British journal of anaesthesia
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The Minto remifentanil pharmacokinetic/pharmacodynamic (PK/PD) model is used in target-controlled infusion (TCI) devices. The endpoint used to calculate the PD parameters, including the ke0, was the electroencephalogram (EEG), which only changes at high remifentanil concentrations. As the ke0 should adequately predict the time course of drug effects at clinically relevant concentrations, we evaluated the temporal agreement between effect-site concentrations estimated with the Minto model and pressure pain thresholds during conscious sedation. ⋯ Our results demonstrate the limitation of the Minto PD model at low target remifentanil concentrations, with a discrepancy in the time course between EEG and pressure pain threshold changes. Clinicians should be aware that the time course of onset of analgesic effects is slower than the estimates of the Minto model. Investigators should consider using algometry data in future opioid PD modelling studies.
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Observational Study
Change in healthcare utilisation after surgical treatment: observational study of routinely collected patient data from primary and secondary care.
Most patients fully recover after surgery. However, high-risk patients may experience an increased burden of medical disease. ⋯ High-risk patients who survive the immediate perioperative period experience large and persistent increases in healthcare utilisation in the years after surgery. The full implications of this require further study.
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Repetitive opioid use does not always alleviate basal pain, procedural pain, or both after burn injury. Mitigation of burn injury-site pain can be achieved by GTS-21 stimulation of α7-acetylcholine nicotinic receptors (α7AChRs) and reduced microglia activation in rat. We tested the hypothesis that morphine exaggerates burn injury-site pain and GTS-21 alleviates both morphine-induced aggravated burn injury pain and microglia activation. ⋯ Morphine or burn injury alone increases pain together with microgliosis and pain-transducer expression. Morphine administration augments burn injury-site nociception sooner and aggravated spinal microgliosis and inflammatory pain-transducer expression. GTS-21 has the potential to treat morphine-induced pain in burn injury.
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A fundamental concept in pharmacology is that increasing dose increases drug effect. This is the basis of anaesthetic titration: the dose is increased when increased drug effect is desired and decreased when reduced drug effect is desired. In the setting of titration, the correlation of doses and observed drug effects can be negative, for example increasing dose reduces drug effect. We have termed this the drug titration paradox. We hypothesised that this could be explained, at least in part, by intrasubject variability. If the drug titration paradox is simply an artifact of pooling population data, then a mixed-effects analysis that accounts for interindividual variability in drug sensitivity should 'flip' the observed correlation, such that increasing dose increases drug effect. ⋯ The relationship between drug dose and drug effect must be determined under carefully controlled experimental conditions. In routine care, where the effect is profoundly influenced by varying clinical conditions and drugs are titrated to achieve the desired effect, it is nearly impossible to draw meaningful conclusions about the relationship between dose and effect.