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Background Propofol is used to induce deep sedation or general anaesthesia for procedures in children. Adjuvants, such as ketamine, are routinely added to reduce the dose of propofol required and propofol-related adverse events. We conducted a randomised controlled trial to determine the effective bolus dose of propofol in combination with ketamine that induces adequate depth of anaesthesia in 50% of children (ED50) undergoing gastro-duodenoscopy. Methods Children were randomised to one of four doses of ketamine: 0 (control), 0.25, 0.5, and 1 mg kg−1, followed by a dose of propofol according to Dixon's up-and-down methodology. Excessive movement, coughing, gagging, or airway obstruction that prevented endoscope insertion was considered a failure. Results The ED50 of propofol (median, 95% CI) was greater in the ketamine 0, 0.25, and 0.5 mg kg−1 groups compared with the ketamine 1 mg kg−1 group (6.1, 4.1–8.1; 4.5, 2.9–6; 4.7, 3.1–6.2 mg kg−1 vs 1.1, 0.5–1.8 mg kg−1, respectively, P Conclusions Ketamine at 0.5–1 mg kg–1 reduces the dose of propofol required to provide general anaesthesia for gastro-duodenoscopy in children and may reduce the incidence of propofol-related changes in haemodynamics. Clinical trial registration NCT 02295553.

Impaired regulation of intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. Comparing young (2–3 months) and aged (23–26 months) Fisher 344 rats, stratum radiatum-evoked CA1 field EPSPs were smaller and long-term potentiation (LTP) was diminished in aged hippocampal slices. Resting calcium, in presynaptic axonal terminals in the CA1 stratum radiatum area, was elevated in aged slices. Loading the slice with the calcium chelator, BAPTA-AM, depressed LTP in young slices, but enhanced this plasticity in old slices. Forty-five minutes following LTP-inducing high frequency stimulation, resting calcium levels were significantly increased in both young and old presynaptic terminals, and significantly reduced by pretreatment with BAPTA-AM. In vivo, intraperitoneal administration of BAPTA-AM prior to training in the reference memory version of the Morris water maze test, significantly improved the acquisition of spatial learning in aged animals, without a significant effect in young rats. These results support the hypothesis that increasing intracellular neuronal buffering power for calcium in aged rats ameliorates age-related impaired synaptic plasticity and learning.

Background Opioids are known to stimulate surface electroencephalographic activity in patients with temporal lobe epilepsy. The objective of the current study was to compare the electrocorticographic activation effects of the newer short-acting opioid remifentanil with those of alfentanil during epilepsy surgery under general anaesthesia. Methods Thirteen patients undergoing temporal lobe epilepsy surgery under general anaesthesia received alfentanil 30 μg kg−1 and remifentanil 1 μg kg−1 as i.v. boluses in sequence. The design was a randomized double-blind cross-over study. After opening the dura, electrocorticogram (ECoG) electrode contact strips were placed over the temporal and supratemporal neocortex and depth electrodes were inserted in the amygdala and hippocampus. Alfentanil 30 μg kg−1 or remifentanil 1 μg kg−1 were administered randomly in a blinded fashion. The ECoG was recorded continuously before and after the injection of each drug. The interictal epileptiform activity (spikes and sharp waves) above baseline was analysed. Results Both drugs increased epileptiform activity especially that recorded from depth electrodes in the temporal limbic structures. No epileptiform activity was recorded from the electrodes overlying the supratemporal neocortex before or after drug administration. The more potent activator was alfentanil, which caused an increase in activation from baseline of 99.8% compared with 67.4% for remifentanil. In addition, alfentanil activated the epileptiform activity in 3 patients in which remifentanil had no effect. There were no changes in heart rate after the opioid boluses. Both remifentanil and alfentanil caused significant reductions in blood pressure at 3 and 5 min after administration. Conclusion We conclude that at the doses used in this study, alfentanil is the better opioid for intraoperative activation of the ECoG in neurosurgical patients undergoing resection of a temporal lobe epileptic focus. This pharmacological activation of epileptiform activity assists in localizing and confirming the site of surgical excision. Neither alfentanil nor remifentanil activated epileptiform activity in non-epileptic brain tissue.