[Drug-drug Interactions in Intensive Care]. / Arzneimittelinteraktionen in der Intensivmedizin.

Drug-drug interactions are common problems in intensive care units. Numerous studies could demonstrate the impact of the total amount of prescribed drugs and the occurrence of potential respectively manifest drug-drug interactions in critically ill patients. The average number of clinically used drugs in this setting is approximately 25 - 35 per patient, thus the profound knowledge of pharmacodynamic and pharmakokinetic mechanisms regarding drug interplay is important for treatment safety. This review aims to summarize the current evidence of drug interactions in intensive care patients. It especially features data regarding pharmacokinetics as main reason for clinically relevant drug-drug interactions. The most important drug classes noted in this context are analgesics and sedatives, antibiotics, antimycotics, antiepileptics, immune suppressive drugs, prokinetics and gastric acid regulating drugs. Furthermore, some pharmacodynamic interactions are described like QTc prolongation or serotonin syndrome. Additionally, a clinical case is demonstrated regarding the malignant impact of rifampin co-medication in a patient suffering from severe hypertension with the use of several antihypertensive drugs.

[Anesthesia and Multiple Sclerosis: What needs to be considered?]. / Anästhesie und Multiple Sklerose - Was gilt es zu beachten?

Patients with rare neurological diseases are always a challenge in routine clinical activity. In particular, anesthetic interventions can be fraught with many problems. This article deals with the current state of knowledge on multiple sclerosis in anesthesia. Here, the authors refer to the safe preparation for and implementation of various forms of anesthesia as well as the prevention and if necessary, treatment of possible complications.

Decreased meropenem levels in Intensive Care Unit patients with augmented renal clearance: benefit of therapeutic drug monitoring.

One of the first-line drugs for empirical antibiotic therapy in patients with hospital-acquired infections is meropenem. An often neglected problem in sepsis is that patients with a normal serum creatinine concentration (SCr) might display augmented renal clearance (ARC). Here we describe two cases of sepsis with subtherapeutic exposures with standard meropenem dosing in whom therapy could be optimised by therapeutic drug monitoring (TDM). A 37-year-old man with acute lymphatic leukaemia and sepsis had a normal SCr at the beginning of his Intensive Care Unit (ICU) stay but showed decreased SCr of between 30 µmol/L and 40 µmol/L during his stay. He failed to achieve effective plasma concentrations with the meropenem standard dose of 3 g/day. Estimated glomerular filtration rate revealed values between 120 mL/min and 160 mL/min. He required a high meropenem daily dosage of 12 g that was far above the approved maximum dose. A 66-year-old patient undergoing surgery of a pulmonary aspergilloma presented SCr persistently <50 µmol/L, indicating ARC between 120 mL/min and 150 mL/min. This patient required 8 g of meropenem to achieve effective plasma concentrations. TDM may represent an invaluable approach to optimising drug exposure of ß-lactam antibiotics in patients with ARC in the ICU. Further trials are clearly needed to become better informed about empirical dosing regimens usable in the ICU setting with regard to the relevance of ARC. In the meantime, daily measurement of creatinine clearance as well as TDM can be used to identify patients who manifest ARC, thereby allowing drug therapy to achieve the therapeutic range.

Detection and quantification of α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid: a metabolite of asymmetric dimethylarginine.

Nitric oxide is an ubiquitary cell signaling substance. Its enzymatic production rate by nitric oxide synthase is regulated by the concentrations of the substrate L-arginine and the competitive inhibitor asymmetric dimethylarginine (ADMA). A newly recognized elimination pathway for ADMA is the transamination to α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid (DMGV) by the enzyme alanine-glyoxylate aminotransferase 2 (AGXT2). This pathway has been proven to be relevant for nitric oxide regulation, but up to now no method exists for the determination of DMGV in biological fluids. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of DMGV. D(6)-DMGV was used as internal standard. Samples were purified online by column switching, and separation was achieved on a porous graphitic carbon column. The calibration was linear over ranges of 10 to 200 nmol/L for plasma and 0.1 to 20 µmol/L for urine. The intra- and interday accuracies and precisions in plasma and urine were better than 10%. In plasma samples, DMGV was present in concentrations between 19.1 and 77.5 nmol/L. In urine samples, concentrations between 0.0114 and 1.03 µmol/mmol creatinine were found. This method can be used as a tool for the scientific investigation of the ADMA conversion to DMGV via the enzyme AGXT2.

Comparison of different ibuprofen-amino acid compounds with respect to emulsifying and cytotoxic properties.

Sodium ibuprofen (Ibu-Na) and different ibuprofen-amino acid compounds, lysinate (Ibu-Lys), arginate (Ibu-Arg) and histidinate (Ibu-His), were evaluated for emulsifying, haemolytic and cytotoxic properties. The highest reduction of surface tension was obtained with Ibu-Lys which shows good emulsifying qualities. At the same time, Ibu-Lys reveals the highest haemolytic activity and affects porcine cornea integrity. However, incorporation of Ibu-Lys into an emulsion system significantly decreases haemolysis. On the contrary Ibu-Arg, which shows a lower surface tension reduction, allows, unlike Ibu-Na and Ibu-His, for comparably stable emulsions with comparable erythrocyte damage.