Glycine and ammonia plasma concentrations during sedation with remifentanil in critically ill patients.

OBJECTIVES: To investigate glycine and ammonia plasma concentrations during a 72-h remifentanil infusion and the relationship between glycine concentration and remifentanil infusion rate. DESIGN AND SETTING: A prospective open-label observational clinical trial in a trauma and a neurosurgical intensive care unit in a university teaching hospital. PATIENTS: Nine consecutive patients requiring sedation and ventilatory support for at least 72 h. One was excluded due to acute cardiac failure. INTERVENTIONS: Patients were sedated with remifentanil and propofol. Glycine and ammonia plasma concentrations were measured every 12 h during an intravenous remifentanil infusion performed over 72 h, and 24 h after the end of the infusion. Cumulative remifentanil dose and rate of infusion were recorded for each patient. Clinical and biological signs of glycine toxicity were evaluated. MEASUREMENTS AND RESULTS: Glycine and ammonia plasma concentrations did not exceed the toxic threshold at any time. Plasma glycine concentration measured at the end of remifentanil infusion was significantly correlated with the mean weighted rate of remifentanil infusion and with the cumulative remifentanil dose. A correlation between plasma glycine concentration and creatinine clearance at the end of remifentanil infusion was also documented. CONCLUSIONS: Plasma glycine concentration was correlated with the remifentanil cumulative dose and the infusion rate and did not reach the toxic threshold. As glycine concentration was also correlated with creatinine clearance and because remifentanil was the only source of exogenous glycine, additional data are necessary to ascertain the safety of remifentanil infusion in ICU patients.

Simple and fast quantification of nitisone (NTBC) using liquid chromatography-tandem mass spectrometry method in plasma of tyrosinemia type 1 patients.

Tyrosinemia type 1, which is caused by a deficiency in fumarylacetoacetate hydrolase, is successfully treatable with nitisone (NTBC), an inhibitor of 4-hydroxyphenyl pyruvate dioxygenase. The recommended average dose of NTBC is 1 mg/kg per day. A rapid liquid chromatography (LC) coupled with negative electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of NTBC in heparinized human plasma. The plasma samples were prepared by precipitation in acetonitrile. NTBC and the internal standard (IS) were chromatographed on a BEH C18 column. Gradient elution was done with a mixture of 10 mM ammonium acetate and methanol. The analyte was analyzed by LC-tandem mass spectrometry with only 2 min run time. Selected reaction monitoring modes for detection of NTBC and the IS were achieved by using m/z 328 > 281 and 234 > 190, respectively. The LC retention times for NTBC and IS were 0.99 and 0.93 min, respectively. The method was linear in the concentration range of 0.75-150 µM with r ≥ 0.998. Thus, this method is suitable for follow-up of patients treated with NTBC, because the current therapeutical concentrations range from 20 to 120 µM.