Curr Hypertens Rep (2014) 16:456

DOI 10.1007/s11906-014-0456-6

HYPERTENSIVE EMERGENCIES (BM BAUMANN, SECTION EDITOR)

Pediatric Hypertensive Emergencies

Rossana Baracco & Tej K. Mattoo

# Springer Science+Business Media New York 2014

Abstract Hypertensive emergency is a life-threatening con-
dition that requires immediate evaluation and treatment. In
children, severe hypertension can be caused by a variety of
different underlying conditions. It usually presents with neu-
rological involvement; however, signs and symptoms of inju-
ry to the kidneys, myocardium and eyes can also be present.
Hospitalization for intravenous treatment with antihyperten-
sive(s) and close monitoring in an intensive care setting are
required for these patients. Few studies in children with hy-
pertensive emergency have been done in the last several years.
The findings and observations of these studies are discussed in
this review.
Keywords Hypertension . Encephalopathy . Retinopathy .
Seizures . Secondary hypertension . Children
Introduction
Hypertensive emergency is defined as acute severe blood
pressure (BP) elevation with evidence of end-organ damage.
It is important to differentiate it from hypertensive urgency,
which is the acute elevation in BP without end-organ damage
and usually accompanied by minor symptoms. With the obe-
sity “epidemic” there has been a rise in the diagnosis of
hypertension in pediatric patients, primary hypertension in
particular. It is unknown whether the prevalence of HE has
also increased as studies on HE in children are lacking. In fact,
over the last 3 years, most of the literature published on this
subject has encompassed review articles. There are very few
original pediatric studies published, and most of them are
retrospective and limited to a small number of patients.
Epidemiology
The incidence of hypertensive crisis in a pediatric emergency
department (ED) has recently been reported to be 0.021 %
[1•]. This study included 110 patients from 2 pediatric EDs; 18
(16.4 %) of these patients had hypertensive emergency. Most
patients presenting with hypertensive crisis were adolescents
(44 %), followed by 7 to 12 year olds (34.5 %). There was a
male predominance with a 5:1 ratio. In contrast to adults, who
frequently present with hypertensive crisis because of non-
compliance to antihypertensive medications, most children
presenting with hypertensive emergency have no previous
diagnosis of hypertension.
There seems to be a seasonal variation in the frequency of
hypertensive emergency in adults. An interesting recent study
looked at the variation in hospitalization of adults with hyper-
tensive emergency in the USA. There was an impressive
seasonal trend with a peak in winter months and minimum
number of hospitalizations in the summer (nadir in June) [2].
This has not been studied in children and might be a relevant
topic of interest for future studies.

This article is part of the Topical Collection on Hypertensive Emergencies Definitions

R. Baracco : T. K. Mattoo (*)
Hypertension in children is defined as systolic or diastolic
Children’s Hospital of Michigan, Wayne State University, 3901
Beaubien St., Detroit, MI 48201, USA blood pressure (BP) greater than or equal to the 95th percentile
e-mail: tmattoo@med.wayne.edu for age, gender and height percentile. Hypertension is further
R. Baracco divided into stage 1 and stage 2 hypertension. Stage 1 hyper-
e-mail: rbaracco@med.wayne.edu tension is systolic or diastolic BP between the 95th percentile
456, Page 2 of 8 Curr Hypertens Rep (2014) 16:456

to 5 mmHg above the 99th percentile. Stage 2 hypertension is Table 1 Causes of hypertensive emergency in children
systolic or diastolic BP higher than 5 mmHg above the 99th Renal
percentile [3]. • Polycystic kidney disease
Hypertensive crisis is an acute rise in BP, and it is further • Acute glomerulonephritis
classified into hypertensive emergency and hypertensive ur- • Acute kidney injury
• Renal transplant rejection
gency. While in adults there are specific cutoffs in BP readings • Obstructive uropathy
to define hypertensive crisis, no such cutoffs exist in children. • Hemolytic uremic syndrome
Hypertensive emergency is an acute rise in BP associated with • End stage renal disease
end-organ damage. Target organ damage usually includes Endocrine
neurologic, renal, ocular, hepatic or myocardial impairment, • Hyperthyroidism
• Cushing syndrome
which can manifest as encephalopathy, seizures, vision com- • Congenital adrenal hyperplasia
plaints, abnormal electrocardiography or echocardiogram Tumors
findings, impaired renal function or elevated liver function • Pheochromocytoma
tests [4•]. The Fourth Task Force Report describes hyperten- • Neuroblastoma
sive urgency as elevation of BP “well above” the 99th per- • Wilms’ tumor
centile and associated with less serious symptoms. Yang et al. Vascular
• Renal artery stenosis
studied 55 children with a diagnosis of hypertensive crisis in • Coarctation of the aorta
the ED and found that 98 % of patients had stage 2 hyperten- Other
sion [4•]. Based on this finding, the authors suggested that an • Toxidromes: sympathomimetic, anticholinergic, hallucinogenic
elevation in the BP higher than the 99th percentile plus • Medication withdrawal: beta-blockers, clonidine, opiates,
5 mmHg may serve as a threshold for risk of hypertensive benzodiazepines
• Pregnancy
crisis in children. • Essential hypertension

Etiology
system activity, decreased nitric oxide due to oxidative stress,
fluid retention, inflammation and endothelial dysfunction [6•].
As with chronic hypertension, the most common causes of
Over the last few years, the most important observation on
hypertensive crisis vary according to the patient’s age. The
the pathophysiology of hypertension has been its association
study by Yang et al., which included children with mostly
with inflammation. Angiotensin II is proinflammatory; it in-
hypertensive urgency, showed that the most common under-
duces and activates inflammatory pathways. Adhesion mole-
lying cause of hypertension was primary in children older than
cules such as VCAM-1 [7] and ICAM-1 are increased under
7 years of age, followed by renal diseases [4•]. The underlying
the influence of angiotensin II. These molecules then promote
renal diseases in this study included acute glomerulonephritis
recruitment of activated T cells [8, 6•]. Interleukins such as IL-
(IgA nephropathy, post-streptococcal, Henoch-Schonlein pur-
6 and IL-17 are increased in response to angiotensin II [9, 8].
pu r a) , en d-s t a ge r ena l dis e ase , f oc al se gm e ntal
Harrison et al. have summarized recent findings and proposed
glomerulosclerosis and ureteropelvic obstruction.
a paradigm of how T cells and inflammation are involved in
For hypertensive emergency in children, the underlying
hypertension. In this model, initial hypertensive stimuli (an-
cause of hypertension is very likely to be secondary in origin
giotensin II, salt consumption and reactive oxygen species)
[5•]. Children with catecholamine-producing tumors have
cause an increase in BP. This leads to increased sympathetic
been reported to present with the highest BP [4•, 1•]; these
activity, oxidation and protein fragmentation, resulting in the
children could be at significant risk for end-organ damage and
formation of neoantigens. These neoantigens promote T cell
hypertensive emergency. Other common causes of hyperten-
activation and release of cytokines, which lead to vasocon-
sive emergency in children are listed in Table 1. The patients
striction and retention of water and salt. This then results in
with primary l hypertension rarely present as hypertensive
severe hypertension [8].
emergency [1•].
Recent studies of hypertensive emergency in adults have
shown high levels of inflammatory markers such as C-
reactive protein, as well as markers of endothelial dysfunc-
Pathophysiology tion such as VCAM-1 and myeloperoxidase [7]. Mean
platelet volume, a marker of platelet activation, has been
Many different factors contribute to the development of hy- found to be elevated in patients with hypertensive crisis,
pertensive emergency. These include increased sympathetic implicating it in the pathogenesis of thrombotic complica-
nervous activity, increased renin-angiotensin-aldosterone tions in hypertensive crisis [10].
Curr Hypertens Rep (2014) 16:456
As the BP rises, because of a complex system of autoreg-
ulation, organs are able to maintain constant perfusion. Dis-
turbances in the autoregulatory mechanisms result in mechan-
ical stress and endothelial damage, which eventually lead to
tissue ischemia [6•]. Vasoactive substances are released, and a
vicious cycle of endothelial damage, tissue ischemia and
inflammation ensues and perpetuates severe hypertension.
Tissue injury then manifests as end-organ damage.
Clinical Presentation
By definition, children with hypertensive emergency present
with evidence of end-organ damage. The common presenting
signs and symptoms are encephalopathy, seizures, vision
complaints, congestive heart failure and acute kidney injury.
Children with hypertensive urgency usually have minor com-
plaints such as headaches. In the study by Yang et al., of 55
children with hypertensive crisis, the most common present-
ing symptoms were headaches (54.5 %), dizziness (45.5 %)
and nausea/vomiting (36.4 %) [4•].
Encephalopathy most commonly presents with headaches,
vomiting, altered mental status and seizures. There have been
two case reports of children presenting with severe hyperten-
sion, hydrocephalus and cerebellar tonsillar herniation requir-
ing ventriculostomy. The initial imaging studies of these chil-
dren were suspicious for intracerebral masses; however, after
blood pressure control, the abnormal MRI findings resolved
and were deemed to be secondary to hypertensive encepha-
lopathy [11, 12]. Focal neurologic deficits, in particular facial
palsy, can also be a manifestation of hypertensive emergency.
Patients with hypertension and underlying renal, rheuma-
tologic and hematologic disorders can sometimes present with
a posterior reversible encephalopathy syndrome (PRES). Al-
though PRES can be present in the absence of significant
hypertension, most of the time it occurs in hypertensive pa-
tients [13]. It is characterized by vasogenic and usually re-
versible brain edema [14]. Clinically, the patients present, as in
hypertensive encephalopathy, with seizures, visual distur-
bances, headache, altered mental status and focal neurological
deficits [13, 15, 16].
Acute visual symptoms may be a manifestation of enceph-
alopathy, PRES or hypertensive retinopathy. Acute ocular
end-organ damage is defined as grade III/IV hypertensive
retinopathy. A recent study done in adults found that patients
with hypertensive retinopathy were significantly younger than
those without. The authors hypothesized that this is because
chronic compensatory mechanisms have not yet developed in
younger patients [17]. In children, a study that looked at
patients undergoing workup for severe hypertension found
that 18 % had hypertensive retinopathy, most of them with
severe changes [18]. In the two recent studies by Wu et al. and
Yang et al., 3.6 % [1•] and 4.4 % [4•] of children with
Page 3 of 8, 456
hypertensive crisis had visual complaints. Additionally, there
have been two case reports in the last few years of children
presenting only with vision complaints and found to have
hypertensive emergency. One of them was a 16-year-old male
with blurry vision [19]; the other was a 7-year-old female with
vision loss in the left eye who was discovered to have a
pheochromocytoma [20•].
Congestive heart failure may manifest as dyspnea on exer-
tion, peripheral edema and a gallop rhythm on cardiac auscul-
tation. The kidney may suffer damage in hypertensive emer-
gency. This damage is manifested as acute kidney injury,
hematuria and/or proteinuria. A recent prospective study in
adults found that patients with hypertensive emergency had
significantly higher creatinine levels. They also measured
neutrophil gelatinase-associated lipocalin (NGAL) as a mark-
er of early kidney injury and found that it was 57 % higher in
patients with hypertensive emergency compared to controls or
patients with hypertensive urgency [21].
A hyponatremic hypertensive syndrome (HHS) is de-
scribed in patients with unilateral renal artery stenosis. Acti-
vation of the renin-angiotensin-aldosterone system on the
kidney with stenosis leads to hyperfiltration, pressure diuresis
and natriuresis on the contralateral kidney. Patients are at risk
for hypertensive emergency and usually present with polyuria,
polydipsia, headaches and a variety of neurological symp-
toms. Laboratory findings usually include hyponatremia, hy-
pokalemia, hypochloremic alkalosis and proteinuria, which
can sometimes be in the nephrotic range [22]. Four children
were reported recently who presented with HHS and whose
symptoms resolved after percutaneous angioplasty of the renal
artery stenosis [22]. Of the four patients, three had hyperten-
sive crisis.
Evaluation
Initial evaluation includes a detailed history and physical
examination focusing on the presenting symptoms. Older
patients may report headaches, nausea/vomiting, vision com-
plaints and focal neurologic deficits such as facial palsy.
Infants and toddlers may present with nonspecific symptoms
such as poor feeding and lethargy or seizures. As part of the
history, it is important to ask about possible head trauma. In
addition to hypertension, patients with increased intracranial
pressure may have bradycardia and irregular breathing or
apnea. This should be identified before instituting antihyper-
tensive treatment, as the primary goal in these patients is to
maintain cerebral perfusion and dropping their BP could result
in devastating cerebral consequences.
An initial brief assessment of the patient should include
palpation of peripheral pulses and measurement of the BP in
the four extremities, assessment of the patient’s mental status,
presence of tachypnea and rales on auscultation of the chest,
456, Page 4 of 8
presence of gallop rhythm, jugular venous distention, periph-
eral edema, abdominal bruit and abdominal mass. An oph-
thalmoscopic examination should be done for papilledema,
hemorrhagic exudates and spasm or tortuosity of the retinal
arteries.
The clinical presentation of the patient may give clues to
the underlying diagnosis. Patients with catecholamine-
producing tumors may have a history of palpitations, sweating
and flushing. Hyperthyroidism may be suspected if the patient
exhibits exophthalmos, tachycardia, diarrhea or weight loss.
Patients with neuroblastoma or Wilms’ tumor may have a
palpable mass on examination of the abdomen. Palpable
masses can also be identified in infants with polycystic kidney
disease or obstructive uropathy. Fluid overload should be the
first suspicion in patients with a history of end-stage renal
disease or in patients who have symptoms suggestive of acute
glomerulonephritis. An abdominal bruit may be heard in
patients with renovascular hypertension. Coarctation of the
aorta should be suspected when there are delayed or weak
femoral pulses or lower BP readings in the lower compared to
the upper extremities. Cushing syndrome should be suspected
in patients with moon fascies, truncal obesity, striae and
hirsutism.
Laboratory and imaging evaluation initially should include
a complete blood count, electrolytes, renal function, urinaly-
sis, a chest radiograph, electrocardiogram, echocardiogram
and renal ultrasound. After the patient has been stabilized
and BP improved, more detailed evaluation should continue
depending on the suspected etiology of hypertension based on
the history and physical examination. Other investigations
depend on the suspected cause for hypertension.
Management
Figure 1 proposes an algorithm for the management of hyper-
tensive emergency in children. Hypertensive emergency is an
indication for hospitalization for gradual lowering of BP and
close patient monitoring. Patients are best managed in an
intensive care unit. There have been no randomized controlled
trials on the use of antihypertensive medications in the treat-
ment of hypertensive emergency in children. Therefore, deci-
sions on which antihypertensives to use are based on adult
literature, pediatric observational studies, and personal or
institutional experience.
Treatment should be instituted immediately in severely
hypertensive children to decrease end-organ damage. Flynn
et al. [23] proposed an initial bolus dose of intravenous (IV)
hydralazine or labetalol, followed by nicardipine or labetalol
infusion. The goal of antihypertensive treatment is to reduce
the blood pressure by ≤25 % in the first 8 h after presentation,
followed by gradual normalization of the blood pressure over
the next 26-48 h [3].
Curr Hypertens Rep (2014) 16:456
Table 2 summarizes the most commonly used intravenous
antihypertensive medications in hypertensive emergency.
First line intravenous agents include nicardipine [24], labetalol
and esmolol, which are usually administered continuously as
drips, and hydralazine, which is given as intermittent doses
[25•]. Nicardipine, a relatively newer agent, is commonly used
in hypertensive emergency in children [26]. It is a calcium
channel blocker that induces vascular smooth muscle re-
laxation and vasodilation, mainly in the arteries. It is safe,
effective and well tolerated with the most common side
effect reported to be tachycardia. Another reported side
effect is thrombophlebitis [27].
Labetalol is a β and α1 blocker. Its main antihypertensive
effect when administered intravenously in severe hyperten-
sion is vasodilation [23], and it has the advantage of not
causing reflex tachycardia, which is a common side effect of
other vasodilators (nitroprusside, nicardipine and hydralazine)
[25•]. Thomas et al. compared labetalol to nicardipine and
nitroprusside infusions in 27 patients less than 2 years of age
with hypertensive crisis [28••]. Labetalol was efficacious, and
similar reductions in BP were obtained compared to the other
antihypertensives. In patients with traumatic or ischemic brain
injury, labetalol had to be discontinued because of hypoten-
sive events; however, it was found to be safe in the rest of
patients. This study found that the blood pressure-lowering
effect of labetalol continued up to doses of 0.59 mg/kg/h, with
little additional effect with higher doses. This was attributed to
a slower rate of metabolism due to the lack of maturation of
metabolic pathways in young children and to a lower volume
of distribution of lipophilic drugs in such patients [28••]. The
other beta-blocker that is used as a continuous infusion is
esmolol. It is a cardioselective β1 blocker with an immediate
onset of action and short half-life. It is typically used for
hypertension intraoperatively [23]. At high doses it loses its
selectivity and can activate β2 receptors, which can cause
bronchoconstriction [25•].
Hydralazine is a direct vasodilator of smooth muscle in the
arteries. It is administered as an IV or intramuscular bolus. Its
peak action occurs at 10–80 min after IV administration [23].
Hydralazine stimulates the sympathetic nervous system with
resulting tachycardia and activation of the renin-angiotensin-
aldosterone system [25•]. Therefore, it is typically used as a
single initial dose before infusion of a different antihyperten-
sive drug is started [25•]. The advantage of being able to
administer it by the intramuscular route makes it a great initial
option for the presenting child with hypertensive emergency
before IV access has been secured [23].
Sodium nitroprusside is reportedly one of the most exten-
sively used drugs in pediatric hypertensive emergency [25•].
Its mechanism of action is vasodilation of both arterial and
venous vascular beds via nitric oxide. With high infusion rates
and prolonged infusions, it has the potential risk of cyanide
and thiocyanate toxicity, especially if there is hepatic
Curr Hypertens Rep (2014) 16:456 Page 5 of 8, 456

Fig. 1 Management of
hypertensive emergency in • Rule out head injury
• Assess mental status, signs of CHF, papilledema, focal neurologic deficits
children. CHF congestive heart • Obtain IV line and give bolus of hydralazine or labetalol
failure, CBC complete blood • If unable to obtain IV, give IM hydralazine
count, ECG electrocardiogram,
ED
• Anticonvulsants for seizures
BP blood pressure, HTN • Obtain initial workup: CBC, chemistry, urinalysis, ECG, chest radiograph
hypertension • Repeat bolus of hydralazine or labetalol if needed

• Obtain intra-arterial line if possible

• Start nicardipine or labetalol continuous drip
• Aim to reduce BP by 25% in the first 8 hours
• Throrough history and physical examination to establish possible underlying

PICU
cause
• Continue laboratoy and imaging workup depending on suspected etiology
• Once patient is stabilized, transition to oral antihypertensive

• Titrate oral antihypertensive aiming to decrease blood pressure to <90th

percentile
• Continue workup of HTN

Wards • Educate patient on lifestyle modifications if needed

(cyanide) or renal (thiocyanate) dysfunction [25•]. A recent However, the patients in this study were on nitroprusside for a
case-control study looked at the use of nitroprusside during mean of about 2 h only [29]. The risk of cyanide accumulation
surgery in children to induce hypotension. This study did not has resulted in this medication falling out of use, especially
find high cyanide levels or presence of metabolic acidosis. with other less toxic options available.

Table 2 Intravenous medications for hypertensive emergency in children

Medication Mechanism Dose Onset Duration Comments

Nicardipine Calcium channel blocker, 0.2–0.5 mcg/kg/min 1–2 min 30 min–4 h Clearance decreased with
peripheral arterial (Max: 3 mcg/kg/min) hepatic dysfunction, reflex
vasodilation tachycardia is common
Labetalol Beta-1, beta-2 and Bolus: 0.2–1 mg/kg 2–5 min 2–6 h May cause hyperkalemia,
alpha-1 blocker (max: 20 mg) bronchospasm in patients
Infusion: 0.25–1 mg/kg/h with asthma, left ventricular
(max: 3 mg/kg/h) failure is a relative
contraindication
Esmolol Beta-1 blocker Bolus: 100–300 mcg/kg IV Immediate 10–30 min Causes bradycardia,
(off label use) over 2 min (max: 500 mcg/kg); loses beta-1 selectivity at
infusion: 50–250 mcg/kg/min high doses and may
(max: 1000 mcg/kg/min) cause bronchospasm
Hydralazine Direct vasodilation in 0.1 – 0.2 mg/kg/dose q 4-6 h PRN 5–30 min 1–4 h May cause reflex tachycardia,
arterioles (max: 0.6 mg/kg or 20 mg) flushing, lupus-like syndrome
Enalaprilat Angiotensin-converting 5 – 10 mcg/kg/dose 4–6 h May cause acute kidney
enzyme inhibition injury and prolonged
hypotension.
Avoid in patients with
GFR<30 ml/min/1.73 m2
456, Page 6 of 8
Enalaprilat, the intravenous angiotensin-converting en-
zyme (ACE) inhibitor, could be considered for select patients,
especially for children thought to have renin-mediated hyper-
tension. Clinicians should be cautious, however, as children
with hypertensive emergency could have renovascular hyper-
tension as the underlying etiology. In this situation use of ACE
inhibitors could cause decreased renal perfusion and acute
kidney injury. For this reason enalaprilat is not the best initial
option, especially when the cause of hypertension is
unknown.
Oral agents are mainly used for hypertensive urgency, and
the ones most commonly used include clonidine, isradipine
and minoxidil [25•]. Although some might include oral hy-
dralazine as a good option [30, 23], in the authors’ experience,
oral hydralazine is not very effective in reducing severe hy-
pertension. Additional oral agents are captopril, labetalol and
prazosin [23]. The use of short-acting nifedipine is controver-
sial in children because of its potency in inducing a rapid
reduction of BP [25•]. The concerns are related to a potential
large drop in BP that can result in decreased perfusion to the
heart, brain and other organs. Studies on the use of short-
acting nifedipine in children are old and retrospective. Blaszak
et al. found no adverse events and noted that doses
<0.25 mg/kg were safe [31], while Egger et al. reported
neurologic events after administration of nifedipine, especial-
ly in children with central nervous injury [32]. Although some
institutions use nifedipine for hypertensive urgency in
children [6•], in view of the concerns and the availability
of several other safe and effective options, it is best to
prefer a different medication. Isradipine has an onset of
action of 1 h and peak of 2–3 h, and a suspension can be
compounded. It was studied in a retrospective group of
children with acute hypertension and found to be effective
for reduction of BP [33].
Specific Antihypertensive Treatment
At our institution, children with catecholamine-producing
tumors are treated initially with phenoxybenzamine for alpha
blockade, followed by the addition of a beta-blocker. In the
absence of cardiac or renal dysfunction and once BP has been
controlled, patients are instructed to keep a high sodium diet to
expand the catecholamine-induced volume contraction. Beta-
blockers should be used with caution, as chronic catechol-
amine excess can result in cardiomyopathy that may become
evident with the use of beta-blockers. A short-acting IV anti-
hypertensive is used intraoperatively when the tumor is
removed.
Early on, patients with hypertensive emergency or hyper-
tensive urgency due to hypertension caused by fluid over-
load benefit from furosemide. This mainly includes patients
with intrarenal pathology such as acute glomerulonephritis.
If the patient has oliguric/anuric acute kidney injury, there
Curr Hypertens Rep (2014) 16:456
might not be any response to diuretic treatment; other anti-
hypertensives should be used concomitantly, and dialysis may
be needed.
Hypertension caused by cocaine or amphetamine drug use
can be treated with lorazepam, which is usually effective for
both agitation and high BP. If the patient has hypertensive
emergency, phentolamine should be used in combination with
lorazepam. [34•]. Beta-blockers as single therapy should
not be used because blockade of vasodilatory peripheral
beta-receptors with unopposed alpha-adrenergic receptor
stimulation will worsen hypertension. In adults, guidelines
suggest that combined alpha and beta blockers can be used
if the patient has received a vasodilator within the previous
hour [35].
Conclusion
Hypertensive emergency is infrequent in children. End organ
damage should be identified quickly and treatment instituted
immediately as this is a life-threatening condition. Patients
should be managed in an intensive care unit until the BP has
been stabilized as they require close monitoring for titration of
antihypertensive medication with BP decrease. The published
literature on hypertensive emergency in pediatric patients is
incomplete and outdated. More studies are needed, including
studies of antihypertensive treatment, as several of the medi-
cations used do not have Food and Drug Administration
approval for use in pediatrics and are used based on experi-
ence in adults.
Compliance with Ethics Guidelines
Conflict of Interest Rossana Baracco declares that she has no conflict
of interest.
Tej K. Mattoo has received grants from NIH/NIDDK and honorarium
payments from UpToDate.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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in collaboration with the American College of Emergency by the American Association of Cardiovascular and Pulmonary
Physicians, the Society fo Cardiovascular Angiography and Rehabilitation and the Society for Academic Emergency
Interventions, and the Society of Thoracic Surgeons: endorsed Medicine. Circulation. 2007;116:803–77.