DR DR . E. SENTHIL KUMAR M.B.B. NATIONAL HOSPITAL
Nov 19, 2014
DR DR . E. SENTHIL KUMAR M.B.B.S
NATIONAL HOSPITAL
57 YEARS OLD MALE PATIENTADMITTED ON 8 / 2 / 09 WITH HISTORY OF
ALTERED SENSORIUM
NOT TAKING FEEDS 2 MONTHS
DROWSINESS ….. PAST ONE DAY
H / O ICU ADMISSION FOR SIMILAR COMPLAINTS …. LAST MONTH
HE WAS FULLY EVALUATED & TREATED .
AT THE TIME OF DISCHARGE …
PATIENT ABLE TO WALKSPEECH AND HIGHER FUNCTIONS .. NORMALICTERIC
PERSONAL HISTORY
ALCOHOLIC FOR THE PAST 37 YEARS
FAMILY HISTORY :
NOT CONTRIBUTORY
PAST HISTORY
INTERMITTENT JAUNDICE FOR THE PAST 4 YEARS (TREATED WITH NATIVE MEDICINES)
K / C / O CIRRHOSIS FOR PAST TWO YEARS AND ON RX
K / C / O HYPERTENSION FOR PAST 2 MONTHS AND ON RX
CLINICAL FINDINGS :
ICTERIC +++ PALLOR +
BILATERAL PITTING PEDAL EDEMA +
RS : BILATERAL CREPITUS +
CNS : GLASGOW COMA SCALE - E1 V 2 M 3 - 6 / 15
PUPILS ….. 4mm , PERLA
PLANTAR ….. WITHDRAWAL RESPONSE
B / L LIMB SPASTICITY ++ , REFLEXES
VITALS :
PULSE : 86 / minBP : 148 / 92 mm HgRR : 22 / minTEMP : N
spO2 : 98 %U / O : ADEQUATEBLOOD SUGAR : 209 mg %
NO INTUBATION DONE @ THE TIME OF ADMISSION
INVESTIGATIONS (9 / 2 / 09 )
TOTAL BILIRUBIN : 5.4 DIRECT : 2.3 INDIRECT : 3.1
URINE UROBILINOGEN : INCREASED
BLOOD AMMONIA : 79
PLATELETS : 1.02 LAKHS
INR : ELEVATED
SR POTASSIUM : REDUCED
CT BRAIN
GROSS AGE RELATED CEREBRAL ATROPHY
FEATURES S / O SMALL VESSEL ISCHEMIC CHANGE
USG ABDOMEN
COARSE ECHOGENIC LIVER S / O CIRRHOSIS
SPLENOMEGALY
MODERATELY DISTENDED BLADDER WITH DEBRIS (CYSTITIS)
CXR – PA VIEW
INHOMOGENEOUS OPACITIES IN RT UPPER AND MIDZONE
CARDIOMEGALY
ATHEROMATOUS AORTA
ECG : SB
DIFFERENTIAL DIAGNOSIS :
1. HYPOGLYCEMIA ….. RULED OUT { SUGAR @ ADMN – 209 }
2. HYPOXIA ….. RULED OUT { NO CYANOSIS , SATURATION – N }
3. UREMIA …. RULED OUT { NORMAL RFT }
4. KETO ACIDOSIS …. RULED OUT { SUGAR – NEAR NORMAL & URINE KETONE NEGATIVE }
5. ELECTROLYTE IMBALANCE …. POSSIBLE { LOW POTASSIUM }
6. HEPATIC COMA …. POSSIBLE { HIGH BILIRUBIN , RAISED INR HYPOKALEMIA LOW UREA LOW ALBUMIN MILDLY ELEVATED AMMONIA USG ABDOMEN .. S/O CIRRHOSIS }
7. ALCOHOL / OTHER INTOXICATION …. NO CONTRIBUTORY HISTORY
8. INTRA CRANIAL CAUSE { SDH, SOL,NEUROPSYCHIATRIC STATE, POST ICTAL ENCEPHALOPATHY , MENINGITIS, ENCEPHALITIS }
COURSE IN HOSPITAL : 8/2/09 … DATE OF ADMISSION
TREATMENT GIVEN :
PROTEIN RESTRICTION
TAB SPIRONOLACTONE , POTASSIUM INFUSIONS
INJ RANITIDINE
INJ MANNITOL
INJ VIT K
LACTULOSE
TAB RIFAXIMIN
RESOURCE HEPATIC POWDER
HEPAMERZ INFUSIONS
BACLOFEN , PHYSIOTHERAPY
14/2/09 … DROWSINESS TO HYPOTENSION18/2/09 HYPOKALEMIA (3.3) FEBRILE ++DAY 6 - 10 CRP , INR INCREASED BLOOD AMMONIA INCREASED ( 110 )
CLINICAL PICTURE :
PATIENT DEVELOPED
MILD NECK STIFFNESS SPASTIC QUADRIPARESIS
NEURO CALL OVER GIVEN
EEG :
BACKGROUND ACTIVITY NORMALRESPONSE TO EYE OPENING NORMAL DURING HYPER VENTILATION SLOW WAVES PRESENT IN ANTI HEAD REGION
ed
CSF ANALYSIS :
PROTEIN – 31
GLUCOSE – 90
CHLORIDE – 117
APPEARANCE – CLEAR
AFB – NEGATIVE
CULTURE – NO GROWTH
VDRL - NEGATIVE
HIV - NEGATIVE
NORMAL CT BRAIN , NORMAL EEG , NORMAL CSF PROFILE , NORMAL VDRL & HIV
RULES OUT INTRA CRANIAL CAUSES , MENINGO ENCEPHALITIS , POST ICTAL STATES
BASED ON THESE , A DIAGNOSIS OF HEPATIC COMA WAS MADE
“ HEPATIC ENCEPHALOPATHY - ESSENTIALLY A DIAGNOSIS OF EXCLUSIONHEPATIC ENCEPHALOPATHY - ESSENTIALLY A DIAGNOSIS OF EXCLUSION “
BUT DESPITE H.E. DIRECTED INTENSIVE MEDICAL CARE
28 / 2 /09 … FURTHER DETERIORATION IN GCS ( E 1 V2 M 1)DAY 20
1/3/09 … CENTRAL VENOUS LINE SECURED
2/3/09 … PATIENT INTUBATED AND PLACED IN MECHANICAL VENTILATORDAY 22 FALLING PLATELET COUNT
TREATMENTTREATMENT RESISTANTRESISTANT HEPATIC HEPATIC COMA …COMA …
??? CAUSE
CAUSES OF PERSISTENT HEPATIC COMA DESPITE TREATMENTCAUSES OF PERSISTENT HEPATIC COMA DESPITE TREATMENT
INFECTION ….. SBP , LRI { VAP } , SEPTICEMIA , UTI
ELECTROLYTE IMBALANCE … PERSISTENT HYPOKALEMIA
ASSOCIATED RENAL FAILURE …. RULED OUT { NORMAL RFT , OUTPUT }
HYPOGLYCEMIA …. RULED OUT { PATIENT WAS ON > 2000 Kcal / Day SUGARS WERE STABLE }
UPPER GI BLEED …. RULED OUT { RT ASPIRATES – NOT BLOOD STAINED STOOL NEGATIVE FOR BLOOD , HB % - N }
CONSTIPATION …. RULED OUT { PT ON LACTULOSE & PASSING 2-4 STOOLS PER DAY}
DEHYDRATION ….. RULED OUT { ADEQUATE FLUID INTAKE PULSE , BP , U / O – NORMAL }
ACID BASE IMBALANCE …. POSSIBLE ( ABG NOT DONE )
DRUGS ….. POSSIBLE { BDZ GIVEN FOR SEDATION IN EARLY STAGES LASIX , PSYCHOTROPIC MEDICINES , NARCOTICS WERE AVOIDED}
FEVER WORK UP DONE :
BLOOD C/S … NON FERMENTING GNB
SPUTUM C/S … KLEBSIELLA
URINE C/S … ENTEROCOCCI & PNEUMOCOCCI
TREATMENT :
DOPAMINE DRIP STARTED
POTASSIUM INFUSIONS MAINTAINED
APPROPRIATE ANTIBIOTICS ADDED ( MEROPENEM , VANCOMYCIN , PIPERACILLIN – TAZOBACTAM )
BACLOFEN AND PHYSIOTHERAPY GIVEN
BDZ STOPPED
OTHER TREATMENT CONTINUED
12/3/09 … TRACHEOSTOMY DONEDAY 32
18/3/09 … PATIENT IMPROVED AND WEANED OFF THE VENTILATORDAY 38 ON NOR ADRENALINE DRIP (DUE TO PERSISTENT HYPOTENSION)
AS ON 25/3/09 : …DAY 45
ICTERIC ++
AFEBRILE
VITALS … STABLE
BLOOD NH3 … STABLE
SERUM K + … STABLE
INR , PLATELETS … STABLE
DISCHARGE BEING PLANNED ON 30 / 3 / 09 ….. DAY 50
SUMMARY SUMMARY
57 YEARS OLD MALE ADMITTED WITH
FLUCTUATING CONSCIOUSNESS LEVEL (FOR WHICH TREATED AT OUTSIDE HOSPITALS FOR PAST FEW MONTHS)
SEVERE HEPATIC DYSFUNCTION AS EVIDENCED BY
HIGH BILIRUBIN & AMMONIA ,HIGH BILIRUBIN & AMMONIA , LOW ALBUMIN , POTASSIUM & UREA LOW ALBUMIN , POTASSIUM & UREA VIT K RESISTANT COAGULOPATHYVIT K RESISTANT COAGULOPATHY
ADMITTED WITH STAGE 3 H.E. WHICH WAS RESISTANT TO TREATMENT
COMPLICATED BY MULTI FOCAL SEPSIS , ELECTROLYTE IMBALANCE , ? BDZ USE PROGRESSED TO STAGE 4 - PATIENT PLACED IN MV
AFTER SUSTAINED TREATMENT WITH DIETARY MGT , ANTIBIOTICS ,HEPAMERZ , VIT K , POTASSIUM INFUSIONS , LACTULOSE , BACLOFEN AND PHYSIOTHERAPY PATIENT IMPROVED TO PRESENT CONDITION
THIS IS THE FIRST CASE OF SEVERE TREATMENT RESISTANT STAGE 3 / 4 HEPATIC COMA ADMITTED IN NATIONAL HOSPITAL
PATIENT – IN ICU FOR NEARLY 50 DAYS WITH CONSTANT MONITORINGAND MANAGEMENT OF THE ENCEPHALOPATHY , MULTI FOCAL SEPSIS, PERSISTENT HYPOTENSION , HYPO KALEMIA , HYPER AMMONEMIA ,HYPER BILIRUBINEMIA & COAGULOPATHY
PATIENT – IN VENTILATOR FOR 14 DAYS
PATIENT - SUCCESSFULLY REVIVED AFTER NEARLY 50 DAYS OF INTENSIVE MEDICAL CARE
ALL OF THIS POSSIBLE ONLY BECAUSE HIS COMPANY AGREED TO PAY FOR THE EXPENSES
HEPATIC ENCEPHALOPATHY
Hepatic encephalopathy is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction characterized bypersonality changes, intellectual impairment, and a depressed level ofconsciousness
Type A hepatic encephalopathy associated with A cute liver failure.
Type B hepatic encephalopathy associated with portal-systemic B ypass
Type C hepatic encephalopathy associated with C irrhosis and portal hypertension or portal-systemic shunts.
Type C hepatic encephalopathy is, in turn, subcategorized as episodic, persistent, or minimal.
PATHOGENESIS
Endogenous Neurotoxins
AmmoniaMercaptansPhenolsShort-medium fatty acids
Increased Permeability of Blood-Brain Barrier
Change in Neurotransmitters and Receptors
GABAMet enkephalin
Altered BCAA/AAA ratio
Zinc deficiency
Manganese deposits
PRECIPITATING FACTORS
DrugsBenzodiazepinesNarcotics, opioidsAnti psychoticsAnti depressantsAlcoholdiuretics
Portosystemic ShuntingRadiographic or surgically placed shuntsSpontaneous shuntsVascular OcclusionPortal or Hepatic Vein Thrombosis
DehydrationVomitingDiarrheaHemorrhageDiureticsLarge volume paracentesis
Increased Ammonia Production, Absorption or Entry Into the BrainExcess Dietary Intake of ProteinRenal failureGI BleedingInfectionElectrolyte Disturbances (ie., hypokalemia)ConstipationMetabolic alkalosisPrimary Hepatocellular
Carcinoma
CLINICAL PICTURE
MINIMAL H.E.
EARLY SYMPTOM ….. ALTERATION OF SLEEP PATTERNEARLY SIGN ….. CONSTRUCTIONAL APRAXIA
OTHER FEATURES …
UNAWARENESS OF CLINICAL SUBJECTIVE SYMPTOMS
ABSENT EEG FINDINGS
PSYCHOMETRIC/NEUROSPYCHOLOGICAL TESTS CAN DISCLOSE DEFICITS
HYPER VENTILATION
REDUCED BODY TEMPERATURE
NEJM Volume 337:473-479
ASTERIXIS IS ABSENT IN STAGES 0 & 4
IT IS SEEN IN OTHER ORGANFAILURES ALSO
EG : RENAL FAILURE PULMONARY FAILURE
ALSO OBSERVED IN BARBITURATETOXICITY
LAB DIAGNOSIS :
PSYCHOMETRIC / NEUROPSYCHOLOGICAL TESTSPSYCHOMETRIC / NEUROPSYCHOLOGICAL TESTS
ELECTRO PHYSIOLOGIC STUDIESELECTRO PHYSIOLOGIC STUDIES
IMAGE TECHNIQUESIMAGE TECHNIQUES
CLINICAL LABORATORY TESTSCLINICAL LABORATORY TESTS
PSYCHOMETRIC / NEUROPSYCHOLOGICAL TESTS
Retelling and interpretation a fable
Forward / backward digit span
Reproduction of simple figures
Block design test
Critical flicker test
WAIS performance IQ
Line tracing tests: LTT
Number connecting test: NCT
Digital-symbol test: DST
EEG :
Classic EEG changes associated with hepatic encephalopathy are high-amplitude , low-frequency waves and tri phasic waves
VEP …. Useful in detecting early H.E.
BRAIN IMAGING
MRI / CT are used mainly to rule out other causes . MRI has the additionaladvantage of being able to demonstrate hyperintensity of the globus palliduson T1-weighted images, a finding that is commonly described in hepatic encephalopathy
LAB PARAMETERS
RENAL FUNCTION DISORDERSELECTROLYTE IMBALANCE { ESP SR POTASSIUM LEVELS }ACID-BASE EQUILIBRIUMLIVER FUNCTIONINFLAMMATORY PARAMETERS
BLOOD AMMONIA LEVELS
Clinical assessment more reliable than serial ammonia estimation
Arterial sample is preferable
Blood drawn from an extremity to which a tourniquet has been appliedmay provide a falsely elevated ammonia level
NORMAL RANGE : 18 TO 60
May also be elevated in other states of hyper ammonemia such as
uretero sigmoidostomyurea cycle disorders
AMMONIA HAS NO RELATION TO CLINICAL STATUS
THIS PATIENT HAD ONLY MILD ELEVATION ( < 120 ) INSPITE OF SEVERE ENCEPHALOPATHY
MANAGEMENT OF H.E.
TREATMENT OF PRECIPITATING FACTORS
DIETARY MANAGEMENT
INTESTINAL CLEANSING
ROLE OF FLUMAZENIL , ZINC , MANGANESE
AMMONIA DETOXIFICATION
TRANSPLANTATION
TREATMENT OF PRECIPITATING FACTORS :
ADEQUATE HYDRATION
HYPOGLYCEMIA : ADEQUATE CARBOHYDRATE SUPPLEMENT
GI BLEEDINGS : STOP BLEEDING AND AVOID ANEMIA
INFECTIONS { ESP. SBP } : ANTIMICROBIALS
ACIDOSIS / ALKALOSIS : TO BE CORRECTED
DIURETICS : ESP LASIX TO BE AVOIDED
SEDATIVES : DISCONTINUED
CONSTIPATION : TO BE CORRECTED WITH LACTULOSE
UREMIA : TO BE CORRECTED
DIETARY MANAGEMENT :
ENSURE ADEQUATE CALORIE & FLUID INTAKE
RESTRICT PROTEINS TO LESS THAN 30 gm PER DAY
PLANT PROTEIN IS BETTER THAN ANIMAL PROTEIN
BRANCHED CHAIN AMINO ACID SUPPLEMENTATION
ZINC SUPPLEMENTATION
INTESTINAL CLEANSING :
LACTULOSE
NEOMYCIN , METRONIDAZOLE , AMPICILLIN , PAROMOMYCIN
RIFAXIMIN
ROLE OF FLUMAZENIL , ZINC , MANGANESE :
FLUMAZENIL IS HIGHLY USEFUL IN THOSE CASES TREATED WITH BDZ
EVEN IN OTHER CASES , IT MAY HAVE A ROLE
ZINC DEFICIENCY IS IMPLICATED IN THE PATHOGENES OF H.E. AND HENCE ITS SUPPLEMENTATION IS HELPFUL IN SOME CASES
MANGANESE EXCESS IS ALSO A PRESUMED PREDISPOSING FACTOR AND THIS IS SAID TO BE RESPONSIBLE FOR THE HYPER DENSITY OF GLOBUS PALLIDUS ON MRI
SO MANGANESE CHELATORS MAY BE USED IN FUTURE
Others :
Modification of intestinal flora : (replacing ammoniagenic coliforms with non ammoniagenic bacilli)
Methionine sulfoximine.
AMMONIA DETOXIFICATION :
Protein restriction
Lactulose
Neomycin , metronidazole , Ampicillin , paromomycin , Rifaximin
L-ornithine L-aspartate (LOLA)
Sodium benzoate, sodium phenylbutyrate, sodium phenylacetate
L-carnitine
Dialysis
LIVER TRANSPLANTATION
SEVERE AND TREATMENT REFRACTORY H.E.
ACUTE LIVER FAILURE WITH H.E.
APPROACH TO A PATIENT WITH H.E.
Exclude nonhepatic causes of altered mental function.
Periodic estimation of blood ( preferably arterial ) ammonia
Precipitants of hepatic encephalopathy, such as metabolic disturbances, gastrointestinal bleeding, infection, and constipation, should be corrected.
Avoid CNS depressants especially BENZODIAZEPINES{ but they may be used in co existing alcohol withdrawal + H.E.}
Prophylactic intubation for grade 3 & 4 H.E. cases to prevent aspiration
Treatment of hyper ammonemia
Zinc , Vit K supplementation
Supportive care & nutrition