Bailliere's clinical anaesthesiology最新文献

Different types of receptor-mediated mechanism play a key role in cellular transmembrane communication. The majority of plasma membrane receptors mediate the effects of neurotransmitters and hormones through activation of GTP-binding proteins (G-proteins). Coupling of the activated receptor to a G-protein initiates (occasionally inhibits) a cascade of enzyme-catalysed reactions leading to the production of one or more second messengers, eventually leading to the physiological response. The most commonly known cascades are the phosphoinositide and the cAMP route. This paper will describe the key concepts of G-protein-mediated signalling of both cascades and introduce the concept of ‘cross-talk’. Further, the effects of anaesthetics on the intracellular components of these signalling pathways will be reviewed.

When more than one drug is used at the same time, there is the potential for an interaction. If a muscle relaxant is being used, there must already be at least one other drug in use, the anaesthetic agent. It is common to use several drugs simultaneously during an anaesthetic, for example, systemic analgesics or antibiotics. In addition, the patient may be receiving therapy for a pre-existing medical disorder. As the number of drugs in use at a time increases, so does the potential for interactions and with the large and increasing number of drugs available on the market it is certain that this problem is set to rise rather than fall. This article examines many of the common interactions involving muscle relaxants which may be encountered during anaesthesia.

Anaphylaxis is a rare event during anaesthesia but may lead to death, even when expertly treated. Reactions may be immune related (anaphylactic) or as a result of direct stimulation (anaphylactoid). The clinical features result from massive release of histamine and the release of other mediators. There is a wide spectrum of severity of reaction but the mainstay of treatment is adrenaline, intravenous colloid and 100% oxygen. Investigation is important, enabling identification of the agent and other agents potentially causing life-threatening reactions. Mast cell tryptase is measured in the first 6 hours, to identify the reaction as anaphylactic, and skin testing 4–6 weeks later is best at identifying the trigger agent. Giving the patient full documentation of the reaction and investigations along with an explanation of the seriousness of the situation is imperative.

A combination of intravenous and inhalational agents to achieve a balanced anaesthetic state is common practice in modern day anaesthetic management. A recent survey of mortality in 100 000 anaesthetics revealed that the practice of combining several drugs to administer anaesthesia may be safer than the use of only one or two drugs (Cohen et al, 1988); the relative odds of dying within 7 days was 2.9 times greater when one or two anaesthetic drugs were used compared to when three or more were used. Hence, the skilful use of multiple anaesthetic agents is preferable in maintaining smooth anaesthesia and optimal patient care while reducing side-effects of the component drugs. Drug combinations may produce additive, synergistic and even antagonistic effects. Through an understanding of the pharmacodynamic interaction involving volatile anaesthetics and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can be developed. This chapter aims to provide a review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anaesthetic and achieve a more rapid recovery.

The cytochrome P450 enzymes are a family of haem-oxygenases that are ubiquitously distributed throughout nature and subserve a variety of metabolic functions in man. They are the products of a gene superfamily comprising over 400 members. In man, four families (comprising about 20 major isoforms) are responsible for most of the oxidative drug metabolism which occurs primarily in the liver but which may also occur to a significant extent in other tissues. The enzymes are capable of inserting a single atom of oxygen into a vast number of structurally unrelated compounds, which explains the unique versatility of this enzyme system. This lack of substrate specificity may lead to substrate competition and thus drug interactions by enzyme inhibition. Several polymorphisms in the genes coding for P450s have been identified which may cause inter-individual variation in rates of drug metabolism, and hence therapeutic response, and in some cases, toxicity. This review describes recent advances in the pharmacology of the P450 enzymes and highlights the role of this versatile drug-oxidizing system in drug response, drug toxicity and drug interactions.

Since 1960 clinicians and researchers have been claiming that there is evidence for an antidepressant-induced analgesic effect. The effect could be accomplished (1) as a secondary effect of a reduction in depression, (2) as a secondary effect of general sedation, or (3) by a biochemical mechanism that is independent of changes in mood or sedation but which is probably related to serotonin reuptake inhibition. Our meta-analysis summarized the results of the available double-blind, placebo-controlled trials for several chronic pain syndromes up to 1990 and found support for an independent biochemical mechanism but not for the crucial role of serotonin reuptake inhibition. Seventeen more recent (since 1990) double-blind, placebo-controlled trials have substantiated the meta-analytical results. Furthermore, recent animal and laboratory studies have confirmed that the antidepressant-induced analgesic effect is not a clinical chimaera and have made important progress with respect to possible sites and mechanisms of action.

Struggle against mortality has become the main motor of developments in twentieth century medicine. However, we realize that, even with the best of our knowledge, people do have to die. Palliative medicine, which emerged in the second half of the twentieth century, accepts death as a normal part of life and supports dying terminal patients. Euthanasia is increasingly considered in some countries to be an option for solving difficult problems in terminal care. Traditionally, hospices oppose the practice of euthanasia, providing good care instead of mercy killing. In the Dutch hospice under study, physicians are frequently confronted with patients who want to die via euthanasia. Experiences gathered in this hospice show that requests for euthanasia are not all the same. Better understanding of the motives for wanting euthanasia may help to design specific interventions preventing situations that may lead to it.

Chronic pain has a great economic impact on society and on the patient with chronic pain. The indirect costs of chronic pain, in the form of lost productivity and increased social security payments, are significantly higher than are the direct costs of the prevention, diagnosis and therapy of pain. The indirect costs in the family are particularly often under-estimated. It is proved that inpatient and outpatient treatment in multidisciplinary pain centres is equally effective. However, inpatient treatment is more expensive. Multi-disciplinary pain programmes increase the return-to-work rate significantly, but in pain therapy, there are economically relevant differences between different providers and different analgesic regimens. Further investigations are needed to uncover the costs and outcomes of different pain treatment strategies.