Effect of intraoperative dexmedetomidine on renal function after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a randomized, placebo-controlled trial

Figures & data

Figure 1. CONSORT diagram showing the flow of participants through each stage of the randomized trial.

Table 1. Patient characteristics.

Variables	Control (n = 19)	Dexmedetomidine (n = 19)	p Value
Age (years)	56 ± 15	51 ± 10	.241
Male sex	10 (53)	11 (58)	.744
Body mass index (kg/m^2)	22.7 ± 2.8	21.6 ± 4.4	.368
Hypertension	3 (16)	2 (11)	.631
Diabetes	3 (16)	2 (11)	.631
Chronic kidney disease	3 (16)	3 (16)	>.999
Prior cerebral vascular accident	1 (5)	0	.500
Chronic pulmonary disease	1 (5)	1 (5)	>.999
Pathology
Colorectal cancer	13 (68)	14 (74)	.721
Gastric cancer	2 (11)	2 (11)	>.999
Appendiceal cancer	1 (5)	3 (16)	.290
Pseudomyxoma peritonei	1 (5)	0	.500
Mesothelioma	2 (11)	0	.243
Preoperative serum hemoglobin level (g/dl)	11.3 ± 3.2	12.4 ± 1.9	.208
Preoperative serum albumin level (g/dl)	4.1 ± 0.5	4.2 ± 0.3	.512
Prior surgical score	1 [0–1]	1 [0–2]	.885
Neoadjuvant chemotherapy	9 (47)	9 (47)	>.999

Values are mean ± SD, median [IQR] or number of patients (%).

Table 2. Perioperative data.

Variables	Control (n = 19)	Dexmedetomidine (n = 19)	p Value
Total surgery time (min)	585 ± 230	615 ± 161	.647
Peritoneal cancer index	19 [12–26]	13 [7–27]	.525
Completeness of cytoreductive score	0 [0–1]	0 [0–1]	.667
Combined diaphragmatic peritonectomy	12 (63)	9 (47)	.328
Combined splenectomy	4 (21)	4 (21)	>.999
Baseline body temperature (ºC)	36.1 ± 0.4	35.9 ± 0.5	.117
The lowest body temperature (ºC)	34.9 ± 0.8	34.9 ± 0.7	.983
The highest body temperature (ºC)	38.7 ± 0.6	38.5 ± 0.9	.332
Crystalloid received during surgery (ml)	7500 [5900–8350]	5250 [4100–8300]	.151
Colloid received during surgery (ml)	500 [500–1000]	500 [0–1000]	.355
pRBC transfused during surgery (ml)	0 [0–460]	250 [0–500]	.422
Blood loss during surgery (ml)	1300 [750–1800]	1440 [400–2250]	.988
Urine output during surgery (ml)	1090 [520–1560]	1010 [635–1390]	.693
Amount of NEPI during surgery (μg/kg)	10.6 [3.8–34.6]	13.9 [8.5–32.4]	.485
Crystalloid received postoperative 48 h	6728 [5780–7712]	7300 [6300–8130]	.297
Colloid received postoperative 48 h	0	0
pRBC transfused postoperative 48 h (ml)	0 [0–540]	0 [0–474]	.850
Mechanical ventilation > postoperative 6 h	1 (5)	1 (5)	>.999
Patients needed NEPI > postoperative 6 h	3 (16)	2 (11)	.631

Values are mean ± SD, median [IQR] or number of patients (%).

pRBC: packed red blood cells; NEPI: norepinephrine.

Table 3. Renal outcomes and 30-day morbidity endpoints.

Variables	Control (n = 19)	Dexmedetomidine (n = 19)	p Value
Baseline serum creatinine (mg/dl)	0.70 ± 0.16	0.73 ± 0.21	.711
Highest serum creatinine (mg/dl)	0.86 ± 0.31	0.78 ± 0.36	.485
Baseline eGFR-EPI (ml/min/1.73m^2)	101.4 ± 16.0	103.4 ± 15.9	.709
Lowest eGFR-EPI (ml/min/1.73m^2)	90.3 ± 23.6	99.2 ± 25.4	.273
Baseline creatinine clearance^a (ml/min)	98.80 ± 33.51	99.29 ± 25.41	.474
Lowest creatinine clearance (ml/min)	82.49 ± 31.20	95.57 ± 30.56	.082
Changes in creatinine clearance (%)	16 [0–28]	2 [–8 to 15]	.037
Acute kidney injury by KDIGO guideline^b	5 (26)	2 (11)	.209
Thirty-day morbidity endpoints	0	0
Cardiovascular complication	0	0
Pulmonary complication	2 (11)	1 (5)	.547
Gastrointestinal complication	2 (11)	0	.243
Need of renal replacement therapy	0	0
Length of intensive care unit stay (day)	2 [2–3]	1 [1–2]	.034
Length of hospital stay (day)	20 [14–30]	15 [13–21]	.319

Values are mean ± SD, median [IQR], or number of patients (%).

eGFR-EPI: estimated glomerular filtration by Chronic Kidney Disease Epidemiology Collaboration equation; NGAL: neutrophil gelatinase-associated lipocaline; KIM: kidney injury molecule.

^aCreatinine clearance = [(140–age) × weight (kg)/72 × serum creatinine (mg/dl)] × (0.85 only if female) derived by Cockroft–Gault equation.

^bAll patients diagnosed as an acute kidney injury were classified stage 1 (an absolute increase in serum Cr ≥0.3 mg/dl within 48 h or an increase to 150–200% of baseline value within 7 days or urine output <0.5 ml/kg/h for 6–12 h).

Figure 2. Serial changes in hemodynamic parameters. (A) MAP (mean arterial pressure), (B) HR (heart rate), (C) CI (cardiac index), (D) SVV (stroke volume index), (E) CVP (central venous pressure). Pre-HIPEC: immediately before hyperthermic intraperitoneal chemotherapy (HIPEC); HIPEC: during HIPEC (average of the values assessed at 15 min interval), OP end: immediately after surgery. P Group × Time = p values of the group and time interaction obtained by the linear mixed model. *p < .05 versus control group; †p < .05 versus before surgery. The values are expressed as mean with SD.

Figure 3. Perioperative urinary biomarkers. Serial changes in urine neutrophil gelatinase-associated lipocaline (NGAL)/creatinine ratio (A) and kidney injury molecule (KIM)-1/creatinine ratio (B). PostIND: after induction of anesthesia; OpEnd: immediately after surgery; OP 24 h: 24 h after surgery. P Group × Time = p values of the group and time interaction obtained by the Brunner–Langer model. *p < .05 versus control group; †p < .05 versus before surgery. The values are expressed as median with IQR.