Cognitive dysfunction after anaesthesia

Current Anaesthesia and Critical Care (1998)9, 307-311

© 1998HarcourtBrace & Co. Ltd

Medicine

Cognitive dysfunction after anaesthesia

L. S. Rasmussen and J. T. Moller

During immediate recovery after general anaesthesia, m e m o r y and other higher brain functions will be impaired. Thus, a deterioration of higher cerebral functions will be present. This may extend from a few minutes to several hours. If m e m o r y and concentration are impaired beyond the first 24 h after recovery, this will represent a postoperative complication belonging to the group of cognitive disorders.

However, no neuropsychological tests were applied in that study. In the search for useful diagnostic criteria, we found the Diagnostic and Statistic Manual o f Mental Disorders (DSM-1V) very helpful) This publication is published by the American Psychiatric Association and it contains a list of cognitive disorders, such as dementia and delirium with descriptions of diagnostic criteria. In the group of other cognitive disorders one is called mild neuro cognitive disorder. The listed research criteria for this condition are fairly easily applicable in the field of postoperative cognitive dysfunction. One important point is that objective evidence is needed and, therefore, neuropsychological testing will be required and an impairment in several cognitive domains should be detected. To summarize, two cognitive disorders are important after anaesthesia:

Delirium The most well-known postoperative cognitive disorder is probably delirium. This is an acute confusional state that tends to fluctuate during the day. The patient has lost orientation and has impairment of attention and memory. The incidence of delirium is approximately 10% in elderly patients but much higher following cardiac procedures and surgery for hip fractures. ~ Delirium is a threatening condition. The uncooperative patient may get dehydrated, pull out catheters, drains, and tubes. Delirious patients are prone to fall out of bed and fractures or intracranial bleedings may result. In addition, it is very important to be aware of eliciting factors that are correctable, such as electrolyte or fluid deficits and withdrawal symptoms.

Postoperative cognitive dysfunction Subtle deterioration in memory and concentration after discharge from hospital is another condition that may persist for weeks or months after surgery. It resembles dementia but in most cases the deficits are not so severe and, therefore, there are no occupational or social consequences. Accordingly, this mental disorder is easily overlooked and is difficult to evaluate. Already in 1955, Bedford reported that long-term deterioration may occur in elderly patients following surgery and anaesthesia?

1. Delirium, which occurs during the first postoperative days as an acute, fluctuating confused state 2. Postoperative cognitive Dysfunction (POCD), which is a subtle deterioration in cognitive function detected by neuropsychological testing from weeks to months postoperatively.

Postoperative cognitive dysfunction after cardiac surgery The vast majority of studies of postoperative cognitive dysfunction has focused on patients undergoing cardiac surgery. Cerebral complications are much more frequent

Dr Lars S. Rasmussen,Dr Jakob TrierMoiler,Departmentof Anaesthesia4132, Centerof Head & Orthopaedics,Blegdamsvej9, DK-2100, Copenhagen,Denmark. 307

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CURRENT ANAESTHESIA AND CRITICAL CARE

after cardiac surgery than after any other types of surgery, excluding neurosurgery. This was already realized in the 1960s and larger studies using neuropsychological testing were published in the 1980s. The incidence of cognitive deficits was 30-80% after approximately 1 week and still nearly 60% after several months. *-7 The results, however, showed a large variation and in some studies much less frequent cognitive deterioration, or even an improvement, has been found. 8 Different methodology is one very important contributing factor to this complicated pattern. The aetiology behind POCD was thought to be related to the use of cardiopulmonary bypass (CPB) and this was plausible because the duration of CPB was found to be an important risk factor. 9 Altered cerebral perfusion is very likely, but perhaps a more important factor is the occurrence of embolisation of various kinds including air, lipids and particulate matter. Embolisation seems to be a very common phenomenon and several attempts to reduce this have been investigated. Arterial line filtration is an example of a technique that seems to have a beneficial effect but the evidence is scarce, lcq3 Different strategies for management of pH during hypothermic CPB have also been examined and it seems that alpha-stat is associated with less POCD than pH-stat, where carbon dioxide is added in order to keep pH constant. 14 During pH-stat, uncoupling of flow and metabolism and brain hyperperfusion have been documented and this might increase the number of emboli reaching the brain. ~5 Thus, embolisation is probably a contributing factor. Other risk factors for POCD after cardiac surgery have been increasing age and impaired cardiac function preoperatively. 9'16q7

Prevention of cognitive dysfunction after cardiac surgery Several preventative strategies have been examined in order to reduce the occurrence of POCD after cardiac surgery. One such method is reduction of embolisation by arterial line filtration but also avoidance of emboli when establishing CPB. Arteriosclerotic plaques in the aorta are possible sources of emboli, especially at cannulation and should, therefore, probably be identified. 18'19 Hypothermia is another method that seems to be effective, even though it seems that temperatures below 30°C offer no additional benefit compared with moderate hypothermia at 30-35°C. 2° One problem in these studies has been the different methodology used where the so-called normothermic CPB may actually allow brain temperatures above normal. Other factors connected with CPB are pump flow, blood pressure, use of pulsatile versus non-pulsatile flow and types of oxygenators. No differences have been found in the rather small studies yet reported. Blood glucose level has been a matter of concern because it was assumed that high levels were associated with worse cerebral outcome. The evidence supporting any blood glucose management strategy is, however, not convincing.

Other methods for reducing POCD have been the use of neuroprotective agents including nimodipine, barbiturates, and prostacyclin. Of these, only barbiturates have been effective21 and this effect could not be confirmed in a later study of neurologic dysfunction in coronary artery bypass patients, where more recent technology was applied. 22 It is possible that coronary artery bypass in some cases can be performed without CPB. This would eliminate the risk factors associated with CPB, but only in one non-randomized study has a comparison been made, and no difference was found. 23 After cardiac surgery, POCD is common and probably related to CPB. Other factors than this must be important and it would be obvious that some were important also after non-cardiac surgery.

Cognitive dysfunction after non-cardiac surgery First of all, the evaluation of cognitive function after non-cardiac surgery has been used as an end-point in studies comparing surgical and anaesthetic regimens. The interesting fact is, however, that most studies of POCD have not been able to detect the phenomenon beyond the first postoperative week. The clinical importance of cognitive deficits in the first postoperative days is not very great and would not dictate preventive strategies. Most of these studies have been assessing the possible difference between regional and general anaesthesia for procedures such as hip or knee arthroplasty, urological or gynaecological procedures, or cataract. 24-27 We would expect a difference in the incidence of postoperative cognitive dysfunction if anaesthetic agents used for general anaesthesia were important in the causation of the deficits. In surgical procedures where both regional or general anaesthesia is possible, a comparison can be made. Williams-Russo, as an example, found no difference although a long-term deterioration of cognitive function after knee replacement was found in 5% of cases) ~ One methodological problem is the lack of a control group who did not undergo surgery. This is really a crucial point and a weakness in most studies within this area. With a control group it is possible to compensate for the practice effect and estimate the variation related to the specific neuropsychological tests.

The ISPOCD study The International Study of Post Operative Cognitive Dysfunction (ISPOCDI) study was the first study that included a correction for the practice effect and considered the normal variation in neurospsychological test results. 29 The ISPOCD1 study included 1218 elderly patients who underwent major non-cardiac surgery with general anaesthesia. The primary hypothesis was that POCD could be detected as long as 3 months after noncardiac surgery. Since arterial hypotension or hypoxaemia were suspected as causative factors, extensive monitoring was performed during surgery and on the first postoperative night using oscillometric blood pres-

COGNITIVE DYSFUNCTION AFTER ANAESTHESIA

ably, the most correct control group would consist of comparable unoperated patients staying in hospital for approximately the same time. Unfortunately, nowadays it will be extremely difficult to identify a sufficient number of patients fulfilling these requirements, especially if a follow-up examination should be done after several months. Did the monitoring and subsequent analysis allow us to reject cerebral hypoxia as an important risk factor? Arterial hypoxaernia and hypotension are global but indirect measures of oxygen delivery. Cerebral blood flow and oxygenation were not measured. Finally, did the cognitive deficits represent a permanent deterioration in brain function? Future studies will hopefully elucidate this important question.

sure monitoring and continuous pulse oximetry. In addition, pulse oximetry data were collected on the second and third postoperative night. The primary hypothesis was clearly confirmed by finding an incidence of POCD of 25.8% after 1 week and 9.9% after 3 months. This was significantly higher than in a control group of 176 healthy volunteers in whom the diagnostic criteria were fulfilled in only 3.4% and 2.8% respectively. Age was found to be an important risk factor, the incidence of POCD after 3 months was 7% in those aged 60--69 and 14% in those above 69 years. Risk factors other than age, after 1 week, included duration of anaesthesia, respiratory complications, infectious complications and new operation. Level of education was also important. Well-educated patients experienced less POCD after 1 week. Surprisingly, no significant correlation was found with hypoxaemia nor hypotensive episodes. The most important results from the risk factor analyses are shown in Table 1. The ISPOCD study confirmed that POCD existed after non-cardiac surgery with general anaesthesia and also that age was a significant risk factor. A disappointing fact was that the risk factor analysis gave no opportunity to propose any preventive strategies, In addition, numerous limitations must be considered.

Consequences of postoperative cognitive dysfunction Generally, the consequences of POCD are not yet well described. Many clinicians have heard anecdotal reports of premature retirement or profound changes in quality of life for an elderly patient owing to deterioration in cognitive function. However, no studies have presented clear evidence how frequently such serious events are associated with POCD, which in most cases is quite subtle. The changes in activities of daily living (ADL) is one way to assess functional status but that is a very crude measure depending very much upon physical ability.

• Were the detected cognitive deficits really clinically important? We do not really know, but no correlation was found between the test results and the patient's self-assessment of cognitive function, Generally, however, classical questionnaires have not been designed for surgical patients and may not be very useful because they do not reflect relevant areas. • Was the control group appropriate, consisting of healthy volunteers who were not hopitalized? Prob-

Methodological problems in the detection of cognitive dysfunction Why has no difference been detected in the incidence of POCD after general versus regional anaesthesia? Perhaps

Table 1 Proportion of patients with postoperative cognitive dysfunction (POCD) at 1 week and 3 months by risk factor. Data from the ISPOCD1 study. 29

Risk factor

1 week Number of Patients patients with POCD (%)

3 months Number of Patients patients with POCD (%)

Age (years) 60-69 >_70

586 425

532 378

39 (7) 52 (14)

Complication hypoxaernia* hypotension+ respiratory complication infectious complication

115 229 99 91

(26) (26) (40) (33)

98 214 88 138

11 (11) 20 (9) 12 (14) 13 (9)

Second operation

309

135 (23) 125 (29) 30 59 40 30

24

13 (54)

50

7 (14)

Duration of anaesthesia (min) <120 121-240 >241

196 503 312

37 (19) 121 (24) 102 (33)

179 448 283

20 (11) 40 (9) 31 (11)

Education less than high school high school more than high school

576 290 145

153 (27) 76 (26) 31 (21)

518 260 132

49 (9) 26 (10) 16 (12)

Benzodiazepines before surgery

116

32 (28)

105

5 (5)

*one or more episodes of oxygen saturation < 80% for > 2 rain +one or more episodes of mean arterial pressure _<60% for >30 min

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CURRENT ANAESTHESIA AND CRITICAL CARE

no such difference exists. Another possibility is that the methodology has been inappropriate_ If neuropsychological tests with low sensitivity are used, it will be impossible to detect any difference. This would also be one factor explaining the inability to detect any long-term deterioration. Another factor is the well-pronounced practice effects associated with neuropsychological tests. All subjects tend to improve their performance after repeated testing. So if a patient obtains exactly the same test result before and after surgery a deterioration in cognitive function has occurred. In fact, the practice effect has been ignored in most studies. This would explain why no long-term effect of anaesthesia and surgery has been found if this is a subtle deterioration not as evident as after cardiac surgery. Accordingly, all studies using neuropsychological testing should include a properly matched control group, to allow for consideration of the practice effect.

Etiological considerations Several etiologic mechanisms behind POCD have been proposed. One possibility is brain hypoxia caused by arterial h y p o x a e m i a or insufficient flow. A t present, detection o f brain o x y g e n a t i o n is b e c o m i n g a possibility by m e a n s of near-infrared spectroscopy ( N I R S ) but the reliability of this n o n - i n v a s i v e m e t h o d has b e e n questioned. O n e plausible cause for P O C D c o u l d be the presence o f slowly m e t a b o l i z e d general anaesthetics such as benzodiazepines. D i a z e p a m has a l o n g terminal half-live and active metabolites that m a y be detected e v e n a w e e k after surgery. H o w e v e r , no correlation b e t w e e n b l o o d levels o f b e n z o d i a z e p i n e s and P O C D c o u l d be detected in one study specifically addressing this h y p o t h e s i s ) ° A n o t h e r explanation could be a toxic effect of general anaesthetics through a l o n g - t e r m effect on cholinergic or other receptors in central neurotransmisson. Finally, p s y c h o l o g i c a l factors c o n n e c t e d with sickness and envir o n m e n t a l factors during hospitalization m a y be important, especially in elderly patients, as causative factors for c o g n i t i v e disorders. Additionally, the p r e v i o u s l y described so-called p o s t o p e r a t i v e fatigue could be either the c o n s e q u e n c e o f or an explanation for p o s t o p e r a t i v e c o g n i t i v e dysfunction.

Conclusion In conclusion, c o g n i t i v e disorders are important cerebral complications. D e l i r i u m is an acute disturbance in brain f u n c t i o n presenting with loss of orientation and shortt e r m c o g n i t i v e deficits. A deterioration in c o g n i t i v e function lasting for from w e e k s to months f o l l o w i n g surgery is called p o s t o p e r a t i v e c o g n i t i v e dysfunction and this c o n d i t i o n can only be detected with the use of n e u r o p s y c h o l o g i c a l testing. It has b e e n w e l l - k n o w n after cardiac surgery w h e r e age and the duration o f cardiop u l m o n a r y bypass are a c k n o w l e d g e d risk factors. M o r e recently, p o s t o p e r a t i v e c o g n i t i v e dysfunction has b e e n

detected by objective methods after non-cardiac surgery in elderly patients. This has confirmed previous reports of long-lasting cognitive deterioration in elderly patients and cognitive dysfunction seems to be the most common cerebral complication after general anaesthesia.

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