(S)-KETAMINE - RENAISSANCE OF A SUBSTANCE

The pharmacological profile of ketamine: Until recently, clinically av ailable ketamine was a racemic mixture containing equal amounts of two enantiomers, (S)- and (R)-ketamine. The pharmacological profile of ra cemic ketamine is characterized by the socalled dissociative anesthesi c state and profound sympathomimetic properties. Among the different s ites of action, N-methyl-D-aspartate (NMDA)-receptor antagonism is con sidered to be the most important neuropharmacological mechanism of ket amine. Effects on opiate receptors, monoaminergic and cholinergic tran smitters, and local anesthetic effects are obvious as well. Following intravenous administration, a rapid onset of action is seen within 1 m in, lasting for about 10 min. The anaesthetic state is terminated due to redistribution, followed by hepatic and renal elimination with a ha lf-life period of 2-3 h. For alternative administration, the intramusc ular and oral route is also appropriate. The most important adverse ef fects are hallucinations and excessive increases in blood pressure and heart rate. These reactions can be attenuated or avoided by combining of ketamine with sedative or hypnotic drugs like midazolam and/or pro pofol. During controlled ventilation, increases in intracranial pressu re are unlikely to occur. The special pharmacological profile of (S)-k etamine: In general, the pharmacological properties of (S)-ketamine ar e comparable to the racemic compound. On the different sites of action , qualitatively comparable effects were found, but significant quantit ative differences also became obvious. When compared with (R)-ketamine and the racmic mixture, the analgesic and anesthetic potency of (S)-k etamine is three-fold or twofold higher. Thus, a 50% reduction of dosa ge is possible to achieve comparable clinical results. Because of the faster elimination of(S)-ketamine, better control of anesthesia will b e provided. In summary, the pharmacokinetic improvements of (S)-ketami ne are characterized by a reduced drug load, along with more rapid rec overy. The clinical use of (S)-ketamine: The clinical use of (S)-ketam ine depends on its analgesic and sympathomimetic properties, whereas t he anaesthetic potency remains in the background. In clinical anesthes iology, (S)-ketamine, especially in combination with midazolam and/or propofol, can be used for short procedures with preserved spontaneous ventilation, for induction of anesthesia in patients with shock or ast hmatic disorders, and for induction and maintenance of anesthesia in c aesarean sections. Additional indications are repeated anesthesia, for example, in burn patients, analgesia during delivery and diagnostic p rocedures and intramuscular administration in uncooperative patients. The value of (S)-ketamine as analgesic component for total intravenous anesthesia has not been defined yet. In comparison with opioides, the advantages are related to improved hemodynamic stability and reduced postoperative respiratory depression. When (S)-ketamine, especially in combination with midazolam, is used for analgosedation in intensive c are medicine, a reduction of exogenous catecholamine demand can be exp ected. Moreover,the effects on intestinal motility are superior to opi oids. In combination with midazolam and propofol, excellent control of analgosedation was found, making both combinations suitable for situa tions in which repeated neurological assessment of patients is necessa ry. In emergency and disaster medicine, (S)-ketamine is of outstanding importance because of its minimal logistic requirements, the chance f or intramuscular administration and the broad range of use for analges ia, anaesthesia and analgosedation as well. Further perspectives of (S )-ketamine may be the treatment of chronic pain and the assumed neurop rotective action of the substance.