Cognitive dysfunction in the postoperative patient.
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The insertion of implantable cardioverter/defibrillators (ICD) requires induction of repeated episodes of ventricular fibrillation (VF). The neuropsychological repercussions associated with repeated inducement of hypotension and cerebral ischemia are unknown. In this prospective clinical trial, 1 day prior to ICD assessment/implantation and 5 days postprocedure, 14 patients underwent neurological and cognitive screening. Cognitive dysfunction was defined as impaired performance in one of four cognitive domains. Neurological impairment was defined as a decrement of 2 or more points from baseline of a total possible score of 45 points. Intraoperative hemodynamics, including the reperfusion interval (RI; end of preceding fibrillation to beginning of the next), were recorded. Patients underwent an average of 12 +/- 6 episodes of VF with average duration of mean arterial pressure (MAP) <50 mm Hg for 17 +/- 9 s (range 6-39 s) and of MAP <30 mm Hg for 11 +/- 5 s (range 2-22 s). Nine patients, in none of whom the predetermined criteria for neurologic impairment was met, demonstrated a new subtle neurologic finding postoperatively. Ten of 14 patients met the criterion for cognitive dysfunction 5 days postoperatively. The mean RI between episodes of VF was significantly different between those patients demonstrating cognitive dysfunction and the unimpaired patients (3.1 +/- 0.5 min in the group with cognitive dysfunction vs 3.9 +/- 0.8 min in the unimpaired group, P = 0.027). Five patients without cognitive impairment had longer RI between episodes of circulatory arrest than those showing impaired cognition. We conclude that cognitive dysfunction can occur after insertion of ICD and is related to the duration of RI.
Cerebral emboli identified as high-intensity transient signals (HITS) occur during total knee arthroplasty (TKA). Their effects on cognitive outcome remain speculative. Intraoperative HITS and postoperative complications were correlated with the cognitive function of TKA patients. Cognitive function was assessed both before and after surgery (1 week and 3 months). High-intensity transient signals occurred in 22 of 37 patients. Counts of HITSs were higher in patients with sonographically detected intracardiac shunts. Cognitive dysfunction was found in 41% of patients at 1 week, but in only 18% at 3 months. High-intensity transient signal counts were not associated with the prevalence of cognitive deficits. At 1 week, 58% of patients with cognitive deficits had at least 1 postoperative complication (6% in nondeficit patients). All cognitively impaired patients at 3 months had complications (17% in the nondeficit group). This raises the possibility that postoperative complications might be associated with cognitive dysfunction in TKA patients.
BACKGROUND: Women are at higher risk than men for stroke after cardiac operation. The purpose of this study was to evaluate for gender influences on the more common postoperative neurologic complication, cognitive dysfunction. METHODS: A standard battery of neuropsychological tests was administered to 117 patients (79 men and 38 women) the day before and again 4 to 6 weeks after cardiac operation. The battery assessed a broad array of cognitive domains, including attention, memory, executive function, and psychomotor processing speed. Analysis was performed only on patients with data from both testing sessions. Data were analyzed to assess for a dichotomous definition of postoperative cognitive impairment and to evaluate for factors influencing test results for specific cognitive domains. RESULTS: The frequency of one standard deviation decline on two or more cognitive tests compared with preoperative results (women, 10.7 % versus men, 9.9 %; p = 0.527), no decline, or one standard deviation improvement on each test postoperatively was no different between genders. After adjusting for age, gender, preexisting medical conditions, level of attained education, preoperative cognitive tests results, type of operation, and duration of cardiopulmonary bypass, female gender was independently associated with poorer performance postoperatively on visuospatial tasks. Other variables significantly related to postoperative cognitive function varied among the specific cognitive domains. CONCLUSIONS: These data suggest that, although the frequency of cognitive dysfunction after cardiac operation is similar for women and men, women appear more likely to suffer injury to brain areas subserving visuospatial processing. Risk factors for postoperative cognitive impairment vary depending on cognitive domain, suggesting multiple etiologies for this form of perioperative neurologic injury.
OBJECTIVE: Neurocognitive dysfunction still remains a frequent problem after heart surgery, complicating early recovery and strongly affecting postoperative quality of life. The aim of our study was to determine incidence of cognitive dysfunction after coronary artery bypass grafting for patients of low risk group and to find operative and postoperative factors associated with early cognitive impairment. MATERIAL AND METHODS: Using exclusion criteria, which are known as risk factors for postoperative neurological complications we selected a group of 30 coronary artery bypass grafting patients. The day before surgery and 7 to 8 days after operation we evaluated cognitive function of each patient using MMSE and standardized test battery of five neuropsychological tests. The incidence of cognitive decline was evaluated using composite z scores and 1 SD criteria. Preoperative ultrasound screening of asymptomatic carotid artery was performed for each patient. RESULTS: Early postoperative cognitive dysfunction was present in 13 (46.3%) of patients. Patients with cognitive decline more often had asymptomic, hemodynamicly significant carotid artery stenosis. Duration of operation and coronary artery bypass time was longer in cognitive dysfunction group. As well there were more grafts performed to this group of patients. We noticed a relationship between lower temperature during coronary artery bypass and cognitive impairment. CONCLUSIONS: Incidence of cognitive dysfunction for patients of low risk group was 46.3%. Cognitive decline was associated with prolonged coronary artery bypass, operation time and number of grafts.
BACKGROUND: Small cerebral infarctions are common in elderly patients, but the association between the magnetic resonance imaging finding and neurologic dysfunction after coronary artery bypass grafting has not been evaluated. METHODS: We determined, prospectively, whether varying degrees of abnormal findings on magnetic resonance images of the brain increased the incidence of preoperative cognitive decline, postoperative neuropsychological dysfunction, and stroke in 421 elderly patients (> or = 60 years) undergoing coronary artery bypass grafting. RESULTS: Control patients (almost normal or leukoaraiosis, n = 212) had rates of postoperative neuropsychological dysfunction (7%) and stroke (1.4%); the small infarctions group (some small infarctions, n = 126) had rates of 13% and 5.6%, respectively; whereas patients with multiple infarctions (multiple small infarctions or broad infarctions, n = 83) had rates of 20% and 8.4%, respectively (p = 0.004, p = 0.013). In the group with multiple infarctions, 49 patients (59%) were asymptomatic and 21 patients (25%) had cognitive decline. Stepwise logistic regression analysis demonstrated that the significant predictors of multiple small infarctions or large infarctions were history of cerebrovascular disease, renal insufficiency, cognitive decline, and cerebral arteriosclerosis. CONCLUSIONS: Multiple infarctions significantly increase the risk of neurologic dysfunction after coronary artery bypass grafting. Routine screening for preoperative cognitive decline should be performed to detect underlying ischemic cerebral disease in elderly patients.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
PURPOSE OF REVIEW: This review is a survey of the recent literature investigating the etiology and the relative incidence of postoperative neurological and cognitive dysfunction after cardiac surgery. RECENT FINDINGS: Several studies reviewed here have employed transcranial Doppler for detection of cerebral emboli and compared results between patients undergoing beating-heart versus conventional cardiopulmonary bypass. A transcranial Doppler device ostensibly discriminating between particulate and gaseous emboli has additionally been employed, yet despite a consistently lower incidence of cerebral emboli associated with avoidance of cardiopulmonary bypass, several groups have reported similar incidences of cognitive dysfunction across these procedures, suggesting other, potentially more important, factors. Two recent studies have focused on the hazards associated with perioperative anemia in both infants and older patients, and which can result in developmental delay or profound changes in cerebral blood flow. A further study has identified an adverse interaction with postoperative hypoxia. The use of intraortic filtration for capture and removal of particulate macroemboli has been associated with a reduction in the incidence of clinically apparent central-nervous-system injury and should be further investigated. Several other studies identify pre-existing levels of central-nervous-system impairment prior to surgery, underscoring the confounding issues introduced by the failure to include a non-surgical comparator group. SUMMARY: While further evidence of cerebral embolization continues to accrue, several studies suggest that other factors may be of equal or greater importance in cognitive dysfunction. Further investigations into the role of perioperative anemia, co-incident hypoxemia and other aspects of perioperative care, e.g. hyperglycemia and postoperative hyperthermia, are warranted.
OBJECTIVE: Repeated induction of ventricular fibrillation with ensuing alterations in electroencephalogram and jugular venous oxygen saturation is common practice during insertion of transvenous implantable cardioverters/defibrillators. We investigated whether these functional changes are also associated with cerebral injury. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: We studied 45 patients undergoing implantable cardioverter/defibrillator insertion. Eleven patients with cardiac pacemaker implantation, which was performed in the same manner yet without the necessity to induce ventricular fibrillation, served as controls. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase and S100 were determined before, immediately postoperatively, and 2 hrs postoperatively. In a randomly composed subgroup, neuron-specific enolase was also determined 6 and 24 hrs after surgery. Implantable cardioverter/defibrillator patients only showed an increase of both markers postoperatively. Median neuron-specific enolase values climbed from a preoperative 9.9 to 12.3 and 14.4 microg/L at 2 and 24 hrs after surgery, respectively. This increase was associated with the number of shocks and the cumulative time in circulatory arrest. The highest median S100 level (0.075 microg/L) was reached 2 hrs after the procedure. Neuron-specific enolase and S100 were extremely elevated (13.7 and 0.970 microg/L, respectively) in one patient after an extended episode of ventricular fibrillation. Plasma hemoglobin levels were in the normal range in implantable cardioverter/defibrillator patients throughout the observation period. CONCLUSIONS: Apparently, even brief successive periods of global cerebral ischemia cause neuronal damage without obvious severe neurologic deficits. However, they may be related to subtle postoperative neurologic or cognitive dysfunctions that a number of implantable cardioverter/defibrillator patients exhibit after implantation.
OBJECTIVE: The best surgical approach for concomitant carotid artery and cardiac disease remains controversial. Many studies proved the safety and efficiency of simultaneous surgery. We aimed to demonstrate the same benefits for patients > or = 70 years. METHODS: We retrospectively evaluated 205 patients simultaneously operated upon between 1988 and 1998. Group A comprised patients < 70 years (n = 110), group B > or = 70 years, (n = 95). Risk factors, neurologic and cardiac history, angiographic findings, operative data, morbidity and mortality (30-day-postoperatively) were analysed. The mean age was 62 years in group A and 75 years in group B. All patients with symptomatic carotid artery disease, stenosis > 70% or ulcerative carotid disease had simultaneous surgery. Always, the carotid artery was addressed first. RESULTS: Patients in group B had a higher prevalence of peripheral vascular disease (P = 0.0005), renal insufficiency (P = 0.0011) and COPD (P = 0.03). Urgent operation was indicated in 19% of group A patients vs. 37% in group B. In group A 70% were asymptomatic regarding the carotid vs. 48% in group B. Left ventricular dysfunction was present in 45% (group A) and 58% (group B). In the present study 4% in group A and 7% in group B suffered a perioperative myocardial infarction. Pathologic changes of the contralateral carotid were found in 42 vs. 57% (A vs. B). Mortality due to cardiac causes was 1 and 5%, respectively. The combination of persistent neurologic deficit and neurologic death occurred in 3% in group A (n = 3) and 5% in group B (n = 5). Postoperative neuro-cognitive dysfunction was more common in group B (35 vs. 16%; P = 0.01). CONCLUSIONS: The incidence of persistent neurologic deficits and neurologic mortality in patients > or = 70 years is acceptable, and low in patients < 70 years. Preoperative risk factors are increasing with age and are related to the higher mortality in elderly patients. Due to our results we will conclude that the combined approach for carotid stenosis and cardiovascular disease is the method of choice in this high-risk population.
BACKGROUND: Lipid microemboli found in shed blood during cardiac surgery have been shown to block capillaries of the brain postoperatively. In this study, the distribution of lipid microemboli in different regions of the brain and other organs was examined. A novel porcine model using radioactive lipid particles was used. METHODS: Ten animals (2 controls and 8 cases) were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Tissue samples were taken postmortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used as a measure of the uptake of lipid microemboli. RESULTS: High levels of radioactivity were found in kidney and spleen (5 to 10 times higher than in the other organs investigated). In the brain, radioactivity was found in all regions examined. The gray matter of cerebrum showed the highest level of the regions examined. CONCLUSIONS: This study shows that embolization of lipids is not a phenomenon restricted to the brain, but affected all the organs examined. The high levels found in the kidneys, and the relatively high levels in the gray matter of the cerebrum further legitimize the debate on the impact lipid microemboli has on postoperative kidney and cognitive dysfunction.
BACKGROUND: Monitoring with pulse oximetry might improve patient outcome by enabling an early diagnosis and consequently, correction of perioperative events that might cause postoperative complications or even death. Only a few randomised clinical trials of pulse oximetry have been performed during anaesthesia and in the recovery room which describe perioperative hypoxaemic events, postoperative cardiopulmonary complications and cognitive dysfunction. OBJECTIVES: To study the effect of perioperative monitoring with pulse oximetry to clearly identify the adverse outcomes that might be prevented or improved by the use of pulse oximetry. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Library, MEDLINE, EMBASE, and by checking the reference lists of trials and review articles. SELECTION CRITERIA: All controlled trials that randomised patients to either pulse oximetry or no pulse oximetry during the perioperative period, including the operating and recovery room. DATA COLLECTION AND ANALYSIS: We collected data in relation to events detectable by pulse oximetry, any serious complications that occurred during anaesthesia or in the postoperative period, intra- or postoperative mortality, and duration of recovery or intensive care stay. Formal statistical synthesis of individual trials was not performed in view of the variety of outcomes studied. MAIN RESULTS: Searching identified six reports; four studies with data from a total of 21,773 patients were considered eligible for analysis. Only two studies specifically addressed the outcomes in question; both found no effect on the rate of postoperative complications using perioperative pulse oximetry. Two studies used hypoxaemia detectable by pulse oximetry to assess the value of perioperative monitoring, although outcomes were not given. It was found that hypoxaemia was reduced in the pulse oximetry group both in the operating theatre and in the recovery room. During observation in the recovery room, the incidence of hypoxaemia in the pulse oximetry group was 1.5-3 times less. The postoperative cognitive function using the Wechsler memory scale and continuous reaction time was independent of perioperative monitoring with pulse oximetry. The other study showed that postoperative complications occurred in 10% of the patients in the oximetry group and in 9.4% in the control group. The two groups did not differ in cardiovascular, respiratory, neurologic, or infectious complications. The duration of hospital stay was a median of 5 days in both groups, and an equal number of in-hospital deaths was registered in the two groups. REVIEWER'S CONCLUSIONS: The studies confirmed that pulse oximetry can detect hypoxaemia and related events. However, we have found no evidence that pulse oximetry affects the outcome of anaesthesia. The conflicting subjective and objective results of the studies, despite an intense, methodical collection of data from a relatively large population, indicates that the value of perioperative monitoring with pulse oximetry is questionable in relation to improved reliable outcomes, effectiveness and efficiency.
OBJECTIVE: To determine the incidence of cerebral dysfunction in cardiac surgical patients exposed to heparin-bonded cardiopulmonary bypass (HB-CPB) versus nonheparin-bonded cardiopulmonary bypass (NH-CPB) circuits through neuropsychometric testing and to correlate these findings with markers of the systemic inflammatory response to CPB. DESIGN: Prospective, randomized, blinded clinical trial. SETTING: University hospital. PARTICIPANTS: Sixty-one patients undergoing elective cardiac surgery. INTERVENTIONS: A cohort of 61 patients scheduled for elective coronary artery bypass graft surgery were prospectively randomized to receive either HB-CPB or NH-CPB circuits during surgery. Patients were evaluated for cerebral injury using a battery of neuropsychometric tests at the following 3 time points: (1) before surgery as a baseline examination, (2) postoperative day 5, and (3) postoperative week 6. Blood samples were drawn to measure inflammatory markers at the following time points: (1) preincision, after induction of anesthesia, (2) 15 minutes after onset of CPB, (3) 30 minutes after CPB, (4) 6 hours postoperatively, and (5) 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Neuropsychometric performance was evaluated by group-rate and event-rate analyses. By group-rate analysis, patients undergoing surgery with HB-CPB performed significantly better at 5 days after surgery on 2 neuropsychometric tests (trails A [p < 0.01] and finger tapping with the dominant hand [p < 0.01]) and at 6 weeks after surgery on one neuropsychometric test (trails A [p < 0.01]). By event-rate analysis, at 5 days, patients undergoing surgery with HB-CPB circuits had less cognitive dysfunction (p < 0.05) compared with patients undergoing surgery with NH-CPB circuits. Serum samples were analyzed to evaluate markers of complement activation (C3a), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6), and coagulation (thrombin-antithrombin complex [TAT]) using the quantitative sandwich enzyme immunoassay technique. Although there were no significant differences in cytokine activation in either group, C3a was significantly higher in the NH-CPB group intraoperatively at 1 hour after CPB (p < 0.05), and TAT was higher in the HB-CPB group at 24 hours after surgery (p < 0.05). CONCLUSIONS: Patients undergoing cardiac surgery with CPB have less postoperative cognitive dysfunction during CPB when HB-CPB circuits are employed. Although there was a relationship, this finding did not correlate with decreased complement activation intraoperatively and activation of coagulation postoperatively.
BACKGROUND: Cerebral dysfunction is common after cardiac surgery and may be reflected in increasing blood concentrations of neuron specific enolase (NSE) and S-100 beta protein. The aim of the study was to determine the optimal timing of blood sampling. METHODS: We studied 15 patients undergoing coronary artery bypass grafting. Serum concentrations of NSE and S-100 beta protein were measured before surgery and after 12, 18, 24, 30, and 36 h. Neuropsychological testing was performed before surgery, at discharge from hospital and after 3 months. RESULTS: Serum concentrations of both NSE and S-100 beta protein increased significantly. At the first postoperative test, seven patients had cognitive dysfunction and a significant correlation was found between the composite z-score and the increase in the NSE level after 36 h (R = 0.76, P=0.001). The median increase in NSE after 36 h was 4.1 microg/l in patients having cognitive dysfunction and 0.9 microg/l in the remaining patients (P<0.05). No significant correlation was found between cognitive dysfunction and the increase in S-100 beta protein. After 3 months, no statistically significant correlation was found between either NSE or S-100 beta protein and cognitive dysfunction. CONCLUSION: NSE seems to be a useful blood marker for early cognitive dysfunction after coronary artery bypass grafting, optimal timing of blood sampling being at approximately 36 h postoperatively.
Elderly patients often suffer from postoperative cognitive deficits (POCD) after serious surgical operations. The reasons for this are not well understood. We investigated the influence of the invasiveness of the operation and the duration of the operation as well as the patient's preoperative physical status on measures of cognitive dysfunction. In a prospective study 59 elderly patients (mean age 69.2 years) were subjected to a neuropsychological test battery and a questionnaire following an abdominal surgical operation. The postoperative recovery with a focus on memory function was assessed using the Wechsler Memory Scale (WMS) seven days after the operation. Self-reported cognitive deficits were studied using the a questionnaire of experienced attention deficits (FEDA) three months after the operation. Postoperative psychological and self-reported test results varied as a function of the invasiveness and the duration of the operation. After more invasive operations patients reported a stronger deficit in activities of daily living and a reduction in drive than after less invasive operations. In addition, the duration of anesthesia influenced the experienced deficits. The self-reported deficits were more strongly influenced by the features of the operation than the psychological test data. The physical status of the patients according to the American Society of Anesthesiologists (ASA) along with the duration of anesthesia as covariate was identified as a good predictor for the cognitive recovery post operation.
BACKGROUND: Monitoring with pulse oximetry might improve patient outcome by enabling an early diagnosis and consequently, correction of perioperative events that might cause postoperative complications or even death. Only a few randomised clinical trials of pulse oximetry have been performed during anaesthesia and in the recovery room which describe perioperative hypoxaemic events, postoperative cardiopulmonary complications and cognitive dysfunction. OBJECTIVES: To study the effect of perioperative monitoring with pulse oximetry to clearly identify the adverse outcomes that might be prevented or improved by the use of pulse oximetry. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Library, MEDLINE, EMBASE, and by checking the reference lists of trials and review articles. SELECTION CRITERIA: All controlled trials that randomised patients to either pulse oximetry or no pulse oximetry during the perioperative period, including the operating and recovery room. DATA COLLECTION AND ANALYSIS: We collected data in relation to events detectable by pulse oximetry, any serious complications that occurred during anaesthesia or in the postoperative period, intra- or postoperative mortality, and duration of recovery or intensive care stay. Formal statistical synthesis of individual trials was not performed in view of the variety of outcomes studied. MAIN RESULTS: Searching identified six reports; four studies with data from a total of 21,773 patients were considered eligible for analysis. Only two studies specifically addressed the outcomes in question; both found no effect on the rate of postoperative complications using perioperative pulse oximetry. Two studies used hypoxaemia detectable by pulse oximetry to assess the value of perioperative monitoring, although outcomes were not given. It was found that hypoxaemia was reduced in the pulse oximetry group both in the operating theratre and in the recovery room. During observation in the recovery room, the incidence of hypoxaemia in the pulse oximetry group was 1.5-3 times less. The postoperative cognitive function using the Wechsler memory scale and continuous reaction time was independent of perioperative monitoring with pulse oximetry. The other study showed that postoperative complications occurred in 10% of the patients in the oximetry group and in 9.4% in the control group. The two groups did not differ in cardiovascular, respiratory, neurologic, or infectious complications. The duration of hospital stay was a median of 5 days in both groups, and an equal number of in-hospital deaths was registered in the two groups. REVIEWERS' CONCLUSIONS: The studies confirmed that pulse oximetry can detect hypoxaemia and related events. However, we have found no evidence that pulse oximetry affects the outcome of anaesthesia. The conflicting subjective and objective results of the studies, despite an intense, methodical collection of data from a relatively large population, indicate that the value of perioperative monitoring with pulse oximetry is questionable in relation to improved reliable outcomes, effectiveness and efficiency.
BACKGROUND: It has been suggested that circadian rhythm disturbances are present after major surgery and that this may play a role in the development of postoperative sleep disturbances, fatigue, cognitive dysfunction and cardiovascular morbidity. The objective of this study was to examine the profile of melatonin, cortisol and core body temperature rhythms before and after major surgery. METHODS: Blood samples (melatonin and cortisol) and core body temperature readings were collected every hour in the 24-h period prior to surgery and the 48 h after surgery from 11 patients undergoing major abdominal surgery. All patients had private rooms. Light exposure was controlled and monitored. Phase markers [50% dim light melatonin onset (DLMO 50%) and offset (DLMOff 50%), cortisol and core body temperature acrophase] for the three circadian rhythm profiles were calculated before and after surgery. The correlation between the melatonin rhythm and time of surgery, duration of surgery and opioid use was examined. RESULTS: A median delay in the onset of melatonin was seen on the first postoperative day [median DLMO 50% 22:46 hours (range: 21:15-01:08 hours) on the preoperative day compared with 23:54 hours (range: 19:09-02:46 hours) on the first postoperative day; P </= 0.05] . A significant positive correlation existed between the duration of surgery and the time of melatonin onset (r = 0.67, P </= 0.05) . There was a significantly reduced basal secretion of melatonin immediately after surgery, with a subsequent significant increase in maximum melatonin values on the second postoperative night. A median delay of up to 4 h was seen in the timing of the peak of the temperature rhythm on the second postoperative day. Both cortisol secretion and core body temperature were increased after surgery and did not return to preoperative values in the 48 h of the postoperative study period. No significant correlation between opioid dose and the basal or maximum melatonin levels or the time of melatonin onset was found. CONCLUSION: We found disturbances in three circadian markers after major surgery. The clinical consequences of postoperative circadian disturbances should be investigated further in the future.
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.