Evidence Table 4Participant Characteristics

Author, yearControl
Interventions
N at baselineGestational age (weeks)Birth weight (grams)Race n(%)Mode of Ventilation, n(%)Participant age at enrollmentOxygenation IndexiNO DoseiNO Duration
Ballard, 20061Placebo288Mean: 26
SD: 1.5
Mean: 759
SD: 155
W: 145 (50.3)
B: 90 (31.3)
H: 43 (14.9)
Other: 10 (3.)
HFV: 74 (25.7)
CMV: 191 (66.3)
CPAP: 23 (8)
Median:16
Range:13-19 IQR
Units: Days
NA
iNO294Mean: 26
SD: 1.5
Mean: 766
SD: 161
W: 170 (57.8)
B: 76 (25.9)
H: 32 (10.9)
Other: 16 (5.4)
HFV: 65 (22.1)
CMV: 202 (68.7)
CPAP: 27 (9.2)
Median:16
Range:12-19
IQR Units: Days
NA20ppm ×48-96hours: titrate every 7days for a minimum of 2 days exposure
Follow-up of Ballard, 20061
Hibbs, 20072
Placebo225Mean: 25.7
SD: 1.5
Mean: 762
SD: 150
W: 121 (53.8)
B: 64 (28.4)
H: 31 (13.8)
Other: 9 (4)
NANANA
iNO230Mean: 25.8
SD: 1.4
Mean: 769
SD: 163
W: 141 (61.3)
B: 56 (24.2)
H: 22 (9.5)
Other:: 11 (4.8)
NANANA20ppm: weaned over at least 24days
Follow-up of Ballard 20061
Walsh, 20103
Placebo gas234Mean: 25.7
SD:1.5
Mean: 764
SD: 153
W: 124(53)
Other: 110(47)
NAMedian: 16
Range: 13-20 IQR
Unit: days
NA
iNO243Mean:25.8
SD: 1.4
Mean: 765
SD: 163
W: 151(62)
Other: 92(38)
NAMedian: 17
Range: 13-19 IQR
Unit: days
NA20ppm ×24hours: decrease to 10ppm ×1week decrease to 5ppm ×1week decrease to 2ppm ×1week
Banks, 19994iNO16Median: 25.5
Range: 24-29
Median: 787 Range: 448-1790NAHFV: 5 (31.25)
CMV :11 (68.75)
Median: 2.5
Range: 1-7
Units: Months
NA20ppm ×72hours: responders weaned by 20% every 3day
Cheung, 19985iNO treated cohort24Median: 25
Range: 24-27 (25% and 75 %)
Median: 860 Range: 668-1068 (25% and 75 %)NACMV : 24 (100)NAMedian:32
Range: 28-52 (25% and 75 %)
20ppm: decrease by 5ppm within 2hours s/p initial dose decrease by 5ppm q15-30min to lowest dose w/+ response
Clark, 20026iNO33Mean: 25.3;
Range: 23-29
Mean: 736
Range: 509-1250
W: 11 (33)
B: 21 (64)
H: 1 (3)
Mean: 19
Range: 9-29
Units: Days
20ppm ×36hours: decrease to 15ppm and decrease by 2-3ppm every1 2hours; discontinued by 7 days.
Dani, 20067Control20Mean: 26.7
SD: 1.9
Mean: 825
SD: 299
NAHFV: 11 (55)NAMean: 15.1
SD: 4.9
iNO20Mean: 26.3
SD: 2.6
Mean: 937
SD: 298
NAHFV: 10 (50)NAMean:16.4
SD: 5.1
5ppm: Increase by 5ppm every 30min to max 15ppm
No responders6Mean: 25.4
SD: 2.6
Mean: 748
SD: 321.4
NACPAP: 4 (67)NAMean:18.1
SD: 4.2
5ppm: Increase by 5ppm every 30min to max 15ppm
Responders14Mean: 26.7
SD: 1.9
Mean: 1022.7
SD: 243.1
NACPAP: 13 (93)NAMean:14.7
SD: 3.9
5ppm: Increase by 5ppm every 30min to max 15ppm
Dewhurst, 20108Responders26Median: 26
Range: 25-29
Median: 920
Range: 655-1538
NAMedian: 53
Range: 37-217
Units: Hours
Median: 47
Range: 30-78
10ppm: titrated
Non-responders8Median: 29
Range: 27-30
Median: 915
Range: 723-183
NAMedian: 75
Range: 20-183
Units: Hours
Median: 23
Range: 8-54
20ppm: titrated
Field, 20059Control53Mean: 26.3
SD: 2.4
Mean: 890
SD: 343
NAHFV: 39 (74%)Median: 1
Range: 1-5 IQR
Units: Days
Median:31.9
Range: 17.4-51.8 IQR
iNO55Mean: 27.4
SD: 2.6
Mean: 1006
SD: 395
NAHFC: 33 (60)Median: 1
Range: 0-6 IQR
Units: Days
Median: 32.9
Range: 22.2-49.8 IQR,
5ppm: double dose every 15min to max 40ppm
Follow-up of Field 20059
Huddy, 200810
Control16Mean: 28.2
SD: 2.7
Mean: 1142
SD: 440
NANAMedian: 1
Range: IQR 1.5
Units: Days
Median: 25.9
Range: IQR 41.3
iNO22Mean: 28.5
SD: 2.4
Mean: 1191
SD: 403
NANAMedian: 1
Range: IQR 3
Units: Days
Median: 30.1
Range: IQR 20.5
5ppm: double dose every 15min until PaO2 increases >22.5mmHg to max 40ppm
Franco-Belgium Collaborativ e NO Trial Group, 199911Control45Median: 29
Range: 3.1 IQR
Median: 1150
Range: 520 IQR
NAHFV: 34 (76)
CMV : 11 (24)
Median:1
Range: 1 IQR
Units: Days
Median: 18
Range: 7.4 IQR
iNO40Median: 29.6
Range: 2.6 IQR
Median: 1200
Range: 570 IQR
NAHFV: 30 (75)
CMV : 10 (25)
Range: 1.5
Units: Days
Median:20.2
Range: 8.3 IQR
10ppm ×2-3hours: decreased to 5ppm then slowly wean off if deteriorating condition, increased dose to 20ppm
Hascoet, 200512Control with hypoxemic respiratory failure84NABW<750: 19 (22)
BW 750-999: 17 (20),
BW 1000-1500: 32 (39)
BW >1500: 16 (19)
NANANAMean:12
SD: 5.6
iNO with hypoxemic respiratory failure61NABW <750g: 10 (16.5)
BW 750-999g: 14 (23)
BW 1000-1500g: 27 (44)
BW >1500g: 10 (16.5)
NANANAOI Mean:14.6
SD: 8.9
5ppm: if aAO2 increase >0.22 decrease iNO to 2ppm if aAO2 increase <0.22 but >25% iNO remains at 5ppm if aAO2 unchanged increase iNO to 10ppm
Follow-up of Hascoet 200512
Hamon, 200513
Hypoxemic respiratory failure, no iNO39Mean: 27.9
SD: 0.4
Mean: 1102
SD: 54
NANAMean:15.9
SD: 1.8
Units: Hours
NA
iNO treated hypoxemic respiratory failure37Mean: 27.3
SD: 0.4
Mean: 1083
SD: 58
NANAMean:14.1
SD:1.4
Units: Hours
NA5ppm: aAO2 increase >0.22 decrease iNO to 2ppm aAO2 increase <0.22 but >25% iNO remains at 5ppm aAO2 unchanged increase iNO to 10ppmMedian: 35.1 hours
Kinsella, 199914Control32Mean: 26.8
SD: 2.5
Mean: 988
SD: 387
NANAMean: 27
SD:37
Units: Hours
NA
iNO48Mean: 27.1
SD: 2.5
Mean: 1040
SD: 461
NANAMean:30
SD: 38
Units: Hours
NA5ppm × 7days: if OI increase >15%, iNO restarted
Kinsella, 200615Placebo gas, Total sample395Mean: 25.6
SD: 1.8
Mean: 788
SD: 185
W: 234 of 394 (59.4)
B: 98 of 394 (24.9)
H: 48 of 394 (12.2)
Other: 14 of 394 (3.6)
HFV: 113 of389 (29)
CMV : 276 of 389 (71)
Mean:30.1
SD:13.2
Units: Hours
Mean:5.8,
SD:6.7
iNO, Total sample398Mean: 25.6
SD: 1.7
Mean: 796
SD: 190
W: 249 of 397(62.7)
B: 94 of 397(23.7)
H: 41 of 397(10.3)
Other: 13 of 397 (3.3)
HFV: 113 of 393 (28.8)
CMV : 280 of 393 (71.2)
Mean:30.5
SD:13.4
Units: Hours
Mean:5.4
SD: 5.2
5ppm × 21daysMedian: 14 days
Follow-up of Kinsella 200615
Watson, 200916
Control-detailed outcome cohort320Mean: 25.7
SD: 1.9
Mean: 791
SD: 186
W: 192 (60)
B: 71 (22.2)
H: 44 (13.8)
Asian/Other: 13 (4.1)
NANAMedian:4.1
Range: 2.7-6.4 IQR
iNO-detailed outcome cohort332Mean: 25.6
SD: 1.7
Mean: 797
SD: 190
W: 205 (61.8)
B: 76 (22.9)
H: 38 (11,5)
Asian/Other: 13 (3.9)
NANAMedian:4.1
Range: 2.8-6.2 IQR
5ppm ×21days or until extubated
Mercier, 201017Control401Mean: 26.6
SD: 1.3
Mean: 864
SD: 192
W: 328 (82)
B: 48 (12)
A: 2 (<1)
Other: 23 (6)
CPAP: 42 (10)NAMean: 8.6
SD: 12.7
5ppm
iNO399Mean: 26.4
SD: 1.3
Mean: 851
SD: 207
W: 329 (82)
B: 39 (10)
A: 4 (1)
Other: 27 (7)
CPAP: 41 (10)NAMean: 8.0
SD: 10.7
5ppm
Schreiber, 200318Placebo102Mean: 27
SD: 2.8
Mean: 949
SD: 387
W: 12 (11.8)
B: 74 (72.6)
Other: 16 (15.7)
HFV: 48 (47)
CMV: 54 (52.9)
Median:114
Range: IQR 7.6-28.5
Median:6.8
Range: 4.4-12.7 IQR
iNO105Mean: 27.4
SD: 2.5
Mean: 1017
SD: 369
W: 18 (17.1)
B: 71 (67.6)
Other: 16 (15.2)
HFV: 54 (51.4)
CMV: 51 (48.6)
Median: 12.9
Range: IQR 7.0-25.2
Median:7.3
Range: IQR 4.1-12.3
10ppm ×12-24hours: decrease to 5ppm and hold 6day or 1 hour before extubation if Pa02 decrease by 15%, restart NO and decrease by 1 ppm every 6hours
Follow-up of Schreiber, 200318
Mestan, 200519
Control68Mean: 27.2
SD: 2.6
Mean: 958
SD: 356
W: 8 (12)
B: 52 (76)
Other:: 8 (12)
NASD: 8.4
Units: Months
Median: 7.2
Range: IQR 4.5-14.3
iNO70Mean: 27.5
SD: 2.4
Mean: 1026
SD: 366
W: 14 (20)
B: 44 (63),
Other:: 12 (17)
NAMean: 24.9
SD: 7.9
Units: Months
Median: 6.6
Range: IQR 4-11.5
10ppm ×24hours: decrease to 5ppm and hold 6d or 1 hours before extubation
Srisuparp, 200220Control18Mean: 27.2
SD: 0.5
Mean: 901
SD: 73
B: 16 (89)HFV: 7 (38.9)NAMean:11.9
SD: 2.2
iNO16Mean: 26.8
SD: 0.5
Mean: 874
SD: 70
B: 16 (100)HFV: 7 (43.8)NAMean:10.8
SD: 1.5
20ppm ×6-12hours: decrease to 10ppm ×12hours decrease to 5ppm ×12hours decrease by 1ppm every 12hours
Su, 200821Received inhaled oxygen placebo only33Mean: 27.9
SD: 1.8
Mean: 1050
SD: 210
NANAMean:2.5
SD: 1.8
Units: Days
Mean: 30.5
SD: 4.7
iNO32Mean: 27.4
SD: 2.3
Mean: 1020
SD: 230
NACMV : 32(100)Mean: 2.45
SD: 1.7
Units: Days
Mean:30.3
SD: 3.5
5ppm ×6hours: if + response, decrease 1ppm every 6hours to min 1ppm if – response, increase 5ppm every 6hours to max. 20ppmMean: 4.9
SD: 2.3
Unit: days
Subhedar, 199722Dexamethasone and standard of care22Median: 27
Range: 22-31
Median: 750
Range: 520-1400
NANAMedian: 104
Range: 96-120
Units: Hours
Median: 3.9
Range: 1.2-11.5
iNO + iNO and dexamethasone)20Median: 27
Range: 24-30
Median: 882
Range: 416-1354
NANAMedian: 99
Range: 96-113 IQR
Units: Hours
Median: 7.9
Range: 1.6-46.7
20ppm: iNo started at 20ppm, given for 2 hours, if responsive weaned by 5 ppm every 15 minutes until 5ppm then continued for 72 hours, then discontinued.
Dexamethasone alone AND dex + iNO)21Median: 27
Range: 22-31
Median: 870
Range: 530-1400
NANAMedian: 104
Range: 96-120
Units: Hours
Median: 7.9
Range: 1.2-46.7
20ppm: iNo started at 20ppm, given for 2 hours, if responsive weaned by 5 ppm every 15 minutes until 5ppm then continued for 72 hours, then discontinued.
iNO AND standard of care21Median: 27
Range: 22-31
Median: 818
Range: 520-1222
NANAMedian: 98
Range: 96-114
Units: Hours
Median: 4.1
Range: 1.4-28
20ppm: iNo started at 20ppm, given for 2 hours, if responsive weaned by 5 ppm every 15 minutes until 5ppm then continued for 72 hours, then discontinued.`
Follow-up of Subhedar, 199722
Bennett, 200123
Control22NANANACMV :22 (100)Mean: 96
Units: Hours
NA
iNO20NANANACMV :20 (100)Mean: 96
Units: Hours
NA5-20ppm iNO × 72hours or until extubated
Tanaka, 200724Control15Median: 26
Range: 24-30
Median: 818
Range: 720-1400 IQR
NAHFV: 9 (60)NAMedian: 23.3
Range: 16-45
iNO16Median: 25.5
Range: 25-28.8
Median: 838
Range: 628-1144 IQR
NAHFV: 14 (87.5)NAMedian: 23.3
Range: 16-45 IQR
10ppm: Increase 10ppm every 30min to max 30ppm
Uga, 200425Control10Mean: 25.8
SD: 2.4
Range: 24-30
Mean: 809
SD: 316
Range: 426-1453
NANANAMean: 13.9
SD: 10.2
iNO8Mean: 27.2
SD: 2.2
Range: 24-30
Mean: 996
SD: 294
Range: 570-1317
NANANAMean: 28.8
SD: 18.3
30-40ppm
Van Meurs, 200526Control210Mean: 26
SD: 2
Mean: 837
SD: 260
W: 96 (46)
B: 78 (37)
H: 32 (15)
Other: 4 (2)
HFV: 124 (59)
CMV: 86 (41)
Mean:28
SD: 22
Units: Hours
Mean:22
SD:17
iNO210Mean: 26
SD: 2
Mean: 840
SD: 264
W: 95 (45)
B: 69 (33)
H: 36 (17)
Other: 10 (5)
HFV: 125 (59)
CMV : 85 (40)
Mean:26
SD: 23
Units: Hours
Mean:23
SD:17
5ppm: Hold if PaO2 increases >=20mmHg or increase to 10ppmMean: 76
SD: 73
Unit: hours
Sub analysis of Van Meurs, 200526
Chock, 200927
Control6Mean: 29
SD: 3
Mean: 1179
SD: 369
W: 4 (67)
B: 1 (17)
H: 0 (0)
Other: 1 (17)
HFV: 6 (100)Mean:11
SD: 4
Units: Hours
Mean:44
SD: 30
Median:39
Range:10-100
iNO6Mean: 27
SD: 2
Mean: 1039
SD: 355
W: 2 (33)
B: 1 (17)
H: 2 (33)
Other: 1 (17)
HFV: 6 (100)Mean:12
SD: 8
Units: Hours
Mean:20
SD:27
Median: 19
Range: 11-64
5ppm ×30min: increase 5ppm if PaO2 did not increase >20mmHgMean: 1
SD: 0.2
Unit: hours
Follow-up of Van Meurs, 200526
Hintz, 200728
Placebo102Mean: 26.2
SD: 2.2
Mean: 864
SD: 271
W: 46 (45)
B: 35 (34)
H: 18 (18)
Other: 1 (1)
HFV: 57 (56)NAMean: 18.1
SD:1 1.3
Median: 149
Range:.5 - 21.6
Median: 2
Range: 1-75 IQR
Unit: hours
iNO Follow-up of group91Mean: 26.8
SD: 2.3
Mean: 958
SD: 276
W: 43 (47)
B: 27 (30)
H: 17 (19)
HFV: 61 (67)NAMean: 20
SD:12.9
Median: 16.3
Range: 12-24
5ppm titratedMedian:72
Range: 42-115IQR
Van Meurs, 200729Control15Mean: 31.4
SD: 1.1
Mean: 2168
SD: 441
W: 5 (33)
B: 4 (27)
H: 6 (40)
HFV: 11 (73)
CMV : 2(13)
HFFI: 2 (13)
NAMean: 28.2
SD:17.3
iNO14Mean: 31.1
SD: 1.2
Mean: 1970
SD: 391
W: 7 (50)
B: 5 (36)
H: 1 (7)
Other:1 (7)
HFV: 6 (43)
CMV : 8 (57)
HFFI 0 (0)
NAMean:25.1
SD:19.4
5ppm ×30min: Increase to 10ppm
Yadav, 199930iNO41Mean:27
SD:2.6
Mean: 1000
SD: 46
NANANAMean: 40
SD: 17
10ppm

B:Non-hispanic black; H:Hispanic; W:non-hispanic white; HFV: High-frequency ventilation; CMV: Conventional mechanical ventilation; CPAP: Continuous Positive Airway Pressure; HFFI: High-frequency flow interruption; mmHg: millimeters of mercury; ppm: parts per million; iNO: inhaled nitric oxide

From: Appendix E, Evidence Tables

Cover of Inhaled Nitric Oxide in Preterm Infants
Inhaled Nitric Oxide in Preterm Infants.
Evidence Reports/Technology Assessments, No. 195.
Allen MC, Donohue P, Gilmore M, et al.

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