Risk factors for post-operative cognitive dysfunction in neurosurgical patients

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BACKGROUND

Post-operative cognitive dysfunction (POCD) is a state which is quite often diagnosed in patients undergoing long-running surgical intervention. POCD is described as impaired attention concentration, memory, speech, learning ability and other higher mental functions [1]. Such a condition can persist for many months and progress into a constant disorder, seriously affecting the quality of the patients’ life and their working capacity. To a great extent, the development of such a set of symptoms depends on certain risk factors [2, 3]. Due to an increase in the number of surgical interventions among the elderly patients, a necessity arises for deeper exploration of such factors. The obtained data allow for providing an individual approach when preparing the patient to surgical intervention and for decreasing the probability of developing POCD by using the means of prevention.

It is known that the occurrence and the severity of POCD vary depending on the presence of pre-operative and intraoperative risk factors, such as the type and the duration of surgery, the type of anesthesia, the age of the patient, the concomitant diseases and the level of education [4–6]. The majority of research works in this field were carried out among the patients of the cardiology and trauma care profile. The research works on the incidence and the severity of POCD in patients having a vertebral column surgery are sparse and concentrated on the influence of the age and the duration of anesthetic support [1, 7]. The analysis of the effects of other risk factors on the cognitive functions among the vertebrology patients will allow for more comprehensive interpreting the results of neuropsychological tests and for preventing the development of POCD.

Research aim — to determine the effects of various extra- and intraoperative risk factors on the development of POCD in neurosurgical patients, undergoing vertebral column surgery with long-running anesthetic support.

METHODS

Research design

Observational selective non-controlled clinical trial.

Conformity criteria

Inclusion criteria: patients with scheduled surgical intervention caused by degenerative-dystrophic diseases of the vertebral column.

Exclusion criteria: patients having ischemic or hemorrhagic stroke in the past medical history; significant blood loss (more than 500 ml); diseases of the nervous system, including the consequences of craniocerebral injuries; alcohol abuse; severe depression; impaired consciousness.

Research facilities

The examination was carried out within the premises of the Neurosurgery Department of the State Budgetary Healthcare Institution of the Tyumen Oblast “Regional Clinical Hospital No. 2” with the participation of a homogeneous group of patients: all of them were neurosurgical patients with long-running (lasting more than 120 minutes) vertebral column surgeries. The research was arranged in the similar settings using the standardized scales, which allowed for maximum increasing the significance of the obtained results.

Research Duration

The research duration was 12 months (from January 2024 until January 2025).

Medical procedure description

The evaluation included the cognitive functions before surgery and on Day 3 after the surgical intervention using the Montreal Cognitive Assessment (MoCA), along with a panel of Isaac tests and the Munsterberg test. For minimizing the practical effect (improvement of parameter values caused by the repeated performing the tests), the second testing employed the parallel versions of tests. The testing was done after evaluating the intensity of pain syndrome using the visual analogue scale. In case of severe pain syndrome, in order to minimize the influence of pain on the testing results, pain treatment was conducted using the non-steroid anti-inflammatory drugs.

Research outcomes

Primary research outcome: the change in the level of cognitive functions in the patients after long-running vertebral column surgeries.

Methods for registration of outcomes

The results of testing and surveying on the paper media were transitioned into the Microsoft Office Excel electronic format for their further statistical processing.

Statistical analysis

For each scale, a difference was calculated between the absolute values of testing results before and after surgery. The obtained parameters were expressed as percentages. The percentages were summed and divided by the number of scales. This approach was used to calculate the mean value of the change (median, Ме) for three scales. The mean decrease of the results of three testing sessions by more than 10% was interpreted as the presence of POCD. Calculations were done for the Pearson’s coefficients (r) and for the point biserial correlation coefficients regarding the extra-operative (the age; the body mass index; the number of education years; the presence of arterial hypertension, diabetes and smoking), as well as the intraoperative (drugs used for anesthetic management and for muscle relaxation, duration and type of surgical intervention) risk factors. Correlations were considered statistically significant at the p level of ≤0.05. The calculations were conducted using the Python language programming means.

RESULTS

Research sample (participants)

During the primary examination of 108 neurosurgical patients, 5 individuals were excluded due to the presence of exclusion criteria in them. Thus, the sample consisted of 103 patients. POCD was reported in 35 (34%) of them. The age of the test subjects varied from 22 to 77 (mean age — 50) years. The gender distribution was the following: 40 females, 63 males. Eleven patients had diabetes, 44 had arterial hypertension, 35 were smokers. The body mass index of the participants varied from 20 to 41 relative units (median, Ме 27.6). The recorded data included the number of years of continuous education at the young age (Ме 12.2), the education level (general secondary — 20, incomplete secondary — 1, complete general secondary in 5, secondary vocational in 39, higher in 38) and profession (non-manual workers — 41, manual workers — 62).

The patients were undergoing scheduled surgical intervention in the lumbar segment of the vertebral column, after which, the treatment results were analyzed before and after decompressive laminectomy (in 8) or hemilaminectomy (in 50) with further discectomy, microdiscectomy (in 18) or laminectomy with further transpedicular fixation (in 27).

The duration of anesthetic support was from 120 to 405 minutes (Ме 154). The patients were receiving propofol as the preanesthetic medication. As for the muscle relaxants used, they were rocuronium bromide (in 77), suxamethonium bromide (in 10), along with their combination (in 16). The type of anesthesia used was the following: general intravenous with artificial pulmonary ventilation. The combinations of the following medications were used: sevoflurane+fentanyl (in 67); propofol+fentanyl in 14); desflurane+fentanyl (in 12); propofol+fentanyl+sodium oxybutyrate (in 3); sevoflurane+fentanyl+ketamine (in 6).

Primary research outcomes

The results of testing with the MoCA scale before and after surgeries have demonstrated the values ranging from 17 to 30 points (Ме — 25 and 23.8 respectively), the Isaac tests — from 17 to 40 points (Ме — 32 and 31, respectively), the Munsterberg test — from 7 to 28 points (Ме — 16 and 15, respectively).

As for the extra-operative factors, a notable positive correlation was observed between the development of POCD and the age (r=0.53; p <0.01), with moderate one for the body mass index (r=0.35; p <0.01) and for the presence of arterial hypertension (r=0.42; p <0.05). A moderate negative interrelation was found between the number of education years and the development of POCD (r=-0.36; p <0.01). The presence of diabetes does not affect the development of POCD. The coefficient of association for smoking had a low significance level, which does not allow for comprehensive interpreting the obtained results as valid.

Regarding the intraoperative risk factors, the following results were obtained: the type of surgical intervention did not correlate with the development of POCD. The duration of anesthetic support (r=0.02; p <0.01) is also not the factor affecting the development of POCD. A moderate correlation was found for using (as the anesthesia means) the desflurane + fentanyl combination of drugs (r=0.31; p <0.05), mild correlation — for using the sevoflurane+fentanyl + ketamine combination (r=0.25; p <0.05). Using fentanyl together with sevoflurane (r=0.07), propofol (r=-0.1) or sodium oxybutyrate (r=0.05) does not lead to the occurrence of POCD (p <0.05).

Undesirable phenomena

No adverse events were registered.

DISCUSSION

The influence in terms of developing POCD was observed for the age, the body mass index, the presence of arterial hypertension and the number of education years. The most prominent association was found between the age and the development of POCD, which corresponds to already available literature data [4, 5, 8, 9]. Due to the variety of the test group, using this factor, one can extrapolate the obtained data to other patients with vertebral diseases.

The high body mass index and the presence of arterial hypertension also have significantly increased the risks of developing POCD, which correlated with the results of a large number of other research works with the participation of cardiology or trauma patients [10–12]. The presence of moderate interrelation indicates the possibility of influence from the endogenous protective factors, such as the genetic markers, the effects of which on the development of POCD still need to be explored.

From the exogenous extra-operative factors, the highest influence was provided by the number of years of education. The detected negative moderate correlation shows that the presence of higher education and long-term learning act as the protective factor, decreasing the probability of developing POCD. Similar data were obtained in other POCD research works [13–15].

As for the diabetes affecting the development of POCD, significantly weaker interrelation was found, which is slightly diverging with the available data on this topic [16, 17]. It is probable that the level of diabetes compensation, the achievement of target glycemia levels and the diseases duration have more significance than the fact of diagnosis itself, due to which, more detailed research is needed for exploring such cause-and-effect associations.

In the latest research works, the data on the effects of smoking on the development of POCD diverge. In one of the research works [18] smoking acts as the protective factor against POCD, while the meta-analysis [9] draws a conclusion on the negative effects of smoking on the cognitive functions in the individuals with past cardiac surgeries. The data obtained in our research, do not allow for completely rejecting or confirming the effects of smoking on the development of POCD.

The association with the duration of anesthetic support was confirmed in multiple research works with cardiology or trauma patients, but in several research works, the data were controversial [16, 19]. The results obtained in our research may indicate that the type of surgery itself (vertebral column surgery) adds its own specific features to the development of POCD. In all appearances, due to the anatomical remoteness of the surgery field and the small blood loss during surgery, the effect of this factor is insignificant, however, further research is required on this issue. Our research has proven that the specific type of vertebral surgery itself does not affect the cognitive functions.

It was found that using fentanyl in combination with desflurane or sevoflurane and ketamine can influence the development of cognitive disorders, for there was a moderate and mild association, respectively. A recent research [20] also contained data obtained that were showing the pathological effect of desflurane and sevoflurane on the cognitive functions.

Comparing the obtained data, a conclusion can be drawn that, when preparing for surgical intervention, it is necessary to collect the past cognitive history of the patient (number of education years, education type, type of work) and comparing it to the forthcoming anesthesiology support. For the elderly patients with multiple concomitant diseases, as well as for patients with low education level, manual type of labor, it is undesirable to use the combinations of desflurane+fentanyl and sevoflurane+fentanyl+ketamine. In patients with several risk factors, the usage of neuroprotective therapy is possible during the pre- and post-operative periods for decreasing the probability of developing POCD.

Based on the data obtained in our research, not all the cases of developing POCD can be explained, especially among young patients without any risk factors. Further research on the endogenous biochemical and genetic risk factors of developing POCD shall allow for drawing a more comprehensive picture of developing this disease and minimizing the risks of cognitive disorders after surgeries.

Research limitations

The clearest limiting factors are the testing conditions: unfavorable environment of the hospital ward, uncomfortable conditions and the presence of other test subjects can significantly affect the results of examining the cognitive functions. In order to minimize this factor, the recommendations include arranging the testing at the same time by a single investigator, in a separate room, after meals and with comfortable temperature and light.

Other limiting factor can be the severity grade of pain syndrome: while having a highly intensive pain, the test subject cannot focus on the test tasks or completely refuses to participate in the testing session. The optimal decision in this case would be the rational use of pain medications.

CONCLUSION

Knowing the risk factors for post-operative cognitive dysfunction will allow for preventing the development of this condition. Based on the obtained results, for older age patients with high body mass index value, with the presence of arterial hypertension and low education level, it is recommended to choose the rational combinations of anesthesia medications and more sparing treatment methods, including the consideration of the possibility of conservative therapy with using neuroprotective drugs.

Further research is required in this field for compiling a more comprehensive picture of the pathogenesis of post-operative cognitive dysfunction.

ADDITIONAL INFORMATION

Author contributions: V.A. Saltanova, patient interviewing, statistical data analysis, literature review; O.A. Kicherova, L.I. Reikhert, formulation of the research goals and objectives; Yu.I. Doyan, development of the study design, formulation of inclusion and exclusion criteria; N.A. Mazurov, selection of patients for interview. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The research protocol was approved by the Ethics Committee at the Tyumen State Medical University of the Ministry of Health of the Russian Federation (extract from Protocol No. 118 dated 18.01.2024). All the study participants voluntarily signed an informed consent form before being included in the research.

Funding sources: The study was carried out without attracting external funding.

Disclosure of interests: The authors declare no conflict of interests.

Statement of originality: The authors did not utilize previously published information (text, illustrations, data) in conducting the research and creating this paper.

Data availability statement: The editorial policy regarding data sharing does not apply to this work, data can be published as open access.

Generative AI: Generative AI technologies were not used for this article creation.

About the authors

Valentina A. Saltanova

Tyumen State Medical University; The Regional Clinical Hospital № 2, Tyumen

Author for correspondence.
Email: valentinaslt72@gmail.com
ORCID iD: 0009-0002-1304-2202
SPIN-code: 6507-3940
Russian Federation, 54 Odesskaya st, Tyumen, 625023; Tyumen

Oksana A. Kicherova

Tyumen State Medical University

Email: pan1912@mail.ru
ORCID iD: 0000-0002-7598-7757
SPIN-code: 3162-0770
Scopus Author ID: 56806916100

MD, PhD, Assistant Professor

Russian Federation, Tyumen

Lyudmila I. Reikhert

Tyumen State Medical University

Email: lir0806@gmail.com
ORCID iD: 0000-0003-4313-0836
SPIN-code: 1703-2302

MD, PhD, Professor

Russian Federation, Tyumen

Yulia I. Doyan

Tyumen State Medical University; The Regional Clinical Hospital № 2, Tyumen

Email: yul-gol25@yandex.ru
ORCID iD: 0000-0002-8486-496X
SPIN-code: 2748-9442

MD, PhD, Assistant Professor

Russian Federation, Tyumen; Tyumen

Nikita A. Mazurov

Tyumen State Medical University

Email: nikita_banzay@mail.ru
ORCID iD: 0009-0002-7289-4587
SPIN-code: 3824-0682
Russian Federation, Tyumen

References

Supplementary files