Introduction
Materials and methods
Ethics
Patients
Study protocol and measurements
Endpoints
Statistical analysis
Results
Patient characteristics
Characteristics | All (n = 34) | CRT responders (n = 15) | CRT non-responders (n = 19) | p value |
---|---|---|---|---|
Anthropometry | ||||
Age, years | 62 [54, 69] | 59 [46, 71] | 64 [57, 68] | 0.435 |
Sex, male/female, n | 25/9 | 13/2 | 12/7 | |
Weight, kg | 71 [62, 80] | 75 [67, 81] | 70 [61, 78] | 0.289 |
Severity scores | ||||
SOFA | 8 [6, 11] | 9 [7, 12] | 8 [6, 10] | 0.485 |
SAPS2 | 42 [33, 51] | 44 [33, 56] | 41 [34, 48] | 0.266 |
Circulatory failure aetiology | ||||
Sepsis | 11 | 3 | 8 | 0.271 |
SIRS | 15 | 8 | 7 | 0.489 |
Cardiogenic shock | 8 | 4 | 4 | 1.0 |
Metabolic and peripheral perfusion | ||||
Mottling score | 1 [0, 2] | 1 [0, 2] | 1 [0, 1] | 0.702 |
Capillary refill time, s | 2.9 [2.4, 3.7] | 3.6 [2.8, 6] | 2.6 [2.3, 3.3] | 0.021 |
PCO2gap, kPa | 1.1 [0.8, 1.7] | 1.4 [1.1, 1.8] | 0.8 [0.7, 1.1] | 0.007 |
Oxygen delivery, mL min−1 m−2 | 337 [272, 417] | 313 [253, 361] | 355 [309, 440] | 0.228 |
Oxygen uptake, mL min−1 m−2 | 101 [84, 116] | 97 [64, 119] | 103 [88, 109] | 0.383 |
Modified RQ, mmHg mL−1 | 2.6 [2.0, 5.4] | 3.5 [2.4, 6.8] | 2.6 [2.0, 4.0] | 0.118 |
Oxygen extraction ratio, % | 30 [25, 35] | 35 [26, 40] | 28 [23, 30] | 0.051 |
Lactate, mmol L−1 | 2.0 [1.2, 3.8] | 2.0 [1.4, 3.8] | 2.0 [1.1, 3.5] | 0.578 |
Thermodilution | ||||
Cardiac index, L min−1 m−2 | 2.6 [2.1, 3.1] | 2.3 [2.0, 3.0] | 2.6 [2.4, 3.2] | 0.499 |
Global end-diastolic volume index, mL m−2 | 710 [549, 827] | 667 [506, 826] | 726 [606, 823] | 0.492 |
Extravascular lung water index, mL kg−1 | 9.1 [7.0, 12.0] | 9.2 [6.5, 12.5] | 9.1 [7.2, 11.5] | 0.931 |
Cardiac function index | 3.6 [2.9, 4.3] | 3.6 [2.8, 4.3] | 3.6 [3.1, 4.3] | 0.718 |
Pulmonary vascular permeability index | 1.8 [1.4, 2.6] | 1.8 [1.5, 2.7] | 1.7 [1.3, 2.5] | 0.772 |
Stroke volume variation, % | 13 [9, 17] | 14 [11, 17] | 13 [8, 17] | 0.676 |
Haemodynamics | ||||
Heart rate, cycle/min | 95 [75, 110] | 96 [73, 104] | 93 [78, 112] | 0.395 |
Mean arterial pressure, mmHg | 68 [61, 72] | 70 [62, 75] | 67 [61, 71] | 0.357 |
Systolic arterial pressure, mmHg | 102 [91, 118] | 97 [90, 116] | 104 [94, 116] | 0.795 |
Diastolic arterial pressure, mmHg | 51 [43, 57] | 52 [46, 57] | 51 [41, 56] | 0.615 |
Pulse pressure, mmHg | 53 [40, 65] | 49 [36, 65] | 53 [41, 64] | 0.532 |
EtCO2, mmHg | 36 [32, 45] | 34 [32, 44] | 37 [31, 46] | 0.737 |
Central venous pressure, mmHg | 7 [4, 11] | 8 [7, 11] | 6 [3, 9] | 0.186 |
Drugs | ||||
Norepinephrine, μg kg−1 min−1 | 0.22 [0.10, 0.51] | 0.17 [0.08, 0.76] | 0.23 [0.11, 0.49] | 0.798 |
Dobutamine, μg kg−1 min−1 | 4 [0, 6] | 4 [0, 5] | 4 [0, 7] | 0.531 |
Epinephrine, μg kg−1 min−1 | 0.00 [0.00, 0.04] | 0.00 [0.00, 0.00] | 0.00 [0.00, 0.05] | 0.472 |
Ventilation | ||||
Tidal volume, mL kg−1 of ideal body weight | 6 [6, 7] | 6 [6, 7] | 6 [6, 8] | 0.702 |
Respiratory rate, cycles min−1 | 24 [20, 27] | 24 [23, 27] | 22 [17, 29] | 0.357 |
Positive end-expiratory pressure, cmH2O | 5 [5, 6] | 6 [5, 6] | 5 [5 6] | 0.937 |
FiO2, % | 40 [30, 60] | 40 [36, 51] | 40 [30, 60] | 0.607 |
Driving pressure, cmH2O | 12 [9, 15] | 12 [10, 14] | 12 [9, 15] | 0.806 |
A | ||||||||
Baseline (T1) | During PLR (T2) | Baseline (T3) | After VE (T4) | Group R/NR | Study period | R/NRstudy period | ||
CRT, s | CRT-R (n = 15) | 3.6 [2.8, 6.0] | 2.3 [1.6, 3.6] | NA | 2.1 [1.8, 2.9]* | < 0.001 | 0.972 | < 0.001 |
CRT-NR (n = 19) | 2.6 [2.3, 3.3] | 2.6 [2.0, 3.1] | NA | 2.6 [2.0, 3.1] | ||||
CI, L min−1 m−2 | CRT-R (n = 15) | 2.5 [2.0, 3.1] | 2.8 [2.5, 3.3] | 2.5 [2.1, 3.2] | 3.0 [2.7, 3.2] | 0.987 | < 0.001 | 0.829 |
CRT-NR (n = 19) | 2.5 [2.2, 3.1] | 2.8 [2.5, 3.5] | 2.4 [2.1, 3.3] | 3.1 [2.6, 3.4] | ||||
SVi, mL m−2 | CRT-R (n = 15) | 31 [24, 35] | 34 [27, 37] | 30 [24, 36] | 33 [30, 40] | 0.787 | 0.001 | 0.997 |
CRT-NR (n = 19) | 27 [22, 35] | 31 [30, 37] | 27 [21, 36] | 32 [27, 36] | ||||
HR, min−1 | CRT-R (n = 15) | 96 [73.0, 104] | 97 [72, 105] | 96 [73, 106] | 93 [70, 105]* | 0.700 | 0.674 | 0.537 |
CRT-NR (n = 19) | 93 [78, 112] | 94 [78, 110] | 95 [79, 110] | 91 [80, 108] | ||||
SAP, mmHg | CRT-R (n = 15) | 97 [90, 116] | 116 [102, 136] | 107 [94, 132.] | 118 [105, 136] | 0.624 | 0.477 | 0.554 |
CRT-NR (n = 19) | 104 [94, 116] | 112 [99, 116] | 98 [94, 110] | 112 [104, 119] | ||||
DAP, mmHg | CRT-R (n = 15) | 52 [46, 57] | 53 [46, 64] | 49 [43, 54] | 57 [45, 66] | 0.958 | 0.524 | 0.249 |
CRT-NR (n = 19) | 51 [41, 56] | 51 [47, 56] | 51 [46, 54] | 51 [46, 57] | ||||
MAP, mmHg | CRT-R (n = 15) | 70 [62, 75.] | 71 [65, 82] | 68 [60, 73] | 76 [69, 81] | 0.714 | 0.101 | 0.932 |
CRT-NR (n = 19) | 67 [61, 70] | 67 [63, 76.] | 64 [58, 70] | 68. [63, 75] | ||||
PP, mmHg | CRT-R (n = 15) | 49 [36, 65.] | 55 [46, 83] | 58 [44, 83] | 60 [46, 75] | 0.321 | 0.051 | 0.548 |
CRT-NR (n = 19) | 53 [41, 64] | 56 [49, 63] | 51 [44, 58] | 58 [50, 72] | ||||
SpO2, % | CRT-R (n = 15) | 98 [97, 100] | 99 [97, 100] | 99 [97, 100] | 100 [97, 100] | 0.353 | 0.143 | 0.575 |
CRT-NR (n = 19) | 99 [95,100] | 98 [95, 100] | 97 [93, 100] | 99 [96, 100] | ||||
EtCO2, mmHg | CRT-R (n = 15) | 34 [32, 44] | 36 [32, 45] | 34 [30, 43] | 34 [29.7, 45.5] | 0.708 | 0.175 | 0.548 |
CRT-NR (n = 19) | 37 [31, 46] | 36 [32, 44] | 35 [30, 43] | 36 [31, 43] | ||||
CVP, mmHg | CRT-R (n = 15) | 8 [7, 11] | 11 [9, 14] | 8 [6, 11] | 10 [7, 13] | 0.678 | 0.906 | 0.543 |
CRT-NR (n = 19) | 6 [3, 9] | 7 [5, 12] | 5 [2, 8] | 6 [4, 9] | ||||
B | ||||||||
Baseline (T1) | After VE (T4) | p value | ||||||
Oxygen delivery, mL min−1 m−2 | CRT-R (n = 14) | 313 [254–361] | 370 [317–399] | 0.002 | ||||
CRT-NR (n = 14) | 355 [309–440] | 397 [327–458] | 0.003 | |||||
p value | 0.24 | 0.697 | ||||||
Oxygen uptake, mL min−1 m−2 | CRT-R (n = 14) | 103 [88–109] | 100 [90–109] | 0.357 | ||||
CRT-NR (n = 14) | 97 [64–119] | 104 [80–133] | 0.375 | |||||
p value | 0.401 | 0.697 | ||||||
Oxygen extraction ratio | CRT-R (n = 14) | 0.34 [0.26–0.40] | 0.28 [0.22–0.33] | 0.024 | ||||
CRT-NR (n = 14) | 0.28 [0.23–0.30] | 0.24 [0.19–0.33] | 0.583 | |||||
p value | 0.051 | 0.608 |
Relationship between CRT responders and CI responders to volume expansion
Reproducibility measurements
Prediction of CRT responsiveness
Discussion
Index test | AUC [95% CI] | Best threshold | Specificity | Sensitivity | PPV | NPV | Youden index | |
---|---|---|---|---|---|---|---|---|
Peripheral perfusion response (decrease of 25% of CRT after VE) | ΔCRT-PLR | 0.94 [0.87–1.0] | − 27% [− 30, − 18] | 1.00 [0.74–1.00] | 0.87 [0.73–1.0] | 1.0 [0.72–1.0] | 0.91 [0.79–1.0] | 0.87 |
PCO2gap | 0.79 [0.61–0.93] | 1.2 kPa [0.9–1.6] | 0.73 [0.53–0.93] | 0.79 [0.57–1.00] | 0.72 [0.58–0.92] | 0.79 [0.62–1.00] | 0.52 | |
Baseline CRT | 0.73 [0.54–0.90] | 2.7 s [2.6–4.1] | 0.74 [0.47–1.0] | 0.80 [0.47–1.00] | 0.69 [0.54–1.00] | 0.67 [0.8–1.00] | 0.49 | |
Cardiac index response (increase of 15% of CI) | ΔCI-PLR | 0.95 [0.86–1.00] | 9.0% [8.7–13.7] | 0.90 [0.71–1.00] | 1.00 [0.77–1.00] | 0.85 [0.68–1.00] | 1.00 [0.86–1] | 0.90 |