Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Sole Use of Dexmedetomidine Has Limited Utility for Conscious Sedation during Outpatient Colonoscopy

Background: This study evaluated the ability of dexmedetomidine to provide analgesia and sedation for outpatient colonoscopy, examining outcomes including cardiorespiratory variables, side effects, and discharge readiness.

Methods: Sixty-four patients were randomly assigned to one of three treatment regimens. In group D, patients received 1 [mu]g/kg dexmedetomidine over 15 min followed by an infusion of 0.2 [mu]g [middle dot] kg-1 [middle dot] h-1. Group P received meperidine (1 mg/kg) with midazolam (0.05 mg/kg), and group F received fentanyl (0.1-0.2 mg intravenous) on demand. The assessment included measurements of heart rate, blood pressure, oxygen saturation, respiratory rate, quality of sedation/analgesia, and an evaluation of the recovery time.

Results: The study was terminated before the planned 90 patients had been recruited because of adverse events in group D. In all groups, negligible hemoglobin oxygen saturation and respiratory rate variations were observed. In group D, there was a significantly larger decrease in heart rate (to approximately 40 beats/min in 2 of 19 cases) and blood pressure (to less than 50% of the initial value in 4 of 19 patients). Supplemental fentanyl was required in 47% of patients receiving dexmedetomidine to achieve a satisfactory level of analgesia (vs. 42.8% of patients in group P and 79.2% of patients in group F). Vertigo (5 patients), nausea/vomiting (5 patients), and ventricular bigeminy (1 patient) were observed only in group D. Time to home readiness was longest in group D (85 +/- 74, 39 +/- 21, and 32 +/- 13 min in groups D, P and F, respectively; P = 0.007).     

Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons: The Effect of Injury

Background: Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown.

Methods: Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes.

Results: Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation.