S(+)-ketamine : Current trends in emergency and intensive care medicine

Helmut Trimmel, Raimund Helbok, Thomas Staudinger, Wolfgang Jaksch, Brigitte Messerer, Herbert Schöchl, Rudolf Likar, Helmut Trimmel, Raimund Helbok, Thomas Staudinger, Wolfgang Jaksch, Brigitte Messerer, Herbert Schöchl, Rudolf Likar

Abstract

S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L‑type calcium chanels have also been described. S(+)-ketamine stimulates the sympathetic nerve system, making it an ideal drug for analgosedation or induction of anesthesia in instable patients. In addition, the neuroprotective properties, bronchodilatory, antihyperalgesic or antiepileptic effects provide interesting therapeutic options. In this article we discuss the numerous effects of S(+)-ketamine under pharmacological and clinical aspects especially for typical indications in emergency medicine as well as intensive care.

Keywords: Analgesia; Critical care; Emergency medicine; Ketamine; Neuroprotection.

Conflict of interest statement

H. Trimmel, R. Helbok, T. Staudinger, W. Jaksch, B. Messerer, H. Schöchl and R. Likar declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mechanisms of action of S(+)-ketamine. NMDA N-methyl-D aspartate, HCN1 hyperpolarization-activated cyclic nucleotide channel, ACh acetylcholine, nACh nicotinergic acetylcholine receptor, AMPA α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, mGluR metabotropic glutamate receptor, ERK1/2 extracellular signal-regulated kinases, NOX NADPH oxidase, BDNF brain-derived neurotrophic factor, mTOR mammalian target of rapamycin, Rgs4 regulator of G protein signalling 4, L-type Ca2+ L-type calcium channel, GFAP glial fibrillary acidic protein. (Figure used by courtesy of Jamie Sleigh et al. [2] with permission of Elsevier GmbH)
Fig. 2
Fig. 2
Reduction of relative probability of spreading depolarization (CI confidence interval). Figure used by courtesy of D.N. Hertle and J.P. Dreier [20], with permission of Oxford University Press

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Further Reading
    1. Liu F, Paule MG, Ali S, Wang C. Ketamine-induced neurotoxicity and changes in gene expression in the developing rat brain. Curr Neuropharmacol. 2011;9(1):256–261. doi: 10.2174/157015911795017155.

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