Best practice & research. Clinical anaesthesiology
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Unwanted side-effects of anaesthetic drugs that occur during anaesthesia or during the post-operative recovery period are what concern anaesthesiologists and anaesthetists. Occupational risks are of concern to all health-care professionals who administer anaesthetics or who are incidentally exposed to anaesthetic gases. After regulatory requirements for marketing drugs are met, the qualitative and quantitative nature of side-effects of the drugs in the target population and the risk of incidental exposure of health-care professionals are generally well defined. ⋯ Numerous scientific disciplines with specialized terminology contribute to the body of knowledge about anaesthetic toxicity. Scientific inquiry spanning a range of disciplines from molecular biology to global ecology provides information essential for predicting, assessing, avoiding and treating the untoward effects of anaesthetics. Contemporary concerns with respect to side-effects of anaesthetic drugs include delayed recovery of cognitive function, addiction and tolerance, local anaesthetic cardiotoxicity and tissue toxicity, relative toxicity of enantiomeric forms of drugs, and the role of biotransformation in unwanted responses to anaesthetic drug administration.
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Intravenous anaesthetic agents are generally remarkably safe. However, it is clear that propofol infusion syndrome is a real, albeit rare, entity. This often lethal syndrome of metabolic acidosis, acute cardiomyopathy and skeletal myopathy is strongly associated with infusions of propofol at rates of 5 mg/kg/hour and greater for more than 48 hours. ⋯ Midazolam causes seizure-like activity in very-low-birthweight premature infants requiring the drug prior to tracheal intubation or during prolonged positive pressure ventilation. This can be successfully reversed with the specific benzodiazepine antagonist flumazenil. Midazolam can also cause paradoxical reactions, including increased agitation, poor co-operation and aggressive or violent behaviour, which has been successfully managed with flumazenil.
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Studies on the toxic effects of muscle relaxants are difficult to design because of the need for mechanical ventilation and, consequently, concomitant administration of anaesthetic drugs which may influence the results. The following overview shows that muscle relaxants are weak toxic agents with regard to their teratogenicity, carcinogenicity and cytotoxic effects (including tissue- and organ-damaging effects). ⋯ Muscle relaxants and their metabolites may interact with muscarinic and nicotinic receptors in other organs and the ganglionic system, for example in the cardiovascular system. Direct stimulation of mast cells, with consequent release of histamine, after administration of muscle relaxants may clinically impose as toxic reactions.
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Opioids are the most potent analgesics. Toxicity results either from effects mediated by variation in affinity and intrinsic efficacy at specific opioid receptors or, rarely, from a direct toxic effect of the drugs. For some adverse effects, opioids exhibit a 'dual pharmacology' whereby these effects are usually observed only in pain-free individuals, and are not seen in patients in pain. ⋯ Non-steroidal anti-inflammatory drugs (NSAIDs) are known to act by inhibiting COX-1 and COX-2 isoenzymes to various degrees. Toxicity arises primarily from undesired inhibition at these enzyme sites. Knowledge of the mechanism of action of these drugs is fundamental to the understanding of their potential for toxicity, the details of which are still emerging.
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The complications of failure, neural injury and local anaesthetic toxicity are common to all regional anaesthetic techniques, and individual techniques are associated with specific complications. All potential candidates for regional anaesthesia should be thoroughly evaluated and informed of potential complications. Central neural blockades still account for more than 70% of regional anaesthesia procedures. ⋯ Pain on injection and paraesthesias while performing regional anaesthesia are danger signals of potential injury and must not be ignored. The incidence of systemic toxicity to local anaesthetics has significantly decreased in the past 30 years, from 0.2 to 0.01%. Peripheral nerve blocks are associated with the highest incidence of systemic toxicity (7.5 per 10,000) and the lowest incidence of serious neural injury (1.9 per 10,000).