title: A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis.
abstract: BACKGROUND
  Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed.
  
  
  OBJECTIVE
  To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge.
  
  
  METHODS
  We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months.
  
  
  RESULTS
  The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi2: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event.
  
  
  CONCLUSIONS
  In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.
authors.affiliation: Gastroenterology and Hepatology, University Hospitals and Faculty of Medicine, 4, Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Saskia
authors.initials: S
authors.lastname: Ditisheim
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giostra
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Burkhard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goossens
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.forename: Antoine
authors.initials: A
authors.lastname: Hadengue
authors.forename: Laurent
authors.initials: L
authors.lastname: Spahr
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002196:Capillaries; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005973:Glutamine / Q000008:administration & dosage*; D006403:Hematologic Tests / Q000379:methods; D006501:Hepatic Encephalopathy / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D015995:Prevalence; D011594:Psychometrics
chemical_list: D015415:Biomarkers; D005973:Glutamine; D000641:Ammonia