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S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans

Une combinaison de S(+) kétamine et de propofol maintient l’autorémulation vasculaire cérébrale dynamique chez l’humain



This study investigates the effects of S(+)-ketamine and propofol in comparison to sevoflurane on dynamic cerebrovascular autoregulation in humans.


Twenty-four patients were randomly assigned to one of the following anesthetic protocols: group I (n = 12): 2.5 mg·kg−1·hr−1 S(+)-ketamine, 1.5–2.5 μg·mL−1 propofol-target plasma concentration; group II (n = 12): 2.0 MAC (4.0 %) sevoflurane. Patients were intubated and ventilated with O2/air (PaO2=0.33). Following 40 min of equilibration dynamic cerebrovascular autoregulation was measured and expressed as the autoregulatory index (ARI), describing the duration of cerebral hemodynamic recovery in relation to changes in mean arterial blood pressure. Statistics: Mann-Whitney U test (statistical significance was assumed whenP < 0.05).


Dynamic cerebrovascular autoregulation was intact in all patients with S(+)-ketamine/propofol anesthesia as indicated by an ARJ of 5.4 ± 1.1. In contrast, dynamic cerebrovascular autoregulation was significantly delayed with 2.0 MAC sevoflurane (ARI =2.6 ± 0.7).


Dynamic cerebrovascular autoregulation is maintained with S(+)-ketamine/propofol-based totaliv anesthesia. In contrast, 2.0 MAC sevoflurane delayed dynamic cerebrovascular autoregulation. This supports the use of S(+)-ketamine in combination with propofol in neurosurgical patients based on its neuroprotective potential along with maintained cerebrovascular physiology.



Examiner les effets de la S(+)kétamlne et du propofol, comparés au sévoflurane, sur l’autorégulatlon vasculalre cérébrale dynamique chez l’humain.


Vingt-quatre patients ont été répartis au hasard et ont reçu un des protocoles anesthéslques suivants: groupe I (n = 12): 2,5 mg·kg−1· h−1 de S(+)kétamlne, une concentration plasmatlque cible de propofol de 1,5-2,5μg·mL−1; groupe II (n = 12): 2,0 CAM (4,0 %) de sévoflurane. On a procédé à l’intubation et à la ventilation avec un mélange de O2/alr (PaO2 = 0,33). Après un temps d’équilibre de 40 min, l’autorégulatlon vasculalre cérébrale a été mesurée et exprimée comme l’indice d’autorégulation (IAR), décrivant la durée de la récupération hémodynamique cérébrale en relation avec les modifications de la tension artérielle moyenne. Données statistiques: test U de Mann-Whitney (signification statistique avec P < 0,05).


L’autorégulatlon vasculalre cérébrale dynamique était Intacte chez tous les patients sous anesthésle avec S(+)kétamlne/propofol comme l’indiquait un IAR de 5,4 ± 1,1. Par ailleurs, elle a été significativement retardée avec les 2,0 CAM de sévoflurane (IAR = 2,6 ± 0,7).


L’autorégulation vasculalre cérébrale dynamique est maintenue avec une anesthésle exclusivement intraveineuse à base de S(+)kétamlne/propofol mais retardée avec 2,0 CAM de sévoflurane. Ces données favorisent l’usage de S(+)kétamlne combinée au propofol, en neurochirurgie, usage fondé sur leur potentiel de neuroprotection et de maintien de la physiologie vasculalre cérébrale.


  1. 1

    Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg 1995; 81: 84–9.

  2. 2

    Nimkoff L, Quinn C, Silver P, Sagy M. The effects of intravenous anesthetics on intracranial pressure and cerebral perfusion pressure in two feline models of brain edema. J Crit Care 1997; 12: 132–6.

  3. 3

    Albanèse J, Arnaud S, Rey M, Thomachot L, Alliez B, Martin C. Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 1997; 87: 1328–34.

  4. 4

    Cavazzuti M, Porro CA, Biral GP, Benassi C, Barbieri GC. Ketamine effects on local cerebral blood flow and metabolism in the rat. J Cereb Blood Flow Metabol 1987; 7: 806–11.

  5. 5

    Adams HA, Thiel A, Jung A, Fengler G, Hempelmann G. Effects of S-( + )-ketamine on endocrine and cardiovascular parameters. Recovery and psychomimetic reactions in volunteers (German). Anaesthesist 1992; 41: 588–96.

  6. 6

    Hoffman WE, Pelligrino D, Werner C, Kochs E, Albrecht RE, Schulte am Esch J. Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats. Anesthesiology 1992; 76: 755–62.

  7. 7

    Reeker W, Werner C, Möllenberg O, Mielke L, Kochs E. High-dose S(+)-ketamine improves neurological outcome following incomplete cerebral ischemia in rats. Can J Anesth 2000; 47: 572–8.

  8. 8

    Shapira Y, Lam A, Eng CC, Laohaprasit V, Michel M. Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury. Stroke 1994; 25: 1637–43.

  9. 9

    Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology 1995; 83: 66–76.

  10. 10

    Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic cerebral autoregulation measurements. Stroke 1995; 26: 1014–9.

  11. 11

    Mahony PJ, Panerai RB, Deverson ST, Hayes PD, Evans DH. Assessment of the thigh cuff technique for measurement of dynamic cerebral autoregulation. Stroke 2000; 31:476–80.

  12. 12

    Wendling WW, Daniels EB, Chen D, Harakal C, Carlsson C. Ketamine directly dilates bovine cerebral arteries by acting as a calcium entry blocker. J Neurosurg Anesth 1994; 6: 186–92.

  13. 13

    Shakunaga K, Kojima S, Jomura K, Shimizu Y, Satone T, Ito Y. Ketamine suppresses the production and release of endothelin 1 from cultured bovine endothelial cells. Anesth Analg 1998; 86: 1098–102.

  14. 14

    Eukuda S, Murakawa T, Takeshita H, Toda N. Direct effects of ketamine on isolated canine cerebral and mesenteric arteries. Anesth Analg 1983; 62: 553–8.

  15. 15

    Oren RE, Rasool NA, Rubinstein EH. Effect of ketamine on cerebral cortical blood flow and metabolism in rabbits. Stroke 1987; 18: 441–4.

  16. 16

    Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology 1972; 36: 69–75.

  17. 17

    Sakai K, Cho S, Fukusaki M, Shibata O, Sumikawa K. The effects of propofol with and without ketamine on human cerebral blood flow velocity and CO(2) response. Anesth Analg 2000; 90: 377–82.

  18. 18

    Dawson B, Michenfelder J, Theye R. Effects of ketamine on canine cerebral blood flow and metabolism: modification by prior administration of thiopental. Anesth Analg 1971; 50: 443–7.

  19. 19

    Engelhard K, Werner C, Lu H, Möllenberg O, Kochs E. Influence of S(+)-ketamine on autoregulation of cerebral blood flow (German). Anästhesiol Intensivmed Notfallmed Schmerzther 1997; 32: 721–5.

  20. 20

    Gupta S, Heath K, Matta BE. Effect of incremental doses of sevoflurane on cerebral pressure autoregulation in humans. Br J Anaesth 1997; 79: 469–72.

  21. 21

    Cho S, Fujigaki T, Uchiyama Y, Fukusaki M, Shibata O, Sumikawa K. Effects of sevoflurane with and without nitrous oxide on human cerebral circulation. Anesthesiology 1996; 85: 755–60.

  22. 22

    Kitaguchi K, Ohsumi H, Kuro M, Nakajima T, Hayashi Y. Effects of sevoflurane on cerebral circulation and metabolism in patients with ischemic cerebrovascular disease. Anesthesiology 1993; 79: 704–9.

  23. 23

    Lu H, Werner C, Engelhard K, Scholz M, Kochs E. The effects of sevoflurane on cerebral blood flow autoregulation in rats. Anesth Analg 1998; 87: 854–8.

  24. 24

    Summors AC, Gupta AK, Matta BE. Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane. Anesth Analg 1999; 88: 341–5.

  25. 25

    Werner C, Lu H, Engelhard K, Droese D, Kochs E. Sevoflurane impairs cerebral blood flow autoregulation in rats: reversal with nitric oxide synthase inhibition. J Cereb Blood Flow Metab 1997; 17(Suppl. 1): S235.

  26. 26

    Strebel S, Kindler C, Bissonnette B, Tschalèr G, Deanovic D. The impact of systemic vasoconstrictors on the cerebral circulation of anesthetized patients. Anesthesiology 1998; 89: 67–72.

  27. 27

    Sokrab T-EO, Johansson BB. Regional cerebral blood flow in acute hypertension induced by adrenaline, noradrenaline and phenylepinephrine in the conscious rat. Acta Physiol Scand 1989; 137: 101–5

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Correspondence to Kristin Engelhard.

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Engelhard, K., Werner, C., Möllenberg, O. et al. S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans. Can J Anaesth 48, 1034 (2001).

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  • Ketamine
  • Sevoflurane
  • Cerebral Blood Flow Velocity
  • Sevoflurane Anesthesia
  • Cerebrovascular Autoregulation