Minerva anestesiologica
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Drug development in anaesthesia poses specific challenges. Describing the development of remifentanil highlights some of these. A new drug in anaesthesia must achieve its clinical goals in all patients and significant levels of toxicity are unacceptable. ⋯ The insertion of an alkyl ester group into this 4-anilidopiperidine molecule has resulted in a compound which, whilst retaining the desired mu-opioid receptor pharmacology, is susceptible to metabolism by non-specific esterases in the blood and tissues. The rapid onset and offset of action means that the anaesthetist can deliver high doses of opioid resulting in stable anaesthesia and the lack of accumulation ensures that even after prolonged infusion remifentanil does not compromise recovery. This ability to control the anaesthetic process has relevance in both short and long procedures and the unique characteristics of remifentanil may also in the future prove to have utility in the intensive care setting.
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The selection of opioid drugs for anesthesia is often based on empirical judgment such as the selection of opioids with rapid elimination half-life for short surgical procedures (e.g. alfentanil), while opioids with longer elimination half-life (e.g. fentanyl, sufentanil) are used for longer procedures. A better insight in the pharmacokinetic and pharmacodynamic differences between opioids allows a more rational selection of the drug and its dosing scheme, and will contribute to rapid recovery after anesthesia. As opioids are adjuncts to other anesthetic drugs, drug interaction principles should be considered when titrating the opioid administration.
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Minerva anestesiologica · May 2000
ReviewTime to reconsider the pre-oxygenation during induction of anaesthesia.
Atelectasis is a frequent finding in paralysed and mechanically ventilated patients. Atelectasis, causing shunt, impairs oxygenation and could contribute to postoperative pulmonary complications. Pre-oxygenation used during anaesthesia induction causes atelectasis. A lowering of oxygen fraction from 100% to 80% does not shorten the safety time of apnoea period, particularly useful for a difficult intubation, but it reduces drastically the atelectasis incidence.
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Sevoflurane and Desflurane are relatively new halogenated agents which make induction and control of depth of anaesthesia easier, recovery rapid and of good quality and they have less side-effects and toxicity. In children sevoflurane could replace halothane because it provides smooth and rapid induction with less cardiovascular depression and arrhythmias. Desflurane is not used because of its pungent odour. In adults sevoflurane could be preferred to desflurane because it allows rapid induction and laryngeal mask insertion or tracheal intubation without myorelaxants, a similar time of recovery, no clinical evidence for renal and hepatic toxicity, no more costs for anaesthesia for a lower MAC.
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Minerva anestesiologica · May 2000
ReviewCytopathic hypoxia. A concept to explain organ dysfunction in sepsis.
The most common cause of death in patients with sepsis is the multiple organ dysfunction syndrome (MODS). One important factor underlying the pathogenesis of MODS may be sepsis-induced alterations in cellular energy metabolism due to acquired intrinsic derangements in cellular respiration, a phenomenon that might be called "cytopathic hypoxia". A number of different biochemical mechanisms have been postulated to account for cytopathic hypoxia in sepsis, including reversible inhibition of cytochrome oxidase by nitric oxide, irreversible inhibition of one or more mitochondrial respiratory complexes by peroxynitrite, and activation of the nuclear enzyme, poly-(ADP-ribosyl)-polymerase.