Interpretation and utility of ammonia level in Hepatic Ence - PowerPoint Presentation

Slide1

Interpretation and utility of ammonia level in Hepatic Encephalopathy

Patrick Fleming, MD

Henry Ford EM; PGY-3Slide2

Goals and Objectives

Review definition/classification of hepatic encephalopathy (HE) and its pathophysiology

Review differential diagnosis, clinical/laboratory findings, and management of HE

Review of literature to make an evidence based assessment of utility testing for ammonia level in diagnosis and management of HESlide3

Hepatic Encephalopathy

“HE is a brain dysfunction caused by liver insufficiency and/or PSS; manifests as a wide spectrum of neuropsychiatric abnormalities ranging from subclinical alteration to coma”Slide4

Classification of HE

Type A - due to acute liver failure

T

ype B - predominantly from

portosystemic

bypass or shunting

Type C - due to cirrhosisSlide5

Severity Classification (West Haven Criteria)

Minimal to Grade I (covert HE)

Grade 1: some cognitive changes,

euphora

/anxiety, shortened attention span, impairment in calculations, or altered sleep—clinical findings usually not reproducible

Grade II-IV (overt HE)

Grade II: lethargy/apathy, disoriented to time, personality change/inappropriate behavior,

asterixis

Grade III: somnolent but responsive to stimuli; confused, disoriented (to time and space), bizarre behavior

Grade IV: coma, unresponsive to painful stimuliSlide6

Precipitating Factors(factor unknown in 20-30% of cases)

Fluid and electrolyte disturbances

Renal failure

Infection

GI bleed

Sedatives

High protein diet

ConstipationSlide7

History and Physical

Presenting complaint

AMS, flapping tremor, mood and behavior changes

Physical Exam

Look for stigmata of cirrhosis

:

Neurologic findings: see HE severity scale

Asterixis

: elicited bilateral flapping tremorSlide8

Differential Diagnosis

Metabolic

encephalopathies

: CO2 narcosis, DKA, hypoglycemia, hypoxia

Toxic

encephalopathies

:

alcohols, narcotics, benzodiazepine

Intracranial event:

infection, head injury, tumor, ICH, stroke

PyschiatricSlide9

Testing (for rule-out of other conditions in differential)

Labs

LFT’s

BUN/

creatinine

Electrolytes

Glucose

ETOH level

Urine toxicology

ABG

Pt

/

ptt/inrAmmonia?Imaging

CT or MRI headSlide10

Ammonia and HE

Time line of theory:

1879: Friedrich von

Frerichs

amongst the earliest commentators on Hepatic Encephalopathy

1893: Hahn et al working in Pavlov’s lab report findings of intoxication following meat feeding in dogs that had undergone Eck fistula

1932: Van

Caulaert

and

Deviller

show high ammonia levels in patients with liver disease, increase in levels after given ammonia salts, and induction of neuropsychiatric symptoms in many of their patients

1936: Kirk’s experimentation of administration of ammonia to cirrhotic patients

1958, 1963: studies by Sherlock and Stahl show in general as ammonia level increase severity of HE increase

Friedrich von

FrerichsSlide11

Pathogenesis

Common theory

Nitrogenous compounds from GI tract adversely affect brain function

Build up of nitrogenous compounds from:

Decreased hepatic function

Porto-systemic shunts

Elgouhari

HM, O’Shea R. What is the utility of measuring the serum ammonia level in patients with altered mental status?

Cleve

Clin

J Med. 2009; 76(4): 252-254Slide12

Ammonia and HESlide13

A 57 yo

patient presents to ED with known alcoholic cirrhosis with altered mental status. Family states for last day he has been less active, is sleeping much of day, and seems confused. On exam patient is

disoriented and drowsy.

You note stigmata of cirrhosis and are able to elicit

asterixis

. Slide14

Q: How many in the audience would obtain an ammonia level in the work-up of this patient

?

Slide15

-T/F: a normal ammonia level can rule out HE (

sensitivity

)

-T/F: an elevated ammonia level can establish the diagnosis of HE (

specificity

)

-T/F: serial ammonia levels are useful in assessing response to therapy for HE Slide16
Slide17

Value of ammonia level still debated

No clear advantage to source of sample (venous vs. arterial vs. partial pressure)

Would ultimately like to know rate of diffusion of ammonia across blood brain barrier (and the variables that alter this)Slide18
Slide19
Slide20
Slide21
Slide22

Ammonia levels in HE

Normal levels do not rule out HE

In one study more than 69% without evidence of HE had elevated levels

Neither sensitive or specific for presence or degree of HE

Evidence for having special prognostic value in patient with acute liver failureSlide23

Technical aspects of ammonia level testing

Venous blood level as reliable as arterial if obtained and handled properly

Prolong use of tourniquet or fist-clenching

false elevation

Venous blood should be transported on ice and handled quickly for analysis

A serum ammonia assay is $27.07 (2013 Medicare reimbursement)Slide24

Dangers of ammonia interpretation

Improper technique can lead to falsely elevated levels

Measurement in patient without signs of HE can lead to improper treatment

Over-reliance on elevated level can lead to anchoring on diagnosis Slide25

Date of download: 12/1/2015

Copyright © 2015 American Medical Association. All rights reserved.

From:

Serum Ammonia Level for the Evaluation of Hepatic Encephalopathy

JAMA. 2014;312(6):643-644. doi:10.1001/jama.2014.2398

Laboratory Test Results in a Patient With Hepatitis C Cirrhosis

Table Title: Slide26

Treatment

Identify and correct precipitating factor

Maintain nutrition: protein intake 1.2-1.5 g/kg/day

Lactulose: 25 mL q 1 hour until defecation, then 15-45 mL q 8-12 for 2-3 soft stools daily

Rifaximin

: 500 mg PO BIDSlide27

Disposition

Disposition

: Consider underlying cause, response to therapy. Grade 1 without complicating factors may possible be discharged. Grade III-IV likely need ICU.Slide28

Summary

A normal ammonia level cannot rule out HE

An elevated ammonia level cannot establish the diagnosis of HE

Serial ammonia levels

does not currently have role

in assessing response to therapy for HE

HE is a clinical diagnosis; focus on excluding other causes of AMSSlide29

References

Vilstrup

H,

Amodio

P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.

Hepatology

. 2014 Aug; 60(2): 715-35

Elgouhari

HM, O’Shea R. What is the utility of measuring the serum ammonia level in patients with altered mental status?

Cleve

Clin

J Med. 2009; 76(4): 252-

254Kramer, L., Tribl, B., Gendo, A., Zauner, C., Schneider, B., Ferenci, P., and

Madl

, C. (2000). Partial pressure of ammonia versus ammonia in hepatic encephalopathy.

Hepatology

31 (1): 30-34.

Ong

, J.P.,

Aggarwal

, A., Krieger, D., Easley, K.A.,

Karafa

, M.T., Van

Lente

, F.,

Arroliga

, A.C., and Mullen, K.D. (2003). Correlation between ammonia levels and the severity of hepatic encephalopathy.

Am. J. Med.

114

(3): 188-193.

Stahl, J. (1963). Studies of the blood ammonia in liver disease: Its diagnostic, prognostic, and therapeutic significance.

Ann. Int. Med.

58:1-24.

Lockwood AH. Blood ammonia levels and hepatic encephalopathy.

Metab

Brain Dis 2004; 19: 345-349.

Nicolao

F,

Efrati

C,

Masini

A, et al. Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy.

J

Hepatol

.

2003, 38 (4): 441-446

Wang V, Saab S. Ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003; 114: 237-8.

Bhatia V, Singh R,

Acharya

SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure.

Gut. 2006; 55(1): 98-104

.

Lockwood AH, Yap EWH, Wong W-H. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J

Cereb

Blood Flow

Metab

1991;11:337-341.