Bailliere's clinical anaesthesiology最新文献

Anti-hypertensive drugs and anaesthesia, general as well as neuro-axial anaesthesia, interfere with the normal regulation of the cardiovascular system. It is therefore not surprising that there are numerous clinically important interactions between the blood pressure-lowering drugs and anaesthetic agents. A thorough knowledge of the mechanisms of action of the individual compounds and a good understanding of the possible interactions is a prerequisite for a safe conduct of anaesthesia in patients treated for hypertension.

Beta-adrenoceptor antagonists seldom show untoward interactions with anaesthesia and anaesthetic agents. In contrast, they have a beneficial effect on the heart and the haemodynamics in hypertensive patients. By preventing an excessive increase in heart rate and myocardial contractility, they decrease the myocardial oxygen demand and protect the myocardium from ischaemia. They should not be withdrawn prior to anaesthesia and surgery, and continuation of the beta-adrenoceptor blockade throughout the peri-operative period is warranted. The interaction between calcium antagonists and volatile and local anaesthetics can lead to adverse effects in cardiac impulse generation and conductance and can increase drug toxicity. Close attention must be paid to the choice and dosage of the individual agents. The renin-angiotensin system plays a pivotal role in blood pressure regulation during the peri-operative period. The inhibition of the angiotensin-converting enzyme or blockade of the angiotensin receptors deranges the neurohumoral defence against the effects of anaesthesia and blood loss, and may induce severe hypotension in patients treated with these drugs. They should therefore be withdrawn before surgery. Centrally acting alpha-2 agonists exert beneficial effects on the haemodynamics and anaesthetic requirements, and they are becoming useful adjuvants of anaesthesia, particularly in patients with arterial hypertension. Considering the large number of treated hypertensive patients undergoing surgery, any newly developed anti-hypertensive agents should be tested for their compatibility and interactions with anaesthesia and anaesthetic agents.

The haemodynamic changes that occur during the development of established essential hypertension can be detected only by longitudinal studies. Several long-term studies thus indicate that the circulation in essential hypertension shifts from a ‘high-output, normal resistance' state in young age toward a ‘low-output, high-resistance’ state in old age. However, this pattern is not a uniform one, and essential hypertension may also start by an increase in peripheral resistance without a prior phase of an elevated cardiac output. The reasons for these different haemodynamic patterns are not yet understood. Sympathetic overactivity may, at least in part, be responsible for the haemodynamic changes seen in the starting phase of essential hypertension.

The haemodynamic characteristics in the different developmental stages of essential hypertension may vary considerably and are also influenced by ageing. Therefore, the proper use of anti-hypertensive drug treatment should be directed individually according to the underlying haemodynamic disturbances.

Left ventricular diastolic function in vivo is still incompletely understood. Extrapolations from in vitro studies are limited mainly owing to the simultaneous occurrence of relaxation and filling in vitro and the presence of haemodynamic loading conditions. The limited understanding of physiological mechanisms is contrasted by a vast number of ‘indices of diastolic function’, many of which originate from ad hoc empirical descriptions of data. At present, no absolute value of any index can discriminate between healthy patients and patients with severe cardiac disease. Moreover, the possibility of load-dependence is commonly ignored in the interpretation of alterations in indices of diastolic function. Future research should focus on the unveiling of physiological principles. It is hoped that an improved insight into the underlying mechanisms of diastolic function in vivo will ultimately lead to the development of meaningful indices that allow assessment and guidance of therapy in patients with cardiac disease.

Endothelin is a naturally occurring polypeptide substance with potent vasoconstrictive actions. It is produced from endothelial as well as non-endothelial cells. There are three closely related isoforms: endothelin-1, −2 and −3 (ET1, ET2 and ET3). The receptors for endothelin have been isolated and their genes cloned. Two receptors, called ET_A and ET_B, and having different affinities for the different endothelin isoforms, are well characterized. The different distribution of endothelin receptors in various tissues is responsible for the multiplicity of actions attributed to endothelin. Endothelin released from endothelial cells has local paracrine and autocrine effects on smooth muscle cells. It appears to be contributory to the pathophysiology of systemic hypertension, atherosclerosis, myocardial ischaemia, left ventricular dysfunction and congestive heart failure, ventricular hypertrophy, renal failure and pulmonary hypertension. Elevations of endothelin in the blod may also be markers of disease. Active research and drug development programmes are evaluating endothelin receptor inhibitors and endothelin-converting enzyme inhibitors for the treatment of patients with various cardiovascular, cerebrovascular, pulmonary vascular and renal diseases. Available agents such as potassium ion channel openers, calcium entry blockers and angiotensin-converting enzyme inhibitors also interfere with endothelin activity.

The endothelium, located between the circulating blood and the vascular smooth muscle cells, is exposed to physical, metabolic, hormonal and pharmaceutical influences, to which it reacts by secreting factors modulating the activity of the underlying vascular smooth muscle cells in a predominantly paracrine fashion.

Under physiological conditions, endothelial mediators promote, as an overall effect, vasodilatation, prevent the adhesion of platelets and monocytes and, in addition, inhibit the proliferation and migration of vascular smooth muscle cells. Complex interactions between the numerous endothelial mediators so far described allow the fine tuning of vascular reactivity and the adaptations of the vasculature to changing demands. Endothelial dysfunction, on the other hand, is characterized by enhanced vasoconstrictor responses and by increased risks of thrombus formation and atherosclerosis.

Ageing and chronic diseases such as hyperlipidemia, atherosclerosis and hypertension are typically associated with restrictions of endothelial function; in addition, some acute disorders seem to be mediated by the same pathomechanism. Certain drugs exert their vascular effects on the endothelial level by directly or indirectly supplying nitric oxide (nitrates and oestrogens) or by inhibiting the action of other endothelial mediators (calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and endothelin antagonists). In conclusion, the endothelium holds a central regulatory role in vascular physiology and disease, and seems to be the target of relevant therapeutic interventions.

Anaesthetists will encounter more patients in the peri-operative period on angiotensin-converting enzyme (ACE) inhibitor therapy because of their efficacy in the treatment of hypertension and cardiac failure. Pre-operative therapy with ACE inhibitors has been associated with severe hypotension after the induction of and during anaesthesia. While ACE inhibitors have not been found especially useful in managing the haemodynamic consequences of laryngoscopy and intubation, they may have a role when induced hypotension is required to minimize blood loss. It is now apparent that the renin-angiotensin system (RAS) plays a critical role in the defence of blood loss, and thus ACE inhibitors may have a deterimental effect in the peri-operative period in this respect. High thoracic epidural anaesthesia may not only have its well-known sympatholytic effect, but may also inhibit activation of the RAS system. However, on the positive side, ACE inhibitors have been shown to diminish the activation of cardiovascular mediators in cardiac surgical patients, are probably renoprotective during aortic surgery and have been shown to reduce myocardial infarct size after coronary occlusion in dogs, suggesting a possible myocardial protective effect. Thus further studies will be required to determine the exact role of ACE inhibitors in the peri-operative period.

This paper addresses the diagnostic issues involved in exertional angina with normal coronary arteriograms in hypertension and describes the results of treatment with the ACE inhibitor enalapril. From the diagnostic point of view, identification of the syndrome is based on the following: chronic arterial hypertension, exertional angina, left ventricular hypertrophy, a normal coronary arteriogram, stress gamma scintigraphy with an abnormal thallium 201 uptake and reduced coronary flow reserve. Of 120 consecutive hypertensive patients, 11 met these conditions (62% of all angina patients).

The 11 patients meeting the criteria were treated with 20–40 mg enalapril per day until blood pressure was normalized. The results were as follows: disappearance of angina in nine, regression of hypertension and of left ventricular hypertrophy in all 11, normalized thallium 201 uptake in 10 of the 11, and improved coronary flow reserve in all.

We conclude that microvascular angina is frequent in hypertensive patients (62% of all cases of anginas) and that treatment with enalapril is consistent with elimination of angina, reduced left ventricular hypertrophy and normalized thallium 201 uptake.

Chronic hypertension is associated with structural as well as functional changes of the vasculature, in particular of the coronary, cerebral and renal circulations. It is important to realize that (1) functional changes are often the result of structural changes, (2) the longer lasting the hypertension, the slower and less complete the regression of structural changes, and (3) acute ‘normalization’ of arterial pressure in longstanding hypertension may initially induce functionally subnormal smooth muscle and/or cardiac activity because the structure of the cardiovascular system is adapted to function at elevated pressures.

Despite a multitude of studies, the impact of hypertension on peri-operative morbidity and mortality remains controversal. There are as many studies seeming to suggest that pre-operative hypertension correlates with adverse outcome as there are studies that fail to establish such a relationship. When looking at the combined evidence, one is inclined to conclude that hypertension is a predictor of ‘soft’ outcomes (e.g. peri-operative myocardial ischaemia and transient post-operative neurologic deficit) rather than an independent predictor of “hard” outcomes (e.g. unstable angina, myocardial infarction and cardiac death).

In view of a lack of convincing outcome data, it is impossible to recommend a generally acceptable management strategy for the hypertensive patient. Although, in general, a gradual reduction of blood pressure over a period of weeks to months is the optimal therapeutic approach, we will be hard-pressed delaying surgery for the sole purpose of ‘better blood pressure control’. With full appreciation and detailed knowledge of the pathophysiology of hypertension, combined with sophisticated haemodynamic monitoring and interventions in the peri-operative period, acutely anaesthetizing an inadequately treated hypertensive patient will probably not adversely affect his outcome. Delaying surgery for additional work-up may possibly improve outcome in patients with target organ disease, evidence of secondary hypertension, in the most severe forms of hypertension or sudden-onset hypertension.

Several pathophysiological mechanisms are involved in the occurrence of hypertension during the peri-operative period. The effective management of blood pressure requires knowledge of the presence of concomitant diseases (e.g. coronary and peripheral atherosclerosis, renal dysfunction and cerebral disease). The patient who is undergoing an aortic or cerebral aneurysm repair will need a different therapeutic approach from someone scheduled for a peripheral procedure. Tailoring of anti-hypertensive therapy requires a detailed understanding of the effects on organ circulation (myocardial, cerebral and renal) as well as the pharmacokinetic and pharmacodynamic effects of the various anti-hypertensive drugs. The complexity of the pathogenesis of peri-operative hypertension offers a large number of opportunities for pharmacological intervention, including direct vasodilators or substances acting via blocking or stimulating various peripheral or central receptors. It is impossible to give definite dose recommendations for the different drugs. Many factors may influence the ‘ideal’ dose—pre-existing anti-hypertensive therapy, concomitant diseases, age, gender, extent of hypertension, time for lowering blood pressure (emergency/urgency), the kind of surgery and other factors—which may markedly affect the dose-response relationship of the different anti-hypertensive substances.

Treating hypertension has its benefits and risks. The complications result either from the nature of therapy (e.g. severe bradycardia after beta-blocker therapy) or from hypotension. Substances with a short duration of action appear to be of advantage in the peri-operative period. Undoubtedly, sudden increase in blood pressure should be urgently avoided; however, a rapid and marked reduction of blood pressure should also be prevented. The cerebral-or cardiac-compromised hypertensive patient particularly requires close monitoring, both during the operation and during recovery from surgery and anaesthesia. Blood pressure in these patients should be controlled only under the precise control of haemodynamics, probably using invasive blood pressure measurement and pulmonary artery catheter monitoring. For example, in patients with an aortic dissection, careful intraarterial monitoring is a prerequisite for optimal peri-operative management.

Financial consequences are becoming more and more important. The climate of cost-consciousness and cost-containment will also influence the treatment of peri-operative hypertension. Thus, although very sophisticated substances for controlling blood pressure (e.g. endothelin antagonists) will enter the market, cost-benefit analyses will more and more influence the choice of anti-hypertensive substance. However, we should always bear in mind that the fundamental step is to minimize the patients' peri-operative risk. Primum nil nocere is of highest importance when tailoring the therapeutic concept of the hypertensive patient i