Effect of Subanesthetic Dose of Esketamine on Perioperative Neurocognitive Disorders in Elderly Undergoing Gastrointestinal Surgery: A Randomized Controlled Trial

Figures & data

Table 1 Baseline Characteristics of Surgical Patients and Volunteers

Variables	Surgical Patients (n=67)	Health Volunteers (n=15)	P value
Age [years, mean (SD)]	70.30(6.92)	72.00(4.64)	0.386
Male [sex, n(%)]	37(55.22)	7(46.67)	0.548
Height [cm, mean (SD)]	165.04(8.60)	164.40(6.33)	0.785
Weight [kg, mean (SD)]	63.62(9.73)	62.07(6.87)	0.560
Body mass index [kg/m^2, mean (SD)]	23.17(2.92)	22.92(1.66)	0.657
MMSE score [point, mean (SD)]	28.24(1.44)	27.87(1.06)	0.347
Smoking [n(%)]	18(26.87)	4(26.67)	1.000
Alcoholism [n(%)]	19(28.36)	5(33.33)	0.702
Education level> 9[n(%)]	17(25.37)	5(33.33)	0.529

Notes: Data are expressed as mean (SD), except for categorical data which are expressed as n(%).

Abbreviation: MMSE, mini-mental state examination.

Figure 1 Enrollment flowchart.

Table 2 Demographic, Clinical, and Surgical Characteristics in Both Groups

Variables	Group S (n=33)	Group C (n=34)	P value
Age [years, mean (SD)]	70.60(7.63)	70.00(6.25)	0.723
Male [sex, n(%)]	18(54.55)	19(55.89)	0.912
Height [cm, mean (SD)]	164.91(9.05)	165.18(8.26)	0.900
Weight [kg, mean (SD)]	63.32(10.04)	63.91(9.56)	0.805
Body mass index [kg/m^2, mean (SD)]	23.13(3.42)	23.21(2.40)	0.907
MMSE score[point, mean (SD)]	28.58(1.15)	27.91(1.62)	0.058
Smoking [n(%)]	10(30.30)	8(23.53)	0.532
Alcoholism [n(%)]	9(27.27)	10(29.41)	0.846
Education level > 9 [years, n(%)]	7(21.21)	10(29.41)	0.484
Propofol [mg, mean (SD)]	1064.15(433.72)	1003.26(229.02)	0.473
Remifentanil [mg, mean (SD)]	0.82(0.32)	1.04(0.27)	0.003^a
Anesthesia duration [min, mean (SD)]	201.97(70.92)	182.41(41.64)	0.172
Surgical duration [min, mean (SD)]	164.79(64.68)	151.21(38.55)	0.299
Recovery time [min, mean (SD)]	10.6(6.20)	8.63(4.08)	0.125
Extubation time [min, mean (SD)]	14.67(6.12)	12.44(3.83)	0.081
Postoperative nausea and vomiting [min, mean (SD)]	8(24.24)	12(35.29)	0.323
Rescue ketorolac dose [mg, mean (SD)]	12.73(16.82)	22.06(19.97)	0.043^a
VAS score [point, mean (SD)]	2.12(0.74)	2.53(0.79)	0.032^a

Notes: Data are expressed as mean (SD), except for categorical data which are expressed as n (%). ^aP<0.05, Student’s t-test, Chi-squared test or Fisher’s exact probability test.

Abbreviations: MMSE, mini-mental state examination; VAS, visual analogue scale.

Table 3 Neuropsychological Test Results

Test	7 Days After Surgery		3 Months After Surgery
	Group S	Group C	Group S	Group C
Rey Auditory Verbal Learning (Immediate)	3	4	1	1
Rey Auditory Verbal Learning (Delayed)	8	13	3	5
Digit Symbol Subtest	3	4	1	2
Grooved Pegboard Test	9	15	4	4
Digit Span Subtests	3	2	1	2
Verbal Fluency Test	2	2	1	2
Finger-tapping Task	6	9	2	1
Trail Making Test	3	2	1	0
Block Test	1	1	0	1
PND	5	13	2	5

Abbreviation: PND, perioperative neurocognitive disorders.

Table 4 Incidence of PND in Both Groups

	Group S	Group C	P value
dNCR [n(%)]	5/33(18.15%)	13/34(38.24%)	P=0.033^a
POCD [n(%)]	2/33(6.06%)	5/34(14.71%)	P=0.247

Notes: ^aP<0.05, Chi-squared test or Fisher’s exact probability test.

Table 5 Performance in Neuropsychological Test

Test	Domain	Baseline, Mean (SD)			7 Days After Surgery, Mean (SD)			3 Months After Surgery, Mean (SD)
		Group S	Group C	P value	Group S	Group C	P value	Group S	Group C	P value
Rey Auditory Verbal Learning (Score)	Immediate recall	36.75(2.73)	36.82(3.07)	0.926	34.33(4.11)	33.47(3.15)	0.338	34.15(2.46)	34.12(3.20)	0.962
Rey Auditory Verbal Learning (Score)	Delayed recall	7.03(0.88)	6.91(0.83)	0.573	6.27(1.42)	5.26(1.24)	0.003^a	6.12(1.32)	5.91(1.46)	0.541
Digit Symbol Subtest (Score)	Information processing speed and attention	18.42(1.70)	18.76(1.46)	0.381	16.97(1.63)	16.85(2.09)	0.800	17.55(1.91)	17.15(2.32)	0.446
Grooved Pegboard Test (Dominant hand, Time, s)	Flexibility and coordination	97.30(10.44)	98.47(8.70)	0.620	106.06(11.94)	118.50(9.96)	<0.001^a	106.21(9.89)	105.26(9.07)	0.684
Digit Span Subtests (forward and backward, Total score)	Attention, concentration and immediate memory	9.18(1.10)	9.00(1.23)	0.527	7.67(1.45)	7.18(1.29)	0.148	7.85(1.87)	7.76(1.28)	0.831
Verbal Fluency Test (score)	Flow of thought organization and ideation	36.79(2.26)	37.53(2.86)	0.245	35.61(1.64)	36.21(2.20)	0.211	35.39(3.08)	35.03(3.37)	0.646
Finger-tapping Task (Score)	Fine motor skills	44.79(3.09)	43.97(3.09)	0.283	43.21(2.80)	41.71(3.22)	0.046^a	42.48(3.42)	41.24(2.36)	0.086
Trail Making Test A (Time, s)	Attention and psychomotor speed	56.48(9.80)	56.18(8.84)	0.893	65.39(9.49)	63.09(11.08)	0.364	60.39(9.51)	59.76(11.00)	0.803
Block Test (Score)	Visual Analysis and Spatial Recognition	5.39(0.19)	5.24(0.85)	0.433	4.48(0.76)	4.32(1.15)	0.500	5.21(0.89)	4.91(1.08)	0.221

Notes: The standard deviation of each test is calculated from all scores of pre-operative, post-operative and healthy volunteers. ^aP<0.05, Student’s t-test.

Figure 2 Plasma IL-6 concentrations (pg/mL) at different time points.*P<0.05.

Figure 3 Plasma S100β concentrations (pg/mL) at different time points. *P<0.05.