Pediatric Nephrology (2019) 34:1671–1681

https://doi.org/10.1007/s00467-018-4070-8

REVIEW

Evaluation and management of elevated blood pressures

in hospitalized children
Abanti Chaudhuri 1 & Scott M. Sutherland 1

Received: 21 March 2018 / Revised: 14 August 2018 / Accepted: 22 August 2018 / Published online: 3 1 August 2018
# IPNA 2018

Abstract
Elevated blood pressures (BP) are common among hospitalized children and, if not recognized and treated promptly, can lead to
potentially significant consequences. Even though we have normative BP data and well-developed guidelines for the diagnosis
and management of hypertension (HTN) in the ambulatory setting, our understanding of elevated BPs and their relationship to
HTN in hospitalized children is limited. Several issues have hampered our ability to diagnose and manage HTN in the inpatient
setting including the common presence of physiologic conditions, which are associated with transient BP elevations (i.e., pain or
anxiety), non-standard approaches to BP measurement, a lack of clarity regarding appropriate diagnostic and therapeutic thresh-
olds, and marginal outcome data. The purpose of this review is to highlight the issues and challenges surrounding BP monitoring,
assessment of elevated BPs, and the diagnosis of HTN in hospitalized children. Extrapolating from currently available clinical
practice guidelines and utilizing the best data available, we aim to provide guidelines regarding evaluation and treatment of
elevated BP in hospitalized children.

Keywords Children . Hypertension . Management

Introduction measurement and inpatient-specific physiologic conditions

Hypertension (HTN) is a significant problem in both adults
and children. The most recent National Health and Nutrition
Examination Survey (NHANES) data suggest that 45.6% of
adults (> 18 years) have HTN [1]. The prevalence among
healthy children is thought to be between 1.6 and 3.5%; an
additional 2.2–9.4% have blood pressures (BP) considered to
be elevated above normal [2–5]. Though pediatric HTN has
been well studied in the ambulatory setting, our understanding
of elevated BP and its relationship to HTN in hospitalized
children is less established. There are a number of issues that
contribute to this, including non-standard approaches to BP
* Abanti Chaudhuri
abanti@stanford.edu
1
Division of Nephrology, Department of Pediatrics, Stanford
University, Palo Alto, California, USA
that cause transient elevations in BP. Thus, while it is straight-
forward to characterize a BP as being Belevated^ above a
certain threshold, the significance of that elevation and the
point at which Belevated BPs^ evolve into true HTN is not
entirely clear. Despite these challenges, the ability to more
accurately identify and more effectively manage inpatient
HTN is of paramount importance. Pediatric hospitalization-
associated HTN has been on the rise over the last decade
across all age groups; while it is challenging to know if these
children are being admitted with HTN or developing it during
their stay, there has been a significant increase in HTN-related
healthcare costs according to data from the Healthcare Cost
and Utilization Project (HCUP) Kids’ Inpatient Database [6].
Furthermore, severe HTN can result in significant complica-
tions if not recognized and treated promptly, underscoring the
need for better diagnostic and management strategies. In this
light, we discuss the best pediatric in-hospital data available
and extrapolate from the most current clinical practice guide-
lines to provide concise recommendations regarding the diag-
nosis, evaluation, and management of elevated BPs in hospi-
talized children.
1672
Epidemiology
Prevalence
Though limited, some data characterizing elevated BPs and
HTN in hospitalized children do exist. For example,
Alperstein et al. conducted a cross-sectional study using data
from the 2012 HCUP database and found that the prevalence
of HTN, based on International Classification of Diseases
coding (ICD-9), was 1.02% in pediatric inpatients [7].
Another study using a nationally representative database of
pediatric hospitalizations found that for approximately 1% of
children, one of the discharge diagnoses were coded as HTN
[6]. Both these studies relied upon billing code data which
does not distinguish between disease present on admission
and disease developed during admission; additionally, billing
code data has historically been insensitive and associated with
an underdiagnosis of HTN. For example, Hansen et al. found
that among children with confirmed HTN based upon office
BP data, only 26% carried an actual diagnosis code for the
disease [4]. For comparative purposes, Sleeper et al. applied
age-based normative data to admission BPs and found that
24% of these BPs were elevated (defined as an admission
BP > 95th percentile) [8]. Notably, this study extrapolated a
diagnosis of HTN from a single elevated measurement, which
has traditionally overestimated the prevalence of HTN [2, 4,
5]. BP data from intensive care units (ICUs) seem to suggest
that elevated BPs are more common in children receiving
critical care. One study demonstrated that approximately
19% of pediatric ICU BP readings, by direct arterial, as well
as indirect oscillometric, and manual measurements, were in
the hypertensive range (defined as > 95th centile for age spe-
cific norms) [9]. Similarly, Ehrmann et al. performed a single-
center retrospective study of 1215 critically ill children and
found that 25% of the population had stage 2 HTN (3 systolic
and/or diastolic readings > 99th percentile + 5 mmHg), based
on arterial BP readings, and automated noninvasive
oscillometric only if arterial readings were unavailable [10].
In summary, the best available data suggest that somewhere
between 1 and 25% of hospitalized children experience ele-
vated BPs during their stay. It is likely that children on acute
care wards have incidences on the lower end of that spectrum
and that the prevalence in pediatric ICUs is on the higher end.
Etiology
HTN is a relatively uncommon primary admission diagnosis.
Children tend to be admitted for exacerbations of pre-existing
HTN, or with initial presentations of secondary forms of HTN.
More commonly, BPs become elevated during the course of
hospitalization. In some patients, the elevated BPs are due to
their underlying disease (acute kidney injury, chronic kidney
disease, obstructive uropathy or its resolution, renal mass
Pediatr Nephrol (2019) 34:1671–1681
effect, etc.) or to the treatments those diseases require (corti-
costeroids, sympathomimetics, intravenous fluids, vasoactive
agents, etc.). In others, the cause may be related to pain or
anxiety, postoperative salt and volume overload, a failure to
administer the patient’s known antihypertensive medication,
or an inability to give oral antihypertensive medication for a
variety of reasons (poor family recall, patient is unable to take
medications orally, or concerns for hypotension outweighs
concern for hypertension). A list of the more common causes
of elevated BP in hospitalized children is shown in Table 1.
Ambulatory diagnosis of hypertension
In 2017, the American Academy of Pediatrics (AAP) pub-
lished revised guidelines for the evaluation and management
of high BP based upon gender, age, and relative height per-
centile; these norms differed from those previously published
primarily in their exclusion of BP data from overweight and
obese children [3]. The AAP recommends that, the diagnosis
of HTN in children less than 13 years of age is made when
BPs on three separate visits are greater than the 95th percentile
for age, gender, and height; in children greater than or equal to
13 years of age, the BPs are categorized as hypertensive if ≥
130/80 mmHg (Table 2). The European Society of
Hypertension (ESH) guidelines, which are based upon the
normative auscultatory data from the US Task Force including
obese/overweight children, are similar [11]. The main differ-
ence is that the age-related inflection point is 16; in children
16 years and older, the definition of HTN is based upon the
absolute adult cutoff, which defines high-normal as 130–139/
85–89 mmHg and HTN as ≥ 140/90 mmHg) [12]. Both sets of
guidelines underscore the importance of choosing an appro-
priately sized cuff. If too small a cuff is used, the pressure
generated by inflating the cuff may not be fully transmitted
to the brachial artery. In this setting, the pressure in the cuff
may be considerably higher than the intra-arterial pressure,
leading to overestimation of the systolic pressure. On the other
hand, too wide a cuff may produce lower readings than the
actual intra-arterial pressure. Of note, all normative data was
based upon auscultatory measurement and though it is reason-
able to use oscillometry for screening, any elevated values
should be confirmed by auscultation.
Which blood pressure is Bnormal^
for pediatric inpatients?
The BP readings used in the AAP and European guidelines
were obtained in a highly controlled setting that differs dra-
matically from the inpatient environment. This raises the ques-
tion of how applicable these guidelines are to inpatients—can
they be accurately applied to hospitalized children? Inpatients
Pediatr Nephrol (2019) 34:1671–1681
Table 1 Etiology of
acutely elevated blood Renal
pressures in hospitalized Acute kidney injury
children
Renovascular disease
Glomerular disease
Renal parenchymal disease
Obstructive uropathy
Polycystic kidney disease
Renal tumors
Endocrine
Pheochromocytoma
Congenital adrenal hyperplasia
Primary aldosteronism
Cushing syndrome
Hyperthyroidism
Neurologic
Increased intracranial pressure (head
trauma/brain tumor)
Familial dysautonomia
Guillain-Barre syndrome
Cerebral hemorrhage or infarction
Cardiovascular
Coarctation of the aorta
Drug induced/toxicology
Sympathomimetics (e.g., cocaine,
amphetamines, pseudoephedrine,
PCP, ephedra-containing
nutraceuticals, caffeine)
Serotonin syndrome
Anabolic steroids
Corticosteroids
Oral contraceptives
Clonidine withdrawal
Miscellaneous
Pain
Anxiety
Neuroleptic malignant syndrome
Neurofibromatosis
Hypercalcemia
are likely to have far greater stress and anxiety when com-
pared with healthy ambulatory children. Additionally, hospi-
talized children may be in pain, and it is reasonable to question
the significance of Bspuriously^ elevated readings. However,
the challenge for the practitioner is to determine if the readings
are due to a treatable underlying condition (pain, stress, fear)
or if it is reflective of true HTN.
Though no definitive data exist, attempts have been made to
define comparative inpatient values for various vital signs. For
example, Bonafide et al. used vital sign data from 14,014 hospi-
talized children to develop heart rate (HR) and respiratory rate
(RR) percentile curves for pediatric inpatients [13]. They found
1673
that up to 54% of HR and up to 40% of RR values fell outside
standardized, textbook reference ranges. In general, their data-
driven reference ranges were higher than the previously
established ranges. Goel et al. performed a similar analysis using
vital sign data from 9489 children admitted to acute care wards
[14]. At every age, the locally derived vital sign ranges were
higher than the established National Institute of Health (NIH)
normative data. For example, the established NIH RR range for
a 12-month old was 20–35 breaths per minute (bpm); the locally
derived range (5th–95th centile) was 19–42 bpm [15]. Though
no similar BP data exists for general pediatric inpatient popula-
tions, Eytan et al. generated age-based centile curves for BP in
critically ill children; these curves were developed independent
of admission or discharge diagnoses, procedures done during the
hospitalization, ventilation status, sedation, or inotropic and va-
sopressor support [16]. Derived from over one billion data points,
the centile curves are based upon intra-arterial (rather than
oscillometric or auscultatory) BP measurements and include only
critically ill children. Not surprisingly, the authors found that BPs
tended to range higher in these critically ill children. While the
95th centile systolic BP for a 1-year-old boy might be as high as
105 mmHg based upon the ambulatory normative values, Eytan
et al. found that the 95th centile for 1 year olds in the ICU was as
high as 127 mmHg (Table 3). It is incredibly challenging to
extrapolate from these data. Being hospitalized is not a Bnormal^
condition and one cannot describe these inpatient-derived centile
data as Bnormative.^ However, it is clear that hospitalized chil-
dren have higher respiratory rates, heart rates, and BPs at baseline
than their ambulatory counterparts. More granularly, the data
suggest that a 12-year-old girl admitted with cellulitis will have
a higher average BP than an equivalent 12-year-old girl will in
the outpatient setting, independent of all other clinical factors.
This information may have an impact on the way we interpret
BPs, elevated or not, in the inpatient setting.
Inpatient-specific challenges to measurement
and diagnosis
More fundamentally, the most important aspect of diagnosing
HTN is accurate BP measurement. Incorrect measurement
techniques can lead to inappropriate diagnosis, unnecessary
investigations and treatments, false negative findings, and
non-treatment of patients with true HTN. In this section, we
will highlight some measurement challenges that are particu-
larly prevalent in the inpatient setting.
Arm vs. leg blood pressures
In younger children in particular, measuring BPs in the leg is
quite common; this is especially true as medical complexity
increases. Often, bedside nurses prefer to avoid repeated oc-
clusion of veins in extremities that have intravenous (IV)
1674 Pediatr Nephrol (2019) 34:1671–1681

Table 2 Definition of hypertension based upon the American Academy of Pediatrics (AAP) 2017 pediatric hypertension guidelines and the 2016
European Society of Hypertension (ESH) guidelines

Category AAP guidelines ESH guidelines

Normal
Elevated BP/high-normal
BP
Hypertension
Stage 1 hypertension
Stage 2 hypertension
Age 1–13 years Age ≥ 13 years Age 1–15 years Age ≥ 16 years
< 90th percentile < 120/80 mmHg < 90th percentile < 130/85 mmHg
≥ 90th percentile to < 95th 120/<80 to ≥ 90th percentile to < 95th 130–139/85–89 mmHg
percentile or 120/80 mmHg 129/<80 mmHg percentile or
to < 95th percentile
(whichever is lower)
≥ 95th percentile ≥ 130/80 ≥ 95th percentile ≥ 140/90
95th percentile to 95th percentile 130–139 / 80–89 mmHg 95th percentile to 99th 140–159/90–99 mmHg
+ 12 mmHg OR percentile + 5 mmHg
130–139/80–89 (whichever is
lower)
≥ 95th percentile + 12 mmHg ≥140/90 mmHg > 99th percentile 160–179/100–109 mmHg
OR + 5 mmHg

Compiled from the most recent pediatric hypertension guidelines [3], this table summarizes the age specific definition of hypertension designed for
children in the ambulatory setting. 2016 European Society of Hypertension guidelines that differ slightly in the age threshold for using the adult
criteria [12]. BP blood pressure, OR odds ratio

lines; many patients receiving critical care may have IV lines
in both upper extremities, precluding BP monitoring in the
arms. Lower extremity monitoring is problematic since calf/
thigh BPs have been shown to be physiologically higher than
arm BPs in adults [17]. It is important to note that while we
believe the same to hold true for children, variable upper/
lower extremity differences in systolic, diastolic, and mean
arterial pressures have been found across different age groups
[18, 19]. Though lower extremity BP readings are clearly
relevant to evaluating for coarctation or peripheral vascular
disease, they should not be used interchangeably with arm
pressures for chronic measurement or compared to established
norms.
BP is the highest in the supine position when compared to the
other positions [20]. Most children who are hospitalized tend
to have their BP taken while in the supine position, which
may, in turn, result in values that are more elevated than the
normative values obtained in the ambulatory setting, which
are taken with children in the sitting position, with their feet
on the ground. In addition, it is recommended that the cuff is
horizontal at the level of the heart at the mid-sternal level as
different cuff positions compared to the heart level have sig-
nificant effects on BP readings [21]. Dependency of the arm
below the heart level leads to an overestimation of systolic and
diastolic BP and raising the arm above heart level leads to
underestimation [22].

Sitting vs. supine blood pressure measurements
When assessing BP in a hospitalized child, it is important to
take the position of the patient into consideration. The BP
(especially systolic) tends to drop in the standing position
compared with the sitting and supine; systolic and diastolic
Arterial line vs. oscillometric vs. auscultatory blood
pressure measurements
Even though practice varies across institutions, inpatient loca-
tions, ages, and severity of illness, mostly BPs in hospitalized
patients will be obtained by oscillometry. It is recommended

Table 3 Comparison of 95th

percentile blood pressure data in 2017 pediatric hypertension guidelines Pediatric ICU population
the ambulatory setting (manual
BP readings) with critically ill 1 year old 105/57 127/76
children (intra-arterial BP 5 years old 112/71 133/80
readings) 10 years old 121/78 144/84
15 years old 135/85 (130/80) 155/85

To insure highest possible value, male gender and 95th percentile height were assumed. This table compares blood
pressures in children of different ages in the ambulatory setting (compiled from data in 2017 pediatric hyperten-
sion guidelines [3]) with those who are critically ill (data obtained from the Supplementary tables in the manu-
script BHeart Rate and Blood Pressure Centile Curves and Distributions by Age of Hospitalized Critically Ill
Children^ by Eytan et al. [16], where only the 95th percentile BP values for males and the average age of a given
age range are chosen for comparison). This table demonstrates Bnormal^ BPs are likely to be higher in inpatients
than in ambulatory children. BP blood pressure, ICU Intensive Care Unit
Pediatr Nephrol (2019) 34:1671–1681
that BP values greater than the 90th percentile obtained by
oscillometric methods are confirmed by auscultation since
oscillometric measurements tend to be higher than those ob-
tained by auscultation [23, 24]. In many critically ill children,
however, real-time BP monitoring is required and measure-
ments from arterial lines are common in the ICU; in fact, these
continuous readings are considered standard of care for pa-
tients with hyper- or hypotensive crises [25]. Despite this, it is
well recognized that over- and underdamping, calibration er-
rors, and movement artifacts can lead to erroneous intra-
arterial BP data and that noninvasive BP measurements may
differ significantly from intra-arterial estimates [26–31].
These differences are most relevant at BP extremes. For ex-
ample, Lehman et al. examined 27,022 simultaneously mea-
sured invasive arterial/noninvasive BP pairs in adults receiv-
ing critical care [32]. They found that noninvasive determina-
tion overestimated systolic pressures when compared with
invasive methods during periods of hypotension. Not only
this, but hypotensive systolic noninvasive BP readings were
associated with a greater acute kidney injury (AKI) and mor-
tality risk than invasively obtained BP in the same range,
suggesting that noninvasive systolic readings may fail to rec-
ognize end-organ hypoperfusion. Similar findings have been
found in children outside the normotensive range as well. Holt
et al. found automated readings to be higher during hypoten-
sion and lower during HTN when compared with intra-arterial
measurements [9]. Thus, though frequent oscillometric mea-
surements (confirmed by auscultation if necessary) are accept-
able in hemodynamically stable patients, arterial BP remains
the preferred method of BP monitoring in critically ill
children.
Mean arterial pressure vs. systolic blood pressure
It has been shown that noninvasive and invasively obtained
mean arterial pressures (MAP) show better agreement [32].
Lehman et al. demonstrated that the AKI prevalence and
ICU mortality risk associated with hypotensive MAPs was
similar regardless of measurement technique [32]. Thus,
oscillometric measurement can be reliably used to assess
MAP (as opposed to systolic or diastolic BP which can be
inaccurate as they are calculated from MAP based on propri-
etary algorithms that vary from device to device) when intra-
arterial monitoring is not available or is not feasible. However,
there is no definitive normative MAP data in children. Haque
et al. derived 5th centile estimates from task force data for
children from 1 to 17 years of age and calculated normal
MAP values using a standard mathematical formula [33].
These values are derived from healthy children and may need
to be applied differently in critically ill children. It is to be
noted that MAP values tend to vary across the height percen-
tile within the same age group, just like systolic and diastolic
1675
BP and this variation may need to be considered when caring
for a very short or tall child.
Diagnosis of hypertension in hospitalized
children
It is unlikely that BP values in the inpatient and ambulatory
settings have identical thresholds and significance. The cur-
rently available inpatient data for other vital signs (HR and
RR) ranges higher in hospitalized children and it is likely that
BP data follows the same trend [13–15]. However, given the
lack of inpatient data and the presence of robust ambulatory
information, we recommend defining HTN in hospitalized
children in concordance with the most recent clinical practice
guidelines, i.e., when BPs are consistently ≥ 95th centile for
the age, gender, and height of the patient (Table 3) [3, 12].
Care should be taken to measure BPs using an appropriately
sized cuff on the arm whenever possible in calm, comfortable
children. In critically ill children, as long as the arterial tracing
is accurate, invasively measured BPs remain the standard of
care. Practitioners should remember that while MAP data
tends to correlate between invasive and noninvasive methods,
oscillometric systolic values tend to be higher than invasively
determined values, but MAP, as well as systolic and diastolic
values, may vary by device and not all devices are validated in
children.
Treatment
Who should be treated?
One of the more challenging aspects of managing elevated BP
is the determination of treatment threshold. Though we rec-
ommend using the most recent data from clinical practice
guidelines for inpatient HTN diagnosis, we do feel that treat-
ment of inpatients diagnosed in this fashion will vary from that
seen in the ambulatory setting. It is important to remember that
treatment recommendations for ambulatory children are based
upon the desire to prevent long-term systemic complications,
which tend to develop over a period of many years. A child
who has similar HTN transiently is unlikely to experience the
same morbidity if the HTN resolves within days or weeks. In
the inpatient setting, unless patients have longstanding HTN,
which is unlikely to resolve, treatment decisions should re-
volve around the prevention of acute, symptomatic hyperten-
sive complications. Ehrman et al. found that in children re-
ceiving intensive care, ≥ 5 readings over the 99th percentile
plus 5 mmHg (stage 2 HTN) within a single day was associ-
ated with a significantly greater risk for AKI and prolonged
length of stay [10]. This suggests that a full day of BPs above
the stage 2 range may have clinical significance acutely in
1676
critically ill children. With lack of robust outcome data in
hospitalized children, we propose that, even though patients
with BPs ≥ 95th percentile are considered hypertensive, treat-
ment be considered acutely in hospitalized patients who have
sustained stage 2 HTN that persists for greater than a day. We
would define stage 2 HTN as described above—a systolic,
diastolic, greater than the 95th percentile plus 12 mmHg or
the specific BP threshold for stage 2 HTN per the AAP or the
ESH guidelines in older children (Table 2). In addition, treat-
ment should be considered in children experiencing a sudden
rise in BP, regardless of whether or not it meets the stage 2
threshold. Patients who have one or several BPs which greatly
exceed the stage 2 threshold should be considered for therapy
as well, regardless of the duration of the elevation. Any patient
with hypertensive emergency or encephalopathy should obvi-
ously be treated immediately. Finally, the underlying risk for
hypertensive complications should be considered. Children at
greater risk for seizures or encephalopathy, as well as those
who might be at greater risk for hypertensive complications
(recent surgery, thrombocytopenia, etc.), should be treated at
lower thresholds. On the other hand, children at greater risk
for hypotensive complications (elevated ICP, etc.) might ben-
efit from treatment at higher thresholds.
Treatment goals
The 2017 AAP pediatric HTN guidelines define Bnormal^ BP in
children to be < 90th percentile or < 120/80 for those ≥ 13 years
[3, 12]. While an ideal treatment goal in outpatients will be to
bring the BP to within the Bnormal^ range, it may not be neces-
sary or feasible in the inpatient setting. It may be sufficient
targeting BPs < 95th percentile or < 130/80 in children ≥ 13 years
as a baseline goal in inpatients; however, some children may
benefit from stricter or more lenient management based on clin-
ical circumstances. It is important to take the rapidity and dura-
tion of the elevated BPs into account when determining how
quickly the goal BP should be reached. In children with chronic
HTN, cerebral autoregulatory mechanisms adapt to protect the
brain from ischemia. A rapid lowering of BP can lead to de-
creased cerebral perfusion and neurologic dysfunction, AKI,
and transverse ischemic myelopathy [34]. It is recommended
the BP is lowered gradually in a controlled fashion to reach the
goal pressure. Per the Clinical Practice Guidelines, BP should be
reduced by no more than 25% of the planned reduction over the
first 8 h, with the remainder of the planned reduction over the
next 12 to 24 h [3]. Children with a very rapid rise in BP from
normal will not have adjusted to the higher BP range with min-
imal cerebral perfusion auto-regulation and are at high risk of
posterior reversible encephalopathy syndrome; thus, they require
aggressive and early antihypertensive therapy, which is usually
well tolerated without evidence of organ ischemia. Many chil-
dren found to have moderately severe elevations of BP can be
managed on the general pediatric ward. Those children with
Pediatr Nephrol (2019) 34:1671–1681
hypertensive emergencies or with symptomatic BPs refractory
to intermittently administered medications will often require
ICU admission for continuous infusion of antihypertensive
agents and close clinical monitoring.
Treatment options
Once BP is found to be elevated, the first step is to eliminate
iatrogenic causes if present and feasible. Pain and anxiety
should be adequately managed and agitation should be re-
duced to the extent possible. Fluid overload, if present, should
be treated with fluid restriction and/or diuretics if appropriate.
If HTN persists, antihypertensive therapy should be consid-
ered. Despite the increase in published data over the last de-
cade, pediatric safety and efficacy of oral antihypertensive
agents remain limited, and technically, many agents are not
cleared for use in children by the United States Food and Drug
Administration. Current treatment relies on the experiences of
individual providers, and an experienced clinician, such as a
pediatric nephrologist or intensivist, should guide therapy of
pediatric hypertensive emergencies.
If treatment is thought to be necessary after initial assess-
ment, the provider should determine whether an oral or IV
agent is appropriate initial therapy based on severity of symp-
toms, patient location within hospital, access available, and
the ability to tolerate oral medications. Oral medications can
be used for gradual BP reduction in patients with asymptom-
atic or mildly symptomatic HTN. In acute hypertensive urgen-
cy or situations where BP has changed rapidly, intermittent
bolus dosing of short-acting IV antihypertensive agents which
have a rapid onset of action can be used. In severe hyperten-
sive crisis, a continuous IV infusion may be ideal since it
allows rapid titration and is best suited to achieve gradual
BP control. However, if patients are in hospital locations such
as the emergency unit or the general pediatric floor where
continuous infusion of antihypertensive medication cannot
be performed, careful administration of an initial IV bolus
therapy is recommended with frequent oscillometric BP mon-
itoring until the patient can be transferred to an ICU. Once in
the ICU, continuous infusion of IV antihypertensive agents is
recommended with intra-arterial BP monitoring. Once symp-
toms are resolved and hypertensive crisis has been mitigated,
patients can be transitioned to long acting oral medications.
By this time, evaluation of HTN may have revealed an etiol-
ogy, and when possible, the choice of agent should be dictated
by this knowledge. The various antihypertensive agents that
can be used are summarized in Table 4.
Intermittent IV therapies
Two of the intermittent IVagents which are commonly used to
treat children with acutely elevated BPs are hydralazine and
labetolol. Single-center retrospective studies evaluating the
Pediatr Nephrol (2019) 34:1671–1681
efficacy and safety of IV hydralazine in hospitalized children
have reported an average reduction in systolic and diastolic
BP of 8–10% with a single dose, though larger decrements
have been reported [35]. In our experience, tachyphylaxis to
the antihypertensive effects of intravenous hydralazine may
occur, making subsequent doses less effective after 48–72 h.
Additionally, efficacy may be limited due to reflex tachycardia
related to stimulation of the sympathetic nervous system.
Alternatively, labetalol is effective in reducing BPs in the set-
ting of acute elevations, though it has been associated with
hypotension when used in infants and young children [36, 37].
Labetalol can also be used as a continuous infusion.
Enalaprilat, the only FDA-approved angiotensin-converting
enzyme inhibitor available in IV form, can also be effective
[38, 39]. However, it can induce AKI as well as hyperkalemia,
and must be used with great caution in neonates and patients
with AKI, chronic kidney disease, and volume depletion [40].
IV continuous infusion
Nicardipine is commonly used as a continuous infusion in
children with severe BP elevation. It is effective in reducing
BP and is associated with minimal adverse effects across
many disease states and age groups [41–43]. One issue which
can be seen with nicardipine is thrombophlebitis and it is
recommended that the medication be administered centrally
if possible. Esmolol, although less pediatric data exists, is
thought to be safe and effective particularly in hypertensive
infants and young children following cardiac surgical repair
[44, 45]. One benefit is that its metabolism is independent of
hepatic and renal metabolism, making it suitable for patients
with multiorgan failure [46]. Sodium nitroprusside is very
effective in reducing BP and can be titrated rapidly. Though
the incidence of complications is low, many practitioners
avoid it due to the risk for cyanide and thiocyanate accumu-
lation after extended use (24–48 h), particularly in children
with concomitant renal or liver dysfunction [47]. It must be
noted, however, that in a randomized, double-blind study, not
a single patient demonstrated overt evidence of toxicity even
in the setting of significantly elevated cyanide levels [48].
Newer IV agents like fenoldopam and clevidipine are promis-
ing based on adult trials, but pediatric experience is still lim-
ited [48, 49].
Oral agents
In hospitalized patients, calcium channel blockers are used
with great frequency due to their efficacy and side effect pro-
file. Options include isradipine, preferred for its rapid onset
and short duration of action (half-life of 1.5 to 2 h),
amlodipine, less preferred in the acute situation for its slow
onset and longer duration of action (half-life of 30–50 h),
hence, typically used if requiring isradipine frequently, and
1677
nifedipine (half-life of 2 h) [50–52]. Nifedipine, however, is
no longer a preferred agent in children due to its association
with large drops in BP in children and an increased risk for
myocardial infarction, stroke, and death reported in the adult
population [53, 54]. Notably, stable solutions of isradipine and
amlodipine can be compounded, which is particularly advan-
tageous in infants and young children. Clonidine, which is
available in a transdermal form as well, is used frequently in
patients with chronic HTN as well as in the ICU [55, 56]. It is
particularly useful in the settings of catecholamine-induced
HTN, HTN associated with withdrawal of sedatives, and in
those with neurologically mediated HTN. Minoxidil is effec-
tive in severe childhood HTN; however, we tend to use it only
in HTN refractory to other medications due to the risk for
cardiac effusions [57, 58].
Transitions, discharge, and follow up
If the patient remains on oral antihypertensive therapy at the
time of hospital discharge, families should go home with an
FDA-cleared BP monitoring device complete with an appro-
priately sized cuff, which should be ideally correlated with the
hospital device prior to discharge, or alternatively, caregivers
should be taught how to measure BP manually. Patients and
families should receive appropriate education regarding HTN,
medication side effects, and a monitoring plan. Many patients
will benefit from parameters below which the medication
should be held (level varies with the physicians preference)
as well as parameters for contacting the nephrology team (i.e.,
hypotension or persistent HTN). Follow up with a nephrolo-
gist or other specialists in the management of hypertension
should be organized prior to discharge, and parents should
be provided with BP logs and instructions to bring them to
clinic.
Future studies and work
Despite well-established ambulatory guidelines, elevated BPs
often go unrecognized in hospitalized pediatric patients, po-
tentially putting them at risk for the sequelae of untreated
HTN. In a retrospective study of 1143 hospitalized children,
a concern for HTN was documented for only 26% of subjects
admitted with stage 2 HTN (admission BP > 99th percentile +
5 mmHg) [8]. Thus, it is clear that we need additional strate-
gies to improve the recognition of HTN. In children, BP ref-
erence tables are complex and require the use of multiple
variables, including sex, age, and height, which makes deter-
mining BP percentiles challenging; we believe that addressing
this issue is likely to have a significant impact on HTN iden-
tification. At a minimum, the BP interpretation tables based on
age, sex, and height percentile need to be readily available in
the hospital setting. However, better recognition rates have
 1678

Table 4 Antihypertensive agents used in acute hypertension

Name Mechanism of Onset of Route Dose Side effects Comments

action action

Hydralazine Direct vasodilator 10–80 min IV bolus or 0.2 to 0.6 mg/kg IV or IM, maximum Reflex tachycardia, headache, fluid retention Duration of action 2–4 h
IM single dose 20 mg, repeated every
4 h as required
Labetalol α and β adrenergic 2–5 min IV bolus or Bolus 0.2–1 mg/kg/dose, up to Hypotension, dizziness, nausea, bradycardia, Contraindicated in asthma, heart
blocker infusion 40 mg/dose; infusion 0.25–3 mg/kg/h bronchospasm failure, and diabetics
Nicardipine Calcium channel Few IV bolus or Bolus 30 μg/kg up to 2 mg/dose; infusion Reflex tachycardia, peripheral edema Risk of thrombophlebitis, central line
blocker minutes infusion 0.5–4 μg/kg/min preferred
Sodium Vasodilator < 2 min IV infusion 0.5–10 μg/kg/min Hypotension, palpitations, flushing Monitor for cyanide and thiocyanate
nitroprusside toxicity, measure cyanide levels
with prolonged use (> 48 h) or in
hepatic or renal failure, or
co-administer with sodium
thiosulfate
Esmolol β-Blocker < 1 min IV infusion 100–500 μg/kg/min, up to 1000 μg/kg/min Bradycardia, decreased cardiac output, Contraindicated in asthma and heart
continuous IV infusion bronchospasm failure. Very short-acting
Fenoldopam Dopamine receptor 10 min IV infusion 0.2–0.8 μg/kg/min Tachycardia, headache, nausea, flushing, Limited pediatric experience
agonist hypotension, hypokalemia
Clevidipine Calcium channel 2 min IV infusion 0.5–3.5 μg/kg/min (limited pediatric data Hypotension, tachycardia Very short acting. Contraindicated in
blocker on dosing) those with egg and soy allergy as
well as lipid disorders
Enalaprilat ACE inhibitor ≤ 15 min IV bolus 5–10 μg/kg/dose up to 1.2 mg/dose Acute kidney injury, hyperkalemia, Neonates are at increased risk for
hypotension prolonged hypotension and acute
kidney injury
Phentolamine α adrenergic IV bolus 0.05–0.1 mg/kg/dose, up to 5 mg Tachycardia Useful in catecholamine and cocaine-
antagonist or pseudoephedrine-induced
hypertension
Isradipine Calcium channel 1h PO 0.05–0.1 mg/kg/dose up to 5 mg/dose Headache, nausea, flushing, hypotension Stable suspension can be
blocker compounded
Clonidine Central α agonist 30–60 min PO 0.05–0.1 mg/dose, may be repeated up to Dry mouth and sedation Risk of rebound hypertension if
0.8 mg total standing doses are withdrawn
abruptly
Minoxidil Direct vasodilator 30 min PO 0.1–0.2 mg/kg per dose Edema, and hypertrichosis with chronic use Long duration of action
Nifedipine Calcium channel 1–5 min PO 0.1–0.25 mg/kg per dose up to 10 mg per Hypotension, flushing, tachycardia, syncope Not recommended for pediatric use
blocker dose
Pediatr Nephrol (2019) 34:1671–1681
Pediatr Nephrol (2019) 34:1671–1681
been observed with simplified abnormal BP screening tables
which is a reasonable alternative [59]. Another option is to use
the electronic medical record (EMR) to our advantage. The
EMR contains all BP data as well as the information needed to
determine percentiles. Simple approaches such as flagging
BPs that meet a certain threshold (i.e., > 95th percentile +
12 mmHg) are likely to be quite beneficial. Additional options
include EMR-based tools such as real-time alerts or applica-
tions capable of calculating BP percentiles automatically;
studies investigating these tools confirm they show promise
in improving elevated BP recognition [60, 61]. In our center,
we have a web-based, EMR-integrated, pediatric HTN diag-
nosis and treatment decision support tool (https://hyperisk.
stanfordchildrens.org/about/). This tool passes Health
Insurance Portability and Accountability Act (HIPAA) com-
pliant data from the EMR to a web-based platform, which then
provides percentile information, diagnosis, and treatment rec-
ommendations (Fig. 1). There is clearly a need for the devel-
opment of similar tools suitable for widespread use that would
improve our ability to diagnose and manage HTN.
Development of inpatient BP data across all age groups of
hospitalized children based on epidemiologic outcome mea-
sures as opposed to statistical population norms will be an
important development in the future as well; this will be im-
portant to help us determine the optimal treatment thresholds
and goals. Finally, pediatric randomized controlled trials are
Fig. 1 Web-based hypertension (HTN) diagnostic platform. This figure is
an example of the information provided for by Hyperisk, a web-based,
electronic medical record (EMR)-integrated, pediatric HTN diagnosis
and treatment decision support tool (https://hyperisk.stanfordchildrens.
org/about/). Linkage with the EMR allows Health Insurance Portability
and Accountability Act (HIPAA) compliant data do be passed directly to
the web-based platform which then calculates blood pressure percentiles,
1679
required to assess treatment efficacy, safety, and outcomes for
the different antihypertensive agents to allow more informed
management decisions.
Summary
Elevated BP is common among hospitalized children and the
prevalence seems to be on the rise; currently we estimate that
between 1 and 25% of pediatric inpatients experience elevated
BP, with higher rates in those receiving critical care. In hospi-
talized children, there are a number of inpatient-specific issues
that plague our ability to obtain accurate, reliable BP measure-
ments, and it is important for the clinician to understand these
challenges and the manner in which they affect BP measure-
ments. One of the biggest challenges facing us is determina-
tion of which patients and which BP values require therapeutic
intervention. While data suggest that BPs, on average, range
higher in the hospital than they do in the ambulatory setting,
we believe the exceptional ambulatory normative data for
children is the best data to use in the inpatient setting as well.
Thus, HTN should be diagnosed at similar threshold in both
locations. However, given the different risks patients have in
the two settings, we recommend initiating treatment at a
higher threshold (stage 2 HTN or 95th percentile +
12 mmHg) and targeting somewhat less aggressive control
a diagnosis based upon the readings available, and treatment recommen-
dations. In this case, the 3-year 7-month-old male has more than 3 values
which are between the 95th percentile and 99th percentile + 5 mmHg,
which is consistent with stage 1 HTN. Treatment recommendations are
customized because the patient is located in an inpatient setting; ambula-
tory recommendations are taken directly from the most recent pediatric
HTN guidelines
1680
when appropriate. Obviously, the ultimate decision is patient
specific and some patients may benefit from higher or lower
treatment thresholds and therapeutic targets; it is clear that
many of these decisions will need to be individualized. Once
the decision is made to begin therapy, a variety of agents are
available in oral and intravenous forms; the choice of agent
will depend on clinical circumstances, underlying disease, eti-
ology, severity of HTN, and rapidity with which the elevation
occurred. Future directions should include the development of
stronger EMR-based diagnostic tools and prospective studies
to help us better understand therapy-related outcomes in these
children.
Compliance with ethical standards
Conflict of interest The authors declare no conflict of interest.
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