Background:
Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.
Methods:
Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 and 2 examined the role of the K+ channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K+ (KCa++) channels (Series 1A+B) or glibenclamide, which blocks the ATP sensitive K+ (KATP) channel (Series 2), modulated sevoflurane-mediated vasodilation. Series 3 – 5 examined the role of the Ca++ channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca++ channel (Series 3), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca++ channels (Series 4A+B), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca++ channel (Series 5A+B), modulated sevoflurane-mediated vasodilation.
Results:
Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the KCa++ and KATP channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K+ channels. Blockade of the voltage-operated Ca++channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca++channels did not alter sevoflurane vasodilation.
Conclusion:
Sevoflurane appears to block chorionic arterial KCa++ and KATP channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the in vitro foeto-placental circulation.

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Background:
The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).
Methods:
We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.
Results:
The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44 % and 21.6 %, respectively.
Conclusions:
Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 ug remifentanil followed by an infusion of 3.7 ug/min before, during and post-CPB, supplemented with a bolus dose of 25 ug given at the start of CPB.

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Background:
The Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction.
Methods:
Thirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA.
Results:
Age and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups.
Conclusion:
Agent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

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Background:
Intrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known.
Methods:
We evaluated the analgesic efficacy and side effect profile of 100 – 300 ?g IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 ?g; (ii) 200 ?g; and (iii) 300 ?g.
Results:
Both 200 ?g and 300 ?g IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 ?g had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention.
Conclusion:
Both 200 ?g and 300 ?g provided comparable postoperative analgesia, which was superior to that provided by 100 ?g IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 ?g IT morphine be used in these patients.Trial registrationClinicalTrials.gov Identifier NCT00695045

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