Ketamine*

Abstract

The use of ketamine is associated with neuropsychiatric, urinary tract and hepatobiliary toxicity. Although most reports involve long-term recreational abusers, it has also arisen after only 1e2 weeks of therapeutic use (Box A). Accordingly, the use of ketamine should be restricted to specialists in pain or palliative care for patients who have failed to obtain relief from standard drug and non-drug treatments.Class: General anesthetic.Indications: Induction and maintenance of anesthesia; yneuropathic, inflammatory, ischemic limb and procedure-related pain unresponsive to standard treatments. 1,2 Contra-indications: Any situation in which an increase in blood pressure would constitute a hazard. PharmacologyKetamine, a derivative of phencyclidine (PCP), is a dissociative anesthetic which has analgesic properties in subanaesthetic doses. 2,3 Ketamine is the most potent NMDA-receptor-channel blocker available for clinical use, binding to the PCP site when the channels are in the open activated state (Fig. 1). 3 It also binds to a second membrane-associated site which decreases the frequency of channel opening. 3 The NMDA receptor-channel complex is closely involved in the development of central sensitization of dorsal horn neurons which transmit pain signals. 4 At normal resting membrane potentials, the channel is blocked by magnesium and is inactive. 3 When the resting membrane potential is changed as a result of prolonged excitation, the channel unblocks and calcium moves into the cell. This leads to neuronal hyperexcitability and results in hyperalgesia and allodynia, and a reduction in opioid-responsiveness. These effects are probably mediated by the intracellular formation of nitric oxide and cyclic guanosine monophosphate. 3 The reduction in opioid-responsiveness arises from cross-talk between opioid receptors and the NMDA receptor-channel. Opioid receptor activation results in phosphorylation and opening of the NMDA receptorchannel leading to a cascade of events which ultimately down-regulates the opioid receptor and its effects, thereby contributing towards tolerance and hyperalgesia. 3

<p>Effects of Anesthesia on Postoperative Recurrence and Metastasis of Malignant Tumors</p>

“…Ketamine has an immunomodulatory effect on macrophages, lymphocytes, and mast cells. 37 – 39 A breast cancer rat model study reported that ketamine, sodium thiopental, and inhaled anesthetic agents could promote tumor metastasis and were inversely associated with NK cell activity. 40 This effect was significantly reduced by pre-administering the β-blocker nadolol or through long-term low-dose immunostimulant administration.…”

Undiscovered morphine. The effects of the long-term use of the opioids

“…Continuous morphine and other opioids administration induce changes in glutaminergic transmission [6] and excitation of the N-methyl-D-aspartase (NMDA) receptors [7]. These changes can be counteracted by the NMDA-inhibitor; ketamine [8,9].…”

Principles of cancer pain management: An overview and focus on pharmacological and interventional strategies

“…26 Although evidence is lacking, ketamine is reportedly effective in the treatment of neuropathic and mucositis-related pain, and some clinicians use this in a 'burst' protocol via subcutaneous infusion. 20,27…”