Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 377-386

Comparative study between general anesthesia and sciatic–femoral–obturator blockade as regards analgesia and incidence of postoperative cognitive dysfunction in elderly patients undergoing unilateral total knee replacement


1 Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Neuropsychiatry, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission20-Sep-2015
Date of Acceptance15-Apr-2016
Date of Web Publication31-Aug-2016

Correspondence Address:
Ayman A El Sayed
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.189566

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  Abstract 

Objectives
The aim of this study was to compare the effect of sevoflurane general anesthesia (GA) and sciatic–femoral–obturator blockade as regards analgesia and incidence of postoperative cognitive dysfunction (POCD) in elderly patients undergoing unilateral total knee replacement.
Patients and methods
The patients were divided in a randomized manner into two groups: the GA group (n=40) received maintenance of anesthesia with inhalational sevoflurane, and the peripheral nerve block (PNB) group (n=40) underwent sciatic nerve block (40 ml), femoral nerve block (20 ml), and obturator nerve block (10 ml) with 0.25% bupivacaine. The following time points were considered: baseline, immediately before induction of anesthesia (T-baseline), immediately after induction of anesthesia (T-induction), at the end of the operation (T-end) and then at 6, 12, 18, and 24 h postoperatively and were represented as T6, T12, T18, and T24, respectively.
Results
A total of 15 of 40 patients from the GA group developed POCD, whereas six of 38 patients in the PNB group developed POCD at T24. This difference was significant. Moreover, there was a significant decrease in Mini-Mental State Examination score in the GA group after 24 h in comparison with the preoperative value. There was a significantly higher value of Aβ (β-amyloid protein) in the GA group compared with the PNB group 24 h postoperatively. Visual analogue score was significantly lower at T-end, T6, T12, T18, and T24 in the PNB group compared with the GA group. Hemodynamics was significantly lower in the PNB group than in the GA group at T-end, T6, T12, T18, and T24. They were significantly higher in the PNB group than in the GA group at T-induction. Total opioid consumption within 24 h postoperatively and the incidence of nausea were lower in the PNB group compared with the GA group. Induction time was significantly longer in the PNB group than in the GA group.
Conclusion
The current study demonstrated that PNB with sciatic–femoral–obturator for total knee replacement was accompanied by less POCD, less pain, less nausea, and less opioid consumption within 24 h postoperatively compared with GA with sevoflurane.

Keywords: amyloid, analgesia, postoperative cognitive dysfunction, sciatic–femoral–obturator, total knee replacement


How to cite this article:
El Sayed AA, Soltan M, Nabil MM. Comparative study between general anesthesia and sciatic–femoral–obturator blockade as regards analgesia and incidence of postoperative cognitive dysfunction in elderly patients undergoing unilateral total knee replacement. Ain-Shams J Anaesthesiol 2016;9:377-86

How to cite this URL:
El Sayed AA, Soltan M, Nabil MM. Comparative study between general anesthesia and sciatic–femoral–obturator blockade as regards analgesia and incidence of postoperative cognitive dysfunction in elderly patients undergoing unilateral total knee replacement. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 14];9:377-86. Available from: http://www.asja.eg.net/text.asp?2016/9/3/377/189566


  Introduction Top


There is a high incidence of early postoperative cognitive dysfunction (POCD), which may account for 40% of all patients undergoing various types of operations under anesthesia. This can affect the quality of life and rehabilitation of patients [1]. POCD is typically defined as a persistent and significant change in mental status compared with the expected performance on postoperative neurocognitive testing [2]. There is an increased risk for death in the first year after surgery in patients with POCD [3]. Although the type of anesthesia and operation may have a role in the development of POCD, there are possible risk factors contributing to the development of POCD, including preoperative cognitive function, age, pain, differences in genes, β-amyloid protein (Aβ), cholinergic system, anesthetics used, duration of operation, hypoperfusion, and embolism [4].

One of the major proteins that are implicated in the pathogenesis of the cognitive dysfunction and Alzheimer disease are Aβ peptides. Aβ peptides are considered normal products of metabolism. However, when there is an imbalance between production and clearance, cognitive dysfunction is likely to occur. In cognitive dysfunction and Alzheimer disease, Aβ aggregate into neurotic plaques and temporal-lobe structures [5].

Both regional anesthesia and general anesthesia (GA) can be used for total knee replacement (TKR) surgery. Peripheral nerve blocks (PNBs) can be used as a sole anesthetic technique for TKR, or can be combined with GA to provide relief from pain postoperatively [6]. It has been proved that anesthesia with sevoflurane developed memory impairment in aged rats through an effect on Aβ deposition and oligomerization [7].

The exact cause of POCD following knee and hip replacement remains unclear. There are several theories that have been included, such as systemic emboli [8] or cerebral emboli [9]. Some researchers have demonstrated few systemic and cerebral emboli after TKR [8],[9].

In this study, we compared GA with sevoflurane versus PNB (using sciatic, femoral, and obturator blockade) as regards the incidence of POCD and analgesia after TKR. POCD was evaluated clinically using the neuropsychological test: Mini-Mental State Examination (MMSE). Moreover, the changes in plasma Aβ levels were measured preoperatively and 1 day postoperatively.


  Patients and methods Top


Patient recruitment

This study was conducted after the approval of the local ethics committee. All patients were operated upon in a tertiary hospital, in Jeddah, Saudi Arabia, between May 2013 and March 2015. Written informed consent was obtained from each patient. This study was a prospective randomized study. Eighty patients of American Society of Anesthesiologists (ASA) classes I–II scheduled for unilateral TKR were recruited from our hospital. Their ages ranged from 60 to 75 years. We abided by the following exclusion criteria: (a) a current or past history of central nervous system disease or psychiatric disorder; (b) preoperative MMSE score less than 23; (c) drug or alcohol dependence; (d) localized infection at the site of the nerve blockade; (e) hepatic failure; (f) renal failure; (g) inability to read or speak; (h) serious hearing or vision impairment; (i) bleeding disorders; (j) sickle cell disease; and (k) allergy of any of the anesthetic drugs.

Anesthetic techniques and study protocol

After arrival at the operating room, an 18-G intravenous cannula was inserted. All patients were monitored with ECG, NIBP, capnography, and oxygen saturation (SpO2). A bispectral index sensor was attached to the forehead and connected to an Aspect A2000 monitor version (Aspect Medical Systems, Inc. 141 Needham St. Newton, MA, USA). The patients were equally divided in a randomized manner into two groups using the closed envelop technique. In the GA group (n=40), continuous maintenance of anesthesia was carried out with inhalation of sevoflurane (Abbott Laboratories Ltd, Abbott Park, Illinois, USA) (1–3%) to maintain bispectral index between 40 and 60. In the PNB group (n=40), sciatic nerve block (40 ml, 0.25% bupivacaine), femoral nerve block (20 ml, 0.25% bupivacaine), and obturator nerve block were performed (10 ml, 0.25% bupivacaine). Bupivacaine was obtained from Hikma Pharmaceuticals (Amman, Jordan).

In the GA group, to induce anesthesia, all patients were ventilated with 100% oxygen through a mask and then anesthesia was induced with midazolam (Hikma Pharmaceuticals) 0.04 mg/kg, propofol (Fresenius Kabi Deutschland GmbH, Germany) 1.5 mg/kg, fentanyl (fentanyl; Fresenius Kabi Deutschland GmbH, Kuehne, Panjiva) 1.5 μg/kg, and cisatracurium (Nimbex; GlaxoSmithKline, GSK) 0.15 mg/kg. All patients were intubated with a cuffed endotracheal tube after 3 min of injection of cisatracurium. Cisatracurium was given as increments of 1 mg/20 min to maintain muscle relaxation. Mechanical ventilation was provided with 6 ml/kg tidal volume and a frequency of 10–14/min with a total of 3 l/min in 50% O2 in nitrous oxide mixture to keep EtCO2 between 30 and 35 mmHg.

In the PNB group, midazolam (0.03 mg/kg) and fentanyl (1 μg/kg) were given intravenously as sedation before applying PNBs. Oxygen (4 l/min) was administered through a facemask.

  1. Sciatic nerve block (anterior approach):The patient was placed supine. The following bony landmarks were detected: (A) the anterior superior iliac spine, which was located as the most prominent area of the iliac crest anteriorly when the curved part of it started to change its orientation abruptly caudally; (F) the pubic tubercle, which is the lateral bony bulge from the symphysis pubis; and (C) the greater trochanter, the bone prominence at the lateral aspect of the upper thigh. Using a skin marker, a line B is drawn between anterior superior iliac spine and pubic tubercle, indicating the inguinal ligament. This line is then divided into three equal parts. A second line (2) parallel to B was drawn. A third line (3) perpendicular to both B and 2, and crossing B at the junction between lateral two-third and medial one-third was drawn. The intersection between 2 and 3, point D, is the needle insertion point, which indicates the lesser trochanter. For an average-sized patient, the lesser trochanter will be encountered at a depth of 7 or 8 cm. The needle should then be withdrawn 1–2 cm, and walked off medially until bone contact disappeared. The sciatic nerve was encountered 2–3 cm deeper than bone depth (i.e. at 9–12 cm from the skin). Palpable or visible twitches of the foot or toes at 0.2–0.5 mA current were our aim. Either plantar flexion and inversion or dorsiflexion and eversion were accepted responses. The insulated needle length was 150 mm. This approach is shown in [Figure 1] [10].
    Figure 1 Sciatic nerve block (anterior approach). The landmarks described by Beck aim at localizing the lesser trochanter. A; Anterior superior iliac spine (ASIS), B; Line joining the pubic tubercle(F) and ASIS, C ;Greater trochanter, D; Lesser trochanter, E; Sciatic nerve, F; Pubic tubercle.

    Click here to view
  2. Femoral nerve block:The femoral artery was identified below the inguinal ligament. The femoral nerve was detected immediately lateral to the artery by eliciting contractions of the quadriceps (patellar twitch). The insulated needle length was 50 mm [11].
  3. Obturator nerve block:The block was performed using the traditional approach. The insulated needle (100 mm) was placed perpendicularly at 2 cm lateral and 2 cm inferior to the pubic tubercle. The needle was then inserted through the skin to the pubic bone (inferior rami). Thereafter, it was withdrawn and redirected laterally and anteriorly, stimulating the nerve at 2–4 cm depth [12]. Our target was adductor muscle contraction.


In all nerve blocks, we sterilized the site of the block using betadine and alcohol. All insulated needles were echoplex (Vygon, France). The nerve stimulator used was plexygon (Vygon Italia, Italy), which delivered a pulsed electrical current at several milliamps (mA). Visible or palpable twitches of the target muscles were achieved at 0.2–0.5 mA current. If persistence of the evoked response occurred at 0.2 mA, the needle was slightly withdrawn to get the response between 0.2 and 0.5 mA. The tested solution was injected slowly with negative aspiration for blood and slow injection (e.g. ≤20 ml/min) was important.

Motor and sensory blocks on the operated side were tested every 5 min, and we did not allow the operation to start except when the patient sensory and motor block was achieved on the operative side.

If failure of sensory loss was faced after 30 min, it was considered block failure.

The sensory block was evaluated with ice as follows:

  1. 2, the same sensation;
  2. 1, diminished sensory level;
  3. 0, sensation lost.


Moreover, the motor block was tested using the modified Bromage scale [13]:

  1. 2, motor activity with full power (no change);
  2. 1, decreased power of motor activity;
  3. 0, motor activity lost.


A tourniquet was put around the thigh and inflated to double the systolic arterial blood pressure. The intraoperative blood pressure and heart rate (HR) were maintained to allow fluctuation less than 20% of the baseline values. Crystalloid solutions (8–10 ml/kg/h) were used as maintenance fluid immediately postoperatively in both groups. The average surgical time procedure was 2 h. After the end of the surgery in both groups, the patients were transferred to the recovery room and observed for 1 h postoperatively. As the effective nerve block using bupivacaine 0.25% was not less than 8.4±1.2 h, it was sufficient for all patients included in the study. We decided to proceed to GA if any surgical complication that would prolong the duration of the operation more than the expected time for effective nerve blockade occurred. Those patients were excluded from our study. However, we didn’t face that problem (very lengthy operation).

For postoperative pain control in both groups, 1 g of perfalgan intravenous infusion over 15 min was administered immediately postoperatively in both groups. In addition, patient-controlled analgesia (SIMS Graseby Limited, Watford, Herts, UK) was initiated immediately postoperatively in both groups using tramadol (tramadol HCl 100 mg, 2 ml; Grunenthal) (4 mg/ml tramadol in 50 ml of 0.9% normal saline, the infusion was 12 mg/h, 16 mg bolus with a 15-min lock-out time and no 4-h limit).

Outcome measures

The following time points were considered: baseline, immediately before induction of anesthesia (T-baseline), immediately after induction of anesthesia (T-induction), at the end of the operation (T-end) and then at 6, 12, 18, and 24 h postoperatively and were represented as T6, T12, T18, and T24, respectively.

The following data were collected:

  1. Patient demographic data (age, sex, BMI, height, ASA, incidence of diabetes mellitus, and hypertension), duration of surgery, anesthesia induction duration, total opioid consumption, incidence of nausea, and duration of PNB.
  2. Pain score using visual analogue score (VAS) [14], which was recorded at T-end, T6, T12, T18, and T24 postoperatively.
  3. Physiological variables: HR and mean arterial pressure (MAP), which were recorded at T-baseline, T-induction, T-end, T6, T12, T18, and T24 postoperatively.
  4. Neuropsychological assessment using the MMSE, which was recorded preoperatively and 24 h postoperatively.
  5. Analysis of plasma Aβ, which was collected preoperatively and 24 h postoperatively.


The primary outcome variable of the present study was MMSE.

The MMSE is a screening test that quantitatively assesses cognitive impairment using some questions asked to the patients before the operation and 1 day after operation (as shown below). The maximum MMSE score is 30 points; the indication of cognitive dysfunction was diagnosed when the score was 23 or less [15]. However, because we excluded patient with MMSE less than 23, we considered the criterion used to evaluate impairment in cognitive function in our study as a reduction of 2 or more points on the MMSE test in comparison with the preoperative value.

Mini-Mental State Examination

Orientation

5 () Where are we: country, state, town, floor, hospital?

5 () What is the year, date, season, month, day?

Registration

3 () Mention three objects at an interval of 1 s. Then ask the patient to list all three objects after you have mentioned them, giving 1 point for each correct answer.Attention and calculation

5 () Serial 7s: 90–7=83–7=76–7=69–7=62–7=55. Give 1 point for each correct answer. Stop after five answers.

Recall

3 () Ask for the three objects to be repeated (vase, car, brick). Give 1 point for each correct answer.

Language

2 () Name a watch and a pencil.

1 () Repeat the following ‘No ifs, ands, or buts’.

3 () You can tell a three-stage command:

‘Take a paper in your right hand, fold it by half, and put it over the floor.’

1 () Read and obey this sentence: CLOSE YOUR EYES

1 () Write a sentence with a meaning.

1 () Copy the diagram shown.

_____Total score 30 [16].

Analysis of plasma Aβ

We analyzed plasma levels of Aβ as a biomarker of brain injury. Blood samples were taken from the patients at T-baseline and T24. Five milliliters of venous blood sample was put into a procoagulant polyvinyl chloride tube and placed in the refrigerator for 2 h, and then it was centrifuged at 3000 r/min at 4°C for 10 min to separate the serum. The supernatant was taken and placed in a polyvinyl chloride tube and put at −20°C. The experimental specimens were adjusted at room temperature before reconstitution and usage. DRG amyloid β 1–40 (human) (EIA-5231) ELISA kit was used (DRG International Inc., Springfield, New Jersey, USA). We performed the assay according to the instructions that were provided by the supplier to construct a standard curve; OD values of the measured specimen were calculated to detect the protein content. The average absorbance values for each set of standards, controls, and specimen samples were calculated. Thereafter, using a linear graph paper, a standard curve was constructed by plotting the mean absorbance obtained from each standard against its concentration, with absorbance value on the vertical (Y) axis and concentration on the horizontal (X) axis. Thereafter, using the mean absorbance value for each sample, the corresponding concentration from the standard curve was determined.

Statistical analysis and sample size calculation

The statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc., Chicago, Illinois, USA). Normally distributed numerical data were presented as mean±SD. Non-normally distributed data were compared using the Mann–Whitney test and were presented as median (interquartile range), and categorical variables were analyzed using the χ2-test and presented as n (%). P value less than 0.05 was considered statistically significant.

Using PASS 11 for sample size calculation, it was calculated that a sample size of 35 patients per group will achieve 80% power to detect a difference of 2 in MMSE score compared with baseline, with a significance level (α) of 0.05 using a two-sided two-sample t-test; 40 patients per group were included to replace any dropouts.


  Results Top


Demographic data

Only 78 patients completed the study. Two patients in the PNB group had failed block after 30 min; we changed them to GA and they were excluded from the study. Anesthesia induction duration was significantly lower in the GA group compared with the PNB group (7.79±1.5 vs. 26.95±2.6, respectively). There was a higher incidence of nausea in the GA group compared with the PNB group (58 vs. 34%, respectively). This difference was statistically significant (P=0.04). As regards total opioid consumption, there was a significantly higher value in the GA group compared with the PNB group (504.6±21.13 vs. 361.3±17.3, respectively). The duration of PNB was 8.4±1.2 h. As regards the demographic data, no significant differences were demonstrated between the two groups, as shown in [Table 1].
Table 1 Demographic data, incidence of nausea, total opioid consumption, and anesthesia induction duration

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Postoperative cognitive dysfunction incidence, neuropsychological test (Mini-Mental State Examination), and Aβ analysis

A total of 15 of 40 patients from the GA group developed POCD, whereas in the PNB group six of 38 patients developed POCD 24 h postoperatively. This difference was statistically significant. The MMSE score was significantly lower in the GA group compared with the PNB group after 24 h postoperatively (< or=2 points) (25.45±1.1 vs. 28.89±0.95, respectively). Moreover, there was a significant decrease in MMSE score in the GA group after 24 h in comparison with the preoperative value (25.45±1.1 vs. 29.08±0.76, respectively). When Aβ levels were compared after 24 h postoperatively, there was a significantly higher value in the GA group compared with the PNB group (110.95±3.64 vs. 80.24±5.3, respectively). When Aβ levels were compared after 24 h postoperatively in the GA group, there was a significant increase in comparison with preoperative value in the GA group (110.95±3.64 vs. 76.63±0.95, respectively). Preoperatively, there was no significant difference between the two groups either for MMSE or Aβ levels, as shown in [Table 2].
Table 2 Postoperative cognitive dysfunction incidence, neuropsychological test (Mini-Mental State Examination), and Aβ levels preoperatively and after 24 h

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Hemodynamic variables (heart rate and mean arterial pressure)

MAP and HR were significantly lower in the PNB group compared with the GA group at T-end, T6, T12, T18, and T24, whereas they were higher in the PNB group compared with the GA group at T-induction. No significant difference was found between the two groups at T-baseline, as shown in [Table 3].
Table 3 Mean arterial pressure (mmHg) and heart rate (beats/min)

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Visual analogue score

VAS was significantly lower at T-end, T6, T12, T18, and T24 in the PNB group compared with the GA group (P<0.05) [Table 4]. The average duration of PNB was 8.4±1.2 h, but we started analgesia (patient-controlled analgesia) in both groups immediately postoperatively.
Table 4 Visual analogue score in group GA and group PNB at different time points

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  Discussion Top


The current study demonstrated that nerve block with sciatic–femoral–obturator for TKR was accompanied by less POCD, less pain, less nausea, and less opioid consumption within 24 h postoperatively compared with GA with sevoflurane anesthesia. Hemodynamics (MAP and HR) were significantly lower in the PNB group compared with the GA group at all time points, except at T-induction. Aβ was significantly higher after 24 h in the GA group compared with the PNB group. However, the major advantage of GA was the duration of induction, which was significantly lower in the GA group compared with the PNB group.

POCD is considered a common postanesthetic neurologic complication, manifested as anxiety, mental confusion, and memory impairment. The exact pathogenesis of POCD is unclear, although it can be influenced by multiple factors. Most researchers believe that POCD is related to age, anesthesia, operation, sleeping disorder, psychologic factors, and pain [17]. Neuroinflammation has been implicated in the pathogenesis of POCD [18].

In our study, the incidence of POCD with TKR 24 h postoperatively was up to 37.5% in the GA group, whereas it was 15.8% in the PNB group; this difference was statistically significant. Our results are in accordance with the results of Shi et al. [19], who compared epidural versus GA for total hip replacement. The incidence of POCD in their study 1 day postoperatively for GA and epidural anesthesia were 36 and 16%, respectively. The difference in both groups may be caused by the neurotoxicity of general analgesia drugs.

There was another study by Mason et al. [20], which was different from our study. It was a systematic review with meta-analysis and presented no significant difference in the occurrence of POCD with regional anesthesia compared with GA. The possible explanation for this lack of difference may be related to the usage of sedatives with regional anesthesia. Thus, regional anesthesia has two advantages: first, it improves analgesia, and, second, it avoids the cognitive effects of opioids [20].

Regional anesthesia has risks, such as local anesthetic toxicity and nerve damage [21]. The total bupivacaine dose of nerve blocks in our study did not exceed 2 mg/kg (70 ml of 0.25% bupivacaine). However, GA also has risks, and the increased exposure to anesthetic drugs could increase the risk, including poor recovery, nausea, and vomiting [21].

The first International Study of POCD reported that the incidence of POCD in patients older than 60 years is 25.8% 1 week after major noncardiac surgery [17].

Another study conducted by Newman et al. [2] showed that the incidence of POCD after noncardiac surgery was 6.2% 22 days following surgery. Monk et al. [3] found that the incidence of POCD was 12.7% 3 months after surgery. All these studies had a lower incidence of POCD compared with our study, which may be due to the choice of operations or the time of testing the POCD. Our study was conducted only for TKR and we examined the patient only 24 h postoperatively.

In contrast to our findings, clinical studies have demonstrated that anesthesia with sevoflurane may be accompanied by better cognitive function compared with anesthesia with propofol for cardiac surgery operations [22]. This apparent difference may be related to the different age groups of both studies (18 years [22] vs. >60 years in our study), and there is evidence that there is a relationship between age and cognitive dysfunction related to inhalational anesthesia [23].

Aβ peptides are normal products of metabolism. Aβ is a polypeptide protein with a folded shape and β sheet structure formed of 39–43 amino acids. Its molecular weight is about 4 kD. Aβ is considered an initiating factor of plaque formation in old age and Alzheimer’s disease. There is a correlation between increased Aβ and cognitive dysfunction [24]. Accumulation of Aβ has also been related to a decrease in cholinergic receptors, which are key mediators of normal electrical transmission in networks associated with attention, memory, and learning. Aβ exposure also inhibits the activity of mitochondria. The resulting mitochondrial dysfunction leads to free radical release, which causes oxidative stress and neuronal dysfunction [25]. Sevoflurane can change the formation of amyloid precursor protein and increase Aβ level, which would result in neurotoxicity [26]. The pathophysiology of POCD can be related to neurodegeneration and anesthesia [27].

There was a significantly higher value of Aβ 1 day after the operation in the GA group compared with the PNB group. Moreover, it increased significantly in the GA group at T24 in comparison with the preoperative values. The previous study [28] demonstrated that the toxicity of Aβ may trigger the early apoptosis of the neurons. In our study, the Aβ level was increased significantly in the GA group, which indicates that the general analgesia drug may stimulate Aβ protein changes. The enhanced Aβ initiates the neurotoxicity of the patients. However, the nerve blockade drug may not be included in this pathway.

Anesthesia and surgery may lead to inflammation of the brain, which is considered one of the mechanisms of increased incidence of POCD [29]. Gold et al. [30] proved that Aβ is one of the potential markers of persistent inflammation and neurologic damage.

There is an increase in Aβ precursor protein (β-APP), which leads to increased brain Aβ. Central inflammatory cytokines in transcription can lead to the accumulation of APP; Aβ would further trigger apoptosis of the neurons. Aβ can inhibit the transmission of information in neurons, leading to dysfunction of memory and learning [31]. There were other factors that may be implicated in the occurrence of POCD, such as the type of anesthesia used.

It was found that halothane and isoflurane can enhance amyloid β oligomerization [32]. Therefore, we should be cautious when inhalational anesthetics are used in patients with pre-existent levels of brain β amyloid (Alzheimer’s disease) [33].

It was found that sevoflurane impaired memory and spatial learning in aged rats through an effect on amyloid β peptide deposition and oligomerization [7].

Some studies found that sevoflurane worsened cognitive functions [34], others reported that sevoflurane may have a beneficial effect on cognition [35], whereas some detected no effects on cognition [36].

The MMSE test has been frequently used in most of the patients in various age groups undergoing either noncardiac or cardiac elective surgery [37]. Wiklund et al. [28] proved that the specificity of MMSE method is 82% and the sensitivity is 87% for cognitive function assessment. In our study, there was no significant difference between the GA and the PNB group preoperatively. However, MMSE had significantly lower values in the GA group compared with the PNB group at T24 (P<0.05).

One of the major drawbacks of TKR is pain, which is considerable and needs adequate analgesia [38]. The single injection of PNBs could maintain 8–12 h of significant analgesia in our study, which was similar to that reported in the previous study [39].

Pain in our study was assessed using the following: first, the VAS, which was significantly lower in the PNB group at T-end, T6, 12, 18, and 24 compared with the GA group; second, the total opioid consumption, which was significantly lower in the PNB group over the 24 h postoperatively compared with the GA group; and, third, its effect on hemodynamics (MAP and HR), which had lower values at T-end, 6, 12, 18, and 24 in the PNB compared with the GA group. However, the only time point with significantly lower values in the GA group compared with the PNB group was T-induction (immediately after induction of anesthesia), which may be related to the depressive effect of general anesthetics and still inadequate blockade of nerves in the PNB group.

Zhang et al. [40] found that the pain of the surgical incision caused learning impairment in mice at 3 and 7 days after incision. This finding indicated that there is a possible effect of pain on POCD in mice.

Wang et al. [41] investigated the relationship between pain and POCD; they found that patients above 72 years of age undergoing noncardiac surgery and not having any symptoms of delirium could develop a significant impairment in cognitive function postoperatively. Patients who received postoperative analgesia orally had the least risk of developing POCD.

The incidence of nausea was significantly lower in the PNB group compared with the GA group. This finding could be explained by the improvement in pain relief in the PNB group. We could not neglect the lower consumption of opioid in the PNB group [42].

Our investigation presents some limitations, which need to be considered. First, education level of the patients was not included in our study. Second, we investigated the variables for 24 h only, which is considered a short period to properly investigate POCD. Third, lack of measurements of other variables, which may be included in POCD, such as glucose level.


  Conclusion Top


The current study demonstrated that nerve blockade with sciatic–femoral–obturator for TKR was accompanied by less POCD, less pain, less nausea, and less opioid consumption within 24 h postoperatively compared with GA with sevoflurane anesthesia. There were significantly higher values of Aβ levels in the GA group compared with the PNB group 24 h postoperatively. Moreover, Aβ levels increased significantly in the GA group at T24 in comparison with the preoperative values. Hemodynamics (MAP and HR) were significantly lower in the PNB group compared with the GA group at all time points except at T-induction. However, the major advantage of GA was the duration of induction, which was significantly lower in the GA group compared with the PNB group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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