The Interactions between β-Blockers and Anaesthetics. Experimental Observations

The possibility of interactions between β-adrenoceptor antagonists and anaesthetic drugs is particularly relevant to the anaesthetic management of patients suffering from arterial hypertension and ischaemic heart disease. Maintenance of adrenergic beta-receptor blockade in patients with ischaemic heart disease and arterial hypertension is now widely accepted in order to avoid the cardiac risks of its sudden withdrawal and also to minimize the effects of sympathetic overactivity on the cardiovascular system. However, maintenance of adrenergic beta-receptor blockade may impose some constraints on the choice of the anaesthetic agent. While no adverse interaction has been found between beta blockade and anaesthesia with halothane, halothane supplementing nitrous oxide, or isoflurane, substantial reductions of cardiac performance have been observed in the case of the association of beta blockade and anaesthesia using methoxyflurane or trichloroethyiene. An adverse interaction has also been observed between propranolol and enflurane anaesthesia but not between oxprenolol and enflurane anaesthesia. Recent studies of the effects of anaesthesia in the presence of critically narrowed coronary arteries have shown that both halothane and enflurane may cause regional myocardial dysfunction. This dysfunction is minimized by oxprenolol and it appears that adrenergic beta-receptor blockade, besides improving cardiovascular stability, protects the myocardium supplied by narrowed coronary arteries.     

Anaesthetics and cardiac preconditioning. Part II. Clinical implications

There is compelling evidence that preconditioning occurs inhumans. Experimental studies with potential clinical implicationsas well as clinical studies evaluating ischaemic, pharmacologicaland anaesthetic cardiac preconditioning in the perioperativesetting are reviewed. These studies reveal promising results.However, there are conflicting reports on the efficacy of preconditioningin the diseased and aged myocardium. In addition, many anaestheticsand a significant number of perioperatively administered drugsaffect the activity of cardiac sarcolemmal and mitochondrialK_ATP channels, the end-effectors of cardiac preconditioning,and thereby markedly modulate preconditioning effects in myocardialtissue. Although these modulatory effects on K_ATP channels havebeen investigated almost exclusively in laboratory investigations,they may have potential implications in clinical medicine. Importantquestions regarding the clinical utility and applicability ofperioperative cardiac preconditioning remain unresolved andneed more experimental work and randomized controlled clinicaltrials. Br J Anaesth 2003; 91: 566–76     

Anaesthetics and immune function

Surgical trauma and anaesthetics may cause immune suppression, predisposing patients to postoperative infections. Furthermore, stress such as surgery and pain per se is associated with immune suppression which, in animal models, leads to an increased susceptibility to infection and tumour spread. Thus, by modulating the neurohumoral stress response, anaesthesia may indirectly affect the immune system of surgical patients. In particular, regional anaesthesia attenuates this stress response and the associated effects on cellular and humoral immunity. Additionally, anaesthetics may directly affect the functions of immune-competent cells. However, the reported effects of commercial preparations of, for example, propofol, etomidate and midazolam are highly dependent on the applied solvent. Immunosuppressive effects may be particularly relevant in the intensive care unit when anaesthetics are used as long-term sedatives. There is a striking body of evidence that long-term exposure to certain sedatives is paralleled by infectious complications. On the other hand, anti-inflammatory effects of anaesthetics may be therapeutically beneficial in distinct situations such as those involving ischaemia/reperfusion injury or the systemic inflammatory response syndrome. Consequently, sedatives should be administered with careful regard to their respective potential immunomodulatory properties, the clinical situation, and the immunity status of the critically ill patient.     

Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms

Cardiac preconditioning represents the most potent and consistentlyreproducible method of rescuing heart tissue from undergoingirreversible ischaemic damage. Major milestones regarding theelucidation of this phenomenon have been passed in the lasttwo decades. The signalling and amplification cascades fromthe preconditioning stimulus, be it ischaemic or pharmacological,to the putative end-effectors, including the mechanisms involvedin cellular protection, are discussed in this review. Volatileanaesthetics and opioids effectively elicit pharmacologicalpreconditioning. Anaesthetic-induced preconditioning and ischaemicpreconditioning share many fundamental steps, including activationof G-protein-coupled receptors, multiple protein kinases andATP-sensitive potassium channels (K_ATP channels). Volatile anaestheticsprime the activation of the sarcolemmal and mitochondrial K_ATPchannels, the putative end-effectors of preconditioning, bystimulation of adenosine receptors and subsequent activationof protein kinase C (PKC) and by increased formation of nitricoxide and free oxygen radicals. In the case of desflurane, stimulationof - and ß-adrenergic receptors may also be of importance.Similarly, opioids activate - and -opioid receptors, and thisalso leads to PKC activation. Activated PKC acts as an amplifierof the preconditioning stimulus and stabilizes, by phosphorylation,the open state of the mitochondrial K_ATP channel (the main end-effectorin anaesthetic preconditioning) and the sarcolemmal K_ATP channel.The opening of K_ATP channels ultimately elicits cytoprotectionby decreasing cytosolic and mitochondrial Ca²⁺ overload. Br J Anaesth 2003; 91: 551–65