The bispectral index (BIS) and a sedation score were used to determine and compare the effect of propofol in the presence of fentanyl, alfentanil, remifentanil and sufentanil. Seventy-five non-premedicated patients were assigned randomly into five groups (15 in each) to receive fentanyl, alfentanil, remifentanil, sufentanil or placebo. Opioids were administered using a target-con-trolled infusion device, to obtain the following predicted effect-site concentrations: fentanyl, 1.5 ng ml(-1); alfentanil, 100 ng ml(-1); remifentanil, 6 ng ml(-1); and sufentanil, 0.2 ng ml(-1). After this, a target-controlled infusion of propofol (Diprifusor) was started to increase concentration gradually, to achieve predicted effect-site concentrations of 1, 2, and 4 microg ml(-1). At baseline and at each successive target effect-site concentration of propofol, the BIS, sedation score and haemodynamic variables were recorded. At the moment of loss of consciousness (LOC), the BIS and the effect-site concentration of propofol were noted. The relationship between propofol effect-site concentration and BIS was preserved with or without opioids. In the presence of an opioid, LOC occurred at a lower effect-site concentration of propofol and at a higher BIS50 (i.e. the BIS value associated with 50% probability of LOC), compared with placebo. Although clinically the hypnotic effect of propofol is enhanced by analgesic concentrations of mu-agonist opioids, the BIS does not show this increased hypnotic effect.

No abstract

Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.

We have investigated the interaction between magnesium sulphate 40 mg kg-1 i.v. and vecuronium. First, we determined the effect of pretreatment with magnesium on the potency of vecuronium using a single bolus dose-response technique. In addition, we compared the time course of vecuronium-induced neuromuscular block (vecuronium 100 micrograms kg-1) with and without magnesium pretreatment. For both parts, neuromuscular block was assessed by electromyography. In addition, the effect of magnesium pretreatment on vecuronium-induced neuromuscular block was investigated in the context of rapid sequence induction of anaesthesia. We found that the neuromuscular potency of vecuronium was increased by pretreatment with magnesium sulphate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50: 21.3 vs 26.9 micrograms kg-1; ED90: 34.2 vs 45.7 micrograms kg-1; P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4-vecuronium group vs 297.3 (122) s for controls (P < 0.05). Clinical duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for controls; P < 0.05). This was also true for the recovery index (20.1 (6.6) min vs 10.6 (3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8 (6.9) min; P < 0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4, reaching the same quality as that with suxamethonium 1 mg kg-1. We conclude that magnesium pretreatment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular block.

Sugammadex, 1.0 mg/kg, rapidly and effectively reverses rocuronium-induced block that has recovered spontaneously to a threshold TOF-count-four. A dose of 0.5 mg/kg was equally effective, but satisfactory antagonism took as long as 8 min to take place.

Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors, was reported to induce neuronal cell death when administered to produce anesthesia in young rodents and monkeys. Subanesthetic doses of ketamine, as adjuvant to postoperative sedation and pain control, are also frequently administered to young children. However, the effects of these low concentrations of ketamine on neuronal development remain unknown. The present study was designed to evaluate the effects of increasing concentrations (0.01-40 microg/ml) and durations (1-96 h) of ketamine exposure on the differentiation and survival of immature gamma-aminobutyric acidergic (GABAergic) interneurons in culture. In line with previous studies (Scallet et al., 2004), we found that a 1-h-long exposure to ketamine at concentrations > or = 10 microg/ml was sufficient to trigger cell death. At lower concentrations of ketamine, cell loss was only observed when this drug was chronically (> 48 h) present in the culture medium. Most importantly, we found that a single episode of 4-h-long treatment with 5 microg/ml ketamine induced long-term alterations in dendritic growth, including a significant (p < 0.05) reduction in total dendritic length and in the number of branching points compared to control groups. Finally, long-term exposure (> 24 h) of neurons to ketamine at concentrations as low as 0.01 microg/ml also severely impaired dendritic arbor development. These results suggest that, in addition to its dose-dependent ability to induce cell death, even very low concentrations of ketamine could interfere with dendritic arbor development of immature GABAergic neurons and thus could potentially interfere with the development neural networks.

Increased or decreased gain in central nervous system processing after surgery, i.e. neuroplasticity, may play an important role in postoperative pain. Identification of patient subgroups particularly vulnerable to either type of post-surgical neuroplasticity is thus of interest. Preoperative pain has also been suggested to increase vulnerability to post-surgical chronic pain complications due to central facilitation. To study if back pain preoperatively is associated with differences in central sensory processing, we measured transcutaneous electric sensation, pain detection and pain tolerance thresholds at the upper arm, lower back and lower leg in 52 consecutive patients scheduled for back surgery in a blinded, prospective fashion. Patients with no pain had significantly lower pain thresholds than patients with pain in the leg, and significantly higher pain thresholds than those with pain in the back. These results suggest that preoperative pain can induce diverse central neuroplastic changes, i.e. inhibition and facilitation, and that the nature of this neuroplasticity depends on the nature of the pain involved. The presence of facilitation may be the basis of the increased vulnerability described in some studies of patients with significant preoperative pain, whereas the implications of reduced pain sensitivity are less clear. The demonstration of neuroplasticity and its diversity are, however, likely to be of significant clinical relevance.

We studied EEG arousal after laryngoscopy and intubation with standardized bolus induction of anaesthesia. Twenty patients were prospectively allocated randomly to induction with propofol 3 mg kg-1 (n = 10) or thiopentone (6 mg kg-1 (n = 10) and 50% nitrous oxide in oxygen. Neuromuscular block was produced with vecuronium 0.2 mg kg-1 given 30 s after induction. Three minutes after induction, laryngoscopy was performed for 60 s, with intubation at 3 min 30 s, and study end at 5 min. Nociception to laryngoscopy and intubation was followed by loss of low (relative delta activity change: thiopentone -30%, propofol -7%; P < 0.05) and a shift to higher frequency EEG activity (beta activity change: thiopentone +647%, propofol +61%; P < 0.05). This EEG arousal was greater in the thiopentone group, despite the fact that EEG depression was similar to that produced by propofol before laryngoscopy and intubation. Propofol and thiopentone in combination with nitrous oxide had similar cortical depressant effects, but propofol appeared to depress subcortical nociceptive processing more than thiopentone. While the degree of cortical EEG depression seems less useful for predicting reaction to subsequent nociception, EEG arousal reactions may prove suitable for monitoring intra-anaesthetic nociception and its modulation.