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

Klinik für Anaesthesiologie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany.
Canadian Journal of Anaesthesia (Impact Factor: 2.53). 11/2001; 48(10):1034-9. DOI: 10.1007/BF03016597
Source: PubMed


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*hr(-1) S(+)-ketamine, 1.5-2.5 microg*mL(-1) propofol-target plasma concentration; group II (n=12): 2.0 MAC (4.0 %) sevoflurane. Patients were intubated and ventilated with O(2)/air (PaO(2)=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 when P <0.05).
Dynamic cerebrovascular autoregulation was intact in all patients with S(+)-ketamine/propofol anesthesia as indicated by an ARI 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 total iv 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.

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    • "The sedation management with propofol in combination with sufentanil did not influence AR in patients under general anaesthesia and after head injury [24-26]. It is therefore, unlikely that the sedative regime affected AR during this investigation. "
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    ABSTRACT: Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured daily during the first 4 days of sepsis. Diagnosis of a SAD was performed using the confusion assessment method for ICU (CAM-ICU) and, furthermore the predominant brain electrical activity in electroencephalogram (EEG) both at day 4 after reduction of sedation to RASS >-2. 30 critically ill adult patients with severe sepsis or septic shock (APACHE II 32 ± 6) were included. AR was impaired at day 1 in 60%, day 2 in 59%, day 3 in 41% and day 4 in 46% of patients; SAD detected by CAM-ICU was present in 76 % of patients. Impaired AR at day 1 was associated with the incidence of SAD at day 4 (p = 0.035). AR is impaired in the great majority of patients with severe sepsis during the first two days. Impaired AR is associated with SAD, suggesting that dysfunction of AR is one of the trigger mechanisms contributing to the development of SAD. Trial registration ID NCT01029080
    Critical care (London, England) 10/2012; 16(5):R181. DOI:10.1186/cc11665 · 4.48 Impact Factor
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    • "e increases cerebral blood flow (CBF) in combination with nitrous oxide or depending on the preexisting cerebral vascular resistance.(Takeshita, Okuda et al. 1972) Mechanisms involved seem to be hypercapnia, regional metabolic demand and L-Type Ca channel mediated vasodilatation. In summary cerebral autoregulation is not affected by S(+) ketamine.(Engelhard, Werner et al. 2001)"
    Article: Ketamine
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    ABSTRACT: There are two optical isomers of the 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone ketamine: S(+) ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Clinically, the anaesthetic potency of the S(+)-isomer is approximately three to four times that of the R(-)-isomer, which is attributable to the higher affinity of the S(+)-isomer to the phencyclidine binding sites on the NMDA receptors. Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. It causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system. In clinics, ketamine and particularly S(+)-ketamine are used for premedication, sedation, and induction and maintenance of general anaesthesia, which is than termed "dissociative anaesthesia". Ketamine and its S(+)-isomer are ideal anaesthetic agents for trauma victims, patients with hypovolemic and septic shock and patients with pulmonary diseases. Even subanaesthetic doses of this drug have analgesic effects, so ketamine is also recommended for post-operative analgesia and sedation. The combination of ketamine with midazolam or propofol can be extremely useful and safe for sedation and pain relief in intensive care patients, especially during sepsis and cardiovascular instability. In the treatment of chronic pain ketamine is effective as a potent analgesic or substitute together with other potent analgesics, whereby it can be added by different methods. There are some important patient side-effects, however, that limit its use, whereby psycho-mimetic side-effects are most common.
    Handbook of experimental pharmacology 02/2008; 182(182):313-33. DOI:10.1007/978-3-540-74806-9_15
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    ABSTRACT: La kétamine, agent anesthésique dissociatif utilisé depuis 1965, a vu son utilisation diminuer en raison de nombreux effets indésirables. Mais depuis quelques années, un réel intérêt est porté sur cette ancienne molécule grâce à une meilleure compréhension de son action neuropharmacologique. Ainsi voit-elle émerger une nouvelle indication majeure en co-analgésie d'autres molécules comme les morphiniques, pour lutter contre le développement de douleurs chroniques et neuropathiques ou encore en analgésie préventive. Elle possède aussi d autres propriétés intéressantes que sont ses actions cardiostimulante, anti-inflammatoire et bronchodilatatrice respectivement utiles lors de choc hémodynamique, septique ou de status asthmaticus. Elle présenterait enfin des avantages en neurochirurgie et en ophtalmologie. Son utilisation dans le cadre de la pratique courante d'une clinique vétérinaire doit donc évoluer, notamment en développant l'analgésie multimodale et l'anesthésie balancée.
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