Capillary Ammonia Research Articles

The effect of induced hyperammonaemia on sleep and melanopsin-mediated pupillary light response in patients with liver cirrhosis: A single-blinded randomized crossover trial.

Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis. The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days. The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS. Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests. Registration number: NCT04771104.

Заболевания органов дыхания и гипераммониемия

Study Objective: To assess the incidence of hyperammoniemia in respiratory diseases. Materials and Methods. 36 patients with respiratory diseases took part in the study: chronic obstructive pulmonary disease (COPD) (21 (58.3%) patients), chronic bronchitis (5 (13.9%) patients), and pneumonia (10 (27.8%) patients). Mean age was 66.8 ± 11.8 years; 9 (25.0%) females and 27 (75.0%) males. Each patient had his/her capillary ammonia measured (microdiffusion). In order to assess the nutrition status, all patients had their primary somatometry measured: height, weight, body mass index, inactive arm circumference, waist circumference, skin-fat rolls thickness under biceps, above triceps, below shoulder blade angle, in inguinal region. Study Results. 9 (25.0%) out of 36 patients had hyperammoniemia (capillary ammonia level: 74.0 ± 7.1 nmol/L); their mean age was 62.3 ± 18.2 years. Patients with COPD/chronic bronchitis had significantly higher ammonia concentration (60.7 ± 16.6 mol/L) vs. patients with pneumonia (48.4 ± 14.3 mol/L; t = 2.2, p < 0.03). COPD patients demonstrated significant differences in ammonia levels depending on duration of disease. In the group of higher ammonia concentration, COPD lasted significantly longer (t = 4.03 p = 0.001). We did not find any sound correlation between nutritional (trophological) status and ammonia concentrations in patients with respiratory diseases (t < 2, p > 0.05). Conclusion. In 25% of cases, respiratory diseases were associated with hyperammoniemia that is non-cirrhotic, because hepatobiliary disorders in this group of patients were an exclusion criterion. Although no statistically significant correlation between non-cirrhotic hyperammoniemia and nutritional (trophological) status was demonstrated, pathogenic relations between them cannot be ruled out. Whether underweight is a determining factor in non-cirrhotic hyperammoniemia is still unclear and requires further research and more observations. Keywords: ammonia, non-cirrhotic hyperammoniemia, nutritional (trophological) status, respiratory diseases.

P: 19 Predictive Value of Induced Hyperammonaemia and Neuropsychiatric Profiling in Relation to the Occurrence of Post-tips Hepatic Encephalopathy (HE)

BACKGROUND: Hepatic encephalopathy (HE) occurs in 20%–50% of patients after transjugular intrahepatic portosystemic shunt (TIPS). While indices such as an older age, a history of overt HE and severe liver failure have been associated with post-TIPS HE, it remains difficult to identify patients at risk. The aim of this study was to evaluate the predictive value of a large set of clinical, laboratory and neuropsychiatric parameters, both at baseline and after the induction of hyperammonaemia, in relation to the development of post-TIPS HE for 12 months in a group of well-characterised TIPS candidates. METHODS: 18 TIPS candidates (58 ± 8 yrs, MELD 11 ± 3; 13 refractory ascites, 1 hydrothorax, 4 uncontrolled bleeding) underwent neurophysiological [Electroencephalography (EEG)], neuropsychological [Psychometric Hepatic Encephalopathy Score (PHES) and Scan test], capillary ammonia and subjective sleepiness assessment both at baseline and after the induction of hyperammonaemia by an oral amino acid challenge (AAC). RESULTS: At baseline, 3 (17%) patients had abnormal EEG, 1 (5%) abnormal PHES, and 6 (33%) abnormal Scan performance; fasting capillary ammonia concentrations were 199 ± 88 μg/dL and subjective sleepiness 2.5 ± 1.2 (1–9 scale). Post-AAC, 3 (17%) patients had abnormal EEG, none abnormal PHES, and 3 (17%) abnormal Scan performance. Post-AAC, patients exhibited the expected increase in ammonia [F(4, 56) = 2.7213, P = 0.038] and subjective sleepiness [F(4, 52) = 5.4002, P = 0.001]. Six months after TIPS, 3 patients had had an HE-related hospitalization. Compared to their counterparts who had not, they showed significantly lower, pre-AAC fasting ammonia concentrations (96 ± 93 vs. 225 ± 58 μg/dL, P = 0.017). They also showed worse PHES and Scan performance at baseline, as well as worse Scan performance and slower EEG post-AAC. Twelve months post-TIPS, 5 patients had had an HE-related hospitalization, and comparisons between the two groups confirmed the findings at 6 months. CONCLUSIONS: TIPS candidates, who are by definition at low risk of HE, seem to encompass two different populations: i) those who are well and have not had overt HE because their ammonia levels are near-normal, ii) those who are well and have not had overt HE despite hyperammonaemia, either because of habituation or a personal inclination not to exhibit the HE phenotype. Fasting ammonia may be a promising and easily obtained parameter for future validation and inclusion in models for the prediction of post-TIPS HE.

Vigilance and wake EEG architecture in simulated hyperammonaemia: a pilot study on the effects of L-Ornithine-L-Aspartate (LOLA) and caffeine.

Hyperammonaemia/mild hepatic encephalopathy (HE) can be simulated by the oral administration of a so-called amino acid challenge (AAC). This study sought to assess the effects of the AAC alone and in combination with either ammonia-lowering [L-ornithine-L-aspartate (LOLA)] or vigilance-enhancing medication (caffeine). Six patients with cirrhosis (5 males; 61.3 ± 9.2years; 5 Child A, 1 Child B) and six healthy volunteers (5 males; 49.8 ± 10.6years) were studied between 08:00 and 19:00 on Monday of three consecutive weeks. The following indices were obtained: hourly capillary ammonia, hourly subjective sleepiness, paper & pencil/computerized psychometry and wake electroencephalography (EEG) at 12:00, i.e. at the time of the maximum expected effect of the AAC. On average, patients had worse neuropsychological performance and slower EEG than healthy volunteers in all conditions but differences did not reach significance. In healthy volunteers, the post-AAC increase in capillary ammonia levels was contained by both the administration of LOLA and of caffeine (significant differences between 10:00 and 14:00h). The administration of caffeine also resulted in a reduction in subjective sleepiness and in the amplitude of the EEG on several frontal/temporal-occipital sites (p < 0.05; paired t-test). Changes in ammonia levels, subjective sleepiness and the EEG in the three conditions were less obvious in patients. In conclusion, both LOLA and caffeine contained the AAC-induced increase in capillary ammonia, especially in healthy volunteers. Caffeine also counteracted the AAC effects on sleepiness/EEG amplitude. The association of ammonia-lowering and vigilance-enhancing medication in the management of HE is worthy of further study.

Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine.

Hyperammonaemia is observed after prolonged, intense exercise, or in patients with hepatic failure. In the latter, it is associated with a set of neurological and psychiatric abnormalities termed hepatic encephalopathy. 1. to measure vigilance in a condition of induced hyperammonaemia; 2. to assess whether caffeine modulates the effects of hyperammonaemia on vigilance, if any. Ten healthy volunteers (28.5 ± 5 years; 5 males) underwent three experimental sessions consisting of two-hourly measurements of capillary ammonia, subjective sleepiness (Karolinska Sleepiness Scale) and vigilance (Psychomotor Vigilance Task, PVT), in relation to the intake of breakfast (+/-coffee), an amino acid mixture which induces hyperammonaemia (amino acid challenge; AAC), and AAC+coffee (only for participants who had coffee with their standard breakfast). The AAC resulted in: 1. the expected increase in capillary ammonia levels, with highest values at approximately 4 h after the administration; 2. a significant increase in subjective sleepiness ratings; 3. a sustained increase in PVT-based reaction times. When caffeine was administered after the AAC, both subjective sleepiness and the slowing in RTs were significantly milder than in the AAC-only condition. In conclusion, acute hyperammonaemia induces an increase in subjective sleepiness and a sustained decrease in vigilance, which are attenuated by the administration of a single espresso coffee.

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

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.

Effects of acute moderate hypoxia on anaerobic capacity in endurance-trained runners

While there is some controversy whether anaerobic capacity might be improved after altitude training little is known about changes in anaerobic capacity during hypoxic exposure in highly trained athletes. In order to analyze the effects of acute moderate normobaric hypoxia on anaerobic capacity, 18 male competitive triathletes, middle- and long-distance runners VO2max 67.4 +/- 3.8 ml kg min(-1) performed 2 supra-VO2max treadmill runs with the same speed, one in normoxia and one after 4 h exposure to normobaric hypoxia (FiO(2) 0.15), for estimation of their maximal accumulated oxygen deficit (MAOD) and measurement of peak capillary lactate and peak capillary ammonia concentration. MAOD was not significantly different in normoxia and in moderate hypoxia while time to exhaustion and accumulated O(2) uptake were significantly (P < 0.001) reduced in hypoxia compared to normoxia by 28 and 45%, respectively. The reduction in time to exhaustion was significantly correlated to the decrement in accumulated O(2) uptake (R = 0.730, P = 0.001). In hypoxia, there was a tendency for peak capillary lactate concentration to be decreased compared to normoxia (12.9 +/- 2.1 vs. 13.8 +/- 2.2 mmol l(-1), P = 0.082); peak capillary ammonia concentration was significantly decreased in hypoxia (97 +/- 52 vs. 121 +/- 44 micromol l(-1), P = 0.032). In conclusion, anaerobic capacity is not significantly changed during acute exposure to moderate hypoxia in endurance-trained athletes. The performance reduction during all-out exercise of short duration has to be attributed to the decrement in aerobic capacity.

Effects Of Acute Moderate Hypoxia On Anaerobic Capacity In Endurance-trained Runners

While there is some controversy whether anaerobic capacity might be improved after altitude training little is known about changes in anaerobic capacity during hypoxic exposure in highly trained athletes. PURPOSE To find out if acute exposure to moderate hypoxia affects anaerobic capacity in endurance-trained athletes. METHODS 18 male middle-/long-distance runners and triathletes (23.9 ± 3.9 yrs, 182 ± 6 cm, 70.8 ± 6.7 kg, VO2max 68.1 ± 4.3 ml · kg-1 · min-1) performed two supra- VO2max treadmill tests with the same speed, one in normoxia and one on a separate day after a 4 h exposure to normobarc hypoxia (FiO2 0.15). Maximal accumulated oxygen de.cit (MAOD) was determined as described by Medbø et al. (1988). Capillary blood samples from the earlobe were drawn at rest and repeatedly during 15 min of recovery for measurement of lactate and ammonia. RESULTS MAOD showed a tendency (p = 0.061) to be increased in hypoxia by 9 % on the average while maximal capillary lactate (12.8 ± 2.0 vs. 13.7 ± 2.1 mmol · L−1, p = 0.036) and maximal capillary ammonia concentration (95 ± 49 vs. 121 ± 42 μmol · L−1, p = 0.008) were significantly decreased. The reduction in time to exhaustion (144 ± 33 vs. 203 ± 55 s, p <0.001) was significantly correlated to the decrement in oxygen uptake during exercise in hypoxia (R = 0.797, p <0.001). CONCLUSION The slight increase in MAOD shows that performance during exhaustive supra-VO2max exercise in moderate hypoxia is not impaired by changes in anaerobic capacity. Supported by the Bundesinstitut für Sportwissenschaft (VF0408/01/01/2000–2001)

Plasma ammonia concentrations in newborns and children

Many, mostly congenital, hyperammonemic syndromes may occur in the first days of life. For the diagnosis of these disorders plasma ammonia levels physiologically present in neonates and early childhood should be known, preferably by the use of an enzymatic method. Full-term newborns had higher capillary ammonia concentrations on the first day of life (30–144 μmol/l) than on the fifth day (31–104 μmol/l). In the same individuals the arterial (38–89 μmol/l) are lower than the capillary concentrations (69–112 μmol/l). The venous concentrations in school children were not higher than in adults. The scatter of capillary values, however, is great. For diagnostic purposes of disorders of ammonia detoxication sampling of arterial or venous blood is preferable.