Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study

Figures & data

Table 1 Baseline Data

Variable	Group C (n=74)	Group D (n=73)	Group ED (n=71)
Age (y)	33 (29, 36)	31 (28, 35)	33 (30, 37)
Height (cm)	158 (155, 162)	160 (156, 163)	159 (155, 161)
Weight (kg)	67.5 (60, 73)	67 (62, 75)	67 (62, 73.5)
BMI (kg/cm^2)	26.81 (25.26, 29.69)	26.85 (24.57, 29.19)	26.53 (24.67, 28.51)
Gestational week (weeks)	38 (38, 39)	38 (38, 39)	38 (38, 39)
Multiparas	36 (48.6%)	27 (37%)	39 (54.9%)
Caesarean section (times)	1 (1, 2)	1 (1, 2)	2 (1, 2)

Notes: Classification variables are expressed as the patient number (%). Continuous variables are expressed as the median (IQR).

Abbreviation: BMI, Body Mass Index.

Figure 1 Flow chart of patient enrollment.

Table 2 Efficacy Outcomes

Traction pain	Group C	Group D	Group ED	Estimated effects (95% CI)		P value
				Group D	Group ED
Total incidence	36 (48.6%)^a	32 (43.8%)^a	9 (12.7%)^b	0.9 (0.6, 1.3)	0.3 (0.1, 0.5)	<0.0001
T1
Incidence	2 (2.7%)	4 (5.5%)	1 (1.4%)	2.0 (0.4, 10.7)	0.5 (0, 5.6)	0.458
VAS score	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.06 (−0.10, 0.21)	−0.01 (−0.02, 0.14)	0.378
T2
Incidence	32 (43.2%)^a	27 (37%)^a	8 (11.3%)^b	0.9 (0.6, 1.3)	0.3 (0.1, 0.5)	<0.0001
VAS score	0 (0, 3)^a	0 (0, 2)^a	0 (0, 0)^b	−0.30, (−0.95, 0.36)	−0.86 (−1.52, −0.20)	<0.0001
T3
Incidence	20 (27%)^a	18 (24.7%)^a,b	7 (9.9%)^b	0.9 (0.5, 1.6)	0.4 (0.2, 0.8)	0.022
VAS score	0 (0, 2)^a	0 (0, 1)^a, b	0 (0, 0)^b	−0.18 (−0.73, 0.37)	−0.44 (−1, 0.11)	0.036

Notes: Classification variables are expressed as the patient number (%). Continuous variables are expressed as the median (IQR). P<0.05 indicates a difference among the three groups. Use letters to display the post-hoc tests results. When two groups are labeled with different letters (a or b), it indicates a significant difference between the two groups. When the same letter is labeled, it indicates no significant difference between the two groups. Estimated effects (95% CI): calculated as the Group D/Group ED minus or vs the Group C and represented as Mean difference or RR (relative risk). T1: placenta delivery; T2: exploring abdominal cavity; T3: suturing muscle layer.

Figure 2 The box plots of VAS score. T1: placenta delivery; T2: handling of intraperitoneal organs; T3: suturing muscle layer; T4: 2 h after surgery; T5: 6 h after surgery; T6 24 h after surgery.

Table 3 Intraoperative and Postoperative Data

Variables	Group C	Group D	Group ED	P value
Intraoperative data
Surgical duration (min)	45 (34, 57)	45 (35, 55)	48 (35, 60)	0.538
MAP (t1, mmHg)	86 (81, 95)	90 (79, 96)	86 (81, 94)	0.823
HR (t1, bpm)	86 (13)	88 (12)	88 (12)	0.564
SpO2 (t1, %)	97 (97, 98)	97 (96, 98)	97 (97, 99)	0.179
MAP (t2, mmHg)	81 (10)	83 (10)	83 (11)	0.256
HR (t2, bpm)	84 (14)	88 (14)	87 (10)	0.183
SpO2 (t2, %)	99 (98, 100)	99 (98, 100)	99 (99, 100)	0.986
MAP (t3, mmHg)	75 (10)^a	83 (9)^b	81 (11)^b	<0.0001
HR (t3, bpm)	86 (14)^a	80 (12)^b	85 (12)^a, b	0.016
SpO2 (t3, %)	99 (99, 100)	99 (98, 100)	99 (98, 100)	0.385
Ergometrine	65 (87.8%)	61 (83.6%)	65 (91.5%)	0.331
Anleek	10 (13.5%)	17 (23.3%)	21 (29.6%)	0.062
Hemabate	2 (2.7%)	5 (6.8%)	0 (0%)	0.053
Colloid (mL)	500 (450, 500)	500 (400, 500)	500 (500, 500)	0.254
Crystal (mL)	550 (500, 600)^a	600 (500, 700)^a, b	600 (500, 850)^b	0.003
Intraoperative Events
Nausea and vomiting	23 (31.1%)	18 (24.7%)	19 (26.8%)	0.674
Stomach spasms	17 (23%)^a	10 (13.7%)^a, b	4 (5.6%)^b	0.011
Contractive pain	7 (9.5%)^a, b	16 (21.9%)^b	4 (5.6%)^a	0.007
Headache	4 (5.4%)	2 (2.7%)	0 (0%)	0.170
Shiver	39 (52.7%) ^a	5 (6.8%)^b	3 (4.2%)^b	<0.0001
Chest tightness	16 (21.6%)	9 (12.3%)	7 (9.9%)	0.110
Chest pain	6 (8.1%)	4 (5.5%)	1 (1.4%)	0.194
Dyspnea	11 (14.9%)	6 (8.2%)	4 (5.6%)	0.176
Hypotension	16 (21.6%)^a	4 (5.5%)^b	5 (7.0%)^b	0.003
Hypertension	1 (1.4%)	0 (0%)	0 (0%)	1.000
Tachycardia	17 (23%)	10 (13.7%)	14 (19.7%)	0.348
Bradycardia	6 (8.1%)^a	8 (11.0%)^a	0 (0%)^b	0.009
Neurologic or mental symptoms	14 (18.9%)^a	17 (23.3%)^a	54 (76.1%)^b	<0.0001
Dizzy	14 (18.9%)^a	17 (23.3%)^a	52 (73.2%)^b	<0.0001
Nystagmus	0 (0%)^a	0 (0%)^a	4 (5.6%)^a	0.011
Diplopia	1 (1.4%)^a	0 (0%)^a	20 (28.2%)^b	<0.0001
Daymare	0 (0%)	0 (0%)	2 (2.8%)	0.105
Hallucination	0 (0%)^a	0 (0%)^a	6 (8.5%)^b	0.001
Somnolence	0 (0%)^a	5 (6.8%)^a	52 (73.2%)^b	<0.0001
Ramsay score at the end of surgery				<0.0001
2 scores	74 (100%)^a	72 (98.6%)^a	62 (87.3%)^b
3 scores	0 (0%)^a	0 (0%)^a	7 (9.9%)^b
4 scores	0 (0%)^a	1 (1.4%)^a	2 (2.8%)^a
Postoperative outcomes
VAS score
T4	2 (1, 2)^a	2 (2, 2)^a	2 (1, 2)^b	0.042
T5	1 (1, 2)	1 (1, 2)	1 (1, 2)	0.410
T6	1 (1, 1)^a	1 (1, 1)^a, b	1 (1, 1)^b	0.049
Lactation time (days)	2 (1, 2)	1 (1, 2)	1 (1, 2)	0.399
Postoperative hospitalization (days)	5 (4, 6)	5 (5, 6)	5 (4, 5)	0.342

Notes: Classification variables are expressed as the patient number (%). Continuous variables are expressed as the median (IQR) or mean (SD). P<0.05 indicates a difference among the three groups. Use letters to display the post-hoc tests results. When two groups are labeled with different letters (a or b), it indicates a significant difference between the two groups. When the same letter is labeled, it indicates no significant difference between the two groups. MAP: mean arterial pressure; HR: heart rate; SpO2: pulse oximetry; t1: when entering the operating room; t2: before the administration of study drug; t3: after the infusion of study drug was completed; T4:2 hours after surgery; T5: 6 hours after surgery; T6: 24 hours after surgery.

Figure 3 Line chart of blood pressure and heart rate. (A) Average value of MAP; (B) Average value of MAP.

Abbreviations: MAP, mean arterial pressure; HR, heart rate.

Data Sharing Statement

Under existing ethical approvals, the availability of these data is limited and therefore cannot be publicly obtained. However, upon reasonable request and with the permission of the author and the Third Affiliated Hospital of Sun Yat-sen University, data may be provided.