Increase in cerebral metabolites during induction of propofol anaesthesia

Abstract

Editor'We performed microdialysis of cerebral interstitial metabolites during induction of propofol anaesthesia and tracheal intubation in a case series of patients undergoing asleep–awake–asleep brain tumour surgery. While it is generally assumed that propofol is associated with suppression of cerebral metabolism,1Zhang H Wang W Gao W et al.Effect of propofol on the levels of neurotransmitters in normal human brain: a magnetic resonance spectroscopy study.Neurosci Lett. 2009; 467: 247-251doi:10.1016/j.neulet.2009.10.052Crossref PubMed Scopus (32) Google Scholar, 2Alkire MT Haier RJ Barker SJ Shah NK Wu JC Kao YJ Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography.Anesthesiology. 1995; 82: 393-403doi:10.1097/00000542-199502000-00010Crossref PubMed Scopus (280) Google Scholar we found an unexpected transient increase in cerebral metabolites in parallel with an increase in heart rate after tracheal intubation. Three patients underwent awake brain surgery for brain tumour resection. Anaesthesia included propofol (4–8 mg kg–1 h−1) supplemented by remifentanil (0.1–1 µg kg−1 h−1) with mivacurium as a neuromuscular blocking agent. After craniotomy and opening of the dura, a microdialysis catheter (CMA, Stockholm, Sweden) was placed in white matter of normal appearance within the predefined tumour resection area. Microdialysis samples (0.5 µl min−1 flow rate, 10–60 min intervals) were analysed for glucose, lactate, pyruvate, glycerol, and glutamate (CMA 600 analyzer). Blood samples were drawn for the determination of plasma metabolite concentrations. Craniotomy was subsequently followed by an awake phase for determination of the resection margins and reintubation during propofol anaesthesia for craniotomy closure. Changes in glutamate, glucose, glycerol, lactate, and pyruvate concentrations during the awake and asleep period are represented in Figure 1. Induction of propofol anaesthesia is marked as an anaesthesia-induced reduction in heart rate (dotted line). In all patients, anaesthesia induction was followed by an immediate (Fig. 1a and b) or slow (Fig. 1c), but transient increase in glutamate, but this was not observed in the arterial blood samples (grey boxes in Fig. 1a–c). In the first patient, the transient increase in glutamate was paralleled by a transient increase in glucose levels (Fig. 1d), whereas the second patient showed a decrease in glucose levels during the increase in glutamate (Fig. 1e). Glucose remained stable in the third patient (Fig. 1f; grey boxes represent plasma glucose levels). The elevation of glutamate was associated with an increase in glycerol (Fig. 1g–i) in all three patients. The increase in the lactate/pyruvate ratio that paralleled the increased glutamate levels in the first and second patients (Fig. 1j and k, respectively) was absent in the third patient (Fig. 1l; grey boxes represent plasma lactate concentrations). Although it is assumed that general anaesthesia suppresses cerebral energy metabolism,1Zhang H Wang W Gao W et al.Effect of propofol on the levels of neurotransmitters in normal human brain: a magnetic resonance spectroscopy study.Neurosci Lett. 2009; 467: 247-251doi:10.1016/j.neulet.2009.10.052Crossref PubMed Scopus (32) Google Scholar we found a transient increase in cerebral metabolites after infusion of propofol and reintubation in the presence of a decrease in heart rate and mean arterial pressure. A similar increase in cerebral glutamate levels during extubation has been shown using cerebral microdialysis.3Reinstrup P Stahl N Mellergard P Uski T Ungerstedt U Nordstrom CH Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery.Neurosurgery. 2000; 47: 701-709Crossref PubMed Google Scholar There are a few possible explanations for this unexpected observation. Although anaesthetic agents primarily inhibit excitatory neurotransmission, others showed increases in blood plasma and cerebrospinal fluid glutamate levels during anaesthesia.4Stover JF Kempski OS Anesthesia increases circulating glutamate in neurosurgical patients.Acta Neurochir (Wien). 2005; 147: 847-853doi:10.1007/s00701-005-0562-yCrossref PubMed Scopus (27) Google Scholar Our findings might be explained by a temporary reduction in synaptic uptake of glutamate, but this should be further investigated in a larger group of patients. Secondly, the interstitial increase in cerebral metabolites could be induced by a stress response associated with induction of general anaesthesia and tracheal intubation due to an increase in catecholamines. We indeed observed an increase in heart rate during tracheal intubation, which might be representative for catecholamine release. This case series shows that propofol anaesthesia and tracheal intubation may be associated with an increase in interstitial cerebral metabolite levels, which is in contrast to the general paradigm of suppression of brain metabolism by general anaesthesia. Our findings warrant further investigation of the relation between anaesthesia induction as a stressful event and brain metabolism in larger patient studies, thereby contributing to further optimization of anaesthetic strategies. None declared.