| 1. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral haemodynamic and electrocortical CO2 reactivity in pigs anaesthetized with fentanyl, nitrous oxide and pancuronium
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral haemodynamic, metabolic and electrocortical reactivity to alterations in arterial CO2 tension (PaCO2) was assessed in seven mechanically ventilated juvenile pigs to test an experimental model designed for cerebral pharmacodynamic and pharmacokinetic studies. The animals were anaesthetized with fentanyl, nitrous oxide and pancuronium and sequentially normo- and hyperventilated over a 100-min period. Five measurements were made at 25-min intervals. The cerebral blood flow (CBF) was measured with the intra-arterial 133Xe technique and the cerebral metabolic rate for oxygen (CMRO2) determined from CBF and the cerebral arteriovenous oxygen content difference. A linear correlation (r = 0.845) was found between CBF and PaCO2. The cerebrovascular reactivity to hypocapnia (delta CBF/delta PaCO2) was maintained throughout the experimental period and amounted to (95% confidence interval) 9.1 (7.1-11.1) ml x 100 g-1 x min-1 x kPa-1 within the PaCO2 range 3.3-6.3 kPa. The CMRO2 was not influenced by hyperventilation. The baseline electroencephalographic (EEG) pattern was stable at normocapnia (mean PaCO2 5.6 kPa), whereas spectral values for delta and total average voltage increased significantly (P < 0.05) at extensive hypocapnia (3.5 kPa). Maintenance of cerebral CO2 reactivity and spectral EEG voltage at a stable plasma level of fentanyl is complementary to the cerebral haemodynamic and metabolic stability previously found at sustained normocapnia in this model.
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| 2. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:2, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved.
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| 3. |
- Åkeson, Jonas, et al.
(författare)
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Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:6, s. 525-531
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Tidskriftsartikel (refereegranskat)abstract
- In order to test the hypothesis that low-dose midazolam reduces excitatory cerebral symptoms by attenuating ketamine-induced increases in the cerebral metabolic rate for oxygen (CMRO2), we compared the cerebral effects of a combination of an anesthetic dose of ketamine hydrochloride (10.0 mg.kg-1 i.v.) and a subanaesthetic dose of midazolam maleate (0.25 mg.kg-1 i.v., n = 6; or 0.10 mg.kg-1 i.v., n = 6) with results recently obtained with ketamine (10.0 mg.kg-1 i.v.) in normoventilated pigs anaesthetized with fentanyl, nitrous oxide and pancuronium. Cerebral blood flow (CBF) was measured with the intra-arterial 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The CMRO2 did not increase significantly. In contrast, the maximal increase in cerebral CaVo2 (by 56-59% at 10 min; P < 0.01) was similar to that induced by ketamine, since CBF was more depressed (by 35-45% at 1 min: P < 0.001) by ketamine-midazolam than by ketamine only. Midazolam was found to increase CVR (P < 0.01) and further depress CBF (P < 0.01), and to antagonize the ketamine-induced increase in CMRO2 (P < 0.05). Ketamine-induced effects on mean arterial pressure (MAP) and spectral electroencephalographic (EEG) voltage were not significantly altered by midazolam. The pharmacokinetics of ketamine, as measured during an 80-min period, were not affected by the concomitant administration of midazolam. We propose that a ketamine-midazolam combination comprising a low-dose fraction (1/100-1/40) of midazolam is superior to ketamine alone for anaesthetic use.
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