Cardiovascular treatments, circulatory measurements and electroencephalographic variables
| Active arm | Moderate arm | Permissive arm | P values | P(c) | |
| n=19 | n=20 | n=21 | |||
| Clinical cardiovascular treatment: intravascular volume expansion | |||||
| Prerandomisation, (mL/kg) | 0 (0–10) | 0 (0–10) | 0 (0–8) | 0.94J | |
| During 72 hours postrandomisation, (mL/kg) | 30 (15–50) | 15 (0–33) | 23 (0–49) | 0.30J | |
| Total volume expansion given in the first week (mL/kg) | 65 (15–85) | 40 (0–68) | 35 (0–89) | 0.28J | |
| Clinical cardiovascular treatment: inotropic agents | |||||
| Inotropic support (n) | 15 (79) | 10 (50) | 10 (48) | 0.05 | |
| Inotrope usage by gestation (n) | – | ||||
| 23–24 weeks | 5/5 (100) | 5/6 (83) | 5/5 (100) | ||
| 25–26 weeks | 8/10 (80) | 4/10 (40) | 4/11 (36) | ||
| 27–28 weeks | 2/4 (50) | 1/4 (25) | 1/5 (20) | ||
| Age inotropes started (hours) | 8 (5–12) | 5 (4–13) | 8 (4–92) | 0.82J | |
| Started before randomised (n) | 2 (11) | 6 (30) | 4 (19) | 0.53 | |
| Started after randomised (n) | 13 (68) | 4 (20) | 6 (29) | 0.01 | * |
| Duration of inotropes (hours) | |||||
| All infants | 44 (20–153) | 7 (0–73) | 0 (0–39) | 0.01J | * |
| Infants receiving inotropes | 56 (31–197) | 68 (37–118) | 39 (34–42) | 0.07J | |
| Inotropic agents used (n) | |||||
| Dopamine | 15 (79) | 10 (50) | 8 (43) | 0.03 | |
| Dobutamine | 2 (10) | 1 (5) | 3 (14) | 0.77F | |
| Maximum dose of dopamine – µg/kg/min | 17 (10–20) | 12 (10–16) | 11 (10–14) | 0.09A | |
| Clinical cardiovascular treatment: other cardioactive drugs and monitoring | |||||
| Hydrocortisone for hypotension (n) | 4 (21) | 3 (15) | 4 (19) | 0.92F | |
| Patent ductus arteriosus (n) | |||||
| Medical treatment (COX inhibitor) | 7 (37) | 9 (45) | 8 (38) | 0.95 | |
| Surgical ligation | 2 (10) | 2 (10) | 5 (24) | 0.48F | |
| Invasive BP monitoring | 17 (89) | 18 (90) | 16 (76) | 0.48F | |
| Duration of umbilical arterial catheterisation – hours | 105 (68–232) | 108 (55–227) | 79 (45–187) | 0.22J | |
| Physiological characteristics on days 1 and 3 of life: circulatory variables | |||||
| Cardiac output (left ventricular output, mL/kg/min) | |||||
| Day 1 | 166 (159–220) | 160 (125–195) | 181 (144–202) | 0.58A | |
| Day 3 | 210 (147–256) | 220 (164–250) | 200 (172–251) | 0.67A | |
| Mean arterial (invasive and non-invasive) blood pressure (mm Hg) during echocardiography | |||||
| Day 1 | 36 (33–38) | 32 (29–35) | 34 (28–37) | 0.65A | |
| Day 3 | 36 (33–39) | 33 (29–41) | 40 (32–51) | 0.33A | |
| Mean arterial (invasive) blood pressure (mm Hg) during echocardiography | |||||
| Day 1 | 35 (32–37) | 32 (29–35) | 31 (27–35) | 0.01A | |
| Day 3 | 34 (32–36) | 32 (28–35) | 33 (30–39) | 0.56A | |
| Common carotid artery blood flow (mL/kg/min) | |||||
| Day 1 | 12 (10–14) | 12 (8–14) | 12 (9–16) | 0.41A | |
| Day 3 | 15 (12–18) | 13 (12–15) | 15 (11–20) | 0.66A | |
| Superior mesenteric artery blood flow velocity (mean of peak velocity envelope – cm/s) | |||||
| Day 1 | 21 (16–29) | 29 (15–35) | 21 (17–28) | 0.84A | |
| Day 3 | 21 (14–27) | 30 (24–40) | 26 (22–31) | 0.04A | |
| Patent ductus arteriosus (PDA) | |||||
| PDA present (n (%)) | |||||
| Day 1 | 18 (95) | 19 (95) | 17 (81) | 0.35F | |
| Day 3 | 12 (63) | 13 (68) | 15 (71) | 0.58 | |
| PDA maximum (colour) diameter (mm) | |||||
| Day 1 | 1.6 (1.2–1.9) | 1.3 (1–1.8) | 1.3 (1.2–1.8) | 0.13A | |
| Day 3 | 1.1 (0–1.6) | 1.1 (0–1.6) | 1.2 (0–1.5) | 0.94A | |
| PDA maximum velocity (m/s) | |||||
| Day 1 | 1.4 (0.8–1.6) | 1.3 (0.9–1.6) | 1.2 (0.4–1.9) | 0.92A | |
| Day 3 | 0.6 (0–1.7) | 0.9 (0–1.4) | 0.7 (0–1.5) | 0.70A | |
| PDA flow pattern (n(%)) as per Su et al 34 | |||||
| Day 1: growing pattern | 6 (50) | 3 (25) | 3 (25) | 0.39F | |
| Pulsatile pattern | 9 (39) | 9 (39) | 5 (22) | ||
| Day 3: growing pattern | 2 (40) | 2 (40) | 1 (20) | 0.80F | |
| Pulsatile pattern | 7 (32) | 7 (32) | 8 (36) | ||
| Physiological characteristics on days 1 and 3 of life: electroencephalographic variables | |||||
| Maximum aEEG amplitude in μV | |||||
| Day 1 | 12.0 (9.8–14.3) | 10.0 (7.3–14.4) | 13.1 (9.6–15.5) | 0.45A | |
| Day 3 | 15.0 (8.3–20.6) | 16.0 (10.0–19.8) | 13.0 (12.9–18.8) | 0.82A | |
| Minimum aEEG amplitude in μV | |||||
| Day 1 | 3.1 (2. –3.9) | 2.5 (2.0–3.7) | 3.5 (2.5–3.9) | 0.63A | |
| Day 3 | 3.5 (2.4–5.1) | 4.0 (2.9–5.2) | 4.2 (3.4–5.3) | 0.87A | |
| Median discontinuity in seconds per one minute epoch | |||||
| Day 1 | 20 (15–26) | 25 (17–37) | 17 (9–30) | 0.41A | |
| Day 3 | 9.5 (1.5–31.9) | 11 (6–23.7) | 8.5 (0–18.6) | 0.49A | |
Values are number (%) or median (IQR), with statistical tests performed for ordered levels (χ2 test with linear-by-linear association and Jonckheere-Terpstra test (J)), ANOVA with contrasts (A) or Fisher’s exact test (F)). Starting inotropic therapy after randomisation and median duration of inotropic therapy for all patients were the only variables that remained significant after Benjamini-Hochberg correction for multiple testing (indicated by * under P(c)).
aEEG, amplitude integrated electroencephalography.