A selective V
1Areceptor agonist, selepressin, is superior to arginine vasopressin and to norepinephrine in ovine septic shock
Xinrong He, Fuhong Su, Fabio Silvio Taccone, Régent Laporte, Anne Louise Kjølbye, Jing Zhang, Keliang Xie, Mouhamed
DjahoumMoussa, Torsten Michael Reinheimer, Jean-Louis Vincent
SUPPLEMENTAL DIGITAL CONTENT
Table S1. Evolution of measured hemodynamic, respiratory, oxygenation, blood flow, and blood gas variables in late intervention groups
Variable Group Baseline 6h 12h 18h Fixed
effects*
Temperature (◦C)
C 39.1 ± 0.9 39.9 ± 1.5 40.7 ± 1.5 41.9 ± 1.0
NS/NS SEL 38.8 ± 0.3 39.4 ± 0.6 40.0 ± 0.5 41.4 ± 0.6
AVP 39.2 ± 0.7 39.8 ± 1.2 40.4 ± 1.7 41.2 ± 2.3 NE 39.3 ± 0.4 39.6 ± 0.9 40.3 ± 0.8 42.1 ± 0.9 Heart rate
(bpm)
C 114 ± 12 167 ± 23 177 ± 30 166 ± 36
NS/<0.05 SEL 119 ± 9 147 ± 19 146 ± 13 183 ± 59
AVP 102 ± 11 155 ± 20 166 ± 23 201 ± 30 NE 117 ± 30 157 ± 11 144 ± 11 229 ± 44#
SVI (mL/beat/m2)
C 43.6 ± 7.6 58.3 ± 8.7 42.9 ± 15.7 20.6 ± 10.0
NS/NS SEL 41.4 ± 4.8 60.7 ± 10.0 50.5 ± 7.7 27.8 ± 15.9
AVP 40.5 ± 7.3 61.0 ± 12.8 45.3 ± 15.3 24.3 ± 5.0 NE 40.9 ± 8.5 64.7 ± 5.8 49.3 ± 11.0 18.3 ± 6.4 MPAP
(mmHg)
C 17.3 ± 2.1 18.3 ± 2.1 21.0 ± 3.8 20.3 ± 4.2
<0.01/NS SEL 18.5 ± 2.7 18.0 ± 3.7 19.8 ± 3.3 19.5 ± 4.0
AVP 15.2 ± 3.1 17.7 ± 2.9 18.5 ± 3.1 19.0 ± 3.2 NE 19.3 ± 3.1 20.3 ± 2.1 23.8 ± 4.5 28.7 ± 4.1#
PAOP (mmHg)
C 5.3 ± 0.8 5.3 ± 0.8 5.9 ± 1.1 5.6 ± 1.1
NS/NS SEL 5.7 ± 0.8 6.3 ± 0.8 7.0 ± 1.7 6.5 ± 1.5
AVP 4.5 ± 1.4 5.0 ± 1.3 4.8 ± 1.5 4.5 ± 1.4 NE 5.3 ± 1.2 5.7 ± 1.2 6.3 ± 1.6 6.3 ± 2.9 SVRI
(dyn.sec/cm5/m2)
C 1645 ± 312 719 ± 118 563 ± 132 499 ± 77
NS/NS SEL 1715 ± 193 776 ± 128 668 ± 43 615 ± 114
AVP 1934 ± 461 788 ± 222 836 ± 405 772 ± 288 NE 1780 ± 149 689 ± 44 767 ± 190 963 ± 429 PVRI
(dyn.sec/cm5/m2)
C 197 ± 44 109 ± 22 190 ± 125 421 ± 224
NS/<0.01 SEL 227 ± 61 104 ± 26 140 ± 29 242 ± 111
AVP 202 ± 56 109 ± 31 150 ± 26 240 ± 42 NE 246 ± 47 116 ± 11 206 ± 61 474 ± 155#
LVSWI (g.m/beat/m2)
C 57.5 ± 7.7 67.9 ± 11.7 31.9 ± 15.4 7.1 ± 6.1
NS/NS SEL 53.7 ± 6.9 69.9 ± 13.9 45.3 ± 11.9 16.0 ± 14.5
AVP 52.5 ± 11.4 73.4 ± 15.0 44.1 ± 16.0 16.1 ± 5.4 NE 54.9 ± 13.0 77.0 ± 8.5 45.4 ± 10.2 11.3 ± 3.0 SvO2
(%)
C 72.1 ± 3.7 82.2 ± 3.4 72.7 ± 6.7 47.2 ± 20.8
NS/NS SEL 71.3 ± 5.6 80.7 ± 4.3 75.2 ± 5.1 56.2 ± 4.5
AVP 69.6 ± 7.2 81.0 ± 3.6 74.4 ± 1.7 59.4 ± 14.5 NE 72.9 ± 3.5 82.0 ± 4.3 74.6 ± 4.4 51.6 ± 11.7 DO2I
(mL/min/m2)
C 697 ± 113 1419 ± 251 1185 ± 364 480 ± 277
NS/NS SEL 655 ± 81 1261 ± 297 1134 ± 107 708 ± 273
AVP 567 ± 133 1313 ± 285 1159 ± 389 755 ± 274 NE 651 ± 85 1378 ± 179 1102 ± 177 678 ± 219 VO2I
(mL/min/m2)
C 197 ± 26 261 ± 35 293 ± 68 200 ± 68
NS/NS SEL 194 ± 33 256 ± 26 291 ± 45 281 ± 112
AVP 172 ± 44 274 ± 76 286 ± 103 256 ± 66
NE 175 ± 24 263 ± 65 259 ± 41 291 ± 72
Lung compliance
(mL/H2O)
C 23.2 ± 3.8 19.5 ± 3.0 14.2 ± 3.3 11.3 ± 4.0
NS/NS SEL 21.0 ± 5.0 18.6 ± 4.0 13.7 ± 3.5 10.9 ± 3.2
AVP 20.9 ± 3.6 18.1 ± 3.9 13.3 ± 3.8 11.4 ± 2.4 NE 20.8 ± 4.6 18.4 ± 2.7 12.9 ± 2.4 10.1 ± 2.2
PaO2/FiO2 C 388 ± 106 342 ± 96 254 ± 121 153 ± 105 NS/NS
SEL 369 ± 92 372 ± 35 289 ± 109 161 ± 128 AVP 365 ± 89 333 ± 72 234 ± 62 153 ± 69
NE 369 ± 76 347 ± 72 248 ± 72 139 ± 55
EVLWI (mL/kg)
C 14.8 ± 3.2 16.6 ± 3.1 17.9 ± 3.9 20.8 ± 3.3
NS/NS SEL 16.4 ± 5.2 15.2 ± 4.3 15.8 ± 1.9 16.1 ± 2.5
AVP 15.6 ± 4.4 16.9 ± 3.4 17.8 ± 4.7 18.7 ± 4.5 NE 15.5 ± 3.7 15.8 ± 4.0 16.2 ± 4.8 17.0 ± 5.8 pH
C 7.41 ± 0.10 7.38 ± 0.06 7.34 ± 0.04 7.27 ± 0.06
NS/NS SEL 7.37 ± 0.11 7.45 ± 0.07 7.39 ± 0.06 7.21 ± 0.10
AVP 7.36 ± 0.09 7.37 ± 0.05 7.34 ± 0.03 7.25 ± 0.10 NE 7.44 ± 0.10 7.42 ± 0.07 7.33 ± 0.11 7.14 ± 0.09 PaCO2
(mmHg)
C 36.1 ± 4.3 38.2 ± 3.8 36.5 ± 5.3 40.7 ± 8.2
NS/NS SEL 39.3 ± 5.3 36.2 ± 3.4 35.3 ± 4.5 44.9 ± 8.7
AVP 37.6 ± 10.2 38.5 ± 5.2 38.9 ± 5.9 48.0 ± 16.7 NE 36.8 ± 6.3 35.2 ± 5.4 40.0 ± 4.0 51.3 ± 16.5 MBF
(mL/min)
C 125 ± 49 275 ± 84 246 ± 134 116 ± 100
NS/NS SEL 124 ± 32 272 ± 38 226 ± 52 123 ± 32
AVP 137 ± 22 297 ± 154 275 ± 110 168 ± 59 NE 133 ± 73 306 ± 162 238 ± 125 108 ± 67 RBF
(mL/min)
C 208 ± 55 244 ± 79 150 ± 74 28 ± 23
NS/NS SEL 198 ± 11 248 ± 58 152 ± 43 72 ± 46
AVP 191 ± 115 224 ± 127 152 ± 84 54 ± 26
NE 216 ± 41 229 ± 35 147 ± 32 20 ± 11
CrCl (mL/min)
C 139.5 ± 64.8 138.6 ± 78.4 55.4 ± 46.9 0.7 ± 2.0
NS/NS SEL 112.0 ± 58.5 116.1 ± 38.0 86.3 ± 60.3 12.2 ± 25.6
AVP 130.9 ± 77.7 94.5 ± 32.7 47.4 ± 31.2 17.5 ± 29.1 NE 132.7 ± 47.7 137.3 ± 45.2 64.3 ± 38.0 2.0 ± 4.0
C, control group; SEL, selepressin; AVP, arginine vasopressin; NE, norepinephrine; SVI, stroke volume index; MPAP, mean pulmonary artery pressure; SVRI/PVRI,
systemic/pulmonary vascular resistance index; LVSWI, left ventricular stroke work index;
DO
2I, oxygen delivery index; VO
2I, oxygen consumption index; PAOP, pulmonary artery occlusion pressure; SvO
2, mixed venous blood oxygen saturation; EVLWI, extravascular lung water index; RBF/MBF, renal or mesenteric arterial blood flow; CrCl, creatinine clearance;
NS, non-significant. *the significant level of group effects/group × time interaction effects in a fixed effects model. Time effects of variables were all significant (P<0.05). # p<0.05
compared to SEL group.
Table S2. Evolution of measured coagulation and protein variables in late intervention groups
Variable Group baseline 6h 12h 18h Fixed effects*
COP (mmHg)
C 14.8 ± 2.4 15.3 ± 2.6 13.7 ± 4.4 11.7 ± 3.8
NS/NS SEL 15.3 ± 2.6 14 ± 2.2 12.5 ± 2.2 10.0 ± 2.2
AVP 14.7 ± 2.7 14.6 ± 3.0 13.7 ± 2.2 10.0 ± 1.8 NE 17.0 ± 2.3 14.5 ± 3.7 12.2 ± 1.8 8.8 ± 1.6 Total Protein
(g/dL)
C 4.6 ± 0.7 2.5 ± 0.6 2.0 ± 0.6 1.7 ± 0.2
NS/NS SEL 4.5 ± 1.1 2.3 ± 0.3 1.6 ± 0.5 1.4 ± 0.3
AVP 5.0 ± 1.0 2.4 ± 0.9 1.7 ± 0.7 1.6 ± 0.9 NE 5.6 ± 1.1 2.8 ± 0.7 1.8 ± 0.6 1.6 ± 0.4 Albumin
(g/dL)
C 1.7 ± 0.4 1.0 ± 0.3 0.8 ± 0.3 0.7 ± 0.1
NS/NS SEL 1.8 ± 0.5 0.9 ± 0.1 0.6 ± 0.2 0.5 ± 0.1
AVP 1.9 ± 0.4 0.9 ± 0.4 0.7 ± 0.3 0.6 ± 0.4 NE 2.1 ± 0.5 1.0 ± 0.2 0.7 ± 0.3 0.7 ± 0.2 Hematocrit
(%)
C 30 ± 6 36 ± 8 49 ± 7 54 ± 13
NS/NS SEL 30 ± 6 31 ± 6 38 ± 13 49 ± 14
AVP 26 ± 3 32 ± 7 39 ± 9 49 ± 11
NE 31 ± 12 27 ± 9 32 ± 6 53 ± 6
PT (sec)
C 15 ± 1 20 ± 3 30 ± 7 60 ± 30
NS/NS SEL 16 ± 2 24 ± 6 70 ± 42 74 ± 28
AVP 16 ± 3 28 ± 13 54 ± 40 71 ± 39
NE 17 ± 3 27 ± 8 43 ± 7 71 ± 35
aPTT (sec)
C 33 ± 5 57 ± 23 113 ± 68 146 ± 74
NS/NS SEL 31 ± 5 84 ± 32 171 ± 78 203 ± 65
AVP 35 ± 9 80 ± 51 128 ± 89 156 ± 74 NE 37 ± 12 91 ± 51 141 ± 80 169 ± 82 Fibrinogen
(mg/dL)
C 277 ± 146 147 ± 79 104 ± 46 76 ± 40
NS/NS SEL 200 ± 82 90 ± 37 70 ± 31 50 ± 0
AVP 233 ± 100 123 ± 65 93 ± 49 89 ± 61 NE 190 ± 117 84 ± 42 57 ± 17 75 ± 27 Platelet
(×109/L)
C 292 ± 116 251 ± 110 244 ± 81 151 ± 89
NS/NS SEL 259 ± 81 245 ± 111 237 ± 118 206 ± 125
AVP 261 ± 96 233 ± 71 224 ± 90 186 ± 79 NE 237 ± 133 156 ± 57 174 ± 82 152 ± 56
C, control group; SEL, selepressin; AVP, arginine vasopressin; NE, norepinephrine; COP, colloid oncotic pressure; PT, prothrombin time; aPTT, activated partial thromboplastin time;
NS, non-significant. *the significant level of group effects/group × time interaction effects in a
fixed effects model. Time effects of variables were all significant (P<0.05).
Table S3. Evolution of measured hemodynamic, respiratory, oxygenation, blood flow, and blood gas variables in early intervention groups
Variable Group baseline 6h 12h 18h 24h Fixed
effects*
Temperature (◦C) C 39.1 ± 0.9 39.9 ± 1.5 40.7 ± 1.5 41.9 ± 1.0
NS/NS SEL 39.1 ± 0.6 39.6 ± 1.2 39.9 ± 1.0 40.7 ± 1.5 40.3 ± 1.0
AVP 39.1 ± 0.5 39.6 ± 0.6 40.1 ± 0.8 41.1 ± 0.8 NE 39.1 ± 0.4 39.4 ± 0.7 40.0 ± 0.8 41.3 ± 0.8 Heart rate
(bmp)
C 114 ± 12 167 ± 23 177 ± 30# 166 ± 36
NS/<0.05 SEL 118 ± 13 140 ± 15 145 ± 17 163 ± 46 122 ± 20
AVP 116 ± 10 142 ± 10 148 ± 13 137 ± 31 NE 108 ± 5 146 ± 24 175 ± 15# 165 ± 33 SVI
(mL/beat/m2)
C 43.6 ± 7.6 58.3 ± 8.7 42.9 ± 15.7# 20.6 ± 10.0#
<0.01/<0.01 SEL 38.7 ± 4.1 58.3 ± 6.1 57.1 ± 8.0 45.7 ± 17.8 36.5 ± 15.3
AVP 39.1 ± 3.1 61.4 ± 3.9 67.1 ± 4.4# 39.0 ± 15.0 NE 42.5 ± 2.1 63.2 ± 8.1 69 ± 15.1 37.4 ± 11.7#
MPAP (mmHg)
C 17.3 ± 2.1 18.3 ± 2.1 21.0 ± 3.8 20.3 ± 4.2
NS/<0.05 SEL 19.7 ± 4.1 18.7 ± 4.0 19.9 ± 4.5 20.9 ± 5.6 17.6 ± 4.3
AVP 16.0 ± 2.4 16.3 ± 1.6 18.1 ± 2.1 18.4 ± 4.0 NE 16.3 ± 2.8 15.9 ± 2.1 17.9 ± 2.5 18.4 ± 2.7 PAOP
(mmHg)
C 5.3 ± 0.8 5.3 ± 0.8 5.9 ± 1.1 5.6 ± 1.1
NS/NS SEL 5.6 ± 1.0 5.4 ± 0.8 5.0 ± 1.3 5.6 ± 1.7 5.4 ± 0.9
AVP 5.1 ± 0.7 5.0 ± 0.6 5.9 ± 0.7 5.6 ± 0.8 NE 5.0 ± 0.8 5.1 ± 0.7 6.0 ± 0.8 5.3 ± 1.3 SVRI
(dyn.sec/cm5/m2)
C 1645 ± 312 719 ± 118 563 ± 132# 499 ± 77#
<0.05/NS SEL 1849 ± 176 908 ± 129 802 ± 150 747 ± 254 830 ± 419
NE 1836 ± 141 816 ± 270 490 ± 110# 546 ± 111#
AVP 1813 ± 154 815 ± 96 581 ± 102# 658 ± 223 PVRI
(dyn.sec/cm5/m2)
C 197 ± 44 109 ± 22 190 ± 125 421 ± 224#
<0.05/NS SEL 248 ± 52$ 128 ± 31 144 ± 58 186 ± 103 255 ± 127
AVP 193 ± 48# 103 ± 14# 100 ± 22 243 ± 163
NE 197 ± 54# 93 ± 6# 79 ± 16 194 ± 96
LVSWI C 57.5 ± 7.7 67.9 ± 11.7 31.9 ± 15.4# 7.1 ± 6.1# <0.01/<0.01
(g.m/beat/m2) SEL 53.7 ± 6.2 72.9 ± 10.5 64.4 ± 9.8 40.5 ± 18.8 24.3 ± 16.2 AVP 53.3 ± 4.0 73.9 ± 5.9 65.8 ± 4.1 23.4 ± 12.7
NE 59.5 ± 6.0 76.6 ± 11.5 67.7 ± 13.9 23.1 ± 11.2#
SvO2
(%)
C 72.1 ± 3.7 82.2 ± 3.4 72.7 ± 6.7 47.2 ± 20.8#
<0.05/<0.01 SEL 70.4 ± 8.5 79.4 ± 3.2 79.6 ± 5.0 71.8 ± 8.1 64.3 ± 11.9
AVP 72.4 ± 2.5 78.4 ± 2.5 75.9 ± 9.5 54.7 ± 20.6 NE 73.4 ± 4.6 80.1 ± 5.7 76.0 ± 5.9 63.0 ± 7.1#
DO2I (mL/min/m2)
C 697 ± 113 1419 ± 251 1185 ± 364 480 ± 277#
<0.05/<0.01 SEL 631 ± 38 1169 ± 253 1273 ± 275 1107 ± 382 647 ± 371
AVP 631 ± 79 1146 ± 108 1471 ± 157 773 ± 430 NE 640 ± 107 1296 ± 318 1789 ± 323# 1014 ± 322#
VO2I (mL/min/m2)
C 197 ± 26 261 ± 35 293 ± 68 200 ± 68#
<0.01/<0.05 SEL 187 ± 46 239 ± 54 264 ± 81 307 ± 81 181 ± 67
AVP 172 ± 37 258 ± 22 361 ± 148# 252 ± 104 NE 168 ± 20 241 ± 51 417 ± 90# 345 ± 113 Lung compliance
(mL/H2O)
C 23.2 ± 3.8 19.5 ± 3.0 14.2 ± 3.3# 11.3 ± 4.0#
NS/<0.05 SEL 22.9 ± 2.2 21.4 ± 1.9 17.7 ± 2.3 14.6 ± 3.5 12.2 ± 4.4
AVP 23.3 ± 4.6 20.2 ± 4 16.3 ± 2 13.4 ± 3.8 NE 22.4 ± 4.3 19.5 ± 3.1 15.3 ± 2.2 12.3 ± 1.3 PaO2/FiO2
C 388 ± 106 342 ± 96 254 ± 121# 153 ± 105#
NS/<0.05 SEL 385 ± 80 350 ± 63 328 ± 64 240 ± 108 161 ± 98
AVP 369 ± 64 349 ± 38 256 ± 63 129 ± 62 NE 372 ± 39 341 ± 69 288 ± 76 158 ± 56#
EVLWI (mL/kg)
C 14.8 ± 3.2 16.6 ± 3.1 17.9 ± 3.9# 20.8 ± 3.3#
<0.01/<0.01 SEL 14.7 ± 2.2 14.4 ± 2.2 13.0 ± 1.9 13.7 ± 1.7 15.2 ± 2.5
AVP 14.8 ± 3.1 17.3 ± 2.3# 19.2 ± 3.2# 20.8 ± 2.9#
NE 14.7 ± 1.4 18.3 ± 2.3# 20.5 ± 3.8# 22.1 ± 3.0#
pH C 7.41 ± 0.10 7.38 ± 0.06 7.34 ± 0.04 7.27 ± 0.06#
<0.01/<0.05 SEL 7.45 ± 0.10 7.38 ± 0.08 7.40 ± 0.09 7.38 ± 0.09 7.31 ± 0.12
AVP 7.35 ± 0.12 7.37 ± 0.11 7.35 ± 0.06 7.19 ± 0.13#
NE 7.36 ± 0.09 7.34 ± 0.09 7.35 ± 0.06 7.22 ± 0.05#
PaCO2
(mmHg)
C 36.1 ± 4.3 38.2 ± 3.8 36.5 ± 5.3 40.7 ± 8.2
<0.05/NS SEL 33.9 ± 4.9 38.9 ± 5.4 36.1 ± 3.1 38.4 ± 4.9 45.8 ± 13.5
AVP 39.1 ± 5.9# 37.8 ± 5.2 35.8 ± 2.7 37.5 ± 16.8 NE 39.9 ± 5.6# 36.7 ± 1.7 37.0 ± 2.8 42.1 ± 5.3
MBF (mL/min)
C 125 ± 49 275 ± 84 246 ± 134 116 ± 100
NS/NS SEL 129 ± 6 227 ± 48 240 ± 79 200 ± 130 93 ± 69
AVP 128 ± 15 252 ± 47 269 ± 131 170 ± 137 NE 131 ± 26 277 ± 70 256 ± 92 123 ± 66 RBF
(mL/min)
C 208 ± 55 244 ± 79 150 ± 74# 28 ± 23#
<0.01/<0.01 SEL 210 ± 27 285 ± 49 265 ± 71 176 ± 109 141 ± 122
AVP 203 ± 55 264 ± 93 238 ± 103 113 ± 89 NE 220 ± 53 222 ± 71 162 ± 52# 39 ± 29#
CrCl (mL/min)
C 139.5 ± 64.8 138.6 ± 78.4 55.4 ± 46.9# 0.7 ± 2.0#
NS/<0.05 SEL 134.5 ± 42.7 140.6 ± 63.8 120.7 ± 40.9 62.9 ± 53.8 47.2 ± 53.1
AVP 115.6 ± 49.0 135.6 ± 50.8 107.8 ± 81.3 22.4 ± 26.5 NE 151.5 ± 39.0 122.1 ± 79.3 65.5 ± 34.3# 10.0 ± 16.1#
C, control group; SEL, selepressin; AVP, arginine vasopressin; NE, norepinephrine. SVI, stroke volume index; MPAP, mean pulmonary artery pressure;
SVRI/PVRI, systemic/pulmonary vascular resistance index; LVSWI, left ventricular stroke work index; DO
2I, oxygen delivery index; VO
2I, oxygen consumption
index; PAOP, pulmonary artery occlusion pressure; SvO
2, mixed venous blood oxygen saturation; EVLWI, extravascular lung water index; RBF/MBF, renal or
mesenteric arterial blood flow; CrCl, creatinine clearance; NS, non-significant. *the significant level of group effects/group × time interaction effects in a
fixed effects model. Time effects of variables were all significant (P<0.05). # P<0.05 compared to SEL group.
Table S4. Evolution of measured coagulation and protein variables in the early intervention groups
Variable Group baseline 6h 12h 18h 24H Fixed effects
COP (mmHg)
C 14.8 ± 2.4 15.3 ± 2.6 13.7 ± 4.4# 11.7 ± 3.8#
<0.01/<0.01 SEL 15.6 ± 2.5 17.8 ± 2.8 18.9 ± 2.5 18.2 ± 3.2 16.2 ± 2.1
AVP 18.3 ± 1.0 14.6 ± 3.4# 14.9 ± 2.6# 12.3 ± 1.7#
NE 17.8 ± 1.4 14.2 ± 2.8# 12.6 ± 2.5# 15.0 ± 2.3#
Total Protein (g/dL)
C 4.6 ± 0.7# 2.5 ± 0.6 2.0 ± 0.6 1.7 ± 0.2
NS/<0.05 SEL 3.8 ± 0.4 2.4 ± 0.5 1.9 ± 0.6 1.4 ± 0.7 1.3 ± 1.0
AVP 4.5 ± 0.7# 2.3 ± 1.0 1.7 ± 0.9 1.6 ± 0.6 NE 3.8 ± 0.6 2.2 ± 0.5 1.3 ± 0.4# 1.6 ± 0.4 Albumin
(g/dL)
C 1.7 ± 0.4 1.0 ± 0.3 0.8 ± 0.3 0.7 ± 0.1
NS/NS SEL 1.5 ± 0.3 0.9 ± 0.2 0.7 ± 0.3 0.5 ± 0.2 0.5 ± 0.3
AVP 1.7 ± 0.3 0.9 ± 0.5 0.6 ± 0.4 0.6 ± 0.2 NE 1.3 ± 0.4 0.7 ± 0.2 0.4 ± 0.2 0.5 ± 0.1 HCT
(%)
C 30 ± 6 36 ± 8 49 ± 7# 54 ± 13#
<0.05/<0.05
SEL 30 ± 6 30 ± 3 34 ± 5 36 ± 11 36 ± 14
AVP 25 ± 7 24 ± 8 31 ± 13 43 ± 12
NE 33 ± 11 27 ± 10 33 ± 12 41 ± 17
PT (sec)
C 15 ± 1 20 ± 3 30 ± 7 60 ± 30#
NS/<0.05
SEL 15 ± 2 20 ± 4 28 ± 11 58 ± 44 61 ± 48
AVP 18 ± 2 23 ± 3 37 ± 14 63 ± 37#
NE 17 ± 2 23 ± 3 34 ± 8 49 ± 26
aPTT (sec)
C 33 ± 5 57 ± 23 113 ± 68# 146 ± 74#
<0.05/<0.05
SEL 30 ± 2 48 ± 14 83 ± 72 142 ± 94 145 ± 105
AVP 32 ± 6 52 ± 15 73 ± 25 116 ± 86#
NE 38 ± 8 56 ± 20 96 ± 35 115 ± 65
Fibrinogen (mg/dL)
C 277 ± 146 147 ± 79 104 ± 46 76 ± 40
NS/<0.05 SEL 215 ± 184 155 ± 176 152 ± 155 137 ± 141 172 ± 161
AVP 191 ± 64 105 ± 44 78 ± 27 92 ± 59 NE 226 ± 155 143 ± 111 105 ± 66 121 ± 66 Platelet
(×109/L)
C 292 ± 116 251 ± 110 244 ± 81 151 ± 89
NS/NS SEL 250 ± 89 266 ± 95 260 ± 122 257 ± 166 230 ± 164
AVP 300 ± 195 259 ± 164 315 ± 171 368 ± 288 NE 381 ± 128 304 ± 139 282 ± 104 258 ± 125
C, control group; SEL, selepressin; AVP, arginine vasopressin; NE, norepinephrine; COP, colloid oncotic pressure; PT, prothrombin time; APTT, activated partial thromboplastin time;
NS, non-significant. *the significant level of group effects/group × time interaction effects in a fixed effects model. Time effects of variables were all significant (P<0.05). # P<0.05
compared to SEL group.
Figure S1. Cumulative infusion volume (c_infusion), cumulative urine output (c_urine), and
fluid balance in late (A) and early (B) intervention groups. Group effects were not significant.
Time effects were significant. Group × time interaction effects in the late intervention were not significant but were significant in the early intervention. C, control group; SEL:
selepressin; AVP: arginine vasopressin; NE: norepinephrine. * / # / $: P<0.05 SEL compared
to the control group, NE or AVP, respectively:
Figure S2. Time to develop to oliguria (urine < 0.5 ml/kg/hour) in late (A) and early (B)
