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B A Orser

Publications and source records attributed to B A Orser.

9 recordsLinked to original sources
PubMed1997

The effects of midazolam on propofol-induced anesthesia: propofol dose requirements, mood profiles, and perioperative dreams.

UNLABELLED: This study examined the effects of midazolam on the doses of propofol required for the induction of hypnosis and the maintenance of propofol/nitrous oxide anesthesia. In addition, the effects of midazolam on the time to patient recovery, perioperative mood profiles, incidence of perioperative dreams, patient satisfaction scores, and requirement for postoperative analgesics were assessed. This investigation was a prospective, randomized, and double-blind study of female patients undergoing dilatation and curettage. Patients received midazolam (30 microg/kg, n = 30) or an equal volume of placebo (n = 30) immediately before the induction of anesthesia. Recall of dreams was assessed immediately postoperatively, in the postanesthesia care unit (PACU), and on the day after surgery using a questionnaire designed for surgical patients. Mood profiles were quantified using the Multiple Affect Adjective Check List-Revised, which was completed preoperatively and 1 h postoperatively. The Client Satisfaction Questionnaire-8, an eight-item self-administered version of the Client Satisfaction Questionnaire, was used to assess patient satisfaction on the day after surgery. Our results indicate that although the time to the loss of the lid reflex was significantly shorter in patients receiving midazolam (43.8 +/- 2.7 vs 74.7 +/- 7.6 s, P < 0.0003), there was no significant difference in the dose of propofol required to induce hypnosis or maintain anesthesia. There were no group differences in postoperative sedation and orientation scores, perioperative mood profiles, incidence of dreams, and patient satisfaction scores. More patients who received midazolam requested analgesics in the PACU (11 vs 4, P < 0.05). In conclusion, midazolam did not reduce the anesthetic dose requirement of propofol in patients undergoing anesthesia with nitrous oxide, nor did it accelerate patient recovery. Our results call into question the benefit of coinducing anesthesia with propofol and midazolam. IMPLICATIONS: Midazolam, administered immediately before anesthetic induction with propofol, did not decrease the dose of propofol necessary for hypnosis, nor the maintenance of surgical anesthesia, in female patients undergoing diagnostic dilatation and curettage. In addition, midazolam did not alter patient recovery characteristics, postoperative mood, incidence of perioperative dreams, or patient satisfaction. The use of midazolam was associated with an increased need for postoperative analgesics. Our study calls into question the benefit of administering midazolam immediately before anesthetic induction with propofol.

Affect↗
PubMed1997

Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors.

BACKGROUND: The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is blocked by ketamine, and this action likely contributes to ketamine's anesthetic and analgesic properties. Previous studies suggest that ketamine occludes the open channel by binding to a site located within the channel pore. This hypothesis was examined by investigating the effects of ketamine on single-channel currents from NMDA receptors. METHODS: The cell-attached and outside-out configurations of the patch clamp technique were used to study NMDA-activated currents recorded from cultured mouse hippocampal neurons. RESULTS: In cell-attached patches, NMDA evoked currents that had an apparent mean open time (tau o) of 3.26 ms. The probability of at least one channel being open (Po') was 0.058. The addition of ketamine (0.1 microM or 1 microM) to the pipette solution decreased Po' to 53% and 24% of control values, respectively. At 1 microM ketamine, this reduction was due to a decrease in both the frequency of channel opening and the mean open time (44% and 68% of control values, respectively). Ketamine did not influence channel conductance and no new components were required to fit the open- or closed-duration distributions. Ketamine (50 microM), applied outside the recording pipette, reduced the opening frequency of channels recorded in the cell attached configuration. This observation suggests that ketamine gained access to a binding site by diffusing across the hydrophobic cell membrane. In outside-out patches, ketamine potency was lower than that observed in cell-attached patches: 1 microM and 10 microM ketamine reduced Po' to 63% and 34% of control values, respectively, and this reduction was due primarily to a decrease in the frequency of channel opening with little change in mean open time. CONCLUSIONS: These observations are consistent with a model whereby ketamine inhibits the NMDA receptor by two distinct mechanisms: (1) Ketamine blocks the open channel and thereby reduces channel mean open time, and (2) ketamine decreases the frequency of channel opening by an allosteric mechanism.

Anesthetics, Dissociative↗
PubMed1995

Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.

1. The effects of propofol (2,6 di-isopropylphenol) on responses to the selective glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, were investigated in cultured hippocampal neurones of the mouse. Whole cell and single channel currents were recorded by patch-clamp techniques. Drugs were applied with a multi-barrel perfusion system. 2. Propofol produced a reversible, dose-dependent inhibition of whole cell currents activated by NMDA. The concentration of propofol which induced 50% of the maximal inhibition (IC50) was approximately 160 microM. The maximal inhibition was incomplete leaving a residual current of about 33% of the control response. This inhibitory action of propofol was neither voltage- nor use-dependent. 3. Analysis of the dose-response relation for whole cell NMDA-activated currents indicated that propofol caused no significant change in the apparent affinity of the receptor for NMDA. 4. Outside-out patch recordings of single channel currents evoked by NMDA (10 microM) revealed that propofol (100 microM) reversibly decreased the probability of channel opening but did not influence the average duration of channel opening or single channel conductance. 5. Whole-cell currents evoked by kainate (50 microM) were insensitive to propofol (1 microM-1 mM). 6. These results indicate that propofol inhibits the NMDA subtype of glutamate receptor, possibly through an allosteric modulation of channel gating rather than by blocking the open channel. Depression of NMDA-mediated excitatory neurotransmission may contribute to the anaesthetic, amnesic and anti-convulsant properties of propofol.

Animals↗
PubMed1994

Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A.

Phosphorylation of glutamate receptors is probably an important mechanism for modulating excitatory transmission. However, there is little direct evidence to indicate which protein phosphatases can dephosphorylate glutamate or other ligand-gated channels, although it is known that protein phosphatases 1 and 2A play a major part in modulating voltage and second-messenger-gated channels. Here we report that in cultured hippocampal neurons, the N-methyl-D-aspartate (NMDA) receptor can be regulated by endogenous and exogenous serine/threonine protein phosphatases. Phosphatase inhibitors enhanced NMDA currents recorded using the perforated patch technique or in cell-attached patches, whereas protein phosphatases 1 or 2A decreased the open probability of these channels in inside-out patches.

Cells, Cultured↗
PubMed1994

An anaesthetic drug error: minimizing the risk.

A medication error caused a near fatal cardiac arrest in a previously healthy patient undergoing elective surgery. Inadvertent epinephrine injection induced ventricular dysrhythmias, hypertension, hypotension and pulmonary oedema. The case was investigated using critical-incident technique and was reviewed by the Risk Management Team of the Department of Anaesthesia. The purpose of this report is to present the recommendations resulting from the investigation. These include: improved resident training in intravenous drug management, the use of anaesthetic drug ampoules with distinct labels, and the development of a standardized colour code system for labels on anaesthetic drug ampoules. Furthermore, it is recommended that all anaesthetic drug errors be reported to the Canadian agencies responsible for drug packaging in order to identify patterns in anaesthetic drug errors, and to facilitate the implementation of effective drug identification systems.

Adult↗
PubMed1994

Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons.

Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole-cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. Propofol evoked current responses (EC50 = 61 microM) and shifted the dose-response curve of GABA-activated current to the left without altering the maximum of the GABA response. Preincubation with propofol and GABA led to desensitization of the GABA response (EC50 = 454 microM and 23 microM, respectively). Saturating concentrations of GABA (600 microM) evoked currents that peaked and then declined in a biexponential fashion with fast and slow time constants of tau f = 1.0 sec and tau s = 3.5 sec. Propofol (10 microM) did not change the amplitude of the peak response but decreased the rates of decay approximately 1.5-fold and enhanced the steady-state current proportionately. Recovery from desensitization was also biexponential (tau f = 11 sec, tau s = 69 sec) but not influenced by propofol. Single-channel recordings from outside-out patches demonstrated that both propofol and GABA activated channels with a 30 pS and 21 pS open state. Propofol increased the frequency but not the duration or conductance of GABA-activated events. Miniature inhibitory postsynaptic currents (mlPSCs) were evoked by the application of hypertonic sucrose to the cell soma. Propofol (2 microM) prolonged the decay time of mlPSCs to an extent similar to which it increased the open probability of GABA-activated channels (2.3- vs 3-fold). A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission.

Animals↗
PubMed1991

Cation selective channel in fetal alveolar type II epithelium.

A cation selective channel was identified in the apical membrane of fetal rat (Wistar) alveolar type II epithelium using the patch clamp technique. The single channel conductance was 23 +/- 1.2 pS (n = 16) with symmetrical NaCl (140 mM) solution in the bath and pipette. The channel was highly permeable to Na+ and K+ (PNa/PK = 0.9) but essentially impermeant to chloride and gluconate. Membrane potential did not influence open state probability when measured in a high Ca2+ (1.5 mM) bath. The channel reversibly inactivated when the bath was exchanged with a Ca(2+)-free (less than 10(-9) M) solution. The Na+ channel blocker amiloride (10(-6) M) applied to the extracellular side of the membrane reduced P(open) relative to control patches; P(control) = 0.57 +/- 0.11 (n = 5), P(amiloride) = 0.09 +/- 0.07 (n = 4, p less than 0.01), however, amiloride did not significantly influence channel conductance (g); g(control) 19 +/- 0.9 pS (n = 5), 18 +/- 3.0 pS (n = 4). More than one current level was observed in 42% (16/38) of active patches; multiple current levels (ranging from 2 to 6) were of equal amplitude suggesting the presence of multiple channels or subconductance states. Channel activity was also evident in cell attached patches. Since monolayers of these cells absorb Na+ via an amiloride sensitive transport mechanism we speculate that this amiloride sensitive cation selective channel is a potential apical pathway for electrogenic Na+ transport in the alveolar region of the lung.

Amiloride↗