British journal of anaesthesia
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Anaesthetists are confronted on a daily basis with patients with coronary artery disease, myocardial ischaemia, or both during the perioperative period. Therefore, prevention and ultimately adequate therapy of perioperative myocardial ischaemia and its consequences are the major challenges in current anaesthetic practice. This review will focus on the translation of the laboratory evidence of anaesthetic-induced cardioprotection into daily clinical practice.
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Review
Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile.
Opioid receptors are currently classified as mu (mu: mOP), delta (delta: dOP), kappa (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. ⋯ For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain.
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Immunotherapy in the critically ill is an appealing notion because of the apparent abnormal immune and inflammatory responses seen in so many patients. The administration of a medication that could alter immune responses and decrease mortality in patients with sepsis could represent a 'magic bullet'. ⋯ However, in some respects, research along these lines has been unsuccessful or disappointing at best. The current state of knowledge is summarized with particular reference to sepsis and the acute respiratory distress syndrome.
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The use of anticholinesterases to reverse residual neuromuscular block is efficacious only if recovery is already established. It was originally advised that at least the second twitch (T2) of the train-of-four response should be detectable before neostigmine is administered. Even in these circumstances, the full effect of anticholinesterases takes up to 10 min to achieve. ⋯ Sugammadex is ineffective in antagonizing the benzylisoquinolinium NMBAs. The dose should be adjusted according to the degree of residual block: sugammadex 16 mg kg(-1) for immediate reversal; 4-8 mg kg(-1) for antagonizing profound block (post-tetanic count 1-2); and 2 mg kg(-1) to antagonize moderate block (when T2 is detectable). As yet, the extent of any side-effects that may occur with this new antagonist is not fully known, although rarely adverse cardiovascular effects (hypotension, hypertension, prolonged QT interval) have already been reported.
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The concept of 'personalized medicine' in which a knowledge of genetic factors guides prescribing tailored to the individual is popularly considered to be an inevitable consequence of completion of the International Human Genome Project. We should not forget, however, that a personal or family history of one of several uncommon pharmacogenetic conditions has influenced the use of the implicated drug(s) during anaesthesia for the past 50 yr. ⋯ The situation is different for most currently available drugs, including those used by anaesthetists, where genetic variability to drug response is presumed to be the result of a complex interaction of multiple factors. We review the nature and investigation of pharmacogenomic variability and contrast the progress made with research into opioid variability with the more limited literature concerning i.v. and inhalation anaesthetics.