Introduction
Materials and methods
Patients
Measurements
Study design
Statistical analysis
Results
Patients
Demographic data
TP (n = 15) | AVP (n = 15) | NE (n = 15) | P value | |
---|---|---|---|---|
Age, years
| 67 (60; 71) | 66 (60; 74) | 64 (59; 72) |
0.889
|
Gender, male
| 73% | 67% | 80% |
0.717
|
Body weight, kg
| 85 (79; 100) | 85 (71; 98) | 85 (78; 90) |
0.612
|
SAPS II
| 62 (57; 72) | 60 (49; 66) | 58 (52; 68) |
0.664
|
Cause of septic shock
| Necrotizing fasciitis (n = 1) | Endocarditis (n = 1) | Pancreatitis (n = 4) |
0.438
|
Pancreatitis (n = 3) | Necrotizing fasciitis (n = 2) | Peritonitis (n = 6) | ||
Peritonitis (n = 5) | Peritonitis (n = 6) | Pneumonia (n = 5) | ||
Pneumonia (n = 6) | Pneumonia (n = 6) | |||
ICU mortality
| 7/15 | 8/15 | 10/15 |
0.533
|
ICU length of stay
| 14 (9; 25) | 17 (5; 27) | 17(7; 23) |
0.878
|
Norepinephrine and dobutamine requirements
Systemic hemodynamic variables
Baseline | 12 hours | 24 hours | 36 hours | 48 hours | |
---|---|---|---|---|---|
HR
(bpm) | |||||
TP | 95 ± 16 | 85 ± 19* | 83 ± 21* | 71 ± 14*‡§ | 71 ± 16*‡§ |
AVP | 100 ± 22 | 98 ± 24 | 97 ± 27 | 92 ± 24† | 93 ± 25† |
NE | 97 ± 21 | 92 ± 26 | 99 ± 29 | 95 ± 24† | 96 ± 21† |
CI
(L/min/m) | |||||
TP | 4.0 ± 1.0 | 3.9 ± 1.0 | 3.7 ± 0.8 | 3.4 ± 0.6 | 3.5 ± 0.6 |
AVP | 4.0 ± 1.1 | 4.2 ± 1.4 | 4.3 ± 1.1 | 3.9 ± 1.1 | 4.2 ± 1.9 |
NE | 4.0 ± 1.0 | 3.9 ± 1.0 | 4.1 ± 1.1 | 3.9 ± 1.2 | 3.9 ± 1.5 |
SVI
(mL/beats/m) | |||||
TP | 46 ± 13 | 46 ± 13 | 47 ± 12 | 48 ± 10 | 50 ± 10 |
AVP | 41 ± 12 | 43 ± 12 | 46 ± 10 | 44 ± 12 | 47 ± 18 |
NE | 43 ± 13 | 44 ± 14 | 44 ± 15 | 43 ± 16 | 42 ± 15 |
MAP
(mmHg) | |||||
TP | 53 ± 6 | 70 ± 3* | 71 ± 3* | 72 ± 3* | 71 ± 4* |
AVP | 53 ± 4 | 70 ± 3* | 70 ± 3* | 71 ± 3* | 71 ± 3* |
NE | 54 ± 3 | 70 ± 4* | 71 ± 2* | 7 0 ± 3* | 71 ± 3* |
MPAP
(mmHg) | |||||
TP | 25 ± 4 | 27 ± 4* | 27 ± 4* | 27 ± 5* | 28 ± 5* |
AVP | 24 ± 4 | 28 ± 5* | 28 ± 5* | 28 ± 5* | 29 ± 4* |
NE | 24 ± 7 | 28 ± 7* | 29 ± 7* | 29 ± 5* | 30 ± 7* |
PAOP
(mmHg) | |||||
TP | 15 ± 2 | 17 ± 2 | 17 ± 2 | 17 ± 2 | 17 ± 2 |
AVP | 15 ± 2 | 17 ± 2* | 17 ± 4* | 17 ± 3* | 17 ± 2* |
NE | 15 ± 2 | 15 ± 2 | 16 ± 2 | 16 ± 2 | 16 ± 3 |
RAP
(mmHg) | |||||
TP | 11 ± 3 | 12 ± 3 | 14 ± 3* | 13 ± 3 | 13 ± 3 |
AVP | 12 ± 3 | 15 ± 3* | 14 ± 3* | 15 ± 3* | 15 ± 4* |
NE | 12 ± 3 | 13 ± 3 | 14 ± 3 | 14 ± 4 | 14 ± 4 |
SVRI
(dyne·s/cm/m) | |||||
TP | 886 ± 291 | 1271 ± 334* | 1287 ± 304* | 1376 ± 241* | 1348 ± 275* |
AVP | 861 ± 246 | 1157 ± 407* | 1091 ± 325* | 1235 ± 334* | 1254 ± 531* |
NE | 874 ± 220 | 1237 ± 320* | 1208 ± 348* | 1266 ± 386* | 1319 ± 471* |
PVRI
(dyne·s/cm/m) | |||||
TP | 196 ± 61 | 227 ± 99 | 219 ± 89 | 256 ± 108 | 260 ± 117 |
AVP | 200 ± 83 | 243 ± 108 | 230 ± 128 | 254 ± 148 | 264 ± 134 |
NE | 192 ± 115 | 266 ± 106* | 275 ± 122* | 298 ± 133* | 313 ± 202* |
RVSWI
(g/m/beat) | |||||
TP | 8 ± 4 | 9 ± 4 | 8 ± 5 | 9 ± 4 | 10 ± 4 |
AVP | 7 ± 3 | 8 ± 3 | 9 ± 3* | 8 ± 3 | 9 ± 4* |
NE | 7 ± 3 | 9 ± 4* | 9 ± 3* | 8 ± 3* | 9 ± 4* |
LVSWI
(g/m/beat) | |||||
TP | 22 ± 7 | 33 ± 9* | 35 ± 10* | 37 ± 8* | 37 ± 9* |
AVP | 21 ± 7 | 31 ± 8* | 32 ± 6* | 33 ± 9* | 34 ± 14* |
NE | 22 ± 7 | 33 ± 11* | 33 ± 12* | 32 ± 13* | 31 ± 11* |
Fluids
(mL/24 h) | |||||
TP | 4833 ± 783 | 4353 ± 853 | |||
AVP | 4860 ± 686 | 4513 ± 781 | |||
NE | 4707 ± 860 | 4807 ± 853 |
New-onset tachyarrhythmias
Acid-base homeostasis, oxygen transport variables
Baseline | 12 hours | 24 hours | 36 hours | 48 hours | |
---|---|---|---|---|---|
PH
(-log10 c(H+)) | |||||
TP | 7.31 ± 0.1 | 7.32 ± 0.1 | 7.32 ± 0.1 | 7.34 ± 0.08 | 7.37 ± 0.08* |
AVP | 7.36 ± 0.09 | 7.35 ± 0.11 | 7.32 ± 0.12 | 7.34 ± 0.12 | 7.32 ± 0.11 |
NE | 7.34 ± 0.1 | 7.34 ± 0.08 | 7.32 ± 0.08 | 7.31 ± 0.09 | 7.28 ± 0.12*† |
PaO
2
/FiO
2
| |||||
TP | 176 ± 105 | 179 ± 82 | 189 ± 86 | 216 ± 95 | 220 ± 78 |
AVP | 219 ± 118 | 231 ± 117 | 222 ± 129 | 211 ± 132 | 225 ± 133 |
NE | 200 ± 97 | 216 ± 113 | 213 ± 101 | 194 ± 73 | 185 ± 85 |
PaO
2
(mmHg) | |||||
TP | 113 ± 44 | 127 ± 45 | 141 ± 47 | 164 ± 66 | 175 ± 64 |
AVP | 123 ± 36 | 140 ± 48 | 130 ± 49 | 127 ± 59 | 139 ± 58 |
NE | 120 ± 46 | 124 ± 44 | 125 ± 31 | 123 ± 34 | 114 ± 49 |
pvO
2
(mmHg) | |||||
TP | 36 ± 6 | 36 ± 6 | 36 ± 5 | 35 ± 5 | 36 ± 5 |
AVP | 35 ± 6 | 38 ± 6 | 38 ± 5 | 38 ± 6 | 38 ± 6 |
NE | 36 ± 7 | 38 ± 6 | 38 ± 6 | 39 ± 7 | 38 ± 6 |
SaO
2
(%) | |||||
TP | 96 ± 4 | 97 ± 3 | 98 ± 2 | 99 ± 2 | 99 ± 2 |
AVP | 97 ± 3 | 98 ± 3 | 98 ± 2 | 96 ± 4 | 98 ± 2 |
NE | 97 ± 2 | 96 ± 7 | 98 ± 1 | 98 ± 2 | 96 ± 7 |
SvO
2
(%) | |||||
TP | 60 ± 7 | 59 ± 11 | 60 ± 9 | 60 ± 8 | 63 ± 8 |
AVP | 61 ± 12 | 65 ± 11 | 64 ± 7 | 63 ± 13 | 64 ± 12 |
NE | 62 ± 10 | 66 ± 10 | 66 ± 9 | 66 ± 9 | 62 ± 12 |
DO
2
I
(mL/min/m) | |||||
TP | 473 ± 105 | 468 ± 117 | 433 ± 92 | 393 ± 73 | 402 ± 70 |
AVP | 464 ± 137 | 519 ± 189 | 550 ± 165 | 484 ± 123 | 520 ± 242 |
NE | 460 ± 131 | 471 ± 157 | 482 ± 136 | 462 ± 136 | 467 ± 162 |
VO
2
I
(mL/min/m) | |||||
TP | 184 ± 58 | 184 ± 49 | 171 ± 32 | 160 ± 43 | 152 ± 38 |
AVP | 173 ± 51 | 173 ± 59 | 193 ± 65 | 168 ± 52 | 173 ± 51 |
NE | 163 ± 41 | 147 ± 35 | 160 ± 57 | 153 ± 51 | 164 ± 67 |
O
2
-ER
(%) | |||||
TP | 38 ± 6 | 40 ± 9 | 40 ± 8 | 41 ± 8 | 38 ± 8 |
AVP | 39 ± 12 | 35 ± 9 | 35 ± 6 | 36 ± 11 | 37 ± 10 |
NE | 37 ± 10 | 32 ± 6 | 34 ± 9 | 34 ± 9 | 36 ± 10 |
PaCO
2
(mmHg) | |||||
TP | 45 ± 6 | 42 ± 6 | 41 ± 9 | 40 ± 8 | 38 ± 6 |
AVP | 43 ± 9 | 40 ± 5 | 42 ± 4 | 41 ± 6 | 41 ± 6 |
NE | 44 ± 9 | 43 ± 9 | 44 ± 8 | 44 ± 8 | 43 ± 9 |
ABE
(mmol/L) | |||||
TP | -2.9 ± 5.1 | -4.6 ± 4.2 | -4.9 ± 4.6 | -4.0 ± 4.2 | -3.1 ± 4.2 |
AVP | -1.8 ± 6.5 | -2.8 ± 7.0 | -3.7 ± 6.7 | -1.6 ± 7.8 | -4.1 ± 6.5 |
NE | -2.5 ± 4.5 | -2.5 ± 4.3 | -3.5 ± 4.3 | -4.2 ± 3.9 | -6.2 ± 5.4* |
Arterial lactate
(mmol/L) | |||||
TP | 3.1 ± 1.8 | 2.9 ± 1.9 | 2.9 ± 2.0 | 3.4 ± 2.4 | 3.6 ± 3.0 |
AVP | 3.0 ± 2.4 | 3.2 ± 2.3 | 3.4 ± 2.3 | 3.2 ± 2.3 | 3.4 ± 3.3 |
NE | 3.1 ± 2.2 | 3.3 ± 2.8 | 3.4 ± 2.8 | 3.6 ± 2.4 | 4.3 ± 3.4* |
Hemoglobin
(g/dL) | |||||
TP | 8.6 ± 0.9 | 8.7 ± 0.7 | 8.4 ± 1.2 | 8.2 ± 0.6‡ | 8.1 ± 0.6 |
AVP | 8.3 ± 0.9 | 8.7 ± 1.1 | 9 ± 1.1* | 9 ± 1*† | 8.8 ± 0.9 |
NE | 8.3 ± 0.8 | 8.7 ± 0.9 | 8.4 ± 0.5 | 8.5 ± 0.8 | 8.9 ± 1 |
Regional hemodynamics
Baseline | 12 hours | 24 hours | 36 hours | 48 hours | |
---|---|---|---|---|---|
CBI
(mL/min/m) | |||||
TP | 353 ± 226 | 387 ± 202 | 367 ± 179 | 299 ± 139 | 351 ± 129 |
AVP | 397 ± 171 | 409 ± 209 | 367 ± 222 | 308 ± 185* | 305 ± 201* |
NE | 327 ± 135 | 358 ± 173 | 312 ± 145 | 271 ± 136 | 252 ± 206 |
PDR
(%) | |||||
TP | 13 ± 6 | 14 ± 5 | 13 ± 4 | 12 ± 5 | 13 ± 4 |
AVP | 15 ± 5 | 15 ± 6 | 13 ± 7 | 12 ± 7* | 11 ± 6* |
NE | 14 ± 5 | 13 ± 5 | 12 ± 6 | 11 ± 6* | 10 ± 7* |
P
g-a
CO
2
(mmHg) | |||||
TP | 23 ± 11 | 24 ± 8 | 22 ± 6 | 20 ± 6 | 20 ± 7 |
AVP | 25 ± 7 | 28 ± 8 | 27 ± 9 | 28 ± 12 | 28 ± 10 |
NE | 24 ± 11 | 28 ± 10 | 28 ± 8 | 26 ± 8 | 31 ± 12 |
Urinary output
(mL/h) | |||||
TP | 34.6 ± 31.3 | 69.3 ± 70.4 | 49.2 ± 49.5 | 48.5 ± 41.4 | 46.6 ± 33.3 |
AVP | 42.3 ± 46.9 | 42 ± 39 | 42 ± 41.6 | 40.7 ± 45.7 | 43.3 ± 58.7 |
NE | 38.6 ± 34.3 | 55.4 ± 74.1 | 66 ± 77 | 58.6 ± 56.1 | 58.6 ± 63.8 |
Variables of organ function and injury
Baseline | 12 hours | 24 hours | 36 hours | 48 hours | |
---|---|---|---|---|---|
Creatinine
(mg/dL) | |||||
TP | 2.5 ± 1 | 2.6 ± 1.2 | 2.8 ± 1.4 | 2.8 ± 1.3 | 2.8 ± 1.4 |
AVP | 2.2 ± 1 | 2.4 ± 1.1 | 2.4 ± 1.2 | 2.5 ± 1.4 | 2.4 ± 1.2 |
NE | 2.2 ± 1.6 | 2.6 ± 1.7 | 2.7 ± 1.7* | 2.9 ± 1.8* | 3.3 ± 2* |
Creatinine, rel. (%) | |||||
TP | -- | 4 ± 16 | 11 ± 23 | 13 ± 27 | 14 ± 35§ |
AVP | -- | 11 ± 17 | 12 ± 26 | 15 ± 31 | 10 ± 21§ |
NE | -- | 19 ± 23 | 23 ± 37 | 34 ± 48 | 54 ± 77†‡ |
Bilirubin, tot. (mg/dL) | |||||
TP | 1.2 ± 0.7 | 1 ± 0.5 | 1 ± 0.5 | 0.9 ± 0.3‡§ | 0.9 ± 0.3‡§ |
AVP | 1.6 ± 1.3 | 1.6 ± 1.2 | 1.8 ± 1.6 | 2.0 ± 2.0† | 2.3 ± 2.8† |
NE | 1.6 ± 0.9 | 1.9 ± 0.8 | 2.0 ± 1.2 | 2.3 ± 1.7*† | 2.8 ± 2.5*† |
Bilirubin, dir. (mg/dL) | |||||
TP | 0.5 ± 0.3 | 0.5 ± 0.4 | 0.5 ± 0.3 | 0.4 ± 0.2§ | 0.3 ± 0.1‡§ |
AVP | 0.8 ± 0.9 | 1 ± 1.2 | 1.1 ± 1.4 | 1.1 ± 1.5 | 1.4 ± 1.9*† |
NE | 0.8 ± 0.5 | 1.2 ± 0.8 | 1.2 ± 0.9 | 1.6 ± 1.7*† | 1.9 ± 2.1*† |
ASAT
(U/L) | |||||
TP | 52 ± 26 | 52 ± 33 | 54 ± 35 | 53 ± 42 | 48 ± 34 |
AVP | 63 ± 49 | 85 ± 57 | 79 ± 66 | 119 ± 163 | 91 ± 95 |
NE | 72 ± 68 | 89 ± 115 | 95 ± 132 | 103 ± 146 | 90 ± 122 |
ALAT
(U/L) | |||||
TP | 30 ± 14 | 34 ± 15 | 33 ± 14 | 35 ± 18 | 30 ± 13 |
AVP | 45 ± 31 | 58 ± 42 | 63 ± 53 | 69 ± 67 | 81 ± 85 |
NE | 43 ± 45 | 62 ± 80 | 68 ± 103 | 73 ± 114 | 63 ± 97 |
Amylase
(U/L) | |||||
TP | 168 ± 97 | 148 ± 90 | 133 ± 79 | 127 ± 79 | 144 ± 124 |
AVP | 165 ± 111 | 152 ± 100 | 143 ± 79 | 147 ± 110 | 123 ± 70 |
NE | 203 ± 191 | 199 ± 182 | 217 ± 221 | 206 ± 212 | 172 ± 152 |
Lipase
(U/L) | |||||
TP | 138 ± 145 | 125 ± 92 | 97 ± 64 | 144 ± 126 | 116 ± 91 |
AVP | 133 ± 90 | 124 ± 68 | 127 ± 64 | 136 ± 72 | 134 ± 65 |
NE | 134 ± 160 | 198 ± 282 | 120 ± 96 | 158 ± 162 | 115 ± 65 |
Troponine I
(ng/mL) | |||||
TP | 0.31 ± 0.3 | 0.31 ± 0.51 | 0.22 ± 0.41 | 0.19 ± 0.35 | 0.18 ± 0.3 |
AVP | 0.56 ± 1 | 0.84 ± 1.5 | 1.23 ± 2.4 | 1.37 ± 2.5 | 1.17 ± 2 |
NE | 0.58 ± 0.9 | 0.66 ± 0.8 | 0.72 ± 0.75 | 0.69 ± 0.86 | 0.63 ± 1 |
Platelet count
(103 cells/μL) | |||||
TP | 119 ± 68 | 103 ± 59 | 93 ± 59* | 78 ± 48* | 73 ± 41* |
AVP | 110 ± 56 | 102 ± 63 | 95 ± 53 | 95 ± 55 | 93 ± 50 |
NE | 114 ± 64 | 102 ± 52 | 99 ± 58 | 94 ± 60 | 94 ± 69 |
INR
| |||||
TP | 1.4 ± 0.2 | 1.4 ± 0.2 | 1.4 ± 0.2 | 1.4 ± 0.2 | 1.4 ± 0.2 |
AVP | 1.5 ± 0.5 | 1.5 ± 0.3 | 1.5 ± 0.5 | 1.5 ± 0.4 | 1.5 ± 0.5 |
NE | 1.5 ± 0.3 | 1.5 ± 0.3 | 1.4 ± 0.4 | 1.3 ± 0.2 | 1.4 ± 0.3 |
APTTr
| |||||
TP | 1.7 ± 0.6 | 1.6 ± 0.5 | 1.6 ± 0.4 | 1.8 ± 0.6 | 1.7 ± 0.7 |
AVP | 1.5 ± 0.5 | 1.5 ± 0.6 | 1.6 ± 0.7 | 1.6 ± 0.7 | 1.7 ± 0.7 |
NE | 1.5 ± 0.2 | 1.4 ± 0.2 | 1.4 ± 0.2 | 1.4 ± 0.2 | 1.6 ± 0.3 |
Markers of systemic inflammation
Baseline | 48 hours | |
---|---|---|
IL-6
(pg/mL) | ||
TP | 612 ± 640 | 296 ± 367 |
AVP | 621 ± 595 | 293 ± 324 * |
NE | 655 ± 585 | 380 ± 251 |
IL-1β
(pg/mL) | ||
TP | 6.6 ± 0.6 | 6.1 ± 0.6 |
AVP | 6.7 ± 1 | 6.5 ± 1 |
NE | 6.5 ± 0.7 | 6.6 ± 0.7 |
TNF-α
(pg/mL) | ||
TP | 24 ± 21 | 18 ± 6 |
AVP | 24 ± 16 | 24 ± 27 |
NE | 28 ± 15 | 29 ± 21 |
Temperature
(°C) | ||
TP | 38.6 ± 2 | 37.8 ± 0.8 |
AVP | 39 ± 0.4 | 38.2 ± 1 |
NE | 38.8 ± 0.2 | 38.5 ± 0.8 |
Length of ICU stay and outcome
Discussion
Conclusions
Key messages
-
Continuous infusion of low-dose TP – when given as first-line vasopressor agent in septic shock – reduces open-label NE requirements.
-
Low-dose AVP or TP infusion do not decrease in CI, DO2I and SvO2 in adequately fluid resuscitated septic shock patients.
-
Continuous TP infusion may be favourable over TP bolus infusion, because the latter approach has been reported to excessively increase SVRI and PVRI as well as decreases in HR and CI.
-
Neither AVP nor TP negatively affected pulmonary hemodynamics and function.
-
There are no differences between TP, AVP and NE in terms of regional hemodynamics or acid-base homeostasis when they are administered as first-line vasopressor agent in septic shock.