Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Pain and Headache Reports
Erschienen in: Current Pain and Headache Reports 9/2021

01.09.2021 | Anesthetic Techniques in Pain Management (D Wang, Section Editor)

Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity

verfasst von: Eric S. Schwenk, Basant Pradhan, Rohit Nalamasu, Lucas Stolle, Irving W. Wainer, Michael Cirullo, Alexander Olson, Joseph V. Pergolizzi, Marc C. Torjman, Eugene R. Viscusi

Erschienen in: Current Pain and Headache Reports | Ausgabe 9/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

While ketamine’s analgesia has mostly been attributed to antagonism of N-methyl-d-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine’s role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine’s neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented.

Recent Findings

Ketamine’s metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing.

Summary

While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine’s neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58(10):911–23.PubMedCrossRef
2.
Maher DP, Chen L, Mao J. Intravenous ketamine infusions for neuropathic pain management: a promising therapy in need of optimization. Anesth Analg. 2017;124(2):661–74.PubMedCrossRef
3.
Pickering G, Pereira B, Morel V, Corriger A, Giron F, Marcaillou F, et al. Ketamine and magnesium for refractory neuropathic pain: a randomized, double-blind, crossover trial. Anesthesiology. 2020;133(1):154–64.PubMedCrossRef
4.
5.
Orhurhu VJ, Roberts JS, Ly N, Cohen SP. Ketamine in acute and chronic pain management. In: StatPearls, edn. eds. Treasure Island: StatPearls Publishing; 2020.
6.
Petrenko AB, Yamakura T, Askalany AR, Kohno T, Sakimura K, Baba H. Effects of ketamine on acute somatic nociception in wild-type and N-methyl-D-aspartate (NMDA) receptor epsilon1 subunit knockout mice. Neuropharmacology. 2006;50(6):741–7.PubMedCrossRef
7.•
Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521–46 Great summary of ketamine’s various receptor interactions.PubMedPubMedCentral
8.
Paul RK, Singh NS, Khadeer M, Moaddel R, Sanghvi M, Green CE, et al. (R,S)-ketamine metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine increase the mammalian target of rapamycin function. Anesthesiology. 2014;121(1):149–59.PubMedCrossRef
9.
Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, et al. Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):456–66.PubMedPubMedCentral
10.
Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, et al. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017;390(10091):267–75.PubMedPubMedCentralCrossRef
11.
Manohar S, Maxwell D, Winters WD. Development of EEG seizure activity during and after chronic ketamine administration in the rat. Neuropharmacology. 1972;11(6):819–26.PubMedCrossRef
12.
DeVore GR, McQueen JK, Woodbury DM. Ketamine hydrochloride and its effect on a chronic cobalt epileptic cortical focus. Epilepsia. 1976;17(1):111–7.PubMedCrossRef
13.
Voss LJ, Sleigh JW, Barnard JP, Kirsch HE. The howling cortex: seizures and general anesthetic drugs. Anesth Analg. 2008;107(5):1689–703.PubMedCrossRef
14.
Fang Y, Wang X. Ketamine for the treatment of refractory status epilepticus. Seizure. 2015;30:14–20.PubMedCrossRef
15.
Green SM, Cote CJ. Ketamine and neurotoxicity: clinical perspectives and implications for emergency medicine. Ann Emerg Med. 2009;54(2):181–90.PubMedCrossRef
16.
Domino EF, Chodoff P, Corssen G. Pharmacologic effects of Ci-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther. 1965;6:279–91.PubMedCrossRef
17.
Corssen G, Miyasaka M, Domino EF. Changing concepts in pain control during surgery: dissociative anesthesia with CI-581. A progress report. Anesth Analg. 1968;47(6):746–59.PubMedCrossRef
18.
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4.PubMedCrossRef
19.
Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–64.PubMedCrossRef
20.
Lapidus KA, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014;76(12):970–6.PubMedPubMedCentralCrossRef
21.
Matveychuk D, Thomas RK, Swainson J, et al. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol. 2020;10:2045125320916657.PubMedPubMedCentralCrossRef
22.
Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481–6.PubMedPubMedCentralCrossRef
23.
24.
Faccio AT, Ruperez FJ, Singh NS, Angulo S, Tavares MFM, Bernier M, et al. Stereochemical and structural effects of (2R,6R)-hydroxynorketamine on the mitochondrial metabolome in PC-12 cells. Biochim Biophys Acta Gen Subj. 2018;1862(6):1505–15.PubMedCrossRef
25.
Moaddel R, Abdrakhmanova G, Kozak J, Jozwiak K, Toll L, Jimenez L, et al. Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in alpha7 nicotinic acetylcholine receptors. Eur J Pharmacol. 2013;698(1-3):228–34.PubMedCrossRef
26.
Suzuki K, Nosyreva E, Hunt KW, Kavalali ET, Monteggia LM. Effects of a ketamine metabolite on synaptic NMDAR function. Nature. 2017;546(7659):E1–3.PubMedCrossRef
27.
Singh NS, Zarate CA Jr, Moaddel R, Bernier M, Wainer IW. What is hydroxynorketamine and what can it bring to neurotherapeutics? Expert Rev Neurother. 2014;14(11):1239–42.PubMedPubMedCentralCrossRef
28.•
Kroin JS, Das V, Moric M, Buvanendran A. Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain. Reg Anesth Pain Med. 2019;44(1):111–7 Preclinical evidence of antinociceptive effects of ketamine metabolite.PubMedCrossRef
29.
Lilius TO, Viisanen H, Jokinen V, et al. Interactions of (2S,6S;2R,6R)-hydroxynorketamine, a secondary metabolite of (R,S)-ketamine, with morphine. Basic Clin Pharmacol Toxicol. 2018;122(5):481–8.PubMedCrossRef
30.
Moaddel R, Venkata SL, Tanga MJ, et al. A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome. Talanta. 2010;82(5):1892–904.PubMedPubMedCentralCrossRef
31.
Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959–64.PubMedPubMedCentralCrossRef
32.
Fukumoto K, Fogaca MV, Liu RJ, et al. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proc Natl Acad Sci U S A. 2019;116(1):297–302.PubMedCrossRef
33.
Aguilar-Valles A, De Gregorio D, Matta-Camacho E, et al. Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature. 2021;590(7845):315–9.PubMedCrossRef
34.
Miller OH, Moran JT, Hall BJ. Two cellular hypotheses explaining the initiation of ketamine’s antidepressant actions: direct inhibition and disinhibition. Neuropharmacology. 2016;100:17–26.PubMedCrossRef
35.
Dwyer JM, Duman RS. Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry. 2013;73(12):1189–98.PubMedPubMedCentralCrossRef
36.
Naughton M, Clarke G, O’Leary OF, Cryan JF, Dinan TG. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. J Affect Disord. 2014;156:24–35.PubMedCrossRef
37.
Udesky JO, Spence NZ, Achiel R, Lee C, Flood P. The role of nicotinic inhibition in ketamine-induced behavior. Anesth Analg 2005; 101(2):407-411, table of contents.
38.
Knott VJ, Millar AM, McIntosh JF, et al. Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention. Biol Psychol. 2011;88(1):83–93.PubMedCrossRef
39.
D’Souza DC, Ahn K, Bhakta S, et al. Nicotine fails to attenuate ketamine-induced cognitive deficits and negative and positive symptoms in humans: implications for schizophrenia. Biol Psychiatry. 2012;72(9):785–94.PubMedCrossRef
40.
Nishimura M, Sato K, Okada T, Yoshiya I, Schloss P, Shimada S, et al. Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells. Anesthesiology. 1998;88(3):768–74.PubMedCrossRef
41.
Wang N, Yu HY, Shen XF, Gao ZQ, Yang C, Yang JJ, et al. The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus. Ups J Med Sci. 2015;120(4):241–8.PubMedPubMedCentralCrossRef
42.•
Pradhan B, Mitrev L, Moaddell R, Wainer IW. D-serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: a pilot study. Biochim Biophys Acta, Proteins Proteomics. 2018;1866(7):831–9 Key article about role of d-serine pathways with ketamine.PubMedCrossRef
43.
Lefevre Y, Amadio A, Vincent P, et al. Neuropathic pain depends upon D-serine co-activation of spinal NMDA receptors in rats. Neurosci Lett. 2015;603:42–7.PubMedCrossRef
44.
Choi SR, Roh DH, Yoon SY, et al. Astrocyte D-serine modulates the activation of neuronal NOS leading to the development of mechanical allodynia in peripheral neuropathy. Mol Pain. 2019;15:1744806919843046.PubMedPubMedCentralCrossRef
45.
46.
Shaked G, Czeiger D, Dukhno O, Levy I, Artru AA, Shapira Y, et al. Ketamine improves survival and suppresses IL-6 and TNFalpha production in a model of Gram-negative bacterial sepsis in rats. Resuscitation. 2004;62(2):237–42.PubMedCrossRef
47.
Yu M, Shao D, Yang R, Feng X, Zhu S, Xu J. Effects of ketamine on pulmonary inflammatory responses and survival in rats exposed to polymicrobial sepsis. J Pharm Pharm Sci. 2007;10(4):434–42.PubMedCrossRef
48.
Yu M, Shao D, Feng X, Duan M, Xu J. Effects of ketamine on pulmonary TLR4 expression and NF-kappa-B activation during endotoxemia in rats. Methods Find Exp Clin Pharmacol. 2007;29(6):395–9.PubMedCrossRef
49.
Park M, Newman LE, Gold PW, Luckenbaugh DA, Yuan P, Machado-Vieira R, et al. Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression. J Psychiatr Res. 2017;84:113–8.PubMedCrossRef
50.•
Chen MH, Li CT, Lin WC, et al. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: a randomized, double-blind control study. Psychiatry Res. 2018;269:207–11 Study that found ketamine has anti-inflammatory effects.PubMedCrossRef
51.
Li Y, Shen R, Wen G, et al. Effects of ketamine on levels of inflammatory cytokines IL-6, IL-1beta, and TNF-alpha in the hippocampus of mice following acute or chronic administration. Front Pharmacol. 2017;8:139.PubMedPubMedCentral
52.
Zhang Z, Zhang L, Zhou C, Wu H. Ketamine inhibits LPS-induced HGMB1 release in vitro and in vivo. Int Immunopharmacol. 2014;23(1):14–26.PubMedCrossRef
53.
Ho MF, Zhang C, Zhang L, Li H, Weinshilboum RM. Ketamine and active ketamine metabolites regulate STAT3 and the type I interferon pathway in human microglia: molecular mechanisms linked to the antidepressant effects of ketamine. Front Pharmacol. 2019;10:1302.PubMedPubMedCentralCrossRef
54.
55.
Olney JW, Labruyere J, Price MT. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989;244(4910):1360–2.PubMedCrossRef
56.
Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986;83(18):7104–8.PubMedPubMedCentralCrossRef
57.
Fix AS, Wozniak DF, Truex LL, McEwen M, Miller JP, Olney JW. Quantitative analysis of factors influencing neuronal necrosis induced by MK-801 in the rat posterior cingulate/retrosplenial cortex. Brain Res. 1995;696(1-2):194–204.PubMedCrossRef
58.
Wozniak DF, Brosnan-Watters G, Nardi A, McEwen M, Corso TD, Olney JW, et al. MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning. Brain Res. 1996;707(2):165–79.PubMedCrossRef
59.
Jiang S, Li X, Jin W, Duan X, Bo L, Wu J, et al. Ketamine-induced neurotoxicity blocked by N-Methyl-d-aspartate is mediated through activation of PKC/ERK pathway in developing hippocampal neurons. Neurosci Lett. 2018;673:122–31.PubMedCrossRef
60.•
Bates MLS, Trujillo KA. Long-lasting effects of repeated ketamine administration in adult and adolescent rats. Behav Brain Res. 2019;369:111928 Animal study showing no cognitive deficits after repeated ketamine doses to rats.PubMedPubMedCentralCrossRef
61.
Anand KJ, Garg S, Rovnaghi CR, et al. Ketamine reduces the cell death following inflammatory pain in newborn rat brain. Pediatr Res. 2007;62(3):283–90.PubMedCrossRef
62.
Liang J, Wu S, Xie W, He H. Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway. Drug Des Devel Ther. 2018;12:845–53.PubMedPubMedCentralCrossRef
63.
Fujikawa DG. Neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia. 1995;36(2):186–95.PubMedCrossRef
64.
Bell JD. In Vogue: ketamine for neuroprotection in acute neurologic injury. Anesth Analg. 2017;124(4):1237–43.PubMedCrossRef
65.
Jevtovic-Todorovic V, Wozniak DF, Powell S, Nardi A, Olney JW. Clonidine potentiates the neuropathic pain-relieving action of MK-801 while preventing its neurotoxic and hyperactivity side effects. Brain Res. 1998;781(1-2):202–11.PubMedCrossRef
66.
Auer RN, Coulter KC. The nature and time course of neuronal vacuolation induced by the N-methyl-D-aspartate antagonist MK-801. Acta Neuropathol. 1994;87(1):1–7.PubMedCrossRef
67.
Purcell R, Lynch G, Gall C, Johnson S, Sheng Z, Stephen MR, et al. Brain vacuolation resulting from administration of the type II ampakine CX717 is an artifact related to molecular structure and chemical reaction with tissue fixative agents. Toxicol Sci. 2018;162(2):383–95.PubMedCrossRef
68.
Olney JW, Labruyere J, Wang G, Wozniak D, Price M, Sesma M. NMDA antagonist neurotoxicity: mechanism and prevention. Science. 1991;254(5037):1515–8.PubMedCrossRef
69.
Garner R, Gopalakrishnan S, McCauley JA, Bednar RA, Gaul SL, Mosser SD, et al. Preclinical pharmacology and pharmacokinetics of CERC-301, a GluN2B-selective N-methyl-D-aspartate receptor antagonist. Pharmacol Res Perspect. 2015;3(6):e00198.PubMedPubMedCentralCrossRef
70.
Koffler SP, Hampstead BM, Irani F, et al. The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome. Arch Clin Neuropsychol. 2007;22(6):719–29.PubMedCrossRef
71.
Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008;9(8):1173–201.PubMedCrossRef
72.
Diamond PR, Farmery AD, Atkinson S, Haldar J, Williams N, Cowen PJ, et al. Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic. J Psychopharmacol. 2014;28(6):536–44.PubMedCrossRef
73.•
Shiroma PR, Thuras P, Wels J, et al. Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2020;277:470–7 Human study that found no evidence of neurocognitive deficits after repeated ketamine doses.PubMedCrossRef
74.
Crisanti C, Enrico P, Fiorentini A, Delvecchio G, Brambilla P. Neurocognitive impact of ketamine treatment in major depressive disorder: a review on human and animal studies. J Affect Disord. 2020;276:1109–18.PubMedCrossRef
75.
Trouvin AP, Perrot S. New concepts of pain. Best Pract Res Clin Rheumatol. 2019;33(3):101415.PubMedCrossRef
76.
Freynhagen R, Parada HA, Calderon-Ospina CA, Chen J, Rakhmawati Emril D, Fernández-Villacorta FJ, et al. Current understanding of the mixed pain concept: a brief narrative review. Curr Med Res Opin. 2019;35(6):1011–8.PubMedCrossRef
77.
Shraim MA, Masse-Alarie H, Hall LM, Hodges PW. Systematic review and synthesis of mechanism-based classification systems for pain experienced in the musculoskeletal system. Clin J Pain. 2020;36(10):793–812.PubMedCrossRef
78.
79.
Cifre I, Sitges C, Fraiman D, Muñoz MÁ, Balenzuela P, González-Roldán A, et al. Disrupted functional connectivity of the pain network in fibromyalgia. Psychosom Med. 2012;74(1):55–62.PubMedCrossRef
80.
Baliki MN, Mansour AR, Baria AT, Apkarian AV. Functional reorganization of the default mode network across chronic pain conditions. PLoS One. 2014;9(9):e106133.PubMedPubMedCentralCrossRef
81.•
Ferro Moura Franco K, Lenoir D, Dos Santos Franco YR, et al. Prescription of exercises for the treatment of chronic pain along the continuum of nociplastic pain: a systematic review with meta-analysis. Eur J Pain. 2021;25(1):51–70 Systematic review that helps put nociplastic pain in perspective.PubMedCrossRef
82.
Undeland M, Malterud K. The fibromyalgia diagnosis: hardly helpful for the patients? A qualitative focus group study. Scand J Prim Health Care. 2007;25(4):250–5.PubMedPubMedCentralCrossRef
83.
Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep. 2009;13(3):185–90.PubMedCrossRef
84.
Bailly F, Cantagrel A, Bertin P, et al. Part of pain labelled neuropathic in rheumatic disease might be rather nociplastic. RMD Open. 2020;6(2):e001326.PubMedPubMedCentralCrossRef
85.
Schwenk ES, Dayan AC, Rangavajjula A, Torjman MC, Hernandez MG, Lauritsen CG, et al. Ketamine for refractory headache: a retrospective analysis. Reg Anesth Pain Med. 2018;43(8):875–9.PubMed
86.
Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine infusions for treatment refractory headache. Headache. 2017;57(2):276–82.PubMedCrossRef
87.
88.
Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2019;129(1):241–54.PubMedCrossRef
89.
Popkirov S, Enax-Krumova EK, Mainka T, Hoheisel M, Hausteiner-Wiehle C. Functional pain disorders—more than nociplastic pain. NeuroRehabilitation. 2020;47(3):343–53.PubMedCrossRef
90.
Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009;145:304–11.PubMedCrossRef
91.
Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009;147(1-3):107–15.PubMedCrossRef
92.
Kirkpatrick AF, Saghafi A, Yang K, Qiu P, Alexander J, Bavry E, et al. Optimizing the treatment of CRPS with ketamine. Clin J Pain. 2020;36(7):516–23.PubMedCrossRef
93.
Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol. 1995;24(6):360–5.PubMedCrossRef
94.
Sorensen J, Bengtsson A, Ahlner J, et al. Fibromyalgia—are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol. 1997;24(8):1615–21.PubMed
95.
Handa F, Tanaka M, Nishikawa T, Toyooka H. Effects of oral clonidine premedication on side effects of intravenous ketamine anesthesia: a randomized, double-blind, placebo-controlled study. J Clin Anesth. 2000;12(1):19–24.PubMedCrossRef
96.
Elia N, Tramer MR. Ketamine and postoperative pain—a quantitative systematic review of randomised trials. Pain. 2005;113(1-2):61–70.PubMedCrossRef
Metadaten
Titel
Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity
verfasst von
Eric S. Schwenk
Basant Pradhan
Rohit Nalamasu
Lucas Stolle
Irving W. Wainer
Michael Cirullo
Alexander Olson
Joseph V. Pergolizzi
Marc C. Torjman
Eugene R. Viscusi
Publikationsdatum
01.09.2021
Verlag
Springer US
Erschienen in
Current Pain and Headache Reports / Ausgabe 9/2021
Print ISSN: 1531-3433
Elektronische ISSN: 1534-3081
DOI
https://doi.org/10.1007/s11916-021-00977-w

Weitere Artikel der Ausgabe 9/2021

Current Pain and Headache Reports 9/2021 Zur Ausgabe

Neuropathic Pain (A Abd-Elsayed, Section Editor)

Chronic Pain in Patients with Rheumatoid Arthritis

Neuropathic Pain (A Abd-Elsayed, Section Editor)

Occipital Neuralgia

Neuromodulation (A Abd-Elsayed, Section Editor)

Temperature-Mediated Nerve Blocks in the Treatment of Pain

Correction

Correction to: Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity

Chronic Daily Headache (SJ Wang, Section Editor)

Hypertension and Migraine: Time to Revisit the Evidence

Neu im Fachgebiet AINS

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Medizinstudium Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Häufigste Gründe für Brustschmerzen bei Kindern

06.05.2024 Pädiatrische Diagnostik Nachrichten

Akute Brustschmerzen sind ein Alarmsymptom par exellence, schließlich sind manche Auslöser lebensbedrohlich. Auch Kinder klagen oft über Schmerzen in der Brust. Ein Studienteam ist den Ursachen nachgegangen.

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

03.05.2024 Fibromyalgiesyndrom Nachrichten

Bewegungs-, Dehnungs- und Entspannungsübungen im Wasser lindern die Beschwerden von Patientinnen mit Fibromyalgie besser als das Üben auf trockenem Land. Das geht aus einer spanisch-brasilianischen Vergleichsstudie hervor.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärzte und Psychotherapeuten.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren
Bildnachweise