Keywords
preterm - neonatal hypotension - inotropes - blood pressure
Blood pressure (BP) charts are increasingly used by neonatologists across NICUs to
monitor the hemodynamic status of neonates.[1]
[2] Among the most important factors influencing BP, gestational age (GA) at birth,
birth weight (BW), and postmenstrual age (PMA) have been identified as key determinants,
reflecting the physiological process of neonatal hemodynamic adaptation to the extrauterine
environment and compensatory cardiovascular responses.[3]
[4] In this context, adequate BP parameters and correct measurement techniques are vital
indicators of clinical stability for neonates.[5]
[6]
[7]
[8] Furthermore, several studies define neonatal hypotension using population-based
normative values, commonly adopting the fifth or 10th percentile as the threshold
for the lowest acceptable BP.[9]
[10]
[11]
[12]
[13]
Neonatal hypotension is a common issue in neonates and carries significant implications
for both short- and long-term outcomes. Inotropes are routinely administered to treat
low BP or poor perfusion in NICUs.[14]
[15] Nonetheless, there is a lack of data on the efficacy of antihypotensive treatment,
and the thresholds relevant to initiating such treatment remain undefined and require
further investigation.[16] Despite extensive research and numerous therapeutic options, neonatologists have
yet to reach a consensus on the optimal pharmacological management of neonatal hypotension.[17]
[18] The challenge for neonatologists working in NICUs is to discern the cause of the
hemodynamic changes, determine whether these changes are transitional or pathological,
and then proceed to customize the treatment regimen accordingly.[19]
[20]
Neonatal hypotension and rapid fluctuations in BP during the first 72 hours of life
in preterm infants are associated with both short- and long-term adverse outcomes,
including neurodevelopmental impairment, hearing loss, and increased mortality.[21] Evidence suggests that fluid bolus administration within the first 48 hours may
be linked to higher rates of home oxygen dependency, patent ductus arteriosus (PDA),
and intraventricular hemorrhage (IVH) among very-low-birth-weight infants.[22] Additionally, treated hypotensive neonates may have lower survival rates or a higher
likelihood of surviving with significant morbidity.[23] These hemodynamic disturbances are particularly pronounced in the first week of
life in premature infants.[24] However, the absence of high-quality randomized controlled trials addressing key
outcomes, coupled with the practical challenges in conducting such studies, continues
to hinder our understanding of optimal strategies for the management of neonatal hypotension.[25]
[26]
Therefore, we conducted this study to assess the impact of implementing a standardized
BP chart and clinical management guidelines on the treatment of neonatal hypotension.
The goal was to support more accurate BP assessment, reduce unnecessary interventions,
and potentially minimize associated morbidity and mortality in preterm infants.
Materials and Methods
This retrospective cohort study involves an examination of preterm infants (<32 weeks
of GA) born at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. The exclusion
criteria included outborn infants and those with birth defects. The project obtained
approval from the ethics committee of the King Abdullah International Medical Research
Centre (KAIMRC; IRB number: NRR24/059/6).
Data were collected before and after the implementation of the BP charts and neonatal
hypotension management guidelines, referred to as EPOCH1 (preimplementation) and EPOCH2
(postimplementation). Information was obtained from an electronic database and included
infant demographics, maternal and neonatal characteristics, and the use of inotropic
support.
We assessed the following neonatal morbidities: bronchopulmonary dysplasia (BPD) at
36 weeks PMA, major IVH defined as grades III and IV, minor IVH as per Papile classification,
necrotizing enterocolitis (NEC) requiring surgical intervention, including intra-abdominal
drain insertion, and culture-positive sepsis confirmed in blood, cerebrospinal fluid,
or urine. Retinopathy of prematurity (ROP) was also evaluated. In addition, we recorded
the duration of respiratory support and the total length of hospital stay until discharge
home.
Implementation of BP Charts and Neonatal Hypotension Management Guidelines
The BP reference values used in this study were based on the Zubrow et al[1] chart, which included 695 infants from 14 NICUs and provides normative values for
both transitional (first 24 hours) and posttransitional (beyond 24 hours) periods
across a broad GA range. ([Tables 1] and [2]) This chart remains the most widely referenced in clinical practice for neonatal
BP thresholds. To support this approach, we also referenced the study by Elsayed et
al,[2] which described similar percentile distributions in 206 infants born at 23 to 28
weeks' gestation. For the first 24 hours of life, a single representative BP measurement
was used. This approach was intended to reduce overtreatment during a time when transient
hypotension is common due to normal physiological adaptation. Differentiating between
physiological and pathological hypotension during this period was critical in guiding
management. Our use of this early BP chart was aimed at avoiding unnecessary inotrope
use and reducing pressure fluctuations that could contribute to adverse neurological
outcomes, particularly in extremely preterm infants.
Table 1
Blood pressure values by GA (at birth) for first 24 hours of life
|
|
Table 2
Blood pressure values by corrected postconceptional age after 24 hours of life
|
|
To guide treatment, we used the Zubrow et al BP chart, which defines normative BP
percentiles by gestational and postnatal age. The fifth percentile was used as the
threshold for initiating therapy for neonatal hypotension, consistent with practices
adopted across multiple Canadian NICUs and presented at the 2022 EPIQ collaborative
meeting. Clinical signs of neonatal shock prompting evaluation included decreased
activity, lethargy, tachycardia or bradycardia, apnea, hypoxemia, prolonged capillary
refill time, abnormal temperature regulation (hypothermia or hyperthermia), metabolic
acidosis, and elevated serum lactate. Inotropes were weaned and discontinued when
three conditions were met: resolution of the primary clinical condition causing hypotension,
achievement of stable BP above the 25th percentile, and absence of significant fluctuations
or overshoots in mean arterial pressure (MAP; [Table 3]).
Table 3
Blood Pressure Values for inotropes weaning after 24 hours of life
|
|
The neonatal hypotension management guidelines were developed following an extensive
review of the literature, particularly focusing on pathophysiologic causes of hypotension
in preterm infants, such as impaired preload, afterload, or contractility, and supported
by evidence-based clinical references, including targeted neonatal echocardiography.
The development process involved multidisciplinary consensus from neonatologists and
senior NICU staff and was approved by the unit's clinical leadership. Educational
sessions were conducted for physicians, fellows, nurses, and respiratory therapists
prior to rollout to ensure familiarity with the standardized BP chart and clinical
algorithm. Implementation commenced in January 2024, and adherence to the guidelines
was monitored by prospective documentation of treatment decisions in infants receiving
cardiovascular support. Ongoing feedback and clinical audits were used to support
the sustained application of the protocol across the unit.
Statistical Analysis
The data was statistically evaluated using SPSS version 26.0 software. The two-sided
tests we applied had significance set at p < 0.05. We showcase categorical variables as numbers and percentages, while continuous
variables are presented as means and standard deviations (SD). The comparison of categorical
variables was done using either Fisher's exact test or the chi-square test. Continuous
variables, depending on their distribution, were compared using either the student's
t-test or the Mann–Whitney U test.
Results
A total of 384 preterm infants born at less than 32 weeks' gestation were included
in the study, with 192 infants in EPOCH1 (before implementation) and 192 in EPOCH2
(after implementation). The mean GA was 29.6 weeks (SD = 2.5) in EPOCH1 and 29.2 weeks
(SD = 2.6) in EPOCH2 (p = 0.090). The mean BW was 1,283.1 g (SD = 423) in EPOCH1 and 1,295.5 g (SD = 459)
in EPOCH2 (p = 0.784). The mean Apgar score at 5 minutes was 7.9 (SD = 1.1) in EPOCH1 and 7.7
(SD = 1.4) in EPOCH2 (p = 0.177). The proportion of male infants was 47.9% in EPOCH1 and 57.3% in EPOCH2
(p = 0.066), while the proportion of female infants was 52.1% in EPOCH1 and 42.7% in
EPOCH2 (p = 0.610). Cesarean section delivery was reported in 159 infants (82.8%) in EPOCH1
and 134 infants (69.8%) in EPOCH2, with this difference reaching statistical significance
(p = 0.003). Multiple pregnancies were noted in 76 cases (39.6%) in EPOCH1 and 65 cases
(33.9%) in EPOCH2 (p = 0.244). Antenatal steroid administration occurred in 176 infants (91.7%) in EPOCH1
and 180 infants (93.8%) in EPOCH2 (p = 0.432). PROM was present in 60 infants (31.3%) in EPOCH1 and 66 infants (34.4%)
in EPOCH2 (p = 0.514). Chorioamnionitis was diagnosed in 18 infants (9.4%) in EPOCH1 and 10 infants
(5.2%) in EPOCH2 (p = 0.116). Preeclampsia occurred in 26 mothers (13.5%) in EPOCH1 and 29 mothers (15.1%)
in EPOCH2 (p = 0.662). Labetalol use was reported in 19 cases (10%) in EPOCH1 and 26 cases (13.8%)
in EPOCH2 (p = 0.258). Early-onset sepsis occurred in eight infants (4.2%) in EPOCH1 and 11 infants
(5.7%) in EPOCH2 (p = 0.480), while late-onset sepsis was reported in 22 infants (11.5%) in EPOCH1 and
19 infants (9.9%) in EPOCH2 (p = 0.620). PDA treatment was recorded in 46 infants (24%) in EPOCH1 and 37 infants
(19.3%) in EPOCH2, with a statistically significant difference between the two groups
(p = 0.004; [Table 4]).
Table 4
Overall, the infants' and maternal characteristics
|
Variables
|
EPOCH1 (no. 192)
|
EPOCH2 (no. 192)
|
p-Value
|
|
GA (SD)
|
29.6 (2.5)
|
29.2 (2.6)
|
0.090
|
|
BW (SD)
|
1,283.1 (423)
|
1,295.5 (459)
|
0.784
|
|
Mean APGAR at 5 min (SD)
|
7.9 (1.1)
|
7.7 (1.4)
|
0.177
|
|
Gender male
|
92 (47.9%)
|
110 (57.3%)
|
0.066
|
|
Gender female
|
100 (52.1%)
|
82 (42.7%)
|
0.610
|
|
C-section
|
159 (82.8%)
|
134 (69.8%)
|
0.003
|
|
Multiple pregnancy
|
76 (39.6%)
|
65 (33.9%)
|
0.244
|
|
Antenatal steroid
|
176 (91.7%)
|
180 (93.8%)
|
0.432
|
|
PROM
|
60 (31.3%)
|
66 (34.4%)
|
0.514
|
|
Chorioamnionitis
|
18 (9.4%)
|
10 (5.2%)
|
0.116
|
|
Preeclampsia
|
26 (13.5%)
|
29 (15.1%)
|
0.662
|
|
Labetalol
|
19 (10%)
|
26 (13.8%)
|
0.258
|
|
Early sepsis
|
8 (4.2%)
|
11 (5.7%)
|
0.480
|
|
Late sepsis
|
22 (11.5%)
|
19 (9.9%)
|
0.620
|
|
PDA treatment
|
46 (24%)
|
37 (19.3%)
|
0.004
|
Abbreviations: BW, birth weight; GA, gestational age; PDA, patent ductus arteriosus;
PROM, premature rupture of membrane.
[Table 5] presents data on overall neonatal morbidity and mortality. In the EPOCH2 group,
the incidence of periventricular leukomalacia (PVL) was significantly lower compared
with EPOCH1 (6.5 vs. 15.1%, p = 0.007). There were no statistically significant differences observed between the
two epochs for BPD (25.1 vs. 24.3%, p = 0.856), major IVH (6.3 vs. 3.8%, p = 0.112), ROP (4.7 vs. 3.8%, p = 0.680), NEC requiring surgery (4.2 vs. 3.7%, p = 0.833), duration of invasive ventilation (13.3 vs. 12.2 days, p = 0.607), duration of oxygen therapy (31.1 vs. 34.4 days, p = 0.333), time to reach full enteral feeds (15.0 vs. 14.8 days, p = 0.905), length of hospital stay (51.4 vs. 50.2 days, p = 0.749), or mortality rate (8.3 vs. 9.4%, p = 0.719; [Table 5]).
Table 5
Overall neonatal outcomes of the study population
|
Variables
|
EPOCH1 (no. 192)
|
EPOCH2 (no. 192)
|
p-Value
|
|
BPD
|
48 (25.1%)
|
45 (24.3%)
|
0.856
|
|
Major IVH
|
12 (6.3%)
|
7 (3.8%)
|
0.112
|
|
Minor IVH
|
62 (32.6%)
|
47 (25.3%)
|
|
|
PVL
|
29 (15.1%)
|
12 (6.5%)
|
0.007
|
|
ROP
|
9 (4.7%)
|
7 (3.8%)
|
0.680
|
|
NEC
|
8 (4.2%)
|
7 (3.7%)
|
0.833
|
|
Duration on invasive ventilation in days (SD)
|
13.3 (17.8)
|
12.2 (16.9)
|
0.607
|
|
Duration on oxygen in days (SD)
|
31.1 (32)
|
34.4 (34.5)
|
0.333
|
|
Time to full feed in days (SD)
|
15 (13.1)
|
14.8 (15)
|
0.905
|
|
Length of stay in days (SD)
|
51.4 (37.5)
|
50.2 (34.4)
|
0.749
|
|
Mortality
|
16 (8.3%)
|
18 (9.4%)
|
0.719
|
Abbreviations: BPD, bronchopulmonary dysplasia; IVH, interventricular hemorrhage;
NEC, necrotizing enterocolitis; PVL, periventricular leukomalacia; ROP, retinopathy
of prematurity.
[Table 6] shows a comparison of neonates with hypotension requiring inotropic support between
EPOCH1 and EPOCH2. The proportion of infants receiving inotropes was significantly
lower in EPOCH2 (33.9 vs. 17.7%, p < 0.001). Invasive BP monitoring was more frequently used in EPOCH2 (67.7 vs. 94.1%,
p = 0.003). GA was higher in EPOCH1 (27.1 vs. 25.3 weeks, p = 0.001), as was BW (935.5 g vs. 704.8 g, p < 0.001). APGAR scores at 5 and 10 minutes were also higher in EPOCH1 (7.3 vs. 6.2,
p = 0.001) and (7.6 vs. 6.6, p = 0.049), respectively. MAP (27.3 vs. 21 mm Hg, p < 0.001), systolic blood pressure (SBP; 39.4 vs. 30.3 mm Hg, p < 0.001), and diastolic blood pressure (DBP; 22.2 vs. 15.5 mm Hg, p < 0.001) were all significantly higher in EPOCH1. The average duration of inotropic
support was longer in EPOCH1 (4.2 vs. 2.6 days, p = 0.034). There were no statistically significant differences in the age at initiation
of inotropes (3.4 vs. 3.1 days, p = 0.844) or in the number of inotropes used (1.87 vs. 2.3, p = 0.209); [Table 6]).
Table 6
Neonatal hypotension group in EPOCH1 and EPOCH2
|
Variables
|
EPOCH1 (no. 65)
|
EPOCH2 (no. 34)
|
p-Value
|
|
Hypotension needs inotropes
|
65 (33.9%)
|
34 (17.7%)
|
<0.001
|
|
Invasive BP monitoring
|
44 (67.7%)
|
32 (94.1%)
|
0.003
|
|
GA (wk; SD)
|
27.1 (2.6)
|
25.3 (1.8)
|
0.001
|
|
BW (g; SD)
|
935.5 (341)
|
704.8 (179)
|
<0.001
|
|
APGAR 5 (SD)
|
7.3 (1.1)
|
6.2 (1.9)
|
0.001
|
|
APGAR 10 (SD)
|
7.6 (0.6)
|
6.6 (1.6)
|
0.049
|
|
MAP (SD)
|
27.3 (3.9)
|
21 (2.9)
|
<0.001
|
|
SBP (SD)
|
39.4 (6.2)
|
30.3 (5.2)
|
<0.001
|
|
DBP (SD)
|
22.2 (5.1)
|
15.5 (2.7)
|
<0.001
|
|
Duration of inotropes in days (SD)
|
4.2 (4.2)
|
2.6 (2.4)
|
0.034
|
|
Age starts inotropes in days (SD)
|
3.4 (6.6)
|
3.1 (4.7)
|
0.844
|
|
Number of inotropes (SD)
|
1.87 (1.8)
|
2.3 (1.3)
|
0.209
|
Abbreviations: BW, birth weight; DBP, diastolic blood pressure; GA, gestational age;
MAP, mean arterial pressure; SBP, systolic blood pressure.
[Table 7] presents the patterns of inotrope and fluid use among hypotensive neonates in EPOCH1
and EPOCH2. Dopamine use significantly declined in EPOCH2 (58.5 vs. 14.7%, p < 0.001), while norepinephrine use increased (26.2 vs. 70.6%, p < 0.001). Dobutamine administration also rose between epochs (38.5 vs. 64.7%, p = 0.013), along with hydrocortisone use (46.2 vs. 82.4%, p = 0.001). In terms of fluid support, there was a reduction in the use of normal saline
(NS) boluses (80 vs. 41.2%, p < 0.001) and a significant increase in the administration of blood products (46.2
vs. 73.5%, p = 0.009). No statistically significant differences were observed in the use of epinephrine
(20 vs. 35.3%, p = 0.096), vasopressin (29.2 vs. 38.2%, p = 0.363), or milrinone (3.1 vs. 8.8%, p = 0.215; [Table 7]).
Table 7
Use of inotropes in EPOCH1 and EPOCH2
|
Variables
|
EPOCH1 (no. 65)
|
EPOCH2 (no. 34)
|
p-Value
|
|
Dopamine
|
38 (58.5%)
|
5 (14.7%)
|
<0.001
|
|
Norepinephrine
|
17 (26.2%)
|
24 (70.6%)
|
<0.001
|
|
Dobutamine
|
25 (38.5%)
|
22 (64.7%)
|
0.013
|
|
Epinephrine
|
13 (20%)
|
12 (35.3%)
|
0.096
|
|
Vasopressin
|
19 (29.2%)
|
13 (38.2%)
|
0.363
|
|
Milrinone
|
2 (3.1%)
|
3 (8.8%)
|
0.215
|
|
Hydrocortisone
|
30 (46.2%)
|
28 (82.4%)
|
0.001
|
|
Normal saline
|
52 (80%)
|
14 (41.2%)
|
<0.001
|
|
Blood products
|
30 (46.2%)
|
25 (73.5%)
|
0.009
|
[Table 8] presents the neonatal outcomes for the subgroup of infants with hypotension. The
incidence of BPD was similar between EPOCH1 and EPOCH2 (46.9 vs. 48.1%, p = 0.912). No statistically significant differences were noted in the rates of major
IVH (19 vs. 13.2%, p = 0.563), minor IVH (42.9 vs. 42.9%, p = not reported), PVL (23.1 vs. 14.3%, p = 0.335), ROP (13.8 vs. 19.2%, p = 0.520), or NEC (10.8 vs. 17.2%, p = 0.385). Similarly, the duration of invasive ventilation (17.4 vs. 22.6 days, p = 0.259), duration on oxygen (53.8 vs. 54.9 days, p = 0.907), time to achieve full enteral feeds (23.8 vs. 27.7 days, p = 0.461), and length of hospital stay (73.4 vs. 62.4 days, p = 0.338) showed no statistically significant differences between the two epochs.
However, early mortality within the first 72 hours was significantly lower in EPOCH2
compared with EPOCH1 (64.3 vs. 26.7%, p = 0.042; [Table 8]).
Table 8
Overall neonatal outcomes of the neonatal hypotension group
|
Variables
|
EPOCH1 (no. 65)
|
EPOCH2 (no. 34)
|
p-Value
|
|
BPD
|
30 (46.9%)
|
13 (48.1%)
|
0.912
|
|
Major IVH
|
12 (19%)
|
3 (13.2%)
|
0.563
|
|
Minor IVH
|
27 (42.9%)
|
12 (42.9)
|
|
|
PVL
|
15 (23.1%)
|
4 (14.3%)
|
0.335
|
|
ROP
|
9 (13.8)
|
5 (19.2%)
|
0.520
|
|
NEC
|
7 (10.8%)
|
5 (17.2%)
|
0.385
|
|
Duration on invasive ventilation in days (SD)
|
17.4 (20.8)
|
22.6 (23.1)
|
0.259
|
|
Duration on oxygen in days (SD)
|
53.8 (40)
|
54.9 (49.8)
|
0.907
|
|
Time to full feed in days (SD)
|
23.8 (18)
|
27.7 (24.5)
|
0.461
|
|
Length of stay in days (SD)
|
73.4 (51)
|
62.4 (55.9)
|
0.338
|
|
Mortality < 72 h
|
9 (64.3%)
|
4 (26.7%)
|
0.042
|
Abbreviations: BPD, bronchopulmonary dysplasia; IVH, interventricular hemorrhage;
NEC, necrotizing enterocolitis; PVL, periventricular leukomalacia; ROP, retinopathy
of prematurity.
Discussion
In this retrospective study, the implementation of a BP chart and a neonatal hypotension
management guideline was associated with a significant reduction in inotrope usage,
suggesting a more standardized and targeted approach to BP management in neonates.
Notably, this reduction was observed despite infants in EPOCH2 having lower GA, lower
BW, and lower APGAR scores at both 5 and 10 minutes compared with those in the previous
period. These findings suggest that the revised management approach may have contributed
to improved hemodynamic stability, reducing the perceived need for inotropic support
even in a cohort with higher baseline risk factors for hemodynamic instability.
Our data indicate that BP monitoring was more frequently performed using invasive
arterial access following the implementation of the new guidelines, improving measurement
accuracy and guiding clinical decisions regarding the initiation and discontinuation
of inotropes. This approach helped prevent unnecessary interventions and reduced the
risk of overtreatment in neonates with neonatal hypotension. In the hypotension group,
MAP, SBP, and DBP were lower postimplementation at the time of initiating the therapy.
Decisions regarding inotrope initiation and fluid boluses were guided by whether the
MAP reached or fell below the fifth percentile, in line with common NICU practices
defining neonatal hypotension as MAP < fifth percentile.[27]
[28]
[29]
Our study demonstrated a significant shift in the management of neonatal hypotension.
Initially, dopamine was administered to all neonates with hypotension, regardless
of the underlying pathophysiological cause. Following the implementation of the neonatal
hypotension management guideline, dopamine use decreased significantly, and treatment
decisions became more individualized, focusing on the specific pathophysiological
mechanisms of hypotension.[30]
[31] While dopamine use decreased, norepinephrine use became more common, reflecting
a fundamental change in our treatment approach. Unlike dopamine, norepinephrine has
minimal effects on pulmonary vascular resistance, making it a more favorable option
in certain clinical scenarios. This shift highlights a more targeted approach to managing
neonatal hypotension, prioritizing individualized treatment based on underlying pathophysiology.[32]
[33]
Following the implementation of the neonatal hypotension management guideline, we
observed a substantial decrease in the use of NS boluses, from 80 to 41%. This reduction
aligns with emerging evidence cautioning against the routine use of NS in preterm
infants due to its potential associations with adverse outcomes.[34] Studies suggest that excessive NS administration within the first 48 hours of life
may contribute to an increased risk of PDA, prolonged dependence on oxygen, and potential
long-term neurodevelopmental consequences.[35]
[36]
[37] By minimizing unnecessary NS boluses, the revised guideline likely contributed to
a more judicious approach to fluid management, reducing the risks associated with
excessive volume expansion in this high-risk population. We revised our treatment
protocol to include hydrocortisone as a second- or third-line therapy for refractory
neonatal hypotension, particularly in cases where initial management strategies, such
as fluid resuscitation and inotropes, failed to achieve adequate BP stabilization.
This adjustment aligns with evidence supporting the role of corticosteroids in addressing
adrenal insufficiency and improving hemodynamic stability in preterm infants with
persistent hypotension.[38]
In EPOCH 2, we implemented a structured and physiology-based approach to the diagnosis
and management of hypotension in preterm infants. Prior to this change, hypotension
was defined solely by the traditional threshold of MAP less than or equal to the infant's
GA in weeks. This criterion lacked specificity and often resulted in inconsistent
clinical responses. To address this, we introduced standardized BP charts and evidence-informed
management guidelines that aligned treatment decisions with the underlying pathophysiological
mechanisms. The BP chart was divided into three segments: within the first 24 hours
of life, after 24 hours, and during the weaning phase once BP exceeded the 25th percentile.
The separation between the first 24 hours and the subsequent period allowed differentiation
between transitional hypotension, which is frequently physiological, and persistent
or pathological hypotension. The management protocol categorized hypotension into
two main pathophysiological types. Diastolic hypotension, typically related to low
preload or vasodilation, was managed initially with fluid boluses when indicated,
followed by vasopressors such as dopamine or norepinephrine. In refractory cases,
vasopressin or hydrocortisone was considered. Systolic hypotension, usually associated
with poor myocardial contractility or elevated afterload, was managed with inotropes
such as epinephrine or dobutamine, with hydrocortisone used selectively based on clinical
judgement. A weaning algorithm was also introduced to taper inotropes gradually once
the infant's BP had stabilized above the 25th percentile. This approach aimed to minimize
the risk of rebound hypotension and reduce the duration of inotropic support. This
transition to a physiology-driven and standardized framework allowed for more targeted
intervention, and we believe it contributed to the observed reduction in early mortality
without increasing late mortality or the overall use of inotropes. This structured
approach may be replicable or adaptable by other neonatal units seeking to improve
the consistency and effectiveness of BP management in preterm infants.
In our study, the rates of major neonatal morbidities, including BPD, major and minor
IVH, PVL, ROP, and NEC, did not significantly differ between EPOCH1 and EPOCH2 in
the hypotension group. Additionally, there was no significant difference in the duration
of invasive ventilation, total oxygen dependence, time to achieve full enteral feeding,
or overall length of hospital stay between the two epochs. These findings suggest
that while the implementation of the neonatal hypotension management guideline standardized
treatment approaches, it did not lead to notable changes in the incidence of these
complications. The similarity in morbidity rates may be attributed to the fact that
factors influencing these outcomes, such as prematurity-related lung disease, hemodynamic
stability, and neonatal intensive care practices, remained consistent between the
two periods. Further research is needed to explore whether refinements in neonatal
BP management strategies could contribute to improved long-term outcomes. Although
overall mortality remained unchanged between the two epochs, early mortality within
72 hours was significantly lower in EPOCH2. We did not observe a corresponding increase
in late mortality after inotrope exposure. Review of individual cases did not suggest
a pattern linking inotrope therapy to subsequent death, and late mortality appeared
attributable to multifactorial complications of extreme prematurity. Nevertheless,
larger prospective studies are needed to better assess the relationship between inotrope
use and late mortality.
Strengths and Limitations
Strengths and Limitations
Our study has several strengths and limitations. One of the primary limitations is
its retrospective design, as data for both maternal and neonatal variables were collected
from medical records, which may be subject to missing or incomplete information. Additionally,
this study was conducted at a single institution, which may restrict the generalizability
of the findings to other neonatal units with different patient populations, clinical
protocols, and resource availability. Despite these limitations, the study has notable
strengths. It provides a systematic comparison of neonatal mortality and major morbidities
before and after implementing standardized BP monitoring and management guidelines.
The use of a clearly defined cohort of preterm infants allows for a focused evaluation
of the impact of these interventions on neonatal outcomes.
Conclusion
The implementation of BP charts and hypotension management guidelines was associated
with a significant reduction in the use of inotropes and fluid boluses, indicating
a more standardized and objective approach to BP management in preterm infants. These
changes reflect improved clinical decision-making based on defined BP thresholds,
resulting in greater consistency in the timing and selection of interventions while
potentially minimizing the risks linked to unnecessary cardiovascular support.
Despite these improvements, further investigations are warranted to assess the long-term
clinical implications of this approach. Specifically, future studies should evaluate
whether reduced inotrope and fluid administration translates into improved neurodevelopmental
outcomes, reduced incidence of complications such as IVH or BPD, and overall survival
benefits. Additionally, ongoing efforts should focus on refining BP chart parameters
to ensure their applicability across diverse neonatal populations while minimizing
the risks of both over- and under-treatment. Establishing the safest and most effective
BP monitoring and management strategies will be crucial in optimizing outcomes for
preterm neonates in the NICU setting.
What Is Already Known on This Topic
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Hypotension in preterm infants is a common problem, with significant implications
for morbidity and mortality.
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Inotropes are often used to manage neonatal hypotension in neonatal intensive care
units. The literature defines neonatal hypotension as the lowest acceptable BP according
to the fifth or 10th percentile of population-based normative values.
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In neonatal hypotension, significant short- and long-term morbidity is associated
with the rapid fluctuations in BP observed after the initiation of inotropes in preterm
infants.
What This Study Adds
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Standardized BP charts have improved therapeutic decision-making for the treatment
of neonatal hypotension by providing accurate information and preventing unnecessary
treatment.
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Approaches based on pathophysiology for managing neonatal hypotension may assist in
reducing the number and duration of inotrope use.
