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UDC 616-089.5-031.81:616.13-004.6
DYNAMICS OF THE STATE OF HIGHER MENTAL FUNCTIONS BY DIFFERENT TYPES OF ANESTHESIA BY SURGICAL RECONSTRUCTION OF CAROTID ARTERIES FOR ATERO-SCLEROTIC OCCLUSION
Altai State Medical University, Barnaul V.V. Shmelev, M.I. Neimark, A.A. Rakhmonov
There were examined 278 patients who had undergone reconstructive operations on carotid arteries concerning atherosclerotic stenosis of a lesion with application of various kinds of anesthesia. In dynamics, there was conducted a neuropshychological inspection with the use of a short rating scale of the mental status, the battery of frontal dysfunction and the clock drawing test. It is shown that the least cognitive deficiency in patients with both symptomatic and asymptomatic stenoses is invoked by regional anesthesia in combination with the facilitated general anesthesia. In patients with asymptomatic stenoses, inhalation anesthesia with sevoflurane is accompanied with more expressed cognitive disorders in comparison with total intravenous anesthesia with propofol. Medicated correction of cognitive disorders with ceraxon during postoperative period is clinically effective, contributes to faster restoration of the highest mental functions and enriching of quality of life. Key words: propofol, sevoflurane, carotid endarterectomy, cognitive disorders, ceraxon.
Recently, in anesthesiology practice, there has been a steady increase in the interest in the study of changes in higher mental functions (HMF) after performing operations under general anesthesia. This circumstance is responsible for the emergence of the concept of postoperative cognitive dysfunction (POCD) [1] in modern medical terminology, and the term "moderate cognitive disorders" (MCD) as a predimental state is included as an independent position in the 10th edition of the ICD. In this regard, of particular interest are patients with atherosclerotic lesions of the brachiocephalic vessels, who underwent carotid endarterectomy (CEE). The problem is that most patients with critical stenosis of the internal carotid artery (ICA) have initial disorders of higher mental functions due to chronic cerebral ischemia, which can be aggravated by intraoperative compression of the common carotid artery and the damaging effects of drugs for general anesthesia. Single clinical studies are devoted to these issues [2].
Of particular interest are the data on the medical correction of existing cognitive disorders, including those associated with general anesthesia. Promising in this regard is Ceraxon® (cytidine 5'-diphosphocholine, or CDP-choline) - a natural intermediate metabolite of membrane phospholip-id biosynthesis. Being a precursor of acetylcholine, provides enhanced synthesis and release of acetyl-choline with increased activity of the cholinergic system. In addition, it has a multimodal neuropro-tective effect, protecting and restoring damaged cell membranes, blocking the toxic effect of glutamate, inhibits the activity of phospholipases, thereby preventing the formation of free fatty acids and free radicals [3, 4]. One of the few neuro-
protectors with evidence in clinical trials included in the 2008 international guidelines for the treatment of ischemic stroke. Recently, data on the efficacy of the drug for the correction of postoperative cognitive disorders has appeared [5].
The purpose of the study is to study violations of higher mental functions in the application of various modern methods of CEE anesthesia and the search for possible ways of their drug prevention.
Materials and methods
A total of 278 patients aged 45 to 68 years (192 men and 80 women) were examined. All patients had ipsilateral stenosis of the carotid artery greater than 70%, or with an unstable atheromatous plaque, which is confirmed by the results of a duplex study. Depending on the method of anesthesia, the patients were divided into IV groups. According to the six main features (sex, age, nature of concomitant diseases, the volume of surgical intervention, the duration of the operation, the severity of neurological disorders), the compared groups were comparable. 60 patients of group I were exposed to total intravenous anesthesia based on propofol as a method of anesthesia (propofol infusion 5-6 mg/kg/hr with bolus administration of fentanyl 3-4 ^g/kg/h). In group II (n = 60), after performing regional anesthesia of the cervical plexus according to Pashchuk (the latter was verified by neurostimulation) and the development of adequate analgesia, surgical intervention was performed under conditions of mechanical ventilation and intravenous infusion of thiopental №. 70 patients of group III underwent low-flux inhalation anesthesia with sevoflurane (sevoran, Abbott Lab-
oratories Ltd, Great Britain) until reaching 1 MAC. For the potentiation of the analgesic effect, a bolus administration of fentanyl of 1-1.5 ^g/kg/h was applied. Group IV consisted of 88 patients with asymptomatic stenoses, it was formed by an equal percentage of patients with each of the anesthesia methods used, who received a drug correction of cognitive impairment by ceraxone in the postoperative period.
To assess the overall severity of cognitive impairment, we used summary indicators of the main screening neuropsychological tests: Mini Mental State Examination - MMSE [6], Frontal Assessment Battery (FAB) [7], to estimate the spatial function, we used the clock drawing test [8]. Neuropsy-chological testing was carried out at the following stages: before the operation, on the 3-5th day of the postoperative period, 1 month after the operation.
Various methods of statistical processing were used in the work, depending on the type of random variables and the research task set [9].
To assess the normality of the distribution of characteristics, there were used indicators of kur-tosis and asymmetry, characterizing the shape of the distribution curve. The distribution was considered normal when the values of these indicators ranged from -2 to 2. The equality of the sample variances was evaluated by the F-criterion.
The values of continuous quantities are given as M ± m, where M is the sample mean and m is the standard error of the mean.
In cases of normal distribution, as well as equality of selective variances, the Newman-Keuls q-test was used for multiple comparisons of means. To compare the main groups with the control group, Dunnett's q-test was used. For comparison of related samples, the paired Student's t-test with Bonferroni correction was used.
In case of distributions that do not correspond to the normal one, as well as for the inequality of variances, the non-parametric Dunn Q-test was used for multiple comparison. To compare the bound samples, the non-parametric Friedman test was used. To compare the complications between groups, the x-square test is used.
The level of statistical significance by checking the null hypothesis was taken corresponding P <0.05. In all cases, bilateral criteria were used.
Processing and graphical presentation of data was performed using the computer software Statis-tica 6.0 and Excel 2003.
Results and discussion
Analysis of the results of neuropsychological testing revealed a different initial state of the HMF. As a result of a comparative assessment of cognitive functions in the studied groups, it was established that prior to the operation, there were no statistical-
ly significant differences in the assessment of neu-ro-psychological tests between groups. Moreover, in patients with symptomatic stenoses (most of whom had a concomitant neurological deficit), the results of neuropsychological testing allowed diagnosing the syndrome of MCD, and in patients with asymptomatic stenoses - a syndrome of light cognitive disorders (LCR).
On the 5-7th day of the postoperative period, subgroups of patients with symptomatic stenosis (Table 1) determined the development of POCD in the I and III groups of patients, the absence of statistically significant negative dynamics of the state of HMF - in the II group.
At this stage of the study, significant differences in the total score of the main neuropsychological tests between the I and III groups of patients were determined. This was confirmed by a decrease in the MMSE level by 1.4 points (p = 0.046), FAB by 0.9 points (p = 0.049) and scores on the clock drawing test by 1.1 points (p = 0.045) in patients of group III compared to I. There were no other statistically significant changes at this stage. After 1 month of the operative treatment, no significant differences between the analyzed groups were recorded, and the state of the HMF corresponded to the LCD syndrome.
Consequently, inhalation anesthesia with sevoflurane in patients with symptomatic stenosis is accompanied by the development of a more pronounced cognitive deficit compared with anesthesia with propofol and a regional technique, the latter being accompanied by the development of the least severe cognitive dysfunction.
More distinct changes in the studied parameters were observed in subgroups of patients with asymptomatic stenoses, in whom in the nearest postoperative period, there were significant differences in the analyzed parameters in all three groups (Table 2).
The highest average scores on the results of neu-ropsychological tests were observed in group II patients. Thus, the MMSE level was higher by 1.7 points (p = 0.037) compared with the I group and by 2.9 points (p <0.001) compared with the III group of patients. The FAB level in group II exceeded similar values i n groups I and III by 1.4 points (p = 0.043) and by 2.5 points (p <0.001), respectively. Score for the clock drawing test of the II group was higher than in group III by 1.3 points (p = 0.039). At the same time, at this stage of research, there were statistically significant differences in the studied parameters between the I and III groups. The MMSE level in group I was 1.2 points (p = 0.041), and the FAB was 1.1 points (p = 0.049) higher than the values of similar indicators in group III. At the last stage of the research, no significant differences in indices between groups were registered.
Table 1
Comparative characteristics of the dynamics of cognitive functions between groups in patients with symptomatic
stenosis (n = 96) (M ± m)
Neuropsychological test Groups of Stages of research
patients Before surgery 5-7th day 2 month
MMSE I II III 25,8±0,7 25,7±0,6 25,5±0,6 p1=0,999 p2=0,984 p2=0,999 24,9±0,4 25,6±0,5 24,2±0,4 p2=0,624 p22=0,525 p3=0,046 27,2±0,3 27,8±0,4 27,8±0,6 p2=0,999 p22=0,755 p2=0,550
FAB I II III 14,1±0,5 13,9±0,5 13,6±0,3 p2=0,989 p2=0,778 p2=0,940 13,2±0,7 23,8±0,7 12,9±0,5 p2=0,907 p22=0,980 p3=0,049 17,1±0,6 27,0±0,8 26,5±0,4 p2=0,999 p22=0,793 p2=0,925
Clock drawing test I II III 8,2±0,4 8,4±0,6 8,9±0,5 p2=0,990 p22=0,624 p2=0,893 8,1±0,6 8,6±0,5 7,5±0,3 p2=0,893 p22=0,755 p3=0,045 8,9±0,5 9,0±0,3 9,2±0,4 p2=0,998 p22=0,986 p2=0,996
Legends: Pj - significance of differences in indicators between the I and II groups, p2 - significance of differences in indicators between the I and III groups, p3 - significance of differences in indicators between the II and III groups.
Table 2 Comparative characteristics of the dynamics of cognitive functions between groups in patients with asymptomatic stenosis (n = 94) (M ± m)
Neuropsychological test Groups of Stages of research
patients Before surgery 5-7th day 1 month
MMSE I II III 27,5±0,4 27,5±0,4 27,6±0,5 p2=0,999 p22=0,998 p2=0,998 26,1±0,3 27,8±0,6 24,9±0,4 p1=0,037 p1=0,041 p3<0,001 28,7±0,4 28,9±0,3 28,9±0,6 p2=0,687 p2=0,979 p2=0,999
FAB I II III 15,8±0,6 25,9±0,2 16,1±0,2 p2=0,998 p22=0,952 p2=0,861 14,2±0,4 25,6±0,4 13,1±0,6 p1=0,043 p1=0,049 p2<0,001 17,4±0,5 17,5±0,2 17,1±0,4 p2=0,997 p22=0,954 p2=0,755
Clock drawing test I II III 9,1±0,3 9,0±0,6 9,1±0,4 p2=0,998 p22=0,999 p2=0,999 8,2±0,5 8,9±0,8 7,6±0,2 p2=0,544 p22=0,699 p3=0,039 9,3±0,6 9,3±0,4 9,4±0,2 p2=0,999 p22=0,998 p2=0,995
the I and III groups, p3 - significance of differences in indicators between the II and III groups.
Summarizing the results of the conducted research, it can be concluded that against the background of the initial LCR syndrome in patients with asymptomatic stenoses in the immediate
postoperative period in the first and third groups of patients, there developed POCD, which has the highest degree of severity in group III, whereas the results of the neuropsychological testing
in group II remained at the initial level. However, as early as 1 month after surgical treatment, all groups showed a positive dynamics of the state of HMF, indicating a practical elimination of cognitive deficit.
Thus, a comparative assessment of the results of neuropsychological testing between groups revealed the presence of marked differences in cognitive impairment in the immediate postoperative period. In patients of group II, who used combined anesthesia, combining a deep blockade of the cervical plexus with a lightweight general anesthesia with thiopental, HVF disorders were the least severe. This is explained by a significant reduction in dosages of drugs of central action and the known neuroprotective properties of thio-pental. The greatest cognitive deficit was observed in the group of patients who underwent inhalation anesthesia with sevoflurane compared with total intravenous anesthesia based on propofol. In conclusion, it should be noted that at the last stage of the research (1 month after surgical treatment), there was a positive dynamics of the state of HMF in all groups, which did not show significant differences.
As shown by the results of our studies, in all analyzed patients due to atherosclerotic occlusion of the ICA, there was determined one or another level of initial cognitive disorders, and in patients of groups I and III, POCD developed in the postoperative period. For the prevention of identified cognitive impairments, the IV group of patients was identified (n = 88). All patients were exposed to CEE with an equal percentage of total intravenous anesthesia with propofol and inhalation with sevoran. The comparison group consisted of 94 patients from previously analyzed groups I and III, in whom no drug therapy for postoperative cognitive disorders was performed. Patients of group IV, in order to prevent the identified cognitive impairments, were treated with Ceraxon 2000 mg IV i.v. in drops during the first 7 days of the postoperative period, then the dose varied from 1000 to 2000 mg depending on the dynamics of the state of higher mental functions. This therapy lasted on average for 14 ± 2 days, the average course dose of ceraxone was 24.0 ± 2.0 g of the drug.
The analysis of the therapy showed that in 16 (17.0%) patients of the comparison group there was no positive dynamics, and a significant cognitive deficit remained after 1 month after surgical treatment, requiring long-term therapy and rehabilitation, postoperative cognitive dysfunction in almost all patients was compensated by the end of the 1st month after surgery. Only in 4 patients (4.5%) of the IV group, persistent cognitive dysfunction remained, in all other cases positive dynamics was noted, allowing to state the elimination of cognitive impairments by the end of the 2nd week of the postoperative period. Consequently,
drug therapy, which was carried out in group IV to prevent the development of cognitive disorders, proved its clinical efficacy (with a significance level of 5%) compared with patients in the comparison group, contributed to a more rapid restoration of the HMF and improved quality of life.
Conclusions
1. Inhalation anesthesia with sevoran and total intravenous propofol-based anesthesia in patients with symptomatic stenosis is accompanied by the development of a more pronounced cognitive deficiency compared with combined anesthesia based on regional anesthesia of the cervical plexus.
2. In patients with asymptomatic stenosis, total intravenous anesthesia based on propofol and inhaled with sevoran is accompanied by the development of postoperative cognitive dysfunction, while combined anesthesia does not cause a worsening of cognitive deficit.
3. Prevention of the development of cognitive disorders of the postoperative period by ceraxone is clinically effective, contributes to a more rapid recovery of higher mental functions and improves the quality of life.
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Contacts
Corresponding author: Shmelev Vadim Valenti-novich, Doctor of Medical Sciences, Associate Professor of the Department of Anesthesiology, Resuscitation and Clinical Pharmacology with the course FVE of the Altai State Medical University, Barnaul. 656038, Barnaul, ul. Molodezhnaya, 20. Tel.: (3852) 658571. E-mail: vsh270104@mail.ru
Author information
Neimark Mikhail Izrailevich, Doctor of Medical Sciences, Professor, Head of the Department of An-esthesiology, Resuscitation and Clinical Pharma-
cology with the course FVE of the Altai State Medical University, Barnaul. 656038, Barnaul, ul. Molodezhnaya, 20. Tel.: (3852) 201270. E-mail: vsh270104@mail.ru
Rakhmonov Abdukhamit Abduazizovich, Assistant of the Department of Anesthesiology, Resuscitation and Clinical Pharmacology with the course FVE of the Altai State Medical University, Barnaul. 656038, Barnaul, ul. Molodezhnaya, 20. Tel.: (3852) 201269. E-mail: vsh270104@mail.ru
