INTRODUCTION
The cause of postoperative cognitive decline (POCD) is unknown and multifactorial, with age above 75 years, comorbidity, preoperative cognitive impairment and abnormal glycaemic control being some of the known risk factors.[1,2] Very few studies have studied the influence of spinal anaesthesia on POCD in elderly patients.
The primary objective of this study was to estimate POCD after spinal anaesthesia for hip surgeries in elderly patients using Mini-Mental State Examination (MMSE). The secondary objectives were functional status assessed with Instrumental Activities of Daily Living (IADL) scores, the spinal anaesthetic factors, serum cortisol and S100B calcium-binding protein (SCP) levels and their relationship with the occurrence of cognitive decline.
METHODS
After approval from the Institutional Ethics Committee (vide approval number KIMS/PGS/SYN: 2019-20:253) and registration of trial with the Clinical Trial Registry-India (vide registration number CTRI/2020/03/024019, www.ctri.nic.in), elderly patients above 60 years of age undergoing hip surgeries under spinal anaesthesia from 1st June 2020 to 1st March 2021 were recruited. Patients with neurological or psychiatric problems, patients with pronounced hearing or visual loss, patients who do not speak local languages and those with contraindications for regional anaesthesia were excluded. Written informed consent was obtained for participation in the study and regarding using the data for research and educational purposes. The study was carried out as per the principles of the Declaration of Helsinki, 2013.
Following recruitment, a resident doctor conducted pre-anaesthetic and cognitive screening using MMSE®[3] (permission was sought from the copyright holders of MMSE®, which is available on the psychological assessment resources website). A functional assessment was performed preoperatively using Lawton’s IADL. Patients received standard perioperative care as per institutional protocol. The drug and volume of local anaesthetic used for spinal anaesthesia, use of an epidural catheter for postoperative analgesia, adjuvant drugs, haemodynamic fluctuations warranting the use of vasoactive drugs, rescue analgesia, sedation and other drugs with probable cognitive effects administered and duration of surgery were noted. The patients were reassessed again by MMSE® and IADL scoring after 30 days on a follow-up visit. Blood was drawn for serum cortisol levels and SCP one day before surgery and on days one and four postoperatively.
Based on the previous study, the standard deviation (SD) of the difference between pre-and three months postoperative MMSE® scores was 1.6; hence, to estimate the mean change in MMSE® score after surgery with 99% confidence, we required 17 subjects.[4] To account for attrition, 25 patients were included. Changes in MMSE® scores and IADL scores were assessed using Friedman’s test, and pairwise comparison was made using Wilcoxon signed rank test. The association of categorical variables with cognitive and functional decline was analysed by the Chi-square/Fisher’s exact test. The relation between continuous variables and cognitive function decline was analysed using the Mann–Whitney test.
RESULTS
Twenty-five elderly patients undergoing hip surgery were recruited for the study [Figure 1].
Figure 1.
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) flowchart of the study
There was a statistically significant decrease in MMSE score with time (baseline and 30th day) (P = 0.016)]. Post hoc pairwise analysis showed a significant decrease in MMSE score between baseline and 30th day (P = 0.021) [Figure 2]. There was a statistically significant decrease in IADL score with time (baseline and 30th day) (P = 0.026)]. Post hoc pairwise analysis showed a significant decrease between baseline IADLs and 30-day IADLs (P = 0.024) [Figure 2].
Figure 2.
Box and whisker plot of pairwise comparison of MMSE scores and IADL scale (MMSE, IADL1 – preoperative scores and MMSE2, IADL2 – 30 days after surgery). *MMSE – mini-mental state examination, †IADL – instrumental activities of daily living
Patients were further categorised into two groups based on any numerical decrease in 30 days MMSE® and IADL values compared to baseline into cognitive/functional decline present or absent. This cognitive and functional decline was noted in ten patients. The cognitive and functional decline was not significantly associated with demographic variables and spinal anaesthetic factors [Tables 1 and 2].
Table 1.
Demographic profile and study parameters
| Total | No cognitive decline (n=10) | Cognitive decline# (n=7) | P | No functional decline (n=10) | Functional decline# (n=7) | P | |
|---|---|---|---|---|---|---|---|
| Gender | |||||||
| Male/Female | 7/10 | 5/5 | 2/5 | 0.622 | 6/4 | 1/6 | 0.134 |
| American Society of Anesthesiologist’s Physical Status I/II/III | 8/8/1 | 4/6/0 | 4/2/1 | 0.416 | 5/5/0 | 3/3/1 | 0.595 |
| Comorbid illness | |||||||
| Present/absent | 9/6 | 6/4 | 3/4 | 0.637 | 5/5 | 4/3 | 0.999 |
| Adjuvant used/not used. | 15/2 | 9/1 | 6/1 | 0.999 | 9/1 | 6/1 | 0.999 |
| Epidural Catheter inserted/not inserted | 14/3 | 10/0 | 4/3 | 0.051 | 10/0 | 4/3 | 0.051 |
| Intravenous Analgesic used | 3/14 | 2/8 | 1/6 | 0.999 | 0/10 | 3/4 | 0.051 |
| Intraoperative hypotension present/absent | 4/13 | 3/7 | 1/6 | 0.603 | 1/9 | 3/4 | 0.250 |
| s100 Calcium-binding protein -increased/not increased | 4/13 | 2/8 | 2/5 | 0.999 | 1/9 | 3/4 | 0.250 |
| Cortisol increased/not increased$ | 5/12 | 3/7 | 2/5 | 0.999 | 2/8 | 3/4 | 0.593 |
Data are presented as numbers. #Based on a decrease in MMSE score and IADL score from baseline to 30-day follow-up. $Based on increased SCP and cortisol levels from baseline to 4-day follow-up. MMSE – Mini-mental state examination; IADL – Instrumental activities of daily living; SD – Standard Deviation
Table 2.
Relation of cognitive and functional decline with respect to demographic and continuous spinal anaesthetic variables
| Cognitive decline# | Mean±SD | P | Functional decline# | Mean±SD | P | |
|---|---|---|---|---|---|---|
| Age (years) | Absent | 68.2±6.8 | 0.364 | Absent | 69.9±6.4 | 0.669 |
| Present | 70.86±5.18 | Present | 68.43±6.16 | |||
| Weight (kilograms) | Absent | 56.1±7.62 | 0.669 | Absent | 54.6±7.14 | 0.536 |
| Present | 54.71±9.78 | Present | 56.86±10.21 | |||
| Duration of Surgery (minutes) | Absent | 115.5±59.18 | 0.193 | Absent | 106.5±58.5 | 0.601 |
| Present | 75±15 | Present | 87.86±35.1 | |||
| Intrathecal hyperbaric bupivacaine plus adjuvant (if used) volume (millimetre) | Absent | 2.8±0.31 | 0.740 | Absent | 2.9±0.25 | 0.364 |
| Present | 2.79±0.5 | Present | 2.64±0.5 |
#Based on a decrease in MMSE score and IADL score from baseline to 30-day follow-up. MMSE – Mini-mental state examination; IADL – Instrumental activities of daily living; SD=Standard Deviation
Serum cortisol levels did not show any statistically significant decrease following surgery. Reduced serum cortisol levels had no significant relation with cognitive and functional decline. When compared preoperatively and immediately postoperatively, SCP levels showed no significant decrease. However, the preoperative and late postoperative SCP levels when compared, it was significantly decreased. This decrease in SCP levels had no significant relation with cognitive and functional decline changes.
DISCUSSION
Our study showed a significant decrease in MMSE® scores occurring postoperatively, indicating a cognitive decline in elderly patients receiving spinal anaesthesia for hip surgery and that the spinal anaesthetic factors like adjuvant used, an epidural catheter inserted, analgesic used, duration and drug volume had no relation with this cognitive decline. The functional status also showed a significant decrease at 30 days, possibly due to hip surgery per se.
There is a contrast in the results of other studies due to differing methodologies of defining POCD, the different time frames and different subsets of patients. Tzimas P et al.[5] concluded that the anaesthesia technique did not seem to influence the emergence of POCD in elderly patients who underwent hip fracture surgery. A recent study stated that the new-onset delirium was similar in spinal and general anaesthesia groups.[6] Ehsani R et al.[7] noted that POCD was higher in patients who underwent hip fixation surgery under general anaesthesia.
Serum cortisol levels did not significantly differ from baseline values in our study but showed a declining trend postoperatively. This could be due to spinal anaesthesia, which suppresses cortisol and inflammatory response and may be related to age factors.[8] Zhong et al.[9] noted an inadequate cortisol response compared to the higher inflammatory stress response in patients above 65 years undergoing total hip arthroplasty under general anaesthesia. Elevated serum S100B is a consequence of amplified inflammation and cell stress.[10] We noted a significant decrease in SCP in the postoperative period that did not run parallel with cognitive and functional decline. Studies investigating this association between SCP and POCD have given varied results.[2,8]
The limitations included the small sample size that is inadequate to generalise the findings, the use of subjective MMSE scoring, a lack of consensus on POCD definition, the biomarkers chosen by us and trauma itself increasing cortisol and SCP levels. A six-month follow-up would be ideal to assess the POCD. Also, randomised trials with adequate sample sizes are required to pinpoint a cause–effect relationship.
CONCLUSION
Elderly patients undergoing spinal anaesthesia for hip surgeries develop postoperative cognitive decline. Spinal anaesthetic factors, including total intrathecal drug volume used, the addition of an adjuvant, intraoperative analgesic used, epidural catheter inserted or haemodynamic fluctuation and duration of surgery, did not show any association with cognitive and functional decline. Serum cortisol levels and S100 B calcium-binding protein did not show any relation to cognitive and functional decline.
Study data availability
De-identified data may be requested with reasonable justification from the authors (email to the corresponding author) and shall be shared after approval as per the authors’ Institution policy.
Financial support and sponsorship
The author would like to thank Multi-Disciplinary Research Unit (MRU), funded by Department of Health Sciences (DHR), Government of India, New Delhi, for providing financial support and laboratory facility. The authors have received support from Medical Research Unit (MRU), Karnataka Institute of Medical Sciences, Hubballi, in the form of ELISA kits and technical/material support for analysis of blood samples.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
Authors acknowledge the support of Dr Ram Kaulgud, Nodal Officer, Dr. Gulamnabi Vanti, Scientist B and Mr. Veeresh of MRU, KIMS, Hubballi for designing and executing the experiments.
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