A PROSPECTIVE STUDY TO INVESTIGATENEUROCOGNITIVE PERFORMANCE IN PATIENTS UNDERGOING MAJOR SPINALPROCEDURE WITH GENERAL ANESTHESIA
*
Abstract
Objective: The impact of major spinal surgery on cognitive functionremains speculative. There are presently limited studies availableconcerning the cognitive dysfunctions in terms of nature and courseafter a major spinal surgery. In this longitudinal cohort study, weexamined the effect of major spinal surgery on cognitive functioning.The other objective of the study is to find the correlation betweenthe risk factors and cognitive functioning after major spinal surgerywith general anesthesia.
Methods:This is a prospective analysis of thirty-two patients enrolled beforeundergoing elective lumbar spine surgery. Seventeen patientsscheduled for lumbar decompression without instrumentation served asa control group and fifteen patients scheduled for major spinalsurgery such as spinal decompression with long posterior instrumentedfusion served as an experimental group.  An examineradministered the Montreal Cognitive Assessment (MoCA) test to bothsubjects to evaluate cognitive abilities preoperatively and onpostoperative days one, thirty and ninety.  
Results: Elderly patients (>60)patients with a lower education background mainly high schooldropouts , and patients who stayed longer in surgery reported adecline in cognitive function compared to other patients. However, nocorrelation exists between the severity of the pain and theneurocognitive function. Patients who utilized the controlled inhaledanalgesic reported initial lower post-operative scores that improvedwith time. In this study, the p value is less than 0.005.
Conclusions: Comparisons of pre- and postoperative assessments of cognitionshowed correlation between major spine surgery and cognitive scores.Performance on the MoCA declined in areas of attention and executivefunction with increasing post-operative pain scores, age and longerduration of surgery. Post-operative cognitive dysfunction hassignificant clinical and financial impacts on the patients.
Keywords:postoperative cognitive dysfunction*, anesthesia, spinal procedure
Abbreviations used in this paper:MoCA= Montreal Cognitive Assessment POCD= Postoperative cognitivedysfunction, *
Neurocognitive functions are cognitivefunctions that are linked to the neural pathways. On the other hand,general anesthesia given post operatively results in changes of thecognitive function. The anesthetics through disruption of functionalinteractivity within the neural networks or suppression of theneuronal activity by dose dependent general and specific locality,modifies the brain activity. Anesthetics modulate theneurotransmitter gated ion channels, namely the receptors forgamma-aminobutyric acid (GABA), glutamate and N-methyl D- aspartate(NMDA), at the synaptic and extrasynaptic sites. For instance,barbiturates, which are intravenous anesthetics, have an inhibitoryeffect on neuronal nicotinic acetycholine receptors (nAchRs). nAchRsare directly associated with cognitive processes such as learning,memory and control of motion (Mandal, Schifilliti, Mafrica &Fodale, 2009).  
Cognitive function is widely recognized as anessential outcome measure that affects patient well-being, quality oflife, and functional status. Postoperative cognitive dysfunction(POCD) is a decline in cognitive function for periods after surgery.It is the disability of the mental processes of processinginformation, memory and perception, and is common after cardiacsurgery. The symptoms of cognitive dysfunctions after surgery includedifficulty in concentration, loss of memory and delirium. Thesesymptoms cause interference with the recovery of the patient aftersurgery resulting to longer stays in the hospital. Moreover, itexists after major non-cardiac surgery, such as major spinal surgeryalthough at a lower incidence (Lars, 2006).Despite recent advances have progressively led to the decline ofrates of morbidity and mortality associated with POCD, more researchneeds to done to address this issues. There is limited number ofstudies examining pre and postoperative neurocognitive function, thetrue incidence and extent of postoperative cognitive dysfunction asit relates to major spinal surgery is unknown. The risk factors forpost-operative cognitive are associated with surgery and anesthesia,age, substance abuse, preexisting psychiatric, neurologicaldisorders, and high intracranial pressure conditions (Mandal,Schifilliti, Mafrica & Fodale, 2009).
This study aims to contribute to literatureconcerning the effect of general anesthesia on neurocognitiveperformance particularly in patients undergoing spinal procedure. Thegoals of this study are quad fold: 1) to evaluate a correlationbetween major spine surgery and postoperative neurocognitive deficit2) to evaluate the impact of postoperative neurocognitive dysfunctionon patients functional recovery and physical performance 3) to findthe risk factors associated to cognitive dysfunction post-operativelyand 4) to evaluate financial and clinical impact on healthcare.
MATERIALS AND METHODS
The Institutional Review Board approved thisstudy. Thirty-two consecutive patients (17males, 15 females, mean age61 years) scheduled for elective posterior lumbar spine surgery wereincluded.  Seventeen patients who underwent lumbar decompressionwithout instrumentation served as a control group and fifteenpatients who had major spine surgery such as posterior lumbardecompression with instrumentation served as experimental group.  Allprocedures were performed at ** Medical Center in ** by theneurosurgical faculty.  Exclusion criteria for this study werenon-English speaking, history of depression, low preoperativekarnofsky performance score, preexisting dementia or brain disease,pregnancy, age older than 80 or younger than 18. We measuredperioperative pain levels using a standardized 11-point Numeric PainRating Scale (NPRS). The numeric pain rating scale is mostresponsive compared to other measures of pain intensity in bothclinical and research settings (Ferreira-Valente, Pais-Ribeiro, &Jensen, 2011).
There was collection of baseline demographics, Montreal CognitiveAssessment (MoCA) test score, preoperative and postoperativeneurological status and short-term clinical outcomes. One examineradministered MoCA to both subjects preoperatively and onpostoperative days one, thirty, and ninety. The Montreal CognitiveAssessment is a brief 30-point scale screening tests that assesseseight neurocognitive domains including visuospatial and executivefunctioning, naming, memory, attention, language, abstraction,orientation and delayed recall.
Statistical analysis
We consider a score of >27 as normalcognitive function a score of 25- 27 as mild, 21-24 as moderate, <20as indicative of cognitive impairment. Data was accumulated, mean,median, standard deviation, and P value were calculated and utilizedto evaluate for significance and correlation. Clinical significanceis defined as the P value less than 0.05. The main use control groupneuropsychological scores is to normalize the performance of thepatients from the experimental group. The mean and the standarddeviation were used in the process while a standard deviation >2indicated significant cognitive dysfunction.
RESULTS
The p value for the research is less than 0.005, indicating that itis clinically significant. The results of our study indicate thatage, duration of surgery, education level, and immediatepostoperative pain level correlated with decline in MoCA score andshort-term cognitive impairment. All the patients (100%) completedthe pre- and postoperative assessment before discharge from hospital.Twenty-two (68.75%) patients showed up for 3months and 9 monthspost-surgery follow up appointment. Four (12.5%) patients did notshow up for 3 months post-surgery follow up appointment. Six patientsdid not show up for 9months post-surgery follow up appointment.  
.  The mean age of the control group was59 years while for the experimental group was 63 years. Most patientswere aged 60 and above (34.38%) with a lower mean of cognitivefunction of 25.98, while 25% of the patients were aged between 50 to60 years had mild cognitive function with a mean of (26.122). 40.63%of the patients were aged between 40 and 50 years with normalcognitive function of 28.39 after the operation. Therefore, there isdirect association between age and cognitive decline after majorspine surgery as determined by comparing the pre and post-operativeassessments. Comparisons of the pre- and postoperative assessmentsrevealed deterioration in cognitive functioning.
The level of education was also dependentvariable. Patients with a college education had a mean post-operativescore of 26.11, which is relatively lower to the pre-operative scoreof 26.5. On average patients with lower education, level demonstratedhigher drop in neurocognitive test score in postoperative period.High school patients had preoperative scores of 26.357 andpost-operative scores of 26 while high school dropouts had very lowpreoperative and post-operative scores of 24.0833 respectively.
Pain severity is indirectly proportional toneurocognitive test performance. The task dependent on attention wasimpaired by acute pain after the operation. The subject using thepatient controlled analgesia pump had lower average score on theinitial post-operative assessment but score improved to or near thebase-line level after 30 days. There was an average of * points dropin MoCA test on postoperative days in experimental group comparedwith controlled group * point drop. The decline was noted mainlyin attention, and executive function domains.
This study found a relationship betweenduration of surgery and postoperative cognitive decline.Specifically, patients that underwent surgery lasting longer than 4hours, mainly from the experimental group had a drop in postoperativeMoCA score.  In addition, the patients also experienced pain fora longer duration of time compared from the experimental group. TheTable 1below demonstrates the summary of the demographic data of both theexperimental and control group.
Table 1 Subject demographics
Variables                                        Controlgroup                         Experimentalgroup
Sample size (N)                                      17                                                15
Age (years)
   Mean                                                    59                                                 63
Gender (N)
    Male                                                     10                                                7
    Female                                                  7                                                  8
Duration of surgery (minutes)
  Mean                                                      70                                                220
 
Education (N)
  High school graduate                              6                                               5
  High school dropout                               1                                                   3
  College graduate                                      9                                                   8           
Ethnicity
White                                                     10                                                 11
African American                                   5                                                   4
  Hispanic                                                  2                                                   0
Duration of pain (years)                            
  Mean                                                       3                                                  12
  
Numeric Pain Rating Scale (NPRS)
 Mean                                                         7                                                    9
 
N= number, SD= standard deviation, NPRS= Numeric Pain Rating Scale isan 11-point scale from 0-10(“0” = no pain “10” = the mostintense pain imaginable).
The Table 2consisting of the test scores, mean, median and standard deviationand Table 3containing individual MoCA domain mean scores are found in theAppendix.
Discussion
Methods of operation
The goal of this study is to determine theeffect of major spinal surgery on cognitive function with generalanesthesia in relation to the risk factors. From the findings,patients in the experimental group had points drop in MoCA test onpostoperative days in experimental group compared with controlledgroup. The decline was noted mainly in attention, and executivefunction domains. This study indicates that in POCD is frequent andsevere in patients who have undergone extensive surgery. Patients inthe control group underwent lumbar decompression withoutinstrumentation and the patients who had undergone major spinesurgery such as posterior lumbar decompression with instrumentationserved as experimental group. With higher MoCA scores in the controlgroup, the study shows that the use of surgical methods that areminimally invasive may reduce the incidence and severity of POCD.
Age
The findings establish that age was a riskfactor in post-operative cognitive dysfunction. Patients aged 60years and older had the least scores in post-operative cognitivescores. They had higher error rate resulting in lower score andperformed slowly. Patients aged between 50 and 60 years had higherscores compared to older patients, while patients aged between 40 to50 years had normal cognitive postoperative scores. This isconsistent with the study by Rundshagen, (2014)in which many older adult patients developed post-operative cognitivedysfunction three months after elective major cardiac surgery. Theincidence of post-operative cognitive dysfunction was also higher inpatients older than 60 years after 3 months of surgery (Monk, Weldon,Garvan, Dede, Heilman & Gravenstein, 2008). Due to advancing age,the cognitive performance and the ability to compensate for deficitsreduce. Additionally, elderly patients may be having underlyingcognitive dysfunctions, which may make them susceptible to POCD.
Education background
This study also shows a correlation betweeneducation and post-operative cognitive dysfunction as patients withlower level of education demonstrated moderate cognitive functionswhich were lower scores in comparison to other groups. This issimilar to findings by Hong, Shim, Choi, et.al.,2008). According to Moller,Cluitmans, Rasmussen, Houx, Rasmussen et.al., (1998),patientswith lower educational level had worse cognitive function scores. Themechanism for this relationship is unknown.
Administration of general anesthesia
Findings in this study indicated that thepatient that used controlled analgesia pump had lower average scoreon the initial post-operative assessment but score improved to ornear the base-line level after 1 month. In many medical procedures,inhaled general anesthetics can readily pass into the brain. Theshorter the time the anesthetic agent takes action, the shorter theduration of impairment of cognitive function (Rundshagen, 2014).Studies show that after the first few days, patients may experiencepain, inflammation and impaired cognition. The incidence of POCD ismore after extensive surgery with administration of generalanesthesia (Rundshagen, 2014). The pharmacodynamics and thepharmacokinetic of the agents used determine the effect of anesthesiaon the cognitive function. Some patients may experience improvementin cognitive function post-operatively as the spinal surgery mayreduce pain and improve the quality of life. Administration ofpost-operative anesthetic is essential in reduction of postoperativecomplications in any age group of patients that have undergone majorspinal surgery.
On the other hand, it is still under debatewhether there is significant correlation between the use of generalanesthetic and post-operative cognitive dysfunction. In olderpatients, studies indicate that inhaled anesthetic exposure may causesymptoms that are similar to Alzheimer’s disease (Eckenhoff,Johansson, Wei, Carnini, Kang, Wei, Pidikiti, Keller & Eckenhoff,2004).However, this study supports the fact that the post-operativeassessments improves over time with administration of analgesics. Theepicenter of recent studies is comparison of regional anestheticsover general anesthetics (Fines & Severn, 2006).
There was no direct relationship between painseverity and neurocognitive test performance according to thefindings. Pain varies between individuals and may be varied innature chronic or acute. This is inconsistent with the study byHeyer, Sharma, Winfree, Mocco, McMahon, et,al., (2000) which established thatpain affected tasks that were dependent on attention. Pain caninterfere with neurocognitive performance such as attention, memoryand concentration. In major spine surgery, pain is present both pre-and post-operatively.
IMPLICATION OF THE PAPER
Neurocognitive functioning is an increasinglyimportant outcome measure even mild neurocognitive impairments maynegatively affect professional reintegration, interpersonalrelationships, leisure activities, self-care, and health-relatedquality of life. Impaired cognitive function after surgery alsoincreases morbidity and mortality. This study will enable developmentof strategies that will help reduce POCD after extensive spinalsurgery and contribute to existing literature.
In development of strategies that will reducemodifiable risk factors for neurocognitive dysfunction, patientswith risk factors for developing POCD are identified erly identification and treatment done under aggressive interventionstrategies. Analysis of variance found independent predictors of therisk of decline in neurocognitive function at 3months included olderage, lower level of education, longer duration of surgery.
These aggressive intervention strategies include cognitive behavioraltherapy before and after the surgery in prevention of furtherdeterioration in cognition. Critical evaluation should be done beforeperforming a major spinal surgery on high-risk patients for POCDparticularly the elderly. A preoperative cognitive assessment isimportant in weighing the potential benefit of the operation againstthe potential harm -POCD. Recommendation of use of minimally invasiveis encouraged because the incidence of POCD is higher after majorsurgery. Non-invasive methods have less trauma on tissues and causeless inflammatory response after the operation.
The identified patient related factors will be essential in allowingthe relevant physicians in providing education and counselling to thepatients and their families from an evidence based information. Thepatients will have the knowledge on the possibilities of the outcomeafter the surgery after both short and longer durations. This studythereby forms significant clinical implications in relation to thepatients making decision on the type of surgery and timing of thesurgery.
Limitations of the study
The main limitations of the study include loss of follow up andinherent limitation of the MoCA test.
Loss of follow up
The main limitations of the study include short term-follow up andloss of follow up. Loss of follow up can cause bias in the results.The bias occurs when the drop-out rates are different between theexperimental and the control groups as well as when the subjects whodrop out have different prognosis from those who complete the study.It is important to note loss of follow up because the patients whocomplete the study have different outcomes to those who are lost tofollow up. Loss of follow up also interferes with the validity of thestudy (Dettori, 2011).
Inherent limitation of the MoCA test.
MoCA is a validated brief screening test to detect cognitiveimpairment of any neuro-degenerative pathology. This test may fail lto detect minor cognitive impairment (Stephanie Lessig, MD, LauraMickes, PhD, et al. 2010). The test isnot able to detect the diffect types or severity of cognitiveconditions. Most conditions require formal neuropsychologicalevaluation and extensive tests. Therefore, the MoCA test alone cannotbe used for differential diagnosis of different types of cognitivedysfunction
To increase the understanding of the relationship between themetabolism in the brain and the neuropsychological test performancethere is need to utilize functional brain imaging and cerebralperfusion in patients who have undergone extensive spinal surgery.This will allow simultaneous evaluation of both surgery inducedmetabolic response and neuropsychological markers of cognitiverecovery.  
This study highly recommends use of a larger sample in futurestudies, a longer duration of follow up study and a multivariateanalysis in identifying more risk factors such as types of generalanesthetics, duration of surgery and hospital stay, underlyingcognitive dysfunction preoperatively. Future studies should alsoinclude how post-operative cognitive dysfunction negatively affectsthe quality of life as well as increasing the rate of morbidity andmortality.
CONCLUSION
The findings from this study underscore theimportance of preventing or reducing perioperative cognitive declinein order to preserve cognitive function and the quality of life inpatients undergoing major surgery. This study will also facilitatethe development of preventive measures that will reduce the rate ofmortality and morbidity related to COPD.
Some patients who have undergone extensive spine surgery achieve anaffirmative neurological outcome despite exhibiting cognitiveimpairment. The evaluation and treatment ofpatients with spinal pathology should not only focus on improvingfocal neurologic deficit or pain, but should also aim at decreasingadverse treatment effects on the normal brain and neurocognitivefunction.
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Appendix
Table 2 Test scores
Patient number | Age (years) | Education Level | NPRS | Preop MoCA score | POD1 MoCA score | POD30 MoCA score | POD90 MoCA score | |
1 | 53 | C | 10 | 29 | 26 | 28 | 29 | |
2 | 46 | C | 8 | 28 | 27 | 29 | 28 | |
3 | 78 | HS | 9 | 26 | 25 | 27 | 28 | |
4 | 64 | C | 8 | 25 | 24 | 25 | 26 | |
5 | 70 | C | 6 | 24 | 23 | 25 | 24 | |
6 | 67 | C | 9 | 28 | 24 | 27 | 28 | |
7 | 77 | C | 5 | 24 | 23 | 24 | 24 | |
8 | 68 | HSD | 6 | 23 | 22 | 24 | 26 | |
9 | 51 | C | 9 | 29 | 25 | 28 | 29 | |
10 | 67 | HS | 7 | 25 | 24 | 25 | 24 | |
11 | 51 | HS | 10 | 30 | 26 | 30 | 30 | |
12 | 49 | C | 11 | 29 | 26 | 29 | 29 | |
13 | 76 | HSD | 9 | 25 | 23 | 26 | 25 | |
14 | 48 | HS | 6 | 28 | 27 | 29 | 30 | |
15 | 58 | C | 11 | 30 | 26 | 30 | 29 | |
16 | 75 | C | 8 | 25 | 21 | 24 | 26 | |
17 | 69 | HS | 8 | 25 | 23 | 26 | 24 | |
18 | 73 | HS | 9 | 24 | 22 | 25 | 23 | |
19 | 42 | C | 8 | 28 | 26 | 30 | 30 | |
20 | 57 | C | 9 | 27 | 27 | 28 | 27 | |
21 | 62 | HSD | 11 | 25 | 23 | 24 | 26 | |
22 | 72 | C | 8 | 26 | 24 | 25 | 25 | |
23 | 62 | C | 7 | 28 | 28 | 30 | 30 | |
24 | 59 | HS | 11 | 29 | 27 | 30 | 30 | |
25 | 51 | C | 9 | 24 | 26 | 27 | 26 | |
26 | 75 | HSD | 10 | 24 | 23 | 23 | 24 | |
27 | 44 | C | 11 | 29 | 25 | 30 | 30 | |
28 | 63 | C | 8 | 25 | 24 | 24 | 24 | |
29 | 68 | C | 9 | 26 | 23 | 26 | 25 | |
30 | 60 | HS | 10 | 27 | 26 | 27 | 28 | |
31 | 48 | C | 7 | 29 | 28 | 29 | 29 | |
32 | 69 | C | 8 | 24 | 21 | 24 | 25 | |
Mean | 61 | C | 20 (62.5%) | 8.59375 | 26.5 | 24.625 | 26.8125 | 26.9063 |
H | 8 (25%) | |||||||
HSD | 4 (12.5) | |||||||
Median | ||||||||
SD | ||||||||
POD=postoperative day Montreal Cognitive Assessment score,Preop=preoperative  Montreal Cognitive Assessment score, HS=HighSchool , C=College , HSD= High School dropout. NPRS= Numeric PainRating Scale is an 11-point scale from 0-10(“0” = no pain “10”= the most intense pain imaginable.
Table 3Individual MoCA Domain Mean Scores
Neurocognitive test | Preop Score | POD1 A score | POD1 B score | POD30    A score | POD30 B score | POD90 A score | POD90 B score |
Visuospatial/Executive Functioning | 4 | 4 | 3 | 4 | 4.5 | 4 | 4 |
Naming | 2.5 | 2.5 | 2 | 2.5 | 2.5 | 2.5 | 25 |
Attention | 5 | 4.5 | 4 | 4.5 | 5 | 5.5 | 5.5 |
Language | 2 | 2 | 2 | 2.5 | 2 | 2.5 | 2.5 |
Abstraction | 1.5 | 1.5 | 1 | 1.5 | 1.5 | 1.5 | 1.5 |
Orientation | 4 | 4 | 4 | 4.5 | 4.5 | 4.5 | 4 |
Delayed Recall | 5.5 | 5.5 | 5 | 5 | 5.5 | 5.5 | 5.5 |
Memory – No points was awarded for memory | – | – | – | – | – | – | – |
MoCA= Montreal Cognitive Assessment, POD= postoperative day MontrealCognitive Assessment score, Preop = preoperative Montreal CognitiveAssessment score, A= control group, B= Experimental group