resistant CE- Sodium Thiopental ( bolus dose 24mg/kg over 15min f/b slow iv infusion bw 1-2mg/kg/hr )
• Refractory ICP- Indomethacin 25mg infused iv over 1min
02.CONVULSIONS
• Phenytoin 10mg/kg iv slowly. Wait for 20 min. if no response then repeat.
• Maintainence 5-8 mg/kg/day.
• If convulsions persist, Phenobarbitone 10-15mg.kg slowly & wait for 20 min.
• Maintainence 5mg/kg/day in two doses
• If no response Thiopentone iv may be used but watch for Hypotension.
03.HEMORRHAGE
• If PT <30sec – FFP only for invasive procedures
• If PT >30sec – FFP 10ml/kg.
• Severe bleeding – FFP & Platelet transfusion.
• Significant hypofibrinogenemia (<100mg/dl) - Cryoprecipitate
• Recombinant factor VIIa – when FFP has failed to correct INR , volume overload, before invasive procedures with high risk of bleeding.
04.RENAL FAILURE
• Due to hepatorenal syndrome, dehydration, acute tubular necrosis.
• Maintain urine o/p >1ml/kg/hr.
• Try colloid challenge 10ml/kg. repeat if no response.
• Diuretics.
• Renal replacement therapy- in fluid overload,
unresponsive renal failure, hyperkalemia.
05.SEPSIS• Signs- tachycardia, raised core-toe temp. gradient,
fall in BP or urine output, hypoglycaemia, hypothermia, deterioration in mental state, fits, acidosis.
• Common organisms- Staphylococci, Gram negative bacteria,Fungal infections.
• Broad spectrum antibiotics - IV Cloxacillin/Ampicillin + IV Cefotaxim/Ceftazidime.
• Antifungals/Metronidazole may be added if no response in 48-72hrs.
• Avoid Aminoglycosides.
LIVER TRANSPLANTATION
LT is the only definitive treatment for ALF.
Several prognostic scoring systems have been devised to predict mortality and to identify those requiring early LT.
These include King’s College Hospital (KCH) criteria, pediatric end-stage liver disease (PELD) score, APACHE II, and Clichy criteria.
The KCH criteria have been shown to have a better performance than the Clichy criteria and is widely
used.
Liver transplantation could be :
CADAVERIC1)Whole graft – When the whole liver is used.2)Spilt graft – When the donor liver is used for two recipients.3)Reduced graft – When the donor liver is reduced to suit the size for recipient.
LIVING RELATEDWhen a live donor gives part of his/her liver to
recipient.
Contraindications for pediatric LT
Active uncontrollable and untreatable sepsis,
Severe cardiopulmonary disease, Multi-organ failure, Extrahepatic malignancy, Mitochondrial disease, Active substance abuse, HE grade IV with severe neurological
impairment
Outcome : In more than 50% of children with ALF there is poorsurvival unless LT is offered at the appropriate time.
Poor Prognostic factors - Liver necrosis- Multi organ failure- INR >4 - Young age of the child (<1 yr)- Need for dialysis before LT
The prognosis is better with hepatitis A,acetaminophen overdose and ischemia (approximately60% spontaneous survival), and
poor with drug-inducedALF (non-acetaminophen), hepatitis B, and indeterminate
cases.
THANK YOU
top related