Arterial Ammonia Levels As a Predictor of Mortality in Acute Liver Failure
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RESEARCH HIGHLIGHTS www.nature.com/clinicalpractice/gasthep linked to adverse events such as nephrotoxicity. The median arterial ammonia concentration Conventional ultrasound is of limited use in at admission was 128.6 μmol/l. The median the diagnosis of acute pancreatitis, primarily time from admission to death (42/80 patients) because it cannot detect pancreatic necrosis was 4 days. Median arterial ammonia con- effectively. Use of echo enhancement improves centration was significantly higher in patients ultrasound imaging of organ perfusion; echo- who died (174.7 μmol/l) than in survivors enhanced ultrasound (EEUS) is less costly than (105.0 μmol/l, P <0.001). By regression analy- CT, has fewer side effects, and can be used to sis, an arterial ammonia level of ≥124 μmol/l diagnose acute pancreatitis. In this prospective was found to have a sensitivity of 78.6% and study, Rickes et al. compared the diagnostic per- specificity of 76.3% as a predictor of death formance of EEUS and CT and the relationship (P <0.001). Ammonia levels above this value between EEUS data and clinical parameters. had an odds ratio of 10.9 as a predictor of An experienced examiner who was blinded death (95% CI 5.9–284.0). Other factors found to prior laboratory and imaging findings per- to be highly predictive of death were cerebral formed conventional ultrasound, EEUS and CT edema (odds ratio 12.6; 95% CI 1.5–108.5) scans of 31 patients (24 men) with acute pan- and blood pH of 7.4 or below (odds ratio 6.6; creatitis, aged 19–67 years (mean 39 years), 95% CI 0.8–57.5). These factors were incorpo- within 72 h after admission. A statistically sig- rated into an equation predicting mortality risk, nificant correlation was found between the scoring risk factors as 0 if absent, or 1 if pres- severity indices established for EEUS and for ent: z = 2.53 + 2.91(ammonia) + 2.41(edema ) + CT (r = 0.807, P <0.01). 1.40(pH). The probability of death, Px, could -z Discordance between diagnoses obtained then be calculated as Px = 1/(1 + e ), where e is by CT and EUS was observed for five patients the Euler number, approximating to 2.718. (16%). EEUS correctly diagnosed all eight The authors conclude that arterial ammonia patients with pancreatic necrosis; however, levels are predictive of patient outcome and it also produced two false-positive and four can be used for risk stratification, and that false-negative results in terms of severity. their results provide a rationale for the use Rickes et al. question whether CT really is the of ammonia-lowering treatment in patients best means of predicting acute pancreatitis, as presenting with ALF. none of the false-negative patients actually had Jim Casey severe pancreatitis, according to clinical crite- Original article Bhatia V et al. (2006) Predictive value of ria. Another potential issue is the large 95% arterial ammonia for complications and outcome in acute confidence intervals, which were possibly due liver failure. Gut 55: 98–104 to the small sample size. The authors conclude that, nevertheless, EEUS has the potential to become a valid, first-choice alternative to CT Prevalence and treatment for diagnosing acute pancreatitis. of Clostridium difficile-related Katherine Sole disease Original article Rickes S et al. (2006) Echo enhanced ultrasound: a new valid initial imaging approach for severe Clostridium difficile is a spore-forming, anaero- acute pancreatitis. Gut 55: 74–78 bic bacillus. Infection with this organism can lead to toxin-mediated diarrhea and colitis, particularly for individuals in whom the balance Arterial ammonia levels of intestinal flora has been altered by antibiotic as a predictor of mortality use. Prevalence of C. difficile-related disease is in acute liver failure increasing, and has been the subject of several recent studies. In patients with acute liver failure (ALF), the Independent research teams in the US and brain is exposed to high levels of ammonia, Canada have confirmed that a previously which has a neurotoxic effect. Researchers uncommon, highly virulent strain of C. difficile in India investigated the relationship between is increasing in prevalence. The so-called ammonia levels at admission and patient BI/NAP1 strain carries the binary toxin CDT outcome by following 80 patients with ALF to (a suspected virulence factor) and a deletion either recovery or death. in a regulatory gene (tcdC) that markedly 124 NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY MARCH 2006 VOL 3 NO 3 © 2006 Nature Publishing Group.