Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Madotto, Fabiana; Rezoagli, Emanuele; Pham, Tài; Schmidt, Marcello; McNicholas, Bairbre; Protti, Alessandro; Panwar, Rakshit; Bellani, Giacomo; Fan, Eddy; van Haren, Frank; Brochard, Laurent; Laffey, John G.

doi:10.1186/s13054-020-2826-6

Critical Care

Table 1 Characteristics of study population (n = 2005), stratified by arterial oxygenation on day 1

From: Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Parameter	Hypoxemia (PaO₂ < 55 mmHg)	Normoxemia (55 mmHg ≤ PaO₂ ≤ 100 mmHg)	Hyperoxemia (PaO₂ > 100 mmHg)	p value (among groups)
N (%)	131 (6.53)	1267 (63.19)	607 (30.27)
Male, n (%)	73 (55.73)	796 (62.83)	359 (59.14)	0.1259
Age (years), mean ± SD	59.20 ± 16.86	62.21 ± 16.74	61.88 ± 16.82	0.1264
BMI (kg/m²), mean ± SD	27.23 ± 6.82	27.66 ± 8.26	26.90 ± 6.84	0.5646
ARDS risk factors, n (%)
None	9 (6.87)	103 (8.13)	52 (8.57)	0.8088
Only non-pulmonary	15 (11.45)	229 (18.07)	106 (17.46)	0.1641
Only pulmonary	92 (70.23)	769 (60.62)	357 (58.81)	0.0525
Both	15 (11.45)	167 (13.18)	92 (15.16)	0.3789
Illness severity at ARDS onset
P_aO₂ (mmHg), mean ± SD	47.1 ± 6.2	76.8 ± 11.9*	137.8 ± 41.0*^†	< 0.0001
P_aO₂/FIO₂ (mmHg), mean ± SD	75.12 ± 38.97	140.49 ± 56.70*	205.90 ± 54.88*^†	< 0.0001
SpO₂ (%), median (q₁–q₃)	88 (82–94)	95 (92–97)*	98 (97–99)*^†	< 0.0001
ARDS severity, n (%)				< 0.0001
Mild	4 (3.05)	205 (16.18)*	330 (54.37)*^†	< 0.0001
Moderate	22 (16.79)	683 (53.91)*	273 (33.98)*^†	< 0.0001
Severe	105 (80.15)	379 (29.91)*	4 (0.66)*^†	< 0.0001
P_aCO₂ (mmHg), mean ± SD	54.3 ± 25.0	46.3 ± 15.3*	44.8 ± 14.6*	0.0031
pH, mean ± SD	7.31 ± 0.15	7.33 ± 0.12	7.32 ± 0.13	0.7446
Bicarbonate (mmol/L), mean ± SD	26.3 ± 10.9	23.3 ± 6.5	22.3 ± 6.3*^†	< 0.0001
Base excess (mEq/L), mean ± SD	0.5 ± 10.8	−2.0 ± 6.8	−3.1 ± 6.8*^†	0.0001
Non-respiratory SOFA score adjusted, mean ± SD	6.14 ± 4.15	6.08 ± 3.94	6.28 ± 4.00	0.6246
SOFA score adjusted, mean ± SD	10.25 ± 4.20	9.51 ± 3.98	8.87 ± 3.93*^†	0.0005
Respiration	3.79 ± 0.46	3.15 ± 0.66	2.45 ± 0.50	< 0.0001
Central nervous system	1.68 ± 1.72	1.74 ± 1.66	1.92 ± 1.69	0.1161
Cardiovascular	1.77 ± 1.74	2.03 ± 1.76	1.93 ± 1.74	0.1760
Liver	0.65 ± 0.98	0.54 ± 0.96	0.51 ± 0.92	0.2855
Coagulation	1.20 ± 1.45	0.95 ± 1.31	0.98 ± 1.34	0.1751
Renal	0.69 ± 1.04	1.77 ± 1.10	0.88 ± 1.22	0.3333
Pressor support infusion rates
Dopamine (μg/kg/min), mean ± SD	8.19 ± 6.94	8.58 ± 5.02	7.73 ± 5.98	0.4151
Dobutamine (μg/kg/min), mean ± SD	5.52 ± 3.74	5.72 ± 4.05	6.75 ± 3.53	0.3565
Noradrenaline (μg/kg/min), mean ± SD	0.50 ± 0.67	0.45 ± 0.75	0.54 ± 1.48	0.6701
Adrenaline (μg/kg/min), mean ± SD	1.10 ± 2.03	0.48 ± 0.69	0.43 ± 0.55	0.8434
Management factors at ARDS onset
Invasive mechanical ventilation, n (%)	102 (77.86)	1000 (78.93)	506 (83.36)	0.0619
Control mode of ventilation, mean ± SD	70 (54.69)	693 (55.89)	386 (64.23)^†	0.0021
FIO₂, median (q₁–q₃)	0.80 (0.50–1.00)	0.60 (0.41–0.80)*	0.65 (0.50–1.00)^†	< 0.0001
FIO₂ ≥ 0.6, n (%)	90 (68.70)	670 (52.88)*	400 (65.90)^†	< 0.0001
FIO₂ ≥ 0.6 at 2nd day, n (%)^‡	64 (73.56)	372 (57.94)*	167 (43.60)*^†	< 0.0001
Tidal volume (ml/kg), mean ± SD	7.9 ± 2.2	7.8 ± 2.0	7.9 ± 2.0	0.2256
PEEP (cmH₂O), mean ± SD	8.7 ± 3.33	8.1 ± 3.2	7.9 ± 3.1*	0.0174
PIP (cmH₂O), mean ± SD	25.7 ± 8.90	25.3 ± 8.5	25.6 ± 8.7	0.6295
Dynamic compliance (ml/cmH₂O), mean ± SD	39.0 ± 38.4	36.9 ± 37.8	35.6 ± 38.9	0.7759
Total respiratory rate (breaths/min), mean ± SD	23.2 ± 7.1	21.9 ± 6.9	21.1 ± 7.0	0.0003
Standardized minute ventilation (L/min), mean ± SD	14.4 ± 7.8	11.4 ± 5.3*	10.8 ± 5.0*^†	< 0.0001
Patients in whom plateau pressure measured, n (%)°	24 (18.32)	304 (23.99)	186 (30.64)	0.0012
Plateau pressure (cmH₂O), mean ± SD	24.3 ± 9.0	23.4 ± 6.1	23.0 ± 5.6	0.7512
Driving pressure (cmH₂O), mean ± SD	16.0 ± 8.2	14.6 ± 5.4	15.0 ± 5.2	0.4941
Clinical outcomes
Hospital mortality (90 days), n (%)	47 (35.88)	486 (38.54)	227 (37.52)	0.7934
Ventilation free days (days), median (q₁–q₃)
All	10.0 (0.0–22.0)	12.0 (0.0–23.0)	16.0 (0.0–24.0)^†	0.0303
Survivors at ICU discharge	20.0 (14.0–24.0)	21.0 (15.0–25.0)	23.0 (18.0–26.0)*^†	0.0002
Duration mechanical ventilation (days), median (q₁–q₃)
All	7.0 (4.0–13.0)	8.0 (4.0–15.0)	7.0 (3.0–13.0)^†	0.0074
Survivors at ICU discharge	9.0 (5.0–15.0)	8.0 (4.0–14.0)	6.0 (3.0–11.0)*^†	0.0002

Abbreviations: ARDS acute respiratory distress syndrome, BMI body mass index, COPD chronic obstructive pulmonary disease, FIO₂ fraction of inspired oxygen, P_aO₂ arterial oxygen partial pressure, P_aCO₂ arterial carbon dioxide partial pressure, PEEP positive end-expiratory pressure, PIP peak inspiratory pressure, q₁ first quartile, q₃ third quartile, SOFA sepsis-related organ failure assessment, SD standard deviation, SpO₂ peripheral oxygen saturation
°Plateau pressure and driving pressure values are limited to patients in whom this value was reported and in whom either an assist control mode was used or in whom a mode permitting spontaneous ventilation was used and where the set and total respiratory rates were equal. Patients receiving HFOV or ECMO were also excluded
^‡Percentage was calculated on patients with FIO₂ available during the second day and with FIO₂ ≥ 0.60 at day 1
*p value < 0.05 (Bonferroni’s correction), comparison with “Hypoxemia” group
^†p value < 0.05 (Bonferroni’s correction), comparison with “Normoxemia” group

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