Intensive Care Med (2007) 33:1179–1182 DOI 10.1007/s00134-007-0574-6 BRIEF REPORT Marie-Pierre Bonnet Vincent Minville Karim Asehnoune Delphine Bridoux Joséphine Poggi-Bach Jacques Duranteau Dan Benhamou Glycine and ammonia plasma concentrations during sedation with remifentanil in critically ill patients Received: 21 December 2005 Accepted: 31 January 2007 Published online: 9 March 2007 © Springer-Verlag 2007 Electronic supplementary material The online version of this article (doi:10.1007/s00134-007-0574-6) contains supplementary material, which is available to authorized users M.-P. Bonnet · V. Minville · K. Asehnoune · J. Duranteau · D. Benhamou (✉) Bicêtre University Hospital, Département d’Anesthésie-Réanimation, AP-HP, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France e-mail: dan.benhamou@bct.aphp.fr Tel.: +33-1-45213447 Fax: +33-1-45212875 D. Bridoux · J. Poggi-Bach Bicêtre University Hospital, Laboratory of Biochemistry, AP-HP, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France V. Minville Paul Sabatier University, Department of Anesthesia and Intensive Care, Toulouse University Hospital, Toulouse, France Abstract Objectives: To investi- gate glycine and ammonia plasma concentrations during a 72-h remifen- tanil 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 sed- ated with remifentanil and propofol. Glycine and ammonia plasma con- centrations 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 biologic- al signs of glycine toxicity were evaluated. Measurements and re- sults: 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 be- tween 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. Keywords Remifentanil · Glycine · Ammonia · Sedation · Intensive care unit Introduction Remifentanil, a short-acting opioid metabolized by plasma and tissue esterases, is associated with a significantly shorter duration of mechanical ventilation than a con- ventional hypnotic-based sedation regimen in critically ill patients [1]. Remifentanil is used in ICU patients with intracranial pathology because it permits a significantly faster and more predictable awakening for neurological assessment [2]. This drug is available as a powder contain- ing glycine excipient (3 mg glycine for 1 mg remifentanil). Consequently some effects of long-term administration of remifentanil on plasma glycine concentration may be expected. A hypothetical effect of remifentanil on cerebrospinal fluid (CSF) glycine concentration may also be expected, in view of the fact that glycine is an inhibitory neurotransmitter [3]. Glycine is normally metabolized by oxidative deamination to produce ammonia [4]. Glycine and ammonia in excess can induce neurological [5, 6, 7] and cardiac symptoms [8, 9] that have been reported in