Hepatic Encephalopathy, Hyperammonemia, and Current Treatment in ICU Room

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1 Hepatic Encephalopathy, Hyperammonemia, and Current Treatment in ICU Room Assoc.Prof. Chan Sovandy Chairman by : Prof.So Saphy and Assoc Prof, Kim chhoung

2 Hepatic Encephalopathy Hepatic (portal systemic ) encephalopathy is a complex neuropsychiatric syndrome May be acute and reversible or chronic and progressive In severe cases,irreversible coma and death may occur. Acute episodes may recur with variable frequency

3 Hepatic Encephalopathy Classifications Table A : HE associated with acute liver failure Type B : HE associated with portosystem bypass Type C : HE associated with chronic liver disease/cirrhosis - Episodic HE single or recurrent - Persistent HE mild or severe - Subclinical HE alteratirely minimal HE

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5 Pathogenesis of HE Endogenous Endotoxins Increased permeability of brain blood barrier Change in neurotransmitter and receptors Others

6 Endotoxins of HE Ammonia Mercaptans Phenols Short-chain and Mid-chain fatty acids

7 Ammonia Healthy individuals : equilibrium between the production and detoxications Main sites of synthesis - Intestine - Muscle - kidneys

8 Ammonia Production Small intestine -> The degradation of glutamine produced ammonia Large intestine -> Breakdown of urea and proteins by normal flora Muscles : Proportion to muscle work Kidney : increased production when hypokalemia and diuretic therapy

9 Ammonia Liver : detoxified ammonia into urea and glutamine Brain : can also detoxified ammonia into glutamine and glutamate

10 Hyperammonemia in Adults Reye s syndrom (postviral, Aspirine induced) Liver failure. Acute or Chronic Hepatitis. Wilson s disease. Alpha 1 Antitrypsin deficiency. Alcohol Cirrhosis.Drug induced (antiseizure medication)

11 Hyperammonemia in Adults High dose Chemotherapy Later onset urea cycle defects Infection

12 Toxic Effects in CNS Brain : detoxification is ATP dependent Hyperammonemia -> more energy consumption Swelling of Astroyctes No linear correlation between ammonia level and CNS dysfunction

13 Toxic Effects in CNS Ammonia infusion : cerebral edema in rats Ammonia -> glutamine -> osmotic gradient Can be blocked by Methoximine sulphate, a glutamine synthase inhibitor Increase NO synthase

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18 Clinical Staging of HE Stage 1 : - sleep disturbance - general restless - mood fluctuation - impaired attension

19 Clinical Staging of HE Stage 2 : - Flapping tremor - Asterixis : inability to sustain muscle tone - Ataxia - dysarthria

20 Clinical Staging of HE Stage 3 : - Somnolence, disorientation - Increased reflex, clonic spasm - Pyramidal symptoms Stage 4 : - Coma - with /without response to pain

21 Precipitation Factors Increased nitrogen load - GI bleeding : about 30 Microgram /100ml -Excess dietary protein - Azotemia - Constipation Electrolyte and Metabolic imbalance Hypokalemia,alkalosis,hypoxia,hyponatremia,hyp ovolemia,acidosis

22 Precipitating Factors Drugs : narcotics,tranquilizers,sedatives,diuretics Miscellaneous : infection,surgery,hypothyroidism,superimpose d acute liver disease, progressive liver disease, portal-systemic shunts, infection with Helicobacter pylori?

23 Differential Diagnosis Intra-cranial lesion (tumor, infection,stroke, bleeding ) Epilepsy Metabolic (electrolyte, uremia, other hyperammonemia disease ) Drugs /Toxic : alcohol, neurodepressant use

24 Diagnosis Tool Psychometric /neuropsychological tests Electrophysiologic studies Image techniques Clinical laboratory tests

25 Treatment Treatment of precipitation factors Diet Intestinal cleansing Anti-bacterials Antipsychotics Ammonia metabolism Transplantation

26 Treatment of Precipitation Factors GI bleeding : stopped and avoid anemia Infections : antimicrobials Acidosis : impair urea synthesis Diuretic : inhibit urea synthesis Sedatives : discontinued Hypoglycemia : adequate carbohydrate supplement

27 Diet Control of HE X : severe protein restriction -> catabolism of protein -> ammonia formation increased and susceptibility to infection Cirrhosis patients : 0.8 to 1.0 g /kg Acute episode of HE : limited to 20g. Day initially,then increased as clinical situations improves

28 Diet Control of HE Adequate caloric intake Increased vegetable protein -improved nitrogen balance - better tolerated - fibers accelerating GI transit - may tolerate 30g to 40 g daily

29 Intestinal Cleansing Lactulose Disaccharides -dosage :30 g to 60 g daily, based on clinical signs and 2 to 4 stools daily

30 Antibacterials Non absorbable aminoglycosides : Neomycin and Paromomycin Dosage : 2 to 4 g divided to 4 doses Should not longer than 1 month Rifaximin may be useful as alternative

31 Antipsychotics Benzodiazepam antagonists : - Flumazenil - Anexate - Lanexat - Romazicon HE patients intake benzodiazepam -> should use Flumazenil

32 Stimulation of Metabolism Major detoxication mechanism : Urea cycle and formation of Glutamine Urea cycle metabolites : - Ornithine - Asparate Formation of Glutamine - glutamate - alpha-ketoglutarate

33 Extracorporeal Detoxication Dialysis : can reduced 50% of ammonia level Liver transplanbtation

34 Conclusion Treat precipitation factors first Lactulose orally or as an enema Flumazenil : treat BZD induced HE Protein restriction in acute stage (daily <20 g) Amino acid solution Transplantation : treat refractory HE

35 Sen Sok International university Hospital Ammonemia level >1000µmol/l >700µmol/l >400µmol/l >100µmol/l >200µmol/l >300µmol/l

36 Cause to Hyperammonemia

37 Thank you