Dexmedetomidine enhances recovery after gastrointestinal cancer surgery by protecting the endothelial glycocalyx: A randomized, double-blind, placebo-controlled study

Table 1 Baseline characteristics of study participants, n (%)

Characteristic	DEX group (n = 55)	Control group (n = 55)	P value
Age (years)	62.6 ± 9.1	61.9 ± 10.9	0.704
Sex (male)	36 (65.5)	39 (70.9)	0.682
ASA II/III	35 (63.6)	40 (72.7)	0.413
Surgical duration (minute)	188.3 ± 29.7	189.5 ± 28.5	0.829
Blood loss (mL)	330.9 ± 59.3	338.1 ± 55.0	0.703
Hypertension	22 (40.0)	21 (38.2)	0.849
Diabetes mellitus	12 (21.8)	14 (25.5)	0.67
CAD	6 (10.9)	5 (9.1)	0.758
Tumor site (gastric)	25 (45.5)	30 (54.5)	0.446
Tumor stage I-II	31 (56.4)	28 (50.9)	0.566
Laparoscopic surgery	38 (69.1)	35 (63.6)	0.545
Hemoglobin (g/L)	124.8 ± 14.7	126.2 ± 13.9	0.589
Albumin (g/L)	38.6 ± 3.2	38.1 ± 3.4	0.436
CRP (mg/L)	6.3 ± 2.7	6.7 ± 3.0	0.483
WBC count (× 109/L)	6.8 ± 1.4	6.9 ± 1.5	0.734
Intraoperative deep hypotension	6 (10.9)	8 (14.5)	0.580
Duration of hypotension [minute, median (IQR)]	3 (2-5)	4 (2-6)	0.420
Norepinephrine use	18 (32.7)	20 (36.4)	0.290
Dose (μg/kg·minute)	0.04 ± 0.01	0.05 ± 0.02
Phenylephrine use	12 (21.8)	14 (25.5)	0.650
Total intraoperative fluid volume [mL, median (IQR)]	2450 (2100-2800)	2500 (2200-2900)	0.62
Crystalloid volume (mL)	2100 ± 450	2150 ± 470	0.59
Colloid volume (mL)	350 ± 120	360 ± 110	0.72
Blood products	3 (5.5)	4 (7.3)	0.69
Trendelenburg tilt (°)	17.5 ± 1.2	17.8 ± 1.4	0.481
Intra-abdominal pressure (mmHg)	13.1 ± 0.8	13.3 ± 0.9	0.355

DEX: Dexmedetomidine; ASA: American Society of Anesthesiologists; CAD: Coronary artery disease; CRP: C-reactive protein; WBC: White blood cell; IQR: Interquartile range.

Table 2 Biomarker levels and between-group comparisons over time

Biomarker	Time point	DEX group (n = 55)	Control group (n = 55)	P value
Syndecan-1 (ng/mL)	T0	20.66 ± 4.43	20.85 ± 5.06	0.832
	T1	44.72 ± 7.10	48.73 ± 6.26	0.002
	T2	34.16 ± 4.81	37.93 ± 5.78	< 0.001
	T3	29.21 ± 3.88	31.06 ± 3.47	0.009
Heparan sulfate (ng/mL)	T0	8.61 ± 1.71	8.70 ± 1.89	0.787
	T1	12.19 ± 2.20	13.76 ± 2.44	0.001
	T2	9.97 ± 2.27	10.98 ± 2.31	0.023
	T3	9.12 ± 2.82	9.29 ± 2.26	0.728
IL-6 (pg/mL)	T0	85.92 ± 24.31	85.50 ± 29.06	0.934
	T1	117.68 ± 40.77	131.03 ± 41.68	0.092
	T2	110.77 ± 29.72	138.86 ± 35.95	< 0.0001
	T3	97.19 ± 38.11	105.00 ± 42.71	0.314
TNF-α (pg/mL)	T0	41.99 ± 9.72	40.30 ± 9.57	0.36
	T1	58.61 ± 11.35	61.52 ± 10.73	0.17
	T2	56.90 ± 10.63	63.75 ± 12.17	0.002
	T3	56.88 ± 11.32	60.36 ± 12.37	0.126

DEX: Dexmedetomidine; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha.

Table 3 Microcirculatory and metabolic parameters between dexmedetomidine and control groups over time

Parameter	Time point	DEX group (n = 55)	Control group (n = 55)	P value
Perfused vessel density (mm/mm2)	T2	21.40 ± 3.50	19.94 ± 2.93	0.019
Mean flow index	T2	2.83 ± 0.28	2.66 ± 0.33	0.005
P(v-a)CO2 (mmHg)	T0	3.07 ± 0.78	3.27 ± 0.65	0.632
	T1	4.59 ± 0.86	4.94 ± 0.85	0.132
	T2	3.89 ± 0.84	4.63 ± 1.06	< 0.001
	T3	4.00 ± 1.03	4.40 ± 0.87	0.128
Lactate (mmol/L)	T0	1.00 ± 0.32	1.09 ± 0.31	0.504
	T1	1.74 ± 0.37	1.82 ± 0.36	0.968
	T2	1.33 ± 0.40	1.65 ± 0.54	0.003
	T3	1.31 ± 0.58	1.51 ± 0.43	0.183

DEX: Dexmedetomidine.

Table 4 Comparison of outcomes between dexmedetomidine and control groups, n (%)

Outcome measure	DEX group (n = 55)	Control group (n = 55)	Mean difference or OR (95%CI)	Absolute/relative effect	P value
Intraoperative fentanyl (μg)	156.9 ± 31.6	175.5 ± 42.1	-18.6 (-32.6 to -4.5)	-	0
Length of hospital stay (days)	6.49 ± 1.29	7.29 ± 1.59	-0.8 (-1.35 to -0.25)	-	0.005
QoR-15 score at 72 hours	124.3 ± 9.2	118.7 ± 8.4	5.6 (2.3-9.0)	-	0.001
Postoperative infection	4 (7.3)	9 (16.4)	OR = 0.40 (0.11-1.37)	ARR 9.1%; RRR 55.5%; NNT approximately 11	0.135
Pneumonia	2 (3.6)	6 (10.9)	OR = 0.30 (0.06-1.47)	ARR 7.3%; RRR 67.0%; NNT approximately 14	0.142
Acute kidney injury	1 (1.8)	4 (7.3)	OR = 0.23 (0.02-2.12)	ARR 5.5%; RRR 75.3%; NNT approximately 18	0.195
Ileus	1 (1.8)	2 (3.6)	OR = 0.49 (0.04-5.53)	ARR 1.8%; RRR 50.0%; NNT approximately 56	0.564
Anastomotic leakage	0 (0)	0 (0)	-	-	-
ICU admission	4 (7.3)	7 (12.7)	OR = 0.54 (0.14-2.04)	ARR 5.4%; RRR 42.5%; NNT approximately 19	0.358
30-day readmission	1 (1.8)	1 (1.8)	OR = 1.00 (0.06-16.06)	-	> 0.05
30-day mortality	0 (0)	1 (1.8)	-	ARR 1.8%; RRR 100%; NNT approximately 56	> 0.05
Overall 30-day complications	7 (12.7)	17 (30.9)	18.2% absolute risk reduction (3.1%-33.2%)	ARR 18.2%; RRR 58.9%; NNT approximately 6	0.036

Overall 30-day complications include pneumonia, acute kidney injury, ileus, surgical site infection, and other clinically significant postoperative adverse events. DEX: Dexmedetomidine; QoR-15: Quality of Recovery-15 Questionnaire; ARR: Absolute risk reduction; RRR: Relative risk reduction; NNT: Number needed to treat; ICU: Intensive care unit.

Table 5 Multivariable Logistic regression results

Variable	Coef.	SE	z	P > |z|	OR (95%CI)
Const	-0.481	2.431	-0.198	0.843	0.618 (0.005-72.488)
Syndecan_high	1.059	0.557	1.902	0.057	2.884 (0.968-8.593)
Age	-0.009	0.029	-0.305	0.76	0.991 (0.936-1.050)
Surgery_duration	-0.005	0.008	-0.605	0.545	0.995 (0.979-1.011)
CRP	-0.006	0.081	-0.075	0.94	0.994 (0.848-1.165)

CRP: C-reactive protein.