British journal of anaesthesia
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Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications. ⋯ We developed a PK-PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation.
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Both anaemia and blood transfusion are associated with poor outcomes in the neurosurgical population. Based on the available literature, the optimal haemoglobin concentration for neurologically injured patients appears to be in the range of 9.0-10.0 g dl-1, although the individual risks and benefits should be weighed. Several perioperative blood conservation strategies have been used successfully in neurosurgery, including correction of anaemia and coagulopathy, use of antifibrinolytics, and intraoperative cell salvage. Avoidance of non-steroidal anti-inflammatory drugs and starch-containing solutions is recommended given the potential for platelet dysfunction.
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Randomized Controlled Trial
Differential role of nitric oxide in the psychedelic symptoms induced by racemic ketamine and esketamine in human volunteers.
Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) hypofunction and subsequent decline in intracellular nitric oxide (NO) are responsible for development of ketamine-induced psychedelic symptoms. To examine this mechanism in humans, we administered the NO donor sodium nitroprusside during infusion of racemic ketamine (RS-ketamine), containing equal amounts of S(+)- and R(-)-ketamine isomers, or esketamine, containing just the S(+)-isomer. ⋯ NTR 5359.
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Methoxyflurane delivered via a hand-held inhaler is a proven analgesic which has been used in Australasia for emergency relief of trauma associated pain since the 1970s. The agent is self-administered by the patient under the supervision of trained personnel. More than 5 million patients have received inhaled methoxyflurane without significant side effects. ⋯ Thus, methoxyflurane may be a suitable and well-tolerated alternative to traditional i.v. sedative agents for outpatient medical and surgical procedures. There are direct advantages to the patient in terms of rapid recovery and an early return to normal activities, and significant benefits for outpatient departments in terms of cost saving and rate of throughput. Further randomised controlled trials comparing the efficacy, safety, and cost-effectiveness of inhaled methoxyflurane against traditional i.v. sedative techniques are currently in progress.
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Atomised intranasal dexmedetomidine administration is an attractive option when sedation is required for paediatric diagnostic procedures, as vascular access is not required. The risk of haemodynamic instability caused by dexmedetomidine necessitates better understanding of its pharmacokinetics in young children. To date, intranasal dexmedetomidine pharmacokinetics has only been studied in adults. ⋯ Mean arterial plasma concentrations of dexmedetomidine in infants and toddlers approached 100 pg ml-1, the low end reported for sedative efficacy, within 20 min of an atomised intranasal administration of 1 μg kg-1. Doubling the dose to 2 μg kg-1 reached this plasma concentration within 10 min and achieved almost twice the peak concentration. Peak plasma concentrations with both doses were reached within 47 min of intranasal administration, with an overall bioavailability of 84%.