Anaesthetics and Mental State Andrew Moore Severn and David Gwyn Seymour

INTRODUCTION

Modern surgery and anaesthesia have transformed the lives of millions of older people. However, while the great majority of these will emerge without any long-term cognitive sequelae, absolute guarantees cannot be given. Anaesthesia is a complicated process in which many drugs are administered synchronously in combinations that allow for considerable individual preferences. It is not surprising that unravelling the mental state side effects is a complicated task. The task of assessing which drugs may contribute to a specific change in mental state is also complicated by the physiological response to surgery, and the ‘stress’, physical and mental, experienced by an elderly patient undergoing elective or emergency surgery.

It is over 50 years since Bedford¹ wrote about 18 elderly patients who had ‘never been the same’ after surgery and anaesthesia, and concluded that ‘operations on elderly people should be confined to unequivocally necessary cases’. While there have been major advances in our understanding of postoperative cognitive dysfunction and the methodology used to investigate it, many questions remain to be answered. Although new drugs and monitoring techniques have supplanted those used in Bedford’s day, much of the practice and process of modern general anaesthesia would be recognizable to him. Indeed, the birth of modern anaesthesia was heralded by the introduction of curare, a skeletal muscle relaxant, some 13 years before the Bedford paper.

General anaesthesia requires hypnosis and suppression of motor and autonomic reflexes: until 1942 this was achieved by using a single agent, such as diethyl ether, in high concentrations. Modern anaesthesia, by contrast, involves combinations of agents, in smaller doses, and the use of specific agents to suppress reflex activity, so called ‘balanced anaesthesia’. In this way the complications associated with large doses of single agents, such as cardiovascular depression and prolonged coma, are avoided. There has also been a realization of the potential and social acceptability of local anaesthesia. ‘Balanced anaesthesia’ in today’s anaesthetic practice may include a combination of an epidural infusion of local anaesthetic with opioids to provide segmental reflex suppression and a ‘light’ general anaesthetic to provide a suitably controlled environment for the theatre team and patient.

Local anaesthesia without the concurrent use of general anaesthesia, whether by peripheral nerve block, or by a more substantial spinal or epidural block (collectively referred to as ‘regional anaesthesia’) is not the panacea for prevention of mental state changes that some might suppose. While it is true that the great ‘unknown’ – the reversible coma – of general anaesthesia is avoided, the metabolic consequences of all but the simplest of operations outlast the duration of the block and exert a humoral effect on the brain. Furthermore, an operation performed under regional anaesthetic may be conducted under sedation, which in itself may have consequences for postoperative mental state changes.

Admission to hospital for major surgery can be considered a ‘major life event’, accompanied as such events are by anxiety and other changes in mental health status. The factors that contribute to delirium in older patients in hospital are well known² but acute surgical wards rarely provide the environment in which these factors can be managed. For example, devices such as urinary catheters and bed restraints, known to be factors that exacerbate delirium, are used as part of routine surgical practice on many wards, arguably as much for the convenience of hospital staff as for the individual benefit to patients.

In an attempt to bring some structure to the complexity of the subject, it will be considered under the following headings:

The state of current knowledge of the clinical syndromes of delirium and postoperative cognitive dysfunction
Mechanisms of anaesthesia and possible interactions with neural pathways involved in higher cortical functions.

In regard to the second heading, mention will also be made of the hypothesis that, in conditions of limited ‘cerebral reserve’, anaesthetic agents might act on the fragile brains of older patients to accelerate or unmask latent changes of dementia.

DELIRIUM

Classic descriptions of the mental changes that can follow general anaesthesia describe ‘emergence delirium’ (on immediate awakening from anaesthesia) and ‘interval delirium’ (occurring in the first few postoperative days). Modern anaesthesia, with its attention to matters such as intensive supervision and pain control by specialist staff in the immediate postoperative period, has almost entirely consigned emergence delirium to history in the case of adults, although publications continue to appear in the field of paediatric anaesthesia. It

Table 131.1 Risk factors for delirium in a group of patients aged 50 and over undergoing non-cardiac surgery

Source: Marcantonio et al.⁵

Age over 70
Alcohol abusePoor cognitive status
Poor functional status
Serum electrolyte/glucose disturbances	Thoracic surgery
Aneurysm surgery

is of note that sub-anaesthetic doses of barbiturates have historically had a role in the psychotherapeutic modality known as abreaction.

Emergence delirium aside, postoperative delirium remains a problem. The causes of postoperative delirium, as in delirium in other settings, include acute illness, drugs and drug withdrawal^2–5. Estimates of the incidence of postoperative delirium in the over-65s range between 7% and 50%, depending on the definitions used and the clinical circumstances^2–5. The incidence tends to rise with age, the urgency of surgery, the use of sedative and anticholinergic drugs and the degree of preoperative cognitive impairment. Factors (such as sepsis) that favour the development of delirium in a non-surgical situation may also be of relevance postoperatively. Inouye and co-workers have made a major contribution to our understanding of delirium in both medical and surgical situations, by introducing the concept of an interplay between one or more predisposing factors (such as age, dementia, co-morbidity and multisensory impairment) and one or more precipitating factors (such as acute sepsis, hypoxia, metabolic derangement, or sedating or anticholinergic drugs)⁶. Thus patients who are highly vulnerable because of significant predisposing factors such as dementia or physical frailty might need only a minor precipitating factor to develop delirium, whereas a more robust patient with few or no predisposing factors would require a more major precipitant. O’Keeffe and Chonchubhair⁴ concluded that, in at least 90% of cases of delirium following general surgery, it is postoperative medical or surgical complications that are to blame, which implies that the appearance of delirium should lead to a diligent search for underlying physical medical problems. The increased incidence of postoperative delirium with age is likely to be due to age-associated predisposing and precipitating factors rather than direct pharmacological effects arising from age-related differences in the actions of anaesthetic agents⁷.

Recent advances in the study of postoperative delirium have included attempts to standardize definitions⁴ and a large study in the USA by Marcantonio et al.⁵, which aimed to develop a clinical prediction rule based on the outcome of 1 341 patients aged 50 and over having major non-cardiac surgery. The latter authors found seven preoperative factors (see Table 131.1) that had an independent relationship with postoperative delirium. When the anaesthetic records of patients who had become delirious were compared with those of patients who had not, certain drugs, notably pethidine and long-acting benzodiazepines, appeared to confer an increased risk of delirium⁷.

POSTOPERATIVE COGNITIVE DYSFUNCTION

The widest interpretation of a ‘changed mental state’ following surgery and/or anaesthesia could embrace many conditions, ranging

Table 131.2 The European Test Battery used in the ISPOCDstudies (see text and Table 131.3 for details)

Verbal learning test

Concept shifting test

Stroop colour word interference test

Letter boxes test

Broadbent Cognitive Failure Questionnaire

Zung Depression Score Questionnaire

(The Geriatric Depression Scale is used in ISPOCD2studies)

from mild subjective alterations in concentration or mood at one extreme to major psychosis or coma at the other. For purposes of detailed study, it is helpful to consider a much narrower definition of postoperative cognitive dysfunction (POCD). Indeed, such has been the influence of the work of Moller, Cluitmans, Rasmussen and other colleagues in the International Study of Postoperative Cognitive Dysfunction (ISPOCD) Group⁸ that their definition has monopolized the use of the term POCD. A key feature of ISPOCD studies has been the use of the European psychometric test battery (EUPT battery; see Table 131.2), which has been designed as a sensitive and standardized research tool for the detection of postoperative neuropsychological deficits and which can be administered over a 45-minute period. The definition of POCD has been reached by comparing changes in the normalized (Z) scores of individual patients with age-matched controls who were not undergoing surgery, who were studied at the same time intervals^8,9. Such an approach has allowed sound epidemiological evidence to be gathered and hypothetical risk factors to be investigated and it has also given us useful information about the time course of mental state changes. However, studies to date have told us little about the precise mechanisms of cognitive decline or the determinants of severity in individual cases, and have largely been confined to those with normal cognitive function prior to surgery.

The first ISPOCD study (ISCPOD1) collected data between 1994 and 1996 on 1 218 patients aged 60+ who were undergoing major non-cardiac surgery in 13 hospitals in 8 European countries and the USA⁸. This was a major undertaking, which was intended to answer many of the questions about early and late postoperative cognitive dysfunction in older people that had been raised in the literature over the previous 30 years. As summarized in Table 131.3 and described below, this landmark study has spawned a series of important follow-up studies using the same methodology.

ISPOCD1⁸ was particularly concerned to test the hypothesis that hypoxaemia and/or hypotension were causative factors in POCD. Accordingly, oxygen saturation was measured by continuous pulse oximetry before surgery, throughout the day of surgery, and for the next three nights. Similarly, blood pressure was recorded by oscillometry during the operation and every 30 min for the rest of the operative day and night. Patients received general anaesthesia but no restriction was placed on the type of anaesthetic or surgical technique, which conformed to local practice in the study centres. In order to avoid the cerebral vasoconstrictor effects of hypocapnia, normocapnia (as assessed by extrapolation from analysis of the end-tidal CO2 concentration of the exhaled gas mixture) was a requirement.

Analysis of the data from ISPOCD1 showed that 25.8% of patients had POCD seven days after surgery and that 9.9% of all patients still had evidence of POCD on the repeat neuropsychological tests carried

out at three months (corresponding values for controls were 3.4% and

Table 131.3

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