Abstract
Consensus on definition and management of hypotension in preterm neonates is lacking. Owing to this, there are wide variations in the reported incidence of hypotension in premature infants, especially during first week of life. Inotropes can often cause vasoconstriction, which may alter brain perfusion especially in the absence of established cerebral autoregulation. Use of these drugs is associated with multiple short- and long-term morbidities.
To evaluate the effect of quality improvement (QI) bundle on rate of inotrope use and associated morbidities.
Inborn preterm neonates born at <29weeks gestational age (GA) and admitted to level III NICU were included. Neonates with major congenital malformations, congenital heart diseases, antenatal diagnosed genetic defects, and neonates admitted after 72 hours of age were excluded from the study. We implemented a QI bundle (Figure 1) focussing on first 72hours from birth which included delayed cord clamping, avoidance of routine echocardiography, addition of clinical criteria to define hypotension, factoring iatrogenic causes of hypotension (ruling out lung hyperinflation), and standardization of respiratory management. Rate of use of inotropes in the first 72hours of life along with acute brain injury and mortality before and after implementation of the QI bundle were compared. The balancing measure was the rate of ischemic lesions in the form of cPVL. Cranial ultrasound was performed to screen for brain injury. Study was approved by the local research ethics board (REB14-1466).
Figure 1. Smart driver diagram
We included 671 neonates (301 before and 364 after the implementation of the bundle) among which 6 neonates were excluded based on the criteria. QI bundle implementation was associated with significant reduction in overall use of inotropes (24% vs 7%, p<0.001), dopamine (18% vs 5%, p<0.001), and dobutamine (17% vs 4%, p<0.001). Rate of acute brain injury decreased significantly: Acute brain injury of any grade (34% vs 20%, p<0.001) and severe brain injury (15% vs 6%, p<0.001). There was no difference in incidence of cPVL (1% vs 1.4%, p=0.66). Associations remained significant after adjusting for confounding factors. The QI bundle implementation was associated with a significant reduction in the use of inotropes when analyzed based on the 6 monthly time intervals (p = 0.006) (Figure 2)
Figure 2. shows drop in inotrope use after the intervention
Our QI bundled approach resulted in reduction in inotrope use and associated brain morbidities in premature babies. Follow-up studies evaluating the impact of this initiative on long-term outcomes in survivors are required to complement findings of improved short-term outcomes seen in this study.
Table 1. Baseline Characteristics of study population
| Characteristics | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | p value |
| Gestation age, weeks, median (IQRa) | 27 (25-28) | 27 (25-28) | 0.63 |
| Caesarean section | 89 (29.8) | 241 (66.2) | † |
| Birth weight, g, mean (S.Db) | 854 (236) | 885 (239) | 0.09 |
| APGAR score <5 at 5min | 63 (21) | 82 (22.5) | 0.70 |
| Cord pH <7 | 11 (3.7) | 7 (2) | 0.23 |
| Male | 160 (53.2) | 201 (55.2) | 0.64 |
| SGAc | 41 (13.6) | 34 (9.3) | 0.09 |
| Antenatal steroids | 270 (90) | 288 (79.8) | † |
| Multiple births | 93 (30.9) | 100 (27.5) | 0.34 |
| SNAPd II scores >20 | 128 (42.5) | 113 (31) | 0.003 |
| Sedation | 57 (18.9) | 25 (6.9) | † |
| RDSe | 249 (82.7) | 248 (68.1) | † |
| Early onset sepsis | 8 (2.6) | 14 (3.8) | 0.52 |
| Medical treatment of PDAf | 115 (38.9) | 157 (43.3) | 0.25 |
| PDA treated in first 72h | 32 (10.6) | 32 (8.8) | 0.29 |
| DCCg | 77 (25.8) | 229 (64.3) | † |
| Characteristics | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | p value |
| Gestation age, weeks, median (IQRa) | 27 (25-28) | 27 (25-28) | 0.63 |
| Caesarean section | 89 (29.8) | 241 (66.2) | † |
| Birth weight, g, mean (S.Db) | 854 (236) | 885 (239) | 0.09 |
| APGAR score <5 at 5min | 63 (21) | 82 (22.5) | 0.70 |
| Cord pH <7 | 11 (3.7) | 7 (2) | 0.23 |
| Male | 160 (53.2) | 201 (55.2) | 0.64 |
| SGAc | 41 (13.6) | 34 (9.3) | 0.09 |
| Antenatal steroids | 270 (90) | 288 (79.8) | † |
| Multiple births | 93 (30.9) | 100 (27.5) | 0.34 |
| SNAPd II scores >20 | 128 (42.5) | 113 (31) | 0.003 |
| Sedation | 57 (18.9) | 25 (6.9) | † |
| RDSe | 249 (82.7) | 248 (68.1) | † |
| Early onset sepsis | 8 (2.6) | 14 (3.8) | 0.52 |
| Medical treatment of PDAf | 115 (38.9) | 157 (43.3) | 0.25 |
| PDA treated in first 72h | 32 (10.6) | 32 (8.8) | 0.29 |
| DCCg | 77 (25.8) | 229 (64.3) | † |
aInterquartile range, bStandard deviation, csmall for gestational age, dScore for neonatal acute physiology, eRespiratory distress syndrome, fPatent ductus arteriosus, gDelayed cord clamping, † <0.001
Unless noted otherwise, results are shown as number (%)
Table 1. Baseline Characteristics of study population
| Characteristics | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | p value |
| Gestation age, weeks, median (IQRa) | 27 (25-28) | 27 (25-28) | 0.63 |
| Caesarean section | 89 (29.8) | 241 (66.2) | † |
| Birth weight, g, mean (S.Db) | 854 (236) | 885 (239) | 0.09 |
| APGAR score <5 at 5min | 63 (21) | 82 (22.5) | 0.70 |
| Cord pH <7 | 11 (3.7) | 7 (2) | 0.23 |
| Male | 160 (53.2) | 201 (55.2) | 0.64 |
| SGAc | 41 (13.6) | 34 (9.3) | 0.09 |
| Antenatal steroids | 270 (90) | 288 (79.8) | † |
| Multiple births | 93 (30.9) | 100 (27.5) | 0.34 |
| SNAPd II scores >20 | 128 (42.5) | 113 (31) | 0.003 |
| Sedation | 57 (18.9) | 25 (6.9) | † |
| RDSe | 249 (82.7) | 248 (68.1) | † |
| Early onset sepsis | 8 (2.6) | 14 (3.8) | 0.52 |
| Medical treatment of PDAf | 115 (38.9) | 157 (43.3) | 0.25 |
| PDA treated in first 72h | 32 (10.6) | 32 (8.8) | 0.29 |
| DCCg | 77 (25.8) | 229 (64.3) | † |
| Characteristics | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | p value |
| Gestation age, weeks, median (IQRa) | 27 (25-28) | 27 (25-28) | 0.63 |
| Caesarean section | 89 (29.8) | 241 (66.2) | † |
| Birth weight, g, mean (S.Db) | 854 (236) | 885 (239) | 0.09 |
| APGAR score <5 at 5min | 63 (21) | 82 (22.5) | 0.70 |
| Cord pH <7 | 11 (3.7) | 7 (2) | 0.23 |
| Male | 160 (53.2) | 201 (55.2) | 0.64 |
| SGAc | 41 (13.6) | 34 (9.3) | 0.09 |
| Antenatal steroids | 270 (90) | 288 (79.8) | † |
| Multiple births | 93 (30.9) | 100 (27.5) | 0.34 |
| SNAPd II scores >20 | 128 (42.5) | 113 (31) | 0.003 |
| Sedation | 57 (18.9) | 25 (6.9) | † |
| RDSe | 249 (82.7) | 248 (68.1) | † |
| Early onset sepsis | 8 (2.6) | 14 (3.8) | 0.52 |
| Medical treatment of PDAf | 115 (38.9) | 157 (43.3) | 0.25 |
| PDA treated in first 72h | 32 (10.6) | 32 (8.8) | 0.29 |
| DCCg | 77 (25.8) | 229 (64.3) | † |
aInterquartile range, bStandard deviation, csmall for gestational age, dScore for neonatal acute physiology, eRespiratory distress syndrome, fPatent ductus arteriosus, gDelayed cord clamping, † <0.001
Unless noted otherwise, results are shown as number (%)
Table 2. Inotrope use during pre and post QI bundle implementation
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | p value |
| Any inotrope use in the first 72h , n(%) | 71 (23.6) | 25 (6.9) | 0.25 | 0.14-0.43 | † |
| Saline bolus, n(%) | 112 (37.2) | 68 (18.7) | 0.28 | 0.18-0.43 | † |
| Dopamine, n(%) | 53 (17.6) | 18 (4.9) | 0.24 | 0.13-046 | † |
| Dobutamine, n(%0 | 50 (16.6) | 13 (3.6) | 0.23 | 0.11-0.46 | † |
| Dopamine and Dobutamine, n(%) | 35 (11.6) | 6 (1.6) | 0.15 | 0.55-0.38 | † |
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | p value |
| Any inotrope use in the first 72h , n(%) | 71 (23.6) | 25 (6.9) | 0.25 | 0.14-0.43 | † |
| Saline bolus, n(%) | 112 (37.2) | 68 (18.7) | 0.28 | 0.18-0.43 | † |
| Dopamine, n(%) | 53 (17.6) | 18 (4.9) | 0.24 | 0.13-046 | † |
| Dobutamine, n(%0 | 50 (16.6) | 13 (3.6) | 0.23 | 0.11-0.46 | † |
| Dopamine and Dobutamine, n(%) | 35 (11.6) | 6 (1.6) | 0.15 | 0.55-0.38 | † |
† <0.001
*adjusted for gestational age, birth weight, antenatal steroid usage, sex, mode of delivery, and APGAR score <5 at 5min of life
Table 2. Inotrope use during pre and post QI bundle implementation
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | p value |
| Any inotrope use in the first 72h , n(%) | 71 (23.6) | 25 (6.9) | 0.25 | 0.14-0.43 | † |
| Saline bolus, n(%) | 112 (37.2) | 68 (18.7) | 0.28 | 0.18-0.43 | † |
| Dopamine, n(%) | 53 (17.6) | 18 (4.9) | 0.24 | 0.13-046 | † |
| Dobutamine, n(%0 | 50 (16.6) | 13 (3.6) | 0.23 | 0.11-0.46 | † |
| Dopamine and Dobutamine, n(%) | 35 (11.6) | 6 (1.6) | 0.15 | 0.55-0.38 | † |
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | p value |
| Any inotrope use in the first 72h , n(%) | 71 (23.6) | 25 (6.9) | 0.25 | 0.14-0.43 | † |
| Saline bolus, n(%) | 112 (37.2) | 68 (18.7) | 0.28 | 0.18-0.43 | † |
| Dopamine, n(%) | 53 (17.6) | 18 (4.9) | 0.24 | 0.13-046 | † |
| Dobutamine, n(%0 | 50 (16.6) | 13 (3.6) | 0.23 | 0.11-0.46 | † |
| Dopamine and Dobutamine, n(%) | 35 (11.6) | 6 (1.6) | 0.15 | 0.55-0.38 | † |
† <0.001
*adjusted for gestational age, birth weight, antenatal steroid usage, sex, mode of delivery, and APGAR score <5 at 5min of life
Table 3. Outcomes during pre and post QI bundle implementation
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | P value |
| Any grade IVHa, n(%) | 103 (34) | 71 (19.5) | 0.44 | 0.29-0.66 | † |
| IVH >grade I, n(%) | 73 (24) | 39 (11) | 0.33 | 0.20-0.54 | † |
| Grade IV IVH, n(%) | 24 (8) | 11 (3) | 0.38 | 0.17-0.89 | 0.025 |
| Severe Brain injury, n(%) | 44 (15) | 21 (5.8) | 0.31 | 0.17-0.58 | † |
| Death/Severe IVH, n(%) | 58 (19.3) | 28 (7.7) | 0.34 | 0.20-0.59 | † |
| Cystic PVLb, n(%) | 3 (1) | 5 (1.4) | 1.7 | 0.37-7.89 | 0.66 |
| Death 1st week, n(%) | 28 (9.4) | 4 (1.6) | 0.31 | 0.13-0.73 | 0.007 |
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | P value |
| Any grade IVHa, n(%) | 103 (34) | 71 (19.5) | 0.44 | 0.29-0.66 | † |
| IVH >grade I, n(%) | 73 (24) | 39 (11) | 0.33 | 0.20-0.54 | † |
| Grade IV IVH, n(%) | 24 (8) | 11 (3) | 0.38 | 0.17-0.89 | 0.025 |
| Severe Brain injury, n(%) | 44 (15) | 21 (5.8) | 0.31 | 0.17-0.58 | † |
| Death/Severe IVH, n(%) | 58 (19.3) | 28 (7.7) | 0.34 | 0.20-0.59 | † |
| Cystic PVLb, n(%) | 3 (1) | 5 (1.4) | 1.7 | 0.37-7.89 | 0.66 |
| Death 1st week, n(%) | 28 (9.4) | 4 (1.6) | 0.31 | 0.13-0.73 | 0.007 |
aIntraventricular hemorrhage, bPeriventricular leukomalacia, † <0.001
*adjusted for gestational age, birth weight, antenatal steroid usage, sex, mode of delivery, and APGAR score <5 at 5min of life
Table 3. Outcomes during pre and post QI bundle implementation
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | P value |
| Any grade IVHa, n(%) | 103 (34) | 71 (19.5) | 0.44 | 0.29-0.66 | † |
| IVH >grade I, n(%) | 73 (24) | 39 (11) | 0.33 | 0.20-0.54 | † |
| Grade IV IVH, n(%) | 24 (8) | 11 (3) | 0.38 | 0.17-0.89 | 0.025 |
| Severe Brain injury, n(%) | 44 (15) | 21 (5.8) | 0.31 | 0.17-0.58 | † |
| Death/Severe IVH, n(%) | 58 (19.3) | 28 (7.7) | 0.34 | 0.20-0.59 | † |
| Cystic PVLb, n(%) | 3 (1) | 5 (1.4) | 1.7 | 0.37-7.89 | 0.66 |
| Death 1st week, n(%) | 28 (9.4) | 4 (1.6) | 0.31 | 0.13-0.73 | 0.007 |
| Characteristics, n(%) | Pre-QI bundle (n=301) | Post-QI bundle (n=364) | aOR* | 95% CI | P value |
| Any grade IVHa, n(%) | 103 (34) | 71 (19.5) | 0.44 | 0.29-0.66 | † |
| IVH >grade I, n(%) | 73 (24) | 39 (11) | 0.33 | 0.20-0.54 | † |
| Grade IV IVH, n(%) | 24 (8) | 11 (3) | 0.38 | 0.17-0.89 | 0.025 |
| Severe Brain injury, n(%) | 44 (15) | 21 (5.8) | 0.31 | 0.17-0.58 | † |
| Death/Severe IVH, n(%) | 58 (19.3) | 28 (7.7) | 0.34 | 0.20-0.59 | † |
| Cystic PVLb, n(%) | 3 (1) | 5 (1.4) | 1.7 | 0.37-7.89 | 0.66 |
| Death 1st week, n(%) | 28 (9.4) | 4 (1.6) | 0.31 | 0.13-0.73 | 0.007 |
aIntraventricular hemorrhage, bPeriventricular leukomalacia, † <0.001
*adjusted for gestational age, birth weight, antenatal steroid usage, sex, mode of delivery, and APGAR score <5 at 5min of life
