Background
Methods
Computational model
Measurements
Patients datasets
Moderate ARDS, High CO [25] | Moderate ARDS, Normal CO [26] | Severe ARDS, High CO [27] | |||||
---|---|---|---|---|---|---|---|
Parameters obtained from data | CO (l min−1) | 8 | 4.09 | 7.3 | |||
FIO2
| 0.5 | 0.45 | 1 | ||||
Vt (ml kg−1) | 12 | 10 | 10 | ||||
PEEP (cm H2O) | 0 | 0 | 0 | ||||
Parameters determined by optimizationa
| VR (b min−1) | 12 | 10 | 10 | |||
Duty Cycle | 0.33 | 0.35 | 0.46 | ||||
RQ | 0.9 | 0.9 | 0.7 | ||||
VO2 (ml min−1) | 307 | 303 | 306 | ||||
Hb (g dl−1) | 9.9 | 14.5 | 10.5 | ||||
Data | Model | Data | Model | Data | Model | ||
Results of fitting the model to the data | PaO2 (kpa) | 10.6 | 11.2 | 10 | 10.8 | 6.6 | 7.5 |
PaCO2 (kpa) | 5 | 4.4 | 5.3 | 5.2 | 3.7 | 4.3 | |
Other results | PvO2 (kpa) | NA | 4.6 | NA | 4.4 | NA | 4.1 |
Shunt Fraction (%) | NA | 22 | NA | 16 | NA | 44 |
All Patients | Severe ARDS | Moderate ARDS | Mild ARDS | ||||||
---|---|---|---|---|---|---|---|---|---|
n
| 20 | 11 | 6 | 3 | |||||
Vt (ml kg−1) | 6 | ||||||||
VR (b min−1) | 12 | ||||||||
PEEP (cm H2O) | 10 | ||||||||
Ventilation mode | Volume controlled | ||||||||
FIO2
| 1 | ||||||||
HR (bpm) | 100 | ||||||||
mean | sd | mean | sd | mean | sd | mean | sd | ||
Parameters determined by optimizationa
| CI (l min−1 m−2) | 5.3 | 0.5 | 5.0 | 0.4 | 5.6 | 0.5 | 6.0 | 0.1 |
RQ | 0.8 | 0.1 | 0.8 | 0.1 | 0.8 | 0.1 | 0.8 | 0.1 | |
VO2 (ml min−1) | 304.4 | 6.3 | 305.8 | 3.8 | 303.8 | 8.0 | 300.3 | 10.6 | |
Duty Cycle | 0.4 | 0.0 | 0.4 | 0.0 | 0.4 | 0.0 | 0.4 | 0.0 | |
Hb (g l−1) | 110.5 | 39.5 | 92.5 | 32.6 | 115.8 | 33.9 | 165.7 | 13.5 | |
Results of fitting the model to the data | PaO2 (mm Hg) | 120.9 | 73.2 | 68.6 | 10.6 | 149.5 | 36.1 | 255.3 | 49.7 |
Cstat (ml/cm H2O) | 25.0 | 6.4 | 22.0 | 4.5 | 27.3 | 4.5 | 31.7 | 10.1 | |
PaCO2 (mmHg) | 61.2 | 3.6 | 59.3 | 2.9 | 62.3 | 3.3 | 65.7 | 1.2 | |
Other results | Shunt Fraction (%) | 37.6 | 12.3 | 46.5 | 5.0 | 30.8 | 5.5 | 18.7 | 11.7 |
Pplat (cm H2O) | 27.4 | 4.1 | 29.4 | 4.1 | 25.3 | 2.1 | 24.0 | 4.4 | |
TOP (cm H2O) | 21.6 | 2.4 | 22.3 | 2.8 | 21.0 | 2.0 | 20.0 | 0.0 |
Recruitment maneuver protocols
Maximal recruitment strategy (MRS) [30]
Sustained inflation (SI) [2]
Results
Model outputs accurately reproduce clinical datasets
Evaluation of the maximal recruitment strategy (MRS) and Sustained inflation (SI) RMs on 3 in silico patients with varying ARDS severity and varying cardiac output
Moderate ARDS, High CO [25] | Moderate ARDS, Normal CO [26] | Severe ARDS, High CO [27] | ||||
---|---|---|---|---|---|---|
RM | MRS | SI | MRS | SI | MRS | SI |
End RM PEEP, cm H2O | 10 | 10 | 10 | 10 | 15 | 10 |
RecruitmentB (baseline), % | 78 | 78 | 8 | 87 | 57 | 57 |
RecruitmentM (maximum), % | 97 | 80 | 100 | 97 | 98 | 65. |
R Ratio | 19.59 | 2.50 | 13.00 | 10.31 | 41.84 | 12.31 |
∆ CO (at max PAW), l min−1
| −2.3 | −1.7 | −1.6 | −1.2 | −2.3 | −1.5 |
∆ RVEDV (at max PAW), ml | −14 | −6 | −55 | −29 | −18 | −10 |
DO2 (baseline), ml min−1
| 1086 | 1086 | 754 | 754 | 902 | 902 |
∆ DO2 (at max PAW), ml min−1
| 810 | 834 | 453 | 540 | 697 | 689 |
∆ DO2 (post RM), ml min−1
| 1144 | 1097 | 790 | 786 | 1012 | 971 |
RAP (baseline), mm Hg | 9 | 9 | 11 | 11 | 11 | 11 |
RAP (at max PAW), mm Hg | 18 | 12 | 21 | 15 | 23 | 16 |
PF ratio (baseline), mm Hg | 199 | 199 | 196 | 196 | 65 | 65 |
PF ratio (post RM), mm Hg | 363 | 213 | 337 | 309 | 347 | 86 |
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In all patients, large increases in PF ratio were observed during the application of the MRS, and PF ratio remained significantly greater than baseline values after the RM ended. Improved recruitment, reduced dynamic lung strain, and falls in arterial carbon dioxide levels were evident during and after the RM, indicating an increase in effective lung area and reduced ventilation/perfusion mismatch.
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DO2 fell by more than 200 ml min−1 in all three patients at maximum PEEP. This was caused by a decrease in CO which outweighed the increase in oxygen content in all cases, with the lowest CO occurring at maximum PEEP. In one patient (moderate ARDS, normal CO) the level of DO2 during the maneuver fell below 500 ml min−1, which would be likely to cause systemic responses, such as blood flow being redirected to critical organ systems, reducing tissue oxygenation in other tissue beds and potentially leading to residual organ dysfunction.
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The end-diastolic volume of the right ventricle fell as PEEP increased in all patients. The end-systolic volume remained relatively constant in the patients with high CO. Both CO and DO2 returned to close-to-baseline levels for the in silico patients with moderate ARDS as PEEP returned to 10 cm H2O.
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A significant post-RM increase in DO2 was maintained only in the in silico patient with severe ARDS.
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Figure 6 shows that in all in silico patients, the MRS led to an increase in static lung strain and a decrease in dynamic lung strain. The largest decrease in dynamic lung strain was observed in the in silico patient with severe ARDS.×
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In the virtual patients with moderate severity ARDS, high CO and severe ARDS, high CO, small numbers of alveoli were re-opened, resulting in only small increases in PF ratio being attained.
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Significantly greater recruitment (and hence a larger increase in PF ratio) was observed in the moderate severity ARDS, normal CO subject. However, the resulting gain in oxygen content was effectively cancelled out by the reduction in cardiac output.
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Only small post-RM improvements in DO2 were observed in all three virtual patients, with the largest improvement being observed in the severe ARDS subject.
Evaluation of the maximal recruitment strategy RM on 20 in silico patients with varying ARDS severity and high cardiac output
All Patients | Severe ARDS | Moderate ARDS | Mild ARDS | |||||
---|---|---|---|---|---|---|---|---|
mean | sd | mean | sd | mean | sd | mean | sd | |
PEEP (baseline), cmH2O | 10.0 | 0 | 10.0 | 0 | 10.0 | 0 | 10.0 | 0 |
PEEP (post RM), cmH2O | 24.5 | 2 | 25.0 | 0 | 25.0 | 0 | 21.7 | 6 |
Recruitment (baseline), % | 63.3 | 18 | 49.7 | 11 | 75.7 | 4 | 88.0 | 11 |
Recruitment (at max PAW), % | 93.7 | 3 | 92.4 | 2 | 94.2 | 3 | 97.7 | 3 |
CO (baseline), l min−1
| 11.6 | 0.2 | 11.7 | 0.1 | 11.6 | 0.2 | 11.3 | 0.3 |
CO (at max PAW), l min−1
| 8.3 | 0.3 | 8.4 | 0.2 | 8.2 | 0.2 | 8.1 | 0.3 |
CO (post RM), l min-1 | 10.3 | 0.2 | 10.3 | 0.1 | 10.2 | 0.1 | 10.4 | 0.1 |
∆ RVEDV (at max PAW), ml | −48 | 6.1 | −49 | 6.2 | −46 | 5.9 | −52 | 4.6 |
∆ RVESV (at max PAW), ml | −33 | 21 | −33 | 23 | −43 | 16.2 | −15 | 18 |
DO2 (baseline), ml min−1
| 1556 | 340 | 1316 | 244 | 1809 | 138 | 1929 | 194 |
DO2 (at max PAW), ml min−1
| 1398 | 81 | 1406 | 94 | 1385 | 74 | 1403 | 63 |
DO2 (post RM), ml min−1
| 1642 | 114 | 1595 | 99 | 1671 | 97 | 1759 | 124 |
PRA (baseline), mmHg | 6.5 | 4 | 6.7 | 4 | 5.5 | 4 | 7.8 | 6 |
PRA (at max PAW), mmHg | 7.8 | 4 | 8.8 | 4 | 7.3 | 4 | 4.9 | 0 |
PRA (post RM), mmHg | 7.6 | 4 | 7.4 | 4 | 6.4 | 4 | 10.7 | 0 |
PF ratio (baseline), mmHg | 102 | 85 | 54 | 10 | 115 | 50 | 250 | 125 |
PF ratio (at max PAW), mmHg | 206 | 72 | 182 | 53 | 207 | 81 | 298 | 48 |
PF ratio (post RM), mmHg | 140 | 78 | 92 | 23 | 179 | 82 | 243 | 78 |
Dynamic strain (baseline), | 0.18 | 0.03 | 0.18 | 0.04 | 0.19 | 0.03 | 0.18 | 0.02 |
Dynamic strain (at max PAW) | 0.10 | 0.02 | 0.12 | 0..02 | 0.10 | 0.02 | 0.09 | 0.01 |
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PF ratio increased on average by 105 mmHg during the application of the MRS, and remained significantly greater than baseline values afterwards. The biggest improvement in PF ratio was seen in the severe ARDS subgroup. Improved recruitment and reduced dynamic strain were evident for all in silico patients during the MRS.
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DO2 fell by more than 150 ml min−1 on average during application of the MRS. This fall in DO2 occurred mostly in the in silico patients with moderate and mild ARDS, whereas in the severe patients DO2 increased by nearly 90 ml min−1 on average during the RM. Due to the high baseline CO of the patients in this cohort, DO2 remained above 1000 ml min−1 in all in silico patients at all times, indicating no risk of tissue de-oxygenation due to application of the RM.
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The end-diastolic and end-systolic volume of the right ventricle fell as PEEP increased. The decrease in end-systolic volume was smaller than the decrease in end-diastolic volume, indicating a smaller stroke volume at maximum PEEP. There was a small increase in the right atrial pressure as PEEP was increased.