Introduction
Materials and methods
Study design
Patients
Randomization
Protocol description
Data collection and follow-up
Study outcomes
Assessment of data quality
Statistical analysis
Results
Characteristics at inclusion
Control
|
Preload dependence
|
P
| |
---|---|---|---|
(n = 30)
|
(n = 30)
| ||
Age (years) | 64 [54-76] | 65 [58-80] | 0.38 |
Male gender | 22 (73%) | 21 (70%) | 1 |
Admission category | |||
Medical | 27 (90%) | 30 (100%) | 0.24 |
Unscheduled surgery | 3 (10%) | 0 (0%) | |
Charlson score | 3 [2-5] | 3 [1-5] | 0.74 |
Immunodeficiency*
| 9 (30%) | 9 (30%) | 1 |
SAPS II | 56 [50-60] | 57 [47-69] | 0.55 |
SOFA score at inclusion | 10 [9-12] | 11 [9-13] | 0.52 |
Time between hypotension and inclusion (H) | 9 [5-11] | 10 [6-11] | 0.64 |
Time between ICU admission and inclusion (H) | 8 [4-15] | 6 [3-12] | 0.55 |
Renal replacement therapy | 6 (20%) | 8 (27%) | 0.76 |
Mechanical ventilation | 26 (87%) | 20 (67%) | 0.13 |
Volume of IV fluids administered between hypotension and inclusion (L) | 3.0 [2.5-4.0] | 3.5 [2.5-4.4] | 0.26 |
Type of infection | |||
Community-acquired infection | 23 (77%) | 21 (70%) | 0.77 |
Hospital-acquired infection | 7 (23%) | 9 (30%) | |
Infection site | |||
Pulmonary | 16 (53%) | 18 (60%) | 0.80 |
Intra-abdominal | 5 (17%) | 7 (23%) | 0.75 |
Urinary tract | 3 (10%) | 6 (20%) | 0.47 |
Catheter-related infection | 1 (3%) | 3 (10%) | 0.61 |
Other | 3 (10%) | 4 (13%) | 1 |
Positive blood cultures | 15 (50%) | 15 (50%) | 1 |
Identification of causative pathogen | 25 (83%) | 27 (90%) | 0.71 |
Causative pathogens | |||
Enterobacteriaceae | 13 (43%) | 16 (53%) | 0.61 |
Non-fermenting gram-negative bacilli | 5 (17%) | 3 (10%) | 0.71 |
Other gram-negative bacilli | 2 (7%) | 4 (13%) | 0.67 |
Staphylococci | 6 (20%) | 7 (23%) | 1 |
Streptococci | 2 (7%) | 6 (20%) | 0.25 |
Gram-positive bacilli | 0 (0%) | 1 (3%) | 1 |
Enterococci | 0 (0%) | 1 (3%) | 1 |
Gram-negative cocci | 0 (0%) | 1 (3%) | 1 |
Fungi | 0 (0%) | 1 (3%) | 1 |
Empirical antibiotic therapy | |||
Adequate | 24 (80%) | 23 (77%) | 0.42 |
Inadequate | 1 (3%) | 4 (13%) | |
Not applicable | 5 (17%) | 3 (10%) |
Control
|
Preload dependence
|
P
| |
---|---|---|---|
(n = 30)
|
(n = 30)
| ||
Mean arterial pressure (mm Hg) | 68 [64-75] | 72 [68-82] | 0.08 |
Central venous pressure (mm Hg) | 9 [7-14] | 10 [8-12] | 0.67 |
Cardiac index (L.min-1.m-2) | 3.5 [2.7-4.7] | 3.6 [2.9-4.8] | 0.43 |
Hemoglobin (g.dL-1) | 9.8 [8.9-11.6] | 10.6 [9.5-11.4] | 0.57 |
Oxygen arterial transport (mL.min-1.m-2) | 414 [352-619] | 468 [395-648] | 0.14 |
ScvO2 (%) | 77 [74-83] | 77 [72-84] | 0.89 |
ScvO2 < 70% | 5 (17%) | 6 (20%) | 1 |
Extravascular lung water index (mL.kg-1 PBW) | 13 [10-16] | 12 [10-16] | 0.65 |
Lactate (mmol.L-1) | 2.7 [2.2-3.6] | 2.9 [2.5-5.7] | 0.32 |
Lactate above upper normal laboratory limit | 22 (73%) | 25 (83%) | 0.53 |
Inotrope treatment | 5 (17%) | 6 (20%) | 1 |
Vasopressor dose (μg.kg-1.min-1) | 0.51 [0.26-1.05] | 0.60 [0.34-1.14] | 0.38 |
Time course of hemodynamic parameters in both groups
Fluid administration and fluid balance in both groups
Control
|
Preload dependence
|
P
| |
---|---|---|---|
(n = 30)
|
(n = 30)
| ||
Intravascular volume expansion ITT (mL.day-1) | 986 [654-1,624] | 446 [295-1,105] | 0.04 |
Intravascular volume expansion PP (mL.day-1) | 917 [639-1,511] | 383 [211-604] | 0.01 |
RBC transfusion (mL.day-1) | 178 [82-304] | 103 (0-183] | 0.04 |
Other blood products (mL.day-1) | 0 [0-122] | 0 [0-125] | 0.76 |
Other fluids (mL.day-1) | 3151 [2,791-3,456] | 2919 [2,533-3,368] | 0.70 |
Fluid intake* (mL.day-1) | 4096 [3,770-4,677] | 3610 [2,982-4,560] | 0.16 |
Diuresis (mL.day-1) | 2116 [368-3,212] | 1854 [513-3,332] | 0.95 |
Fluid output (mL.day-1) | 2550 [1,914-3,331] | 2609 [2,079-3,202] | 0.95 |
Fluid balance (mL.day-1) | 1749 [146-2,788] | 888 [153-2,816] | 0.68 |
Intravascular volume expansion/fluid intake (%) | 23% | 15% | 0.04 |
Associated treatments
Outcomes
Control
|
Preload dependence
|
P
| |
---|---|---|---|
(n = 30)
|
(n = 30)
| ||
Time to shock resolution (days) | 2.0 [1.2-3.1] | 2.3 [1.4-5.6] | 0.29 |
Ventilator-free days at day 28 | 8 [0-21] | 14 [0-24] | 0.35 |
Number of days with lactates above upper normal laboratory limit | 1 [1-4] | 2 [1-4] | 0.14 |
Number of days with pulmonary edema (that is ELWI >10 ml.kg-1 PBW) | 4 [1-5] | 4 [1-6] | 0.94 |
Number of days with organ system failure (that is SOFA ≥6) | 4 [3-5] | 4 [2-8] | 0.61 |
ICU length of stay (days) | 10 [7-20] | 14 [6-28] | 0.55 |
In survivors | 14 [9-28] | 22 [6-28] | 0.89 |
In non-survivors | 8 [5-11] | 5 [3-17] | 0.85 |
Mortality at day 28 | 14 (47%) | 7 (23%) | 0.10 |
Protocol violations
Discussion
Limitations and strengths
Effect of preload dependence-driven intravascular volume expansion on plasma lactate
Effect of preload dependence-driven intravascular volume expansion on fluid administration
Effects on outcomes
Clinical relevance of PPV
Conclusions
Key messages
-
In septic shock patients, titrating intravascular volume expansion with preload dependence indices may have no effect on time to shock resolution.
-
This strategy is, however, associated with a decrease in both the daily amount of intravascular fluids and red blood cell transfusion, with no outcome penalty.