A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis

Abstract

BackgroundHepatic 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.AimTo 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.MethodsWe 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.ResultsThe 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.ConclusionsIn 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.

Ammonia Levels and Hepatic Encephalopathy in Patients with Known Chronic Liver Disease

“…Furthermore, ammonia levels are not a valid tool to diagnose HE even with an oral glutamine challenge. 20 Most importantly, HE is a clinical diagnosis reached following the exclusion of other likely causes of cerebral dysfunction, independent of the ammonia level.…”

Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy

“…The cut‐offs for the baseline hyperammonemia (>78 μg/dL) and impaired OGC (Δ ammonia levels >32 μg/dL) were identified by ROC analysis in the main cohort. Regarding the baseline ammonia concentration, our population showed a similar cut‐off than other cohorts previously published . The secondary aim was to assess whether the features and conditions of the first HE event were different depending on the OGC interpretation, which could guide to different therapeutic strategies.…”

“…Regarding the baseline ammonia concentration, our population showed a similar cut-off than other cohorts previously published. [7][8][9]11,12 The secondary aim was to assess whether the features and conditions of the first HE event were different depending on the OGC interpretation, which could guide to different therapeutic strategies.…”

Management of hepatic encephalopathy in Germany: a survey among physicians

“…Recently published papers suggest that the animal-naming test and the clinical covert HE score have the potential to fill this diagnostic gap [24][25][26]. Another promising strategy may be point-of-care testing for elevated ammonia levels [27,28]. However, it is currently unknown whether this holds true for detection of CHE since many of the affected patients have ammonia levels within the normal range.…”