Articles: general-anesthesia.
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An overview is given of the influence of age on the pharmacodynamics of drugs used during general and locoregional anaesthesia. For some groups of agents a distinct separation into age-related changes in the pharmacokinetics and pharmacodynamics is possible, whereas for others the literature indicates only that responses in the elderly are enhanced. I start with an overview of the influence of age on cardiovascular and neuroendocrine function and include a short account of the state-of-the-art in pharmacodynamic modelling. ⋯ For opioids and local anaesthetics applied for blockade of the central nervous system, the pharmacodynamic involvement is not always clear. For neuromuscular blocking agents, pharmacodynamic involvement appears to be nearly absent in the reduced dose requirements seen with age--so that the latter appear to be caused by altered pharmacokinetics. Future studies, using pharmacokinetic-pharmacodynamic (PK-PD) mixed-effects modelling, should further explore this area to obtain clinically applicable data for improving our insight into the delivery of anaesthetics to the elderly and improving the quality of anaesthesia in this fast-growing population.
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The first cases of general anesthesia were already cases with awareness. Until today, case reports of patients with awareness are published. These published cases are likely to be the top of the iceberg, as most patients with postoperative recall do not inform their anesthesiologist. ⋯ The anesthetist should not disbelieve reported recall. Explanation of what had happened and referral to an experienced psychologist must be offered. Thus, the incidence of severe sequelae should decrease.
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Deteriorated neurological outcome is not rare after major surgeries. With aging of the surgical population in Japan, an increasing frequency of perioperative cerebral ischemia is expected. To avoid neurological deterioration after surgery and general anesthesia, especially in high-risk patients, it is important to provide appropriate CNS-oriented anesthesia management. ⋯ Among these inhalational anesthetics, isoflurane has been most extensively studied regarding neuroprotection against cerebral ischemic insult. Although no clinical outcome trials have been performed, both in vivo and in vitro studies have consistently shown that the isoflurane provides neuroprotection. However, it is also suggested that factors such as sympathetic reactivity, brain temperature, anesthetic dosage, timing of anesthetic administration, and co-administration of nitrous oxide might affect the neuroprotective effect of isoflurane.
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Propofol (Diprivan) is a phenolic derivative with sedative and hypnotic properties but is unrelated to other sedative/hypnotic agents. Formulated as an oil-in-water emulsion for intravenous use, it is highly lipophilic and rapidly crosses the blood-brain barrier resulting in a rapid onset of action. Emergence from sedation is also rapid because of a fast redistribution into peripheral tissues and metabolic clearance. The depth of sedation increases in a dose-dependent manner. In well designed clinical trials in patients receiving sedation in the intensive care unit (ICU) for a variety of indications, propofol provided adequate sedation for a similar proportion of time to midazolam, but the rate of recovery was faster with propofol. Even after periods of prolonged sedation (>72 hours), propofol was generally associated with a faster time to recovery than midazolam. Propofol facilitated better predictability of recovery and an improved control of the depth of sedation in response to titration than midazolam. In patients sedated following head trauma, propofol reduced or maintained intracranial pressure. Propofol is associated with generally good haemodynamic stability but induces a dose-dependent decrease in blood pressure and heart rate. Bolus administration may cause transient hypotension, and slow initial infusions are recommended in most patients. Serum triglyceride concentrations should be monitored during prolonged infusions (>3 days) because of the risk of hypertriglyceridaemia. The administration of 2% propofol can reduce this risk. Strict aseptic technique must be used during the handling of the product to prevent accidental extrinsic microbial contamination. Despite a higher acquisition cost with propofol, most studies of short-term sedation (approximately <3 days) showed that overall costs were lower with propofol than with midazolam, because a faster time to extubation reduced total ICU costs. However, as the period of sedation increased, the cost difference decreased. ⋯ The efficacy of propofol in the sedation of adults in the ICU is well established, and clinical trials have demonstrated a similar quality of sedation to midazolam. Because of a rapid distribution and clearance, the duration of action of propofol is short and recovery is rapid. Emergence from sedation is more rapid with propofol than with midazolam, even after long-term administration (>72 hours), which enables better control of the depth of sedation in response to titration and more predictable recovery times. Thus, for the ICU sedation of adults in a variety of clinical settings, propofol provides effective sedation with a more rapid and predictable emergence time than midazolam.