Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

BACKGROUND: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level. METHODS: We studied 187 patients aged over 60 years undergoing major non-cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre-operatively and at 1 day, 7 days and 3 months post-operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre-operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96. RESULTS: After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre-operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post-operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week. CONCLUSION: The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.

Odour identification as a marker for postoperative cognitive dysfunction: a pilot study.

The onset of postoperative cognitive dysfunction is delayed in some elderly surgical patients and the condition may persist. Increasing age is a risk factor for both postoperative cognitive dysfunction and dementia. Major surgery may unmask an underlying dementia; we report findings of a pilot study designed to inform this hypothesis. Impaired odour identification ability is a characteristic of the preclinical phase of some neuro-degenerative diseases. This pilot study was designed to establish whether odour identification deficit is a marker for postoperative cognitive dysfunction, particularly in elderly patients genetically predisposed to develop late-onset Alzheimer's disease. We found no association between odour identification ability and postoperative cognitive dysfunction in 53 patients aged 62-86, undergoing major non-cardiac surgery under general anaesthesia. Our pilot study showed that a high number of patients genetically predisposed to develop Alzheimer's disease is required to test the utility of odour identification as a marker for postoperative cognitive dysfunction.

Cognitive dysfunction after minor surgery in the elderly.

BACKGROUND: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery. METHODS: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis. RESULTS: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04). CONCLUSIONS: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible.

Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. METHODS: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. RESULTS: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)). CONCLUSION: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.

Effects of repeated anaesthesia on central cholinergic function in the rat cerebral cortex.

BACKGROUND AND OBJECTIVE: General anaesthesia may contribute to postoperative cognitive decline in the elderly. The aim was to determine the effects of repeated pentobarbital anaesthesia throughout life on central cholinergic function in the rat. METHODS: Young Lewis rats were randomly allocated to two groups. The anaesthesia group (n = 15) was anaesthetized with pentobarbital 20 mg kg(-1) intraperitoneally at 6, 8.5, 11, 13.5, 16, 18.5, 21 and 23.5 months of age. The control group (n = 12) was treated identically, apart from the anaesthesia. At 26 months of age, the animals were killed and the brain dissected and stored for analysis. Central cholinergic function in the cortex and hippocampus was assessed by measuring [3H]-epibatidine and [125I]alpha-bungarotoxin binding to nicotinic receptors and choline acetyltransferase (ChAT) activity. RESULTS: Tissue from nine rats in the anaesthesia group and eight in the control group was available for analysis. There was a significant reduction in alpha-bungarotoxin binding in the anaesthetized compared with the control group in the superior cortex (P < 0.0002) and molecular cortex (P < 0.04). There were no significant differences between the groups for epibatidine binding or ChAT. CONCLUSIONS: Repeated anaesthesia in rat reduces central nicotinic cholinergic binding in the cortex. The findings may have implications for postoperative cognitive function studies.

The assessment of postoperative cognitive function.

Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature.

Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a well-recognised complication of cardiac surgery, but evidence of POCD after general surgery has been lacking. We recently showed that POCD was present in 9.9% of elderly patients 3 months after major non-cardiac surgery. The aim of the present study was to investigate whether POCD persists for 1-2 years after operation. METHODS: A total of 336 elderly patients (median age 69 years, range 60-86) was studied after major surgery under general anesthesia. Psychometric testing was performed before surgery and at a median of 7, 98 and 532 days postoperatively using a neuropsychological test battery with 7 subtests. A control group of 47 non-hospitalised volunteers of similar age were tested with the test battery at the same intervals. RESULTS: 1-2 years after surgery, 35 out of 336 patients (10.4%, CI: 7.2-13.7%) had cognitive dysfunction. Three patients had POCD at all three postoperative test sessions (0.9%). From our definition of POCD, there is only a 1:64000 likelihood that a single subject would have POCD at all three test points by chance. Logistic regression analysis identified age, early POCD, and infection within the first three postoperative months as significant risk factors for long-term cognitive dysfunction. Five of 47 normal controls fulfilled the criteria for cognitive dysfunction 1-2 years after initial testing (10.6%, CI: 1.8-19.4%), i.e. a similar incidence of age-related cognitive impairment as among patients. CONCLUSION: POCD is a reversible condition in the majority of cases but may persist in approximately 1% of patients.

Obstructive sleep apnoea and upper airway reactivity.

Upper airway reactivity was measured in 13 patients with obstructive sleep apnoea (OSA), using transient reflex laryngeal closure in response to dilute inhaled ammonia vapour. Upper airway reactivity was measured before and after 3 months of treatment with nasal continuous positive airway pressure (CPAP). Upper airway reactivity decreased significantly after treatment with nasal CPAP to values which were similar to those seen in normal subjects. We hypothesise that patients with OSA have increased upper airway reactivity, secondary to inflammation of the epithelial lining of the upper airway following the repeated injury of nocturnal airway obstruction, allowing the facilitated passage of inhaled irritants to the subepithelial receptors. Treatment of OSA with nasal CPAP may reverse these changes, although in the absence of a control group, these findings are provisional.

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

The design of an optical fiber pressure transducer for use in the upper airways.

The development of an optical fiber transducer for use in biomedical applications has been presented. The design was targeted for use in the upper airways of patients with sleep disorders stemming from partial or total occlusion of the airway. The transducer's preliminary specification was suited for that of upper airway manometry: a resolution of 10 Pa over the range +/- 5 kPa, a single transducer being less than 0.94 mm in diameter. Amplitude modulated optical fiber sensors are susceptible to loss due to bending of the fiber core and cladding. The design of the transducer uses a series of three optical fibers, one emitting and two receiving, the combination of the two receiving optical fibers is used to reduce effects of light loss: a bend radius of 50 mm is typical for the insertion into the naso-pharynx. The transducer transduction element is a silicone gel coated with reflective titanium dioxide, the meniscus deforms under pressure and modulates the intensity of light reflected back into the receiving optical fibers. The main disadvantage of optical fiber pressure transducers is their susceptibility to temperature drift. Temperature in the airway rarely changes more than 17 degrees C. The frequency of breathing and the high thermal mass of the catheter means that temperature drift in this application is not significant, and will cause an insignificant error of 12 Pa. The transducer is inexpensive to produce, and may be deemed disposable: approximately $20 in material costs (using current manufacturing techniques this can be halved). The system has the added advantage of being electrically, magnetically, and chemically passive. The potential for miniaturization is limited only by the mechanical strength of the optical fibers as mechanical problems associated with fragile elastic membranes do not apply.

Sleepiness, snoring and driving habits.

A self-report postal questionnaire was sent to 5000 (3612 male) drivers randomly selected from the policy holders of an insurance company which insures only motorists who have achieved a maximum 'no-claims bonus'. The questionnaire sought demographic and physical details (sex, age, height, weight and collar size), driving history (number of years, average mileage), accident history (number, number of 'near misses'), frequency of events due to sleepiness (accidents, pulling off the road, falling asleep at the wheel), frequency and severity of snoring and sleep pattern and severity of EDS. Of the 2247 (44.9%) responses received, 1609 (44.5%) were male and 638 (46%) female. Snorers were more likely to report daytime sleepiness than non-snorers and were more likely to have had to pull off the road due to sleepiness. Despite this increased sleepiness there were no significant differences in overall accident rate. These results were obtained from a population with a maximum 'no-claims bonus' which would have excluded any subjects who had already had a recent accident due to sleepiness. Thus the results probably underestimate the problem. It is concluded that snorers tend to be sleepier than non-snorers and are more likely to have modified their driving habits as a result. Snoring and daytime sleepiness should be further investigated as contributory factors to road traffic accidents.

Uvulopalatopharyngoplasty: The Leicester experience.

Twenty-nine patients undergoing uvulopalatopharyngoplasty (UPPP) for snoring are presented. Ninety per cent expressed an overall improvement in their symptoms: 21 per cent had complete abolition of snoring. Post-operative complications included nasal regurgitation of food/fluids and hyponasal speech development.