ICU ( ) ICU ( ) ICU SpO 2 ICU ( ) -297 S.E DEX: N=30 DEX: N= 6 (J-DEX Placebo: N=30 Placebo: N= 3 65 DEX: N=16 DEX: N= 3 Placebo: N=

ICU ( ICU ( ICU SpO 2 ICU ( -297 S.E. -75-94 65 DEX: N=30 DEX: N= 6 ( Placebo: N=30 Placebo: N= 3 65 DEX: N=16 DEX: N= 3 Placebo: N=19 Placebo: N= 4 65 DEX: N=53 DEX: N=42 DEX: N=21 DEX: N=10 ( Placebo: N=42 Placebo: N=38 Placebo: N=17 Placebo: N=12 65 DEX: N=37 DEX: N=17 DEX: N=21 DEX: N= 2 Placebo: N=48 Placebo: N=23 Placebo: N=15 Placebo: N= 3 561

a baseline (N=30/30 10min (N=30/30 1 20min (N=29/30 30min (N=30/30 1h (N=30/30 1 2h (N=30/29 3h (N=30/29 1 4h (N=30/29 5h (N=30/29 1 6h (N=30/28 7h (N=30/28 8h 9h (N=29/27 (N=29/28 10h (N=29/28 11h (N=29/28 12h (N=18/16 12-15h (N=30/28 15-18h (N=26/26 18-21h (N=30/27 21-24h (N=26/24 24-27h (N=15/17 27-30h (N=21/19 30-33h (N=29/25 33-36h (N=24/23 (N= / 1 1 1 1 baseline (N=42/53 10min (N=42/53 20min (N=42/53 30min (N=42/53 1h (N=41/53 2h (N=41/51 3h (N=42/52 4h (N=41/51 5h (N=41/52 6h (N=42/52 7h (N=41/ 8h (N=41/51 9h (N=41/51 10h (N=41/ 11h (N=/51 12h (N=35/42 12-15h (N=42/52 15-18h (N=42/52 18-21h (N=41/ 21-24h (N=41/ 24-27h (N=/51 27-30h (N=38/48 30-33h (N=/49 33-36h (N=38/49 (N= / 562

baseline (N=19/16 10min (N=19/16 20min (N=19/15 1 30min (N=19/15 1h (N=19/15 1 2h (N=19/15 3h (N=19/15 1 4h (N=19/15 5h (N=19/15 1 6h 7h (N=19/15 (N=19/15 8h (N=19/15 9h (N=19/15 10h (N=19/15 11h (N=19/15 12h (N=8/10 12-15h (N=19/15 15-18h (N=15/13 18-21h 21-24h (N=16/14 (N=16/11 24-27h (N=15/11 27-30h (N=12/11 30-33h (N=15/13 33-36h (N=15/10 (N= / 1 1 1 1 baseline (N=48/37 10min (N=48/37 20min (N=48/37 30min (N=48/37 1h (N=48/37 2h (N=47/37 3h (N=46/36 4h (N=47/36 5h (N=46/35 6h (N=44/36 7h (N=46/35 8h (N=45/35 9h (N=45/35 10h (N=46/35 11h (N=45/35 12h (N=37/33 12-15h (N=46/36 15-18h (N=45/35 18-21h (N=44/35 21-24h (N=46/35 24-27h (N=44/32 27-30h (N=45/34 30-33h 33-36h (N=45/33 (N=42/30 (N= / 563

baseline (N=3/6 1 10min (N=3/6 20min (N=3/6 1 2h (N=2/6 30min (N=3/6 1h (N=3/6 1 3h (N=2/6 4h (N=2/6 1 5h (N=2/6 6h (N=2/6 7h (N=2/6 8h (N=2/6 9h (N=2/6 10h (N=2/6 11h (N=2/6 12h (N=2/4 12-15h (N=2/6 15-18h (N=2/6 18-21h (N=2/4 21-24h (N=2/6 24-27h (N=0/3 27-30h (N=2/5 30-33h (N=2/4 33-36h (N=2/6 (N= / 1 1 1 1 baseline (N=38/42 10min (N=38/42 20min (N=38/42 30min (N=38/42 1h (N=38/41 2h (N=38/41 3h (N=38/41 4h (N=38/41 5h (N=37/ 6h (N=38/41 7h (N=38/42 8h (N=38/41 9h (N=38/41 10h (N=38/42 11h (N=38/41 12h (N=31/27 12-15h (N=33/42 15-18h (N=38/41 18-21h (N=37/42 21-24h (N=34/42 24-27h (N=37/42 27-30h (N=37/41 30-33h (N=37/ 33-36h (N=37/41 (N= / 564

1 1 1 1 baseline (N=4/3 10min (N=4/3 20min (N=4/3 30min (N=4/3 1h (N=4/3 2h (N=4/3 3h (N=4/3 4h (N=4/3 5h (N=4/3 6h (N=4/3 7h (N=4/3 8h (N=4/3 9h (N=4/3 10h (N=4/3 11h (N=4/3 12h (N=0/1 12-15h (N=4/3 15-18h (N=4/2 18-21h (N=4/3 21-24h (N=4/3 24-27h (N=1/2 27-30h (N=3/2 30-33h (N=4/3 33-36h (N=4/3 (N= / 1 1 1 1 baseline (N=23/17 10min (N=23/17 20min (N=23/16 30min (N=23/17 1h (N=23/17 2h (N=23/17 3h (N=23/17 4h (N=23/17 5h (N=23/17 6h (N=23/17 7h (N=23/17 8h (N=23/17 9h (N=23/17 10h (N=23/17 11h (N=23/17 12h (N=19/15 12-15h (N=22/16 15-18h (N=21/17 18-21h (N=22/17 21-24h (N=23/16 24-27h (N=23/17 27-30h (N=23/16 30-33h (N=21/17 33-36h (N=23/17 (N= / 565

1 1 1 1 baseline (N=17/21 10min (N=17/21 20min (N=17/21 30min (N=17/20 1h (N=17/20 2h (N=17/20 3h (N=17/21 4h (N=17/20 5h (N=17/20 6h (N=17/21 7h (N=17/20 8h (N=17/20 9h (N=17/21 10h (N=17/20 11h (N=17/20 12h (N=12/18 12-15h (N=15/20 15-18h (N=17/21 18-21h (N=16/21 21-24h (N=17/21 24-27h (N=16/21 27-30h (N=15/19 30-33h (N=14/20 33-36h (N=14/19 (N= / 1 1 1 1 baseline (N=15/21 10min (N=15/21 20min (N=15/21 30min (N=15/21 1h (N=15/21 2h (N=15/21 3h (N=15/21 4h (N=15/21 5h (N=15/20 6h (N=15/20 7h (N=15/20 8h (N=15/20 9h (N=15/19 10h (N=15/19 11h (N=15/20 12h (N=15/12 12-15h (N=14/19 15-18h (N=14/20 18-21h (N=15/20 21-24h (N=14/19 24-27h 27-30h (N=14/19 (N=15/20 30-33h (N=15/19 33-36h (N=15/18 (N= / 566

a baseline (N=30/30 10min (N=30/30 20min (N=29/30 30min (N=30/30 1h (N=30/30 2h (N=30/29 3h (N=30/29 4h (N=30/29 5h (N=30/29 6h (N=30/28 7h (N=30/28 8h (N=29/27 9h (N=29/28 10h (N=29/28 11h (N=29/28 12h (N=18/16 12-15h (N=30/28 15-18h (N=26/26 18-21h (N=30/27 21-24h (N=24/24 24-27h (N=15/17 27-30h (N=19/18 30-33h (N=27/25 33-36h (N=21/23 (N= / baseline (N=42/53 10min (N=42/53 20min (N=42/53 30min (N=42/53 1h (N=41/53 2h (N=41/51 3h (N=42/51 4h (N=41/ 5h (N=41/51 6h (N=42/51 7h (N=41/49 8h (N=41/ 9h (N=41/ 10h (N=41/49 11h (N=/49 12h (N=35/41 12-15h (N=42/51 15-18h (N=42/52 18-21h (N=41/ 21-24h (N=41/ 24-27h (N=/51 27-30h (N=38/47 30-33h (N=/48 33-36h (N=38/49 (N= / 567

baseline (N=19/16 10min (N=19/16 20min (N=19/15 30min (N=19/15 1h (N=19/15 2h (N=19/15 3h (N=19/15 4h (N=19/15 5h (N=19/15 6h (N=19/15 7h (N=19/15 8h (N=19/15 9h (N=19/15 10h (N=19/15 11h (N=19/15 12h (N=8/10 12-15h (N=19/15 15-18h (N=15/13 18-21h (N=16/14 21-24h (N=16/11 24-27h (N=15/11 27-30h (N=12/11 30-33h (N=15/13 33-36h (N=15/10 (N= / baseline (N=48/37 10min (N=48/37 20min (N=48/37 30min (N=48/37 1h (N=48/37 2h (N=47/37 3h (N=46/36 4h (N=47/36 5h (N=46/35 6h (N=44/36 7h (N=46/35 8h (N=45/35 9h (N=45/35 10h (N=45/35 11h (N=44/35 12h (N=37/33 12-15h (N=46/36 15-18h (N=45/35 18-21h (N=44/35 21-24h (N=46/35 24-27h (N=44/32 27-30h (N=45/34 30-33h (N=44/33 33-36h (N=41/30 (N= / 568

baseline (N=3/6 10min (N=3/6 20min (N=3/6 30min (N=3/6 1h (N=3/6 2h (N=2/6 3h (N=2/6 4h (N=2/6 5h (N=2/6 6h (N=2/6 7h (N=2/6 8h (N=2/6 9h (N=2/6 10h (N=2/6 11h (N=2/6 12h (N=2/4 12-15h (N=2/6 15-18h (N=2/6 18-21h (N=2/4 21-24h (N=2/6 24-27h (N=0/3 27-30h (N=2/5 30-33h (N=2/4 33-36h (N=2/6 (N= / baseline 10min 20min 30min 1h 2h (N=38/42 (N=38/42 (N=38/42 (N=38/42 (N=38/41 (N=38/41 3h (N=38/41 4h (N=38/41 5h (N=37/ 6h (N=38/41 7h (N=38/42 8h (N=38/41 9h (N=38/41 10h (N=38/42 11h (N=38/41 12h (N=31/27 12-15h (N=33/42 15-18h (N=38/41 18-21h (N=37/42 21-24h (N=34/42 24-27h (N=37/42 27-30h (N=37/41 30-33h (N=37/ 33-36h (N=37/41 (N= / 569

baseline (N=4/3 10min (N=4/3 20min (N=4/3 30min (N=4/3 1h (N=4/3 2h (N=4/3 3h (N=4/3 4h (N=4/3 5h (N=4/3 6h (N=4/3 7h (N=4/3 8h (N=4/3 9h (N=4/3 10h (N=4/3 11h (N=4/3 12h (N=0/1 12-15h (N=4/3 15-18h (N=4/2 18-21h (N=4/3 21-24h (N=4/3 24-27h (N=1/2 27-30h (N=3/2 30-33h (N=4/3 33-36h (N=4/3 (N= / baseline (N=23/17 10min (N=23/17 20min (N=23/16 30min (N=23/17 1h (N=23/17 2h (N=23/17 3h (N=23/17 4h (N=23/17 5h (N=23/17 6h (N=23/17 7h (N=23/17 8h (N=23/17 9h (N=23/17 10h (N=23/17 11h (N=23/17 12h (N=19/15 12-15h (N=22/16 15-18h (N=21/17 18-21h (N=22/17 21-24h (N=23/16 24-27h (N=23/17 27-30h (N=23/16 30-33h (N=21/17 33-36h (N=23/17 (N= / 5

baseline 10min 20min 30min 1h 2h (N=17/21 (N=17/21 (N=17/21 (N=17/20 (N=17/20 (N=17/20 3h (N=17/21 4h (N=17/20 5h (N=17/20 6h (N=17/21 7h (N=17/20 8h (N=17/20 9h (N=17/21 10h (N=17/20 11h (N=17/20 12h (N=12/18 12-15h (N=15/20 15-18h (N=17/21 18-21h (N=16/21 21-24h (N=17/21 24-27h (N=16/21 27-30h (N=15/19 30-33h (N=14/20 33-36h (N=14/19 (N= / baseline 10min 20min 30min (N=15/21 (N=15/21 (N=15/21 (N=15/21 1h (N=15/21 2h (N=15/21 3h (N=15/21 4h (N=15/21 5h (N=15/20 6h (N=15/20 7h (N=15/20 8h (N=15/20 9h (N=15/19 10h (N=15/19 11h (N=15/20 12h (N=15/12 12-15h (N=14/19 15-18h (N=14/20 18-21h (N=15/20 21-24h (N=14/19 24-27h (N=14/19 27-30h (N=15/20 30-33h (N=15/19 33-36h (N=15/18 (N= / 571

a baseline (N=30/30 10min (N=30/30 20min (N=29/30 30min (N=30/30 1h (N=30/30 2h (N=30/29 3h (N=30/29 4h (N=30/29 5h (N=30/29 6h (N=30/28 7h (N=30/28 8h (N=29/27 9h (N=29/28 10h (N=29/28 11h (N=29/28 12h (N=18/16 12-15h (N=30/28 15-18h 18-21h (N=26/26 (N=30/27 21-24h (N=26/24 24-27h (N=15/17 27-30h 30-33h (N=21/19 (N=29/25 33-36h (N=24/23 (N= / baseline (N=42/53 10min (N=42/53 20min (N=42/53 30min (N=42/53 1h (N=41/53 2h (N=41/51 3h (N=42/52 4h (N=/51 5h (N=41/52 6h (N=42/52 7h (N=41/ 8h (N=41/51 9h (N=41/51 10h (N=41/ 11h (N=/51 12h (N=35/42 12-15h (N=42/52 15-18h (N=42/52 18-21h (N=41/ 21-24h (N=41/ 24-27h (N=/51 27-30h (N=38/48 30-33h (N=/49 33-36h (N=38/49 (N= / 572

baseline (N=19/16 10min (N=19/16 20min (N=19/15 30min (N=19/15 1h (N=19/15 2h (N=19/15 3h (N=19/15 4h (N=19/15 5h (N=19/15 6h (N=19/15 7h (N=19/15 8h (N=19/15 9h (N=19/15 10h (N=19/15 11h (N=19/15 12h (N=8/10 12-15h (N=19/15 15-18h (N=15/13 18-21h (N=16/14 21-24h (N=16/11 24-27h (N=15/11 27-30h (N=12/11 30-33h (N=15/13 33-36h (N=15/10 (N= / baseline (N=48/37 10min (N=48/37 20min (N=48/37 30min (N=48/37 1h (N=48/37 2h (N=47/37 3h (N=45/36 4h (N=47/36 5h (N=46/35 6h (N=44/36 7h (N=46/35 8h (N=45/35 9h (N=45/35 10h (N=46/35 11h (N=45/35 12h (N=37/33 12-15h (N=46/36 15-18h (N=45/35 18-21h (N=44/34 21-24h (N=46/35 24-27h (N=44/32 30-33h (N=45/33 27-30h (N=45/34 33-36h (N=42/30 (N= / 573

b baseline (N=3/6 10min (N=3/6 20min (N=3/6 2h (N=2/6 30min (N=3/6 1h (N=3/6 3h (N=2/6 4h (N=2/6 5h (N=2/6 6h (N=2/6 7h (N=2/6 8h (N=2/6 9h (N=2/6 10h (N=2/6 11h (N=2/6 12h (N=2/4 12-15h (N=2/6 15-18h (N=2/6 18-21h (N=2/4 21-24h (N=2/6 24-27h (N=0/3 27-30h (N=2/5 30-33h (N=2/4 33-36h (N=2/6 (N= / baseline (N=38/42 10min (N=38/42 20min (N=38/42 30min (N=38/42 1h (N=38/41 2h (N=38/41 3h (N=38/41 4h (N=38/41 5h (N=37/ 6h (N=38/41 7h (N=38/42 8h (N=38/41 9h (N=38/41 10h (N=38/42 11h (N=38/41 12h (N=31/27 12-15h (N=33/42 15-18h (N=38/41 18-21h (N=37/42 21-24h (N=34/42 24-27h (N=37/42 27-30h (N=37/41 30-33h (N=37/ 33-36h (N=37/41 (N= / 574

baseline (N=4/3 10min (N=4/3 20min (N=4/3 30min (N=4/3 1h (N=4/3 2h (N=4/3 3h (N=4/3 4h (N=4/3 5h (N=4/3 6h (N=4/3 7h (N=4/3 8h (N=4/3 9h (N=4/3 10h (N=4/3 11h (N=4/3 12h (N=0/1 12-15h (N=4/3 15-18h (N=4/2 18-21h (N=4/3 21-24h (N=4/3 24-27h (N=1/2 27-30h (N=3/2 30-33h (N=4/3 33-36h (N=4/3 (N= / baseline (N=23/17 10min (N=23/17 20min (N=23/16 30min (N=23/17 1h (N=23/17 2h (N=23/17 3h (N=23/17 4h (N=23/17 5h (N=23/17 6h (N=23/17 7h (N=23/17 8h (N=23/17 9h (N=23/17 10h (N=23/17 11h (N=23/17 12h (N=19/15 12-15h (N=22/16 15-18h (N=21/17 18-21h (N=22/17 21-24h (N=23/16 24-27h (N=23/17 27-30h (N=23/16 30-33h (N=21/17 33-36h (N=23/17 (N= / 575

c baseline 10min 20min 30min 1h 2h 3h 4h 5h 6h (N=17/21 (N=17/21 (N=17/21 (N=17/20 (N=17/20 (N=17/20 (N=17/21 (N=17/20 (N=17/20 (N=17/21 7h (N=17/20 8h (N=17/20 9h (N=17/21 10h (N=17/20 11h (N=17/20 12h (N=12/18 12-15h (N=15/20 15-18h (N=17/21 18-21h (N=16/21 21-24h (N=17/21 24-27h (N=16/21 27-30h (N=15/19 30-33h (N=14/20 33-36h (N=14/19 (N= / baseline (N=15/21 10min (N=15/21 20min (N=15/21 30min (N=15/21 1h (N=15/21 2h (N=15/21 3h (N=15/21 4h (N=15/21 5h (N=15/20 6h (N=15/20 7h (N=15/20 8h (N=15/20 9h (N=15/19 10h (N=15/19 11h (N=15/20 12h (N=15/12 12-15h (N=14/19 15-18h (N=14/20 18-21h (N=15/19 21-24h (N=14/19 24-27h (N=14/19 27-30h (N=15/20 30-33h (N=15/19 33-36h (N=15/18 (N= / 576

a 25 20 15 10 baseline (N=30/30 10min (N=30/30 20min (N=29/30 30min (N=30/30 1h (N=30/30 2h (N=30/29 3h (N=30/29 4h (N=30/29 5h (N=30/29 6h (N=30/28 7h (N=30/28 8h (N=29/27 9h (N=29/28 10h (N=29/28 11h (N=29/28 12h (N=18/16 12-15h (N=30/28 15-18h (N=26/26 18-21h (N=29/27 21-24h (N=25/24 24-27h (N=15/17 27-30h (N=21/19 30-33h (N=29/25 33-36h (N=23/23 (N= / 25 20 15 10 baseline (N=42/53 10min (N=42/53 20min (N=42/53 30min (N=42/53 1h (N=41/53 2h (N=41/51 3h (N=42/52 4h (N=41/51 5h (N=41/52 6h (N=42/52 7h (N=41/ 8h (N=41/51 9h (N=41/51 10h (N=41/ 11h (N=/51 12h (N=35/42 12-15h (N=42/52 15-18h (N=42/52 18-21h (N=/49 21-24h (N=37/48 24-27h (N=38/48 27-30h (N=36/48 30-33h (N=38/48 33-36h (N=37/47 (N= / 577

25 20 15 10 baseline (N=19/16 10min (N=19/16 20min (N=19/15 30min (N=19/15 1h (N=19/15 2h (N=19/15 3h (N=19/15 4h (N=19/15 5h (N=19/15 6h (N=19/15 7h (N=19/15 8h (N=19/15 9h (N=19/15 10h (N=19/15 11h (N=19/15 12h (N=8/10 12-15h (N=19/15 15-18h (N=15/13 18-21h (N=16/14 21-24h (N=16/11 24-27h (N=15/11 27-30h (N=12/11 30-33h (N=15/13 33-36h (N=15/10 (N= / baseline 25 10min 20min 30min 20 15 10 (N=48/37 (N=48/37 (N=48/37 (N=48/37 1h (N=48/37 2h (N=47/37 3h (N=46/36 4h (N=47/36 5h (N=46/35 6h (N=44/36 7h (N=45/35 8h (N=45/35 9h (N=45/35 10h (N=46/35 11h (N=45/35 12h (N=36/33 12-15h (N=46/36 15-18h (N=45/34 18-21h (N=44/35 21-24h (N=46/35 24-27h (N=43/31 27-30h (N=42/33 30-33h (N=41/32 33-36h (N=38/29 (N= / 578

b 25 20 15 10 25 20 15 10 baseline (N=3/6 10min (N=3/6 20min (N=3/6 30min (N=3/6 1h (N=3/6 2h (N=2/6 3h (N=2/6 4h (N=2/6 5h (N=2/6 6h (N=2/6 7h (N=2/6 8h (N=2/6 9h (N=2/6 10h (N=2/6 11h (N=2/6 12h (N=2/4 12-15h (N=2/6 15-18h (N=2/6 18-21h (N=2/4 21-24h (N=2/6 24-27h (N=0/3 27-30h (N=2/5 30-33h (N=2/4 33-36h (N=2/6 (N= / baseline (N=38/42 10min (N=38/42 20min (N=38/42 30min (N=38/41 1h (N=38/41 2h (N=38/41 3h (N=38/41 4h (N=38/ 5h (N=37/ 6h (N=38/41 7h (N=38/41 8h (N=38/41 9h (N=38/41 10h (N=38/41 11h (N=38/41 12h (N=31/27 12-15h (N=33/41 15-18h (N=38/ 18-21h (N=37/41 21-24h (N=34/41 24-27h (N=37/42 27-30h (N=37/41 30-33h (N=37/39 33-36h (N=37/ (N= / 579

25 20 15 10 baseline (N=4/3 10min (N=4/3 1h (N=4/3 20min (N=4/3 30min (N=4/3 2h (N=4/3 3h (N=4/3 4h (N=4/3 5h (N=4/3 6h (N=4/3 7h (N=4/3 8h (N=4/3 9h (N=4/3 10h (N=4/3 11h (N=4/3 12h (N=0/1 12-15h (N=4/3 15-18h (N=4/2 18-21h (N=4/3 21-24h (N=4/3 24-27h (N=1/2 27-30h (N=3/2 30-33h (N=4/3 33-36h (N=4/3 (N= / 25 20 15 10 baseline (N=23/17 10min (N=23/17 20min (N=23/16 30min (N=23/17 1h (N=23/17 2h (N=23/17 3h (N=23/17 4h (N=23/17 5h (N=23/17 6h (N=23/17 7h (N=23/17 8h (N=23/17 9h (N=23/17 10h (N=23/17 11h (N=23/17 12h (N=19/15 12-15h (N=22/16 15-18h (N=21/17 18-21h (N=22/17 21-24h (N=23/16 24-27h (N=23/16 27-30h (N=23/15 30-33h (N=21/16 33-36h (N=23/16 (N= / 5

c 25 20 15 10 baseline (N=17/21 10min (N=17/21 20min (N=17/21 30min (N=17/19 1h (N=17/20 2h (N=17/20 3h (N=17/21 4h (N=17/20 5h (N=17/20 6h (N=16/21 7h (N=16/20 8h (N=16/20 9h (N=16/21 10h (N=17/20 11h (N=17/20 12h (N=12/18 12-15h (N=15/20 15-18h (N=17/21 18-21h 21-24h (N=16/21 (N=16/21 24-27h (N=14/21 27-30h (N=13/19 30-33h (N=13/20 33-36h (N=12/19 (N= / baseline 10min 25 20 15 10 (N=15/21 (N=15/21 20min (N=15/21 30min (N=15/21 1h (N=15/21 2h (N=15/21 3h (N=15/21 4h (N=15/21 5h (N=15/20 6h (N=14/20 7h (N=15/20 8h (N=15/20 9h (N=15/19 10h (N=15/19 11h (N=15/20 12h (N=15/12 12-15h (N=14/18 15-18h (N=14/20 18-21h (N=15/20 21-24h (N=14/18 24-27h (N=14/19 27-30h (N=15/19 30-33h (N=15/18 33-36h (N=15/17 (N= / 581