Bailliere's clinical anaesthesiology最新文献

The primary goal of pre-operative evaluation is to assess adequately the patient's preoperative condition and to diagnose and possibly to treat disturbances and diseases which may be of relevance to the course of anaesthesia, surgery and the post-operative period. A pertinent medical history and a physical examination by an experienced anaesthetist are compulsory. A minimal set of tests should be carried out in all patients. The results obtained from these tests were very abnormal in a variety of studies; the information was not always apparent from the history and the examination although it was of relevance to anaesthesia and the post-operative period. Further laboratory tests such as haematocrit and blood glucose and potassium (K⁺) concentrations should only be ordered if indicated on the basis of the history and the examination. This small set of tests seems to be justified for the following reasons:• to identify unexpected risk factors not apparent from the history and the examination;

1. • to avoid additional costs resulting from deferring a case due to incomplete tests;

2. • to avoid medicolegal consequences of a possibly incomplete pre-operative evaluation;

3. • to protect patients from unnecessary invasive investigations.

Pre-anaesthetic preparation is a vital component of safe anaesthesia. The emergency patient is at higher risk in almost all surgical circumstances, not least because adequate preparation is more difficult. A variety of factors, including the nature of the emergency, cardiovascular disturbance, fluid shifts and the presence of a full stomach will render the patient more at risk. Furthermore, the presence of pre-existing disease, often poorly controlled, may further hazard the delivery of safe anaesthesia. This chapter, explores these aspects in greater detail.

The incidence of pulmonary aspiration of gastric content according to prospective and retrospective studies lies between 1.4 and 4.7 aspirations per 10 000 operations. Mortality has decreased to 1/71 829 anaesthesias. Reasons for an increased incidence of aspiration are higher American Society of Anesthetists status, emergency surgery, pregnancy and intestinal obstruction. New guidelines for elective surgical patients include no solid food for 6–8 hours but clear fluids up to 2 hours before operation. Acid antagonists and gastrokinetics should be given to patients with increased risk.

Chronic pulmonary diseases are among the leading causes of death, and pulmonary complications are frequent causes of peri-operative morbidity and mortality in thoracic and in non-thoracic surgery. Pre-operative risk assessment is important to prevent perioperative complications. It is the aim of this chapter to review recent reports on perioperative pulmonary risk factors and to discuss controversial aspects. Patients at risk in non-thoracic surgery are best identified by a detailed history, careful clinical examination and overall co-morbidity scoring systems. Pulmonary function tests, however, do not predict peri-operative complications and therefore should not be used alone to decide on the patient's operability. Also, conventional, so-called prohibitive lung function parameters should no longer be used to deny a potentially curative resection of lung tissue. Alternatively, more significant parameters need to be identified. Because evidence-based data are not available, an interdisciplinary approach to specific problems of severely compromised or co-morbid patients is mandatory.

A 12-lead electrocardiogram (ECG) allows the recognition of cardiac diseases that may have evolved without causing subjective disturbances. ST changes, bundle branch blocks or left ventricular hypertrophy as well as arrhythmias or premature ectopies are the most important findings. In younger patients the detection of a pre-excitation syndrome (especially Wolff-Parkinson-White) is essential, as it does require special therapeutic management. At our pre-operative clinic a resting ECG is part of the screening programme. The data of 18 939 patients were evaluated over a 3 year period, divided into two categories, with (category I) or without (category II) previous cardiac disturbances in their history. In comparison the resting ECGs of 10 523 healthy firemen (category III) were evaluated. The percentage of pathological ECG findings in the patients scheduled for noncardiac surgery was high. Depending on the decade of their life, 9.5–45.2% of subjects in category I (without any previous cardiac disturbances) and 13.2–80.2% in category II had a pathological ECG. In contrast, only 1.6–4.2% of subjects in category III had pathological ECG findings. The statement that the percentage of relevant pathological findings is increasing with age can be emphasized although a threshold cannot actually be defined: there is no difference in the incidence of changes in the age groups from 40 to 60 years. On the other hand, surgical patients without any cardiac history showed an incidence of pathological findings of 7.6%. The ECG is an inexpensive, easy-to-perform non-invasive procedure. In combination with an exact physical examination and a careful judgement of the impact of the findings on anaesthesia it allows a reliable pre-operative evaluation.

Most high-risk patients scheduled for surgery benefit from treatment designed to improve both their symptoms and their life expectancy. Cardiovascular treatments interfere with regulatory mechanisms of blood pressure and regional circulations, or they affect the cardiac electrophysiology and contractility. This explains why most peri-operative circulatory abnormalities are not due to the effect of anaesthetic agents on the circulation but to the interactions between cardiovascular and anaesthetic agents, both of which alter the functioning of several physiological systems. On the other hand, when given perioperatively, some treatments are effective in blunting the circulatory response to surgical stimulation and post-operative stress. In this chapter we describe the interactions between treatments chronically taken by high-risk patients and anaesthesia. This subject makes one look at-physiology and pharmacology and allows a better understanding of the compensatory mechanisms activated in response to the stress of surgery and anaesthesia.

Glucuronidation is a major biotransformation reaction for xenobiotics, including the intravenous anaesthetic propofol and several analgesics. The UDP glucuronosyltransferases (UGTs) catalyse this reaction which requires UDP glucuronic acid (UDPGA) as its group-donating co-substrate. Each substrate is converted by one or several of the UGT enzyme forms. Therefore, competition for glucuronidation may occur for drugs; as yet there is little evidence that this plays an important role in the clinical situation. Volatile anaesthetics such as diethyl ether, halothane or the fluranes decrease the hepatic UDPGA concentration in animal experiments. Subsequently, glucuronidation of xenobiotics (and endobiotics such as bilirubin) may be decreased. Whether this plays a role in the patient is as yet unclear because data are lacking. In propofol elimination in man glucuronidation plays a dominant role: most of the dose is excreted in urine as propofol glucuronidation plays a dominant role: most of the dose is excreted in urine as propofol glucuronide or as a glucuronide of a secondary propofol metabolite. As yet no clear clinical interactions of propofol with other drug substrates for glucuronidation have been observed. Biological variation in glucuronidation due to, for instance, liver disease, drug interaction or genetic polymorphism in humans is reviewed.

Interactions between intravenous anaesthetic agents can be either pharmacokinetic or pharmacodynamic. The clinical significance of a pharmacokinetic drug-drug interaction will depend on the magnitude of the change in the concentration of the drug at the site of pharmacological action. Intravenous anaesthetic agents can influence the distribution and elimination and/or the effect of other co-administered intravenous anaesthetic agents. Because of the larger pharmacodynamic variability (300–400%) compared to the pharmacokinetic variability (60–80%), pharmacodynamic interactions are more important clinically than pharmacokinetic interactions. Many pharmacodynamic interactions involving intravenous anaesthetics are synergistic, and this allows lower doses or concentrations to be used to achieve adequate depth of anaesthesia, with a corresponding reduction in the incidence of side-effects.

The cytochrome P450 enzyme system is involved in the metabolism of many drugs used in anaesthesia, including benzodiazepines, opioids and most volatile anaesthetic agents. Most intravenous anaesthetic drugs are metabolized by the specific isoform, CYP3A, while the volatile agents are metabolized by CYP2E1. Many substances are inducers or inhibitors of cytochrome P450, including several commonly used drugs, and these may interact with anaesthetic drugs, giving rise to unpredictable pharmacokinetic and pharmacodynamic changes. Enzyme inhibition will result in reduced drug metabolism, with higher than expected blood concentrations and thus greater and more prolonged clinical effects. These can manifest as prolonged awakening times, and particularly with the opioids, prolonged and potentially life-threatening respiratory depression. In contrast, enzyme induction will result in lower than expected plasma concentrations and a reduction in pharmacological effect. This could increase the risk of intra-operative awareness and diminished analgesia after surgery. This article reviews the current knowledge with respect to drug interactions involving the cytochrome P450 enzyme system and drugs used in anaesthesia.

Drug combinations are of increasing importance in modern medicine, and particularly in anaesthesia where drugs are given acutely and usually intravenously. Anaesthesia involves the co-administration of several drugs, with a variety of pharmacological effects and different modes of action. When drugs are given in combination there is the possibility that they may interact to either enhance or antagonize each other's effects. It is important, therefore, that the nature of potential drug interactions be properly analysed and quantified. The analysis of drug interactions has a long history, and many different approaches have been tried. One of the most commonly used methods is isobolographic analysis, and the closely related technique of fractional analysis. Other methods that have been used to study interactions related to anaesthesia are those based on logistic regression and parallel line assays. The advantages and disadvantages of these methods are discussed.