Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-19T22:52:11.029Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of a low-dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double-blind, placebo-controlled trial

Published online by Cambridge University Press:  01 February 2008

F. Aubrun ,
C. Gaillat ,
D. Rosenthal ,
M. Dupuis ,
P. Mottet ,
F. Marchetti ,
P. Coriat  and
B. Riou
F. Aubrun*
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
C. Gaillat
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
D. Rosenthal
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
M. Dupuis
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
P. Mottet
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
F. Marchetti
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
P. Coriat
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Anesthesiology and Critical Care, Paris, France
B. Riou
Affiliation:
Université Pierre et Marie Curie-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Emergency Medicine and Surgery, Paris, France
*
Correspondence to: Frédéric Aubrun, Département d’Anesthésie-Réanimation, CHU Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail: [email protected]; Tel: +33 1 42 16 22 59; Fax: +33 1 42 16 22 69
Get access

Summary

Background and objective

Major gynaecological abdominal surgery is associated with moderate to severe postoperative pain, hyperalgesia and the need for multimodal analgesia to reduce high morphine consumption. A low-dose ketamine regimen appears to prevent postoperative hyperalgesia. We examined the potential beneficial effect of ketamine on postoperative pain management and cognitive function.

Methods

Ninety patients were included in this double-blind, randomized, placebo-controlled study to test the efficacy and adverse effects of ketamine (as an intraoperative bolus of 0.15 mg kg−1, followed postoperatively by ketamine 0.5 mg per morphine 1 mg in a patient-controlled analgesia device). All patients received additionally ketoprofen. The main end-point was morphine consumption over the first 24 h. Secondary efficacy and safety end-points were morphine consumption during the titration period and during the patient-controlled analgesia period (48 h), the number of morphine-related adverse effects and the results of psychometric tests.

Results

Ketamine, in combination with morphine and ketoprofen, did not improve postoperative pain scales and did not reduce morphine consumption and the incidence of morphine-related adverse effects. Ketamine did not modify mood, cognitive and memory functioning.

Conclusion

Adding a low dose of ketamine to an efficacious multimodal analgesic regimen did not improve analgesia after gynaecological surgery. Although this combination appears to be safe, the lack of benefit suggests that a low dose of ketamine should not be used for routine care.

Keywords

PAIN ACUTE AND POSTOPERATIVESURGERY GYNAECOLOGICALKETAMINEMORPHINECOGNITIVE FUNCTION
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 2 , February 2008 , pp. 97 - 105
Copyright
Copyright © European Society of Anaesthesiology 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Ellstrom, M, Olsen, MF, Olsson, JH, Nordberg, G, Bengtsson, A, Hahlin, M. Pain and pulmonary function following laparoscopic and abdominal hysterectomy: a randomized study. Acta Obstet Gynecol Scand 1998; 77: 923–928.Google Scholar
2.Ng, A, Swami, A, Smith, G, Davidson, AC, Emembolu, J. The analgesic effects of intraperitoneal and incisional bupivacaine with epinephrine after total abdominal hysterectomy. Anesth Analg 2002; 95: 158–162.CrossRefGoogle ScholarPubMed
3.Choinière, M, Rittenhouse, BE, Perreault, S et al. . Efficacy and costs of patient-controlled analgesia vs. regularly administered intramuscular opioid therapy. Anesthesiology 1998; 89: 1377–1388.CrossRefGoogle Scholar
4.Kehlet, H, Rung, GW, Callesen, T. Postoperative opioid analgesia: time for reconsideration? J Clin Anesth 1996; 8: 441–445.Google Scholar
5.Celerier, E, Rivat, C, Jun, Y et al. . Long-lasting hyperalgesia induced by fentanyl in rats. Anesthesiology 2000; 92: 465–472.Google Scholar
6.Rivat, C, Laulin, JP, Corcuff, JB, Celerier, E, Pain, L, Simonnet, G. Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-d-aspartate receptor antagonist ketamine. Anesthesiology 2002; 96: 381–391.CrossRefGoogle ScholarPubMed
7.Kehlet, H. Postoperative opioid sparing to hasten recovery. What are the issues? Anesthesiology 2005; 102: 1083–1085.CrossRefGoogle ScholarPubMed
8.Tallarida, RJ, Raffa, RB. Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram. Life Sci 1996; 58: 23–28.Google Scholar
9.Kehlet, H, Dahl, JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003; 362: 1921–1928.Google Scholar
10.Fletcher, D, Benoist, JM, Gautron, M, Guilbaud, G. Isobolographic analysis of interactions between intravenous morphine, propacetamol, and diclofenac in carrageenin-injected rats. Anesthesiology 1997; 87: 317–326.Google Scholar
11.Chapman, V, Dickenson, AH. The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn. Brain Res 1992; 573: 321–323.Google Scholar
12.Honoré, P, Chapman, V, Buritova, J, Besson, JM. Concomitant administration of morphine and an N-methyl-d-aspartate receptor antagonist profoundly reduces inflammatory evoked spinal c-fos expression. Anesthesiology 1996; 85: 150–160.CrossRefGoogle Scholar
13.Marret, E, Kurdi, O, Zufferey, P, Bonnet, F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects. Meta-analysis of randomized controlled trials. Anesthesiology 2005; 102: 1249–1260.CrossRefGoogle ScholarPubMed
14.Reich, DL, Silvay, G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989; 36: 186–197.CrossRefGoogle ScholarPubMed
15.Woolf, CJ, Thompson, SWN. The induction and maintenance of central sensitization is dependant on N-methyl-d-aspartate acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 1991; 44: 293–299.Google Scholar
16.Stubhaug, A, Breivik, H, Eide, PK, Kreunen, M, Foss, A. Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery. Acta Anaesthesiol Scand 1997; 41: 1124–1132.Google Scholar
17.Kissin, I, Bright, CA, Bradley, EL. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg 2000; 91: 1483–1488.Google Scholar
18.Schmidt, RL, Sandler, AN, Katz, J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999; 82: 111–125.CrossRefGoogle Scholar
19.Himmelseher, S, Durieux, ME. Ketamine for perioperative pain management. Anesthesiology 2005; 102: 211–220.Google Scholar
20.Reeves, M, Lindholm, DE, Myles, PS, Fletcher, H, Hunt, JO. Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blinded, randomized controlled trial. Anesth Analg 2001; 93: 116–120.CrossRefGoogle ScholarPubMed
21.Jensen, MP, Karoly, P, Braver, S. The measurement of clinical pain intensity: a comparison of six methods. Pain 1986; 27: 117–126.Google Scholar
22.Aubrun, F, Paqueron, X, Langeron, O, Coriat, P, Riou, B. What pain scales do nurses use in the postanaesthesia care unit? Eur J Anaesthesiol 2003; 20: 745–749.CrossRefGoogle ScholarPubMed
23.Aubrun, F, Monsel, S, Langeron, O, Coriat, P, Riou, B. Postoperative titration of intravenous morphine. Eur J Anaesthesiol 2001; 18: 159–165.Google Scholar
24.Ramsay, MA, Savege, TM, Simpson, BR, Goodwin, R. Controlled sedation with alphaxalone–alphadolone. Br Med J 1974; 2: 656–659.CrossRefGoogle ScholarPubMed
25.Aubrun, F, Langeron, O, Quesnel, C, Coriat, P, Riou, B. Relationships between measurement of pain using visual analog score and morphine requirements during postoperative intravenous morphine titration. Anesthesiology 2003; 98: 1415–1421.CrossRefGoogle ScholarPubMed
26.Norris, H. The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology 1971; 10: 181–191.Google Scholar
27.Bond, A, Lader, M. The use of analogue scales in rating subjective feelings. Br J Med Psychol 1974; 47: 211–218.CrossRefGoogle Scholar
28.Folstein, MF, Folstein, SE, McHugh, PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.Google Scholar
29.Lezak, MD, Howieson, DB, Loring, DW, Hannay, HJ, Fischer, JS. Neurophysiological assessment, 4th edn. New York: Oxford University Press, 2004.Google Scholar
30.Wechsler, DA. Manual for the Wechsler Adult Intelligence Scale. National Foundation for the Education Research, London. 1955; Lichtor JL. Recovery testing and evaluation. In: White, PF, ed. Ambulatory Anesthesia and Surgery, 2nd edn. London: WB Saunders Company Ltd, 1997: 469–470.Google Scholar
31.Vance, HB, Singer, MG. Recategorization of the WISC-R subtest scaled scores for the learning disabled student. J Learn Disabil 1979; 12: 487–491.CrossRefGoogle Scholar
32.Greenhouse, SW, Geisser, S. On the methods in the analysis of profile data. Psychometrika 1959; 24: 95–102.Google Scholar
33.Joly, V, Richebe, P, Guignard, B et al. . Rémifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology 2005; 103: 147–155.Google Scholar
34.Elia, N, Tramèr, MR. Ketamine and postoperative pain – a quantitative systematic review of randomized trials. Pain 2005; 113: 61–70.Google Scholar
35.Burstal, R, Danjoux, G, Hayes, C, Lantry, G. PCA ketamine and morphine after abdominal hysterectomy. Anaesth Intensive Care 2001; 29: 246–251.Google Scholar
36.Murdoch, CJ, Crooks, BA, Miller, CD. Effect of the addition of ketamine to morphine in patient-controlled analgesia. Anaesthesia 2002; 57: 484–500.CrossRefGoogle ScholarPubMed
37.Sveticic, G, Eichenberger, U, Curatolo, M. Safety of mixture of morphine with ketamine for postoperative patient-controlled analgesia: an audit with 1026 patients. Acta Anaesthesiol Scand 2005; 49: 870–875.CrossRefGoogle ScholarPubMed
38.Subramaniam, K, Subramaniam, B, Steinbrook, RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg 2004; 99: 482–495.Google Scholar
39.Van Elstraete, AC, Lebrun, T, Sandefo, I, Polin, B. Are preemptive analgesic effects of ketamine linked to inadequate perioperative analgesia? Anesth Analg 2004; 99: 1575–1579.Google Scholar
40.Varrassi, G, Marinangeli, F, Agro, F et al. . A double-blinded evaluation of propacetamol vs. ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery. Anesth Analg 1999; 88: 611–616.Google Scholar
41.Ng, A, Temple, A, Smith, G, Emembolu, J. Early analgesic effects of parecoxib vs. ketorolac following laparoscopic sterilization: a randomized controlled trial. Br J Anaesth 2004; 92: 846–849.Google Scholar
42.Aubrun, F, Kalfon, F, Mottet, P et al. . Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects. Br J Anaesth 2003; 90: 314–319.Google Scholar
43.Gottschalk, A, Schroeder, F, Ufer, M, Oncü, A, Buerkle, H, Standl, T. Amantadine, a N-methyl-d-Aspartate receptor antagonist, does not enhance postoperative analgesia in women undergoing hysterectomy. Anesth Analg 2001; 93: 192–196.CrossRefGoogle ScholarPubMed
44.Jaksch, W, Lang, S, Reichhalter, R, Raab, G, Dann, K, Fitzal, S. Perioperative small-dose S (+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used. Anesth Analg 2002; 94: 981–986.Google Scholar
45.Mortero, RF, Clark, LD, Tolan, MM, Metz, RJ, Tsueda, K, Sheppard, RA. The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain. Anesth Analg 2001; 92: 1465–1469.CrossRefGoogle ScholarPubMed
46.Krystal, JH, Karper, LP, Seibyl, JP et al. . Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: psychotomimetic, perceptual, cognitive and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199–214.Google Scholar
47.Kudoh, A, Takahira, Y, Katagai, H, Takazawa, T. Small-dose ketamine improves the postoperative state of depressed patients. Anesth Analg 2002; 95: 114–118.Google Scholar