Ketamine therapy for chronic pain in The Netherlands: a nationwide survey

Thomas J P Mangnus, Krishna D Bharwani, Dirk L Stronks, Maaike Dirckx, Frank J P M Huygen, Thomas J P Mangnus, Krishna D Bharwani, Dirk L Stronks, Maaike Dirckx, Frank J P M Huygen

Abstract

Objectives: Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands.

Methods: All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting.

Results: The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5-5). The median maximum dose was 27.5 mg/h (IQR=100-11.9). The median infusion duration was 6 h (IQR=8-4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5-1.5) and the median maximum dose was 25 mg/h (IQR=25-14). Patients were admitted to hospital for a median of 4 days (IQR=5-1).

Conclusions: The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment.

Keywords: chronic pain; inpatient/outpatient setting; ketamine; treatment indications.

© 2021 Thomas J.P. Mangnus et al., published by De Gruyter, Berlin/Boston.

References

    1. Breivik, H, Collett, B, Ventafridda, V, Cohen, R, Gallacher, D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006;10:287–333. .
    1. Treede, RD, Rief, W, Barke, A, Aziz, Q, Bennett, MI, Benoliel, R, et al.. Chronic pain as a symptom or a disease: the IASP classification of chronic pain for the international classification of diseases (ICD-11). Pain 2019;160:19–27. .
    1. Maniadakis, N, Gray, A. The economic burden of back pain in the UK. Pain 2000;84:95–103. .
    1. Bekkering, GE, Bala, MM, Reid, K, Kellen, E, Harker, J, Riemsma, R, et al.. Epidemiology of chronic pain and its treatment in The Netherlands. Neth J Med 2011;69:141–53.
    1. Elliott, AM, Smith, BH, Penny, KI, Smith, WC, Chambers, WA. The epidemiology of chronic pain in the community. Lancet 1999;354:1248–52. .
    1. Woolf, CJ, Decosterd, I. Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients. Pain 1999;(Suppl 6):S141–7. .
    1. Niesters, M, Martini, C, Dahan, A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol 2014;77:357–67. .
    1. Yang, Y, Maher, DP, Cohen, SP. Emerging concepts on the use of ketamine for chronic pain. Expet Rev Clin Pharmacol 2020;13:135–46. .
    1. Sleigh, J, Harvey, M, Voss, L, Denny, B. Ketamine–More mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care 2014;4:76–81. .
    1. Pochwat, B, Nowak, G, Szewczyk, B. An update on NMDA antagonists in depression. Expert Rev Neurother 2019;19:1055–67. .
    1. Loix, S, De Kock, M, Henin, P. The anti-inflammatory effects of ketamine: state of the art. Acta Anaesthesiol Belg 2011;62:47–58.
    1. Anis, NA, Berry, SC, Burton, NR, Lodge, D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 1983;79:565–75. .
    1. Thomson, AM, West, DC, Lodge, D. An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? Nature 1985;313:479–81. .
    1. Fisher, K, Coderre, TJ, Hagen, NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manag 2000;20:358–73. .
    1. Woolf, CJ, Thompson, SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293–9. .
    1. Davies, SN, Lodge, D. Evidence for involvement ofN-methylaspartate receptors in ‘wind-up’of class 2 neurones in the dorsal horn of the rat. Brain Res 1987;424:402–6. .
    1. Dickenson, AH, Sullivan, AF. Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation. Neuropharmacology 1987;26:1235–8. .
    1. Hocking, G, Cousins, MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg 2003;97:1730–9. .
    1. Cohen, SP, Bhatia, A, Buvanendran, A, Schwenk, ES, Wasan, AD, Hurley, RW, 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;43:521–46. .
    1. Visser, E, Schug, SA. The role of ketamine in pain management. Biomed Pharmacother 2006;60:341–8. .
    1. 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;129:241–54. .
    1. Bell, RF, Kalso, EA. Ketamine for pain management. Pain Rep 2018;3:e674. .
    1. Michelet, D, Brasher, C, Horlin, AL, Bellon, M, Julien-Marsollier, F, Vacher, T, et al.. Ketamine for chronic non-cancer pain: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur J Pain 2018;22:632–46. .
    1. Zhao, J, Wang, Y, Wang, D. The effect of ketamine infusion in the treatment of complex regional pain syndrome: a systemic review and meta-analysis. Curr Pain Headache Rep 2018;22:12. .
    1. Perez, RS, Zollinger, PE, Dijkstra, PU, Thomassen-Hilgersom, IL, Zuurmond, WW, Rosenbrand, KC, et al.. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol 2010;10:20. .
    1. Bell, RF, Moore, RA. Intravenous ketamine for CRPS: making too much of too little? Pain 2010;150:10–1. .
    1. Correll, GE, Maleki, J, Gracely, EJ, Muir, JJ, Harbut, RE. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med 2004;5:263–75. .
    1. Willert, RP, Woolf, CJ, Hobson, AR, Delaney, C, Thompson, DG, Aziz, Q. The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor. Gastroenterology 2004;126:683–92. .
    1. Dahan, A, Olofsen, E, Sigtermans, M, Noppers, I, Niesters, M, Aarts, L, et al.. Population pharmacokinetic—pharmacodynamic modeling of ketamine‐induced pain relief of chronic pain. Eur J Pain 2011;15:258–67. .
    1. Sigtermans, MJ, van Hilten, JJ, Bauer, MCR, Arbous, SM, Marinus, J, Sarton, EY, et al.. Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain 2009;145:304–11. .
    1. 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;147:107–15. .
    1. Finch, PM, Knudsen, L, Drummond, PD. Reduction of allodynia in patients with complex regional pain syndrome: a double-blind placebo-controlled trial of topical ketamine. Pain 2009;146:18–25. .
    1. Noppers, IM, Niesters, M, Aarts, L, Bauer, MCR, Drewes, AM, Dahan, A, et al.. Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases. Pain 2011;152:2173–8. .
    1. Peltoniemi, MA, Hagelberg, NM, Olkkola, KT, Saari, TI. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet 2016;55:1059–77. .
    1. Zekry, O, Gibson, SB, Aggarwal, A. Subanesthetic, subcutaneous ketamine infusion therapy in the treatment of chronic nonmalignant pain. J Pain Palliat Care Pharmacother 2016;30:91–8. .
    1. Blonk, MI, Koder, BG, van den Bemt, PM, Huygen, FJ. Use of oral ketamine in chronic pain management: a review. Eur J Pain 2010;14:466–72. .
    1. Martinez, V, Derivaux, B, Beloeil, H, Regional, A. The pain committee of the French society of A, intensive C. Ketamine for pain management in France, an observational survey. Anaesth Crit Care Pain Med 2015;34:357–61. .
    1. Vranken, JH, Dijkgraaf, MG, Kruis, MR, van Dasselaar, NT, van der Vegt, MH. Iontophoretic administration of S(+)-ketamine in patients with intractable central pain: a placebo-controlled trial. Pain 2005;118:224–31. .
    1. Anaya, AMC, Choi, JK, Lee, CS, Oh, E, Kim, Y, Moon, JY, et al.. Ketamine infusion therapy for chronic pain management in South Korea: a national survey for pain physicians with a narrative review. Medicine 2018;97:e11709. .
    1. Xu, J, Herndon, C, Anderson, S, Getson, P, Foorsov, V, Harbut, RE, et al.. Intravenous ketamine infusion for complex regional pain syndrome: survey, consensus, and a reference protocol. Pain Med 2019;20:323–34. .
    1. Maher, DP, Chen, L, Mao, J. Intravenous ketamine infusions for neuropathic pain management: a promising therapy in need of optimization. Anesth Analg 2017;124:661–74. .
    1. Noppers, I, Niesters, M, Aarts, L, Smith, T, Sarton, E, Dahan, A. Ketamine for the treatment of chronic non-cancer pain. Expet Opin Pharmacother 2010;11:2417–29. .
    1. Farrar, JT, Young, JPJr, LaMoreaux, L, Werth, JL, Poole, MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58. .
    1. Turk, DC, Dworkin, RH, Allen, RR, Bellamy, N, Brandenburg, N, Carr, DB, et al.. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain 2003;106:337–45. .
    1. Grieve, S, Perez, RSGM, Birklein, F, Brunner, F, Bruehl, S, Harden, N, et al.. Recommendations for a first Core Outcome Measurement set for complex regional PAin syndrome Clinical sTudies (COMPACT). Pain 2017;158:1083. .
    1. Bosma, RL, Cheng, JC, Rogachov, A, Kim, JA, Hemington, KS, Osborne, NR, et al.. Brain dynamics and temporal summation of pain predicts neuropathic pain relief from ketamine infusion. Anesthesiology 2018;129:1015–24. .

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa