Hypertensive crisis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has hypertensive crisis? What are the typical findings for this disease?

A hypertensive urgency is when a patient is asymptomatic with elevated BP and without evidence of target organ damage. If untreated, the patient can develop target organ damage imminently, leading to a hypertensive emergency.

A hypertensive emergency is when a patient has elevated BP (often Stage 2 or greater) with evidence of target organ damage.

Patients may present with:

• Headache

• Nausea

• Vomiting

Commonly affected organs/systems include:

• Central Nervous System

  Findings include: Hypertensive encephalopathy, subarachnoid or intracerebral hemorrhage

  Symptoms include: seizures, altered mental status (lethargy, coma, confusion), change in behavior, facial nerve palsy, hemiplegia

• Kidney

  Findings include: renal insufficiency/failure

  Symptoms include: flank pain, dysuria, hematuria, frothy or tea-colored urine, oliguria/anuria

  Note: often renal disease is the cause of hypertension in children, but rarely hypertension in children can lead to kidney damage as described above

• Cardiovascular System

  Findings include: congestive heart failure

  Symptoms include: tachypnea, shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, edema, S3 or S4, new or changed heart murmur

• Eye

  Findings include: papilledema, retinal hemorrhages, exudates

  Symptoms include: visual changes, deficits in peripheral vision

Definition of hypertension

A child is diagnosed with hypertension when his or her BP measured via manual auscultation is at or above the 95th percentile for his/her age, sex and height percentile. The normative values used were compiled from over 60,000 healthy children in the United States, and a table that lists the sex-, age- and height percentile-specific 50th, 90th, 95th and 99th percentile systolic and diastolic BPs was published in Pediatrics in August 2004 (PUBMED:15286277).

It is important to recognize that hypertension is defined by an elevated systolic ORdiastolic blood pressure – both systolic and diastolic blood pressures do not need to be elevated to diagnose a child with hypertension. Additionally, hypertension is defined as the sustained elevation of blood pressure, which in children requires documentation of multiple elevated BP values on three separate occasions, with the average of all measurements > 95th percentile. Referral to care and initiation of work up is determined by degree of blood pressure elevation and the presence of symptoms.

• Normal Blood Pressure: Both systolic and diastolic BPs are less than the 90th percentile.

• Prehypertension: Systolic and/or diastolic BP is between the 90th percentile and the 95th percentile, or between 120/80 and the 95th percentile if 120/80 happens to be higher than the reported 90th percentile for the individual child based on his/her age, sex, and height percentile.

• Stage I Hypertension: Systolic and/or diastolic BP between the 95th percentile and the 99th percentile PLUS 5 mmHg (ie, if the reported 99th percentile for the child’s age, sex and height percentile is 75 mmHg, the upper limit of this stage of hypertension would be 80 mmHg).

• Stage II Hypertension: Systolic and/or diastolic BP above the 99th percentile + 5 mmHg.

How do I measure blood pressure? How do I know if I have the right cuff size?

Any blood pressure above the 90th percentile should be confirmed with a measurement conducted via manual auscultation. Automated devices, while can be useful as screening tools, can be inaccurate and not uniform across devices. However, an advantage to these devices in the management of hypertensive crises is their ability to be programmed to take repeated/frequent measurements.

Proper BP measurement requires that the patient’s:

• Arm is supported

• Feet are supported

• Back is supported

• Cubital fossa is at heart level

It is also imperative that the measurement be taken after FIVE minutes of rest, the cuff is applied to the child’s bare arm and that the correct cuff size is used. An inappropriately small cuff will give a reading that is higher than the actual BP. When in doubt, because the cuff bladder (easily felt inside of the cuff) is often much smaller than the cuff itself, choose a larger cuff.

The blood pressure cuff that is chosen should be measured against the child’s arm. The following conditions should be met:

• The bladder width should encircle at least 40% of the child’s mid-arm circumference.

• The bladder length should encircle 80-100% of the mid-arm circumference.

There are several factors that can lead to inaccurate blood pressure estimation. These are summarized in Table I.

Table I.n

What caused this disease to develop at this time?

Hypertensive crises are thought to occur secondary to the following:

• Loss of autoregulation

• Primary or secondary renin release

• Oxidative stress

• Endothelial dysfunction

Loss of autoregulation: Under normal conditions, when an individual experiences mild to moderate blood pressure elevations, autoregulatory mechanisms lead to arterial and arteriolar vasoconstriction. This constriction of the vasculature serves to maintain tissue perfusion at a constant level and prevents transmission of elevated pressure to smaller vessels.

When blood pressure is elevated above the “autoregulatory zone” (Figure 1.), autoregulation fails, blood pressure increases in the smaller vessels, and vascular wall damage occurs. Ultimately, the vascular endothelium is disrupted and damaged and the lumen narrows or becomes obliterated. These changes cause tissue edema, vasoconstriction, and tissue ischemia. When occurring in the brain, this results in cerebral edema and hypertensive encephalopathy.

Figure 1.

The blood pressure threshold at which autoregulation fails is dependent on the individual’s baseline BP. Normotensive children who experience an increase in BP may manifest target organ damage at a lower absolute and percentile of BP than a child who is chronically hypertensive. This is because chronically hypertensive children manifest arteriolar thickening, an adaptive response that serves to further minimize transmission of blood pressure elevations to the smaller blood vessels. As such, their “autoregulatory zone” ranges over higher values of blood pressure, and they will experience hypertensive sequelae at higher BPs (gray dotted line in Figure 1.).

This is important to remember, because just as blood pressure increases above the upper limit of the “autoregulatory zone” can lead to adverse events, lowering BP below the lower limit of this zone can lead to tissue hypoperfusion, and can have adverse events as significant as cerebral ischemia. See the section on treatment for guidance regarding proper treatment and goals of initial therapy.

Renin release: The renin-angiotensin-aldosterone system leads to hypertension via multiple pathways. Angiotensin II, in addition to causing direct vasoconstriction, increased NaCl and water reabsorption in the renal tubules directly and via the secretion of aldosterone and increased sympathetic activity, it also increases NADPH and proinflammatory cytokines. Angiotensin II also increases the presence of adhesion molecules such as VCAM-1 and ICAM-1 which lead to an increase in activated T-cell recruitment. This leads to the generation of reactive oxygen species, inflammation, vascular smooth muscle cell proliferation and endothelial damage, ultimately resulting in cytotoxicity and tissue ischemia.

Oxidative stress: Hypertension can lead to increased levels of reactive oxygen species such as superoxide, hydrogen peroxide and peroxynitrite, which can lead to vasoconstriction, vascular and cardiac hypertrophy and kidney insufficiency. Nitric oxide, a potent antihypertensive that causes endothelium-dependent relaxation, preferentially degrades superoxide. As levels of superoxide increase, the levels of nitric oxide decrease which can inhibit vasodilatation and further exacerbate existing hypertension.

Endothelial dysfunction: This occurs as a result of the combined effects of BP elevation, renin release and increased oxidative stress. Vasoconstriction, coagulation cascade activation and inflammation of the perivasculature are typical characteristics of endothelial dysfunction.

The combination of the events described above lead to vascular obstruction, target organ damage and severe elevation in blood pressure. When the coagulation cascade is activated, microangiopathic hemolytic anemia can result.

Clinical assessment:

The initial approach to a child with a severely elevated blood pressure should always include a repeat measurement done by manual auscultation utilizing proper technique, in a calm environment. Often, a child’s blood pressure will decrease without intervention when in a calm, quiet room.

After confirming blood pressure elevation, one should aim to quickly determine the etiology and assess for the presence of target organ damage. Important history and physical exam components include:

• History:

  Head injury?

  Occult injury (i.e. child abuse)?

  Prior history of hypertension or treatment of hypertension?

  Is the measured blood pressure consistent with prior blood pressure measurements in children with longstanding hypertension, or is this an acute increase in blood pressure from baseline?

  Did the child abruptly stop a prescribed beta-blocker or alpha-adrenergic agonist (i.e. clonidine)? This can lead to severe rebound hypertension.

  Did the child recently stop another prescribed anti-hypertensive medication? Poor adherence to anti-HTN meds is the #1 cause of accelerated HTN in adults

  Medications – both prescribed and over the counter

  Pseudoephedrine, corticosteroids, oral contraceptives, calcineurin inhibitors

  Pain assessment

  Pregnancy?

  Urinary changes?

  Bloody, tea-colored, or foamy urine?

  Decreased urine output

  Illicit drug use?

  Cocaine, amphetamines, anabolic steroids, phencyclidine (PCP), MDMA (ecstasy)

  Symptoms concerning for hyperthyroidism

  Tremor, nervousness, palpitations, weight loss, heat intolerance

  Symptoms concerning for catecholamine excess

  Diaphoresis, flushing, headache, palpitations

• Physical Exam:

  Obtain a full set of vital signs, including:

  4-limb blood pressures

  Respiratory rate

  Heart rate

  Oxygen saturation

  Obtain an accurate weight and height, and appropriate percentiles

  Determine the 50th, 90th, 95th and 99th percentile blood pressures for the child’s age, sex and height percentile

  General: assess for growth failure (chronic disease, particularly chronic kidney disease), and assess volume status (i.e. fluid overload as would be seen in renal or heart failure).

  Fundoscopic exam: evaluate for papilledema, retinal hemorrhage, exudates, cotton wool spots, AV nicking

  Papilledema, retinal hemorrhage, or exudates may be the only sign of a hypertensive emergency

  The presence of papilledema should prompt investigation and treatment of increased intracranial pressure; lowering the blood pressure in individuals with increased intracranial pressure is contraindicated.

  HEENT: Evaluate for signs of head trauma:

  Contusions or lacerations

  Palpable skull defect

  Hemotympanum

  Evaluate for hyperthyroidism:

  Exophthalmos

  Thyromegaly

  Cardiovascular exam: Evaluate for the presence of the following:

  Additional heart sounds

  Tachycardia

  Displaced apical pulse

  Strong femoral pulse

  Pulmonary exam: Evaluate for the presence of the following:

  Accessory muscle use

  Crackles

  Wheeze

  Abdominal exam: Assess for hepatomegaly, bruits (which could point toward renal artery stenosis), mass

  Extremity exam: A ssess for edema and assess peripheral perfusion

  Neurologic exam: Perform a full neurologic exam, including a mental status evaluation

  Skin exam: Evaluate for signs of systemic diseases such as:

  Neurofibromatosis

  Cafe au lait spots, axillary freckling, neurofibromas

  Tuberous sclerosis

  Ash leaf patches, angiofibromas

  Also evaluate for signs of child abuse:

  Bruising

  Fractures

  Retinal hemorrhage

  Evaluate for presence of a toxidrome

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The evaluation of a child experiencing a hypertensive crisis should be focused, with the goal of determining the presence of target organ damage, conditions requiring emergent intervention, and ruling out causes in which blood pressure lowering is contraindicated. Once the patient is stabilized, a more thorough and controlled evaluation should be conducted to determine the underlying etiology. The scope of this text will be to describe the initial evaluation of a child in hypertensive crisis; please see the chapter on pediatric hypertension for a more thorough description of the full work up of pediatric hypertension.

Initial laboratory examinations should include:

• Urinalysis with microscopy, urine culture

• Serum electrolytes, calcium, BUN and creatinine

• Complete blood count to rule out anemia which can be seen in renal failure and rheumatological disease

• Urine toxicology screen (if suspected)

• Urine pregnancy test in all postmenarchal females to rule out preeclampsia

Additionally, one should consider a chest x-ray and EKG to evaluate for cardiac hypertrophy and congestive heart failure. If immediately available, an echocardiogram should be performed to better evaluate heart function and size.

Would imaging studies be helpful? If so, which ones?

If the child has any abnormal neurologic finding, or if there is any concern for head trauma or increased intracranial pressure, the child should have Computed Tomography (CT) of the head to evaluate for cerebral edema, intracranial hemorrhage, cerebrovascular accident, or mass lesion. If any of these findings are present, the child’s blood pressure should NOT be lowered, as the increased blood pressure is necessary for adequate cerebral perfusion.

In addition, children with headache, altered mental status, vision changes and/or seizures may have posterior reversible encephalopathy syndrome (PRES). This typically reversible condition seen with hypertensive encephalopathy can be diagnosed by magnetic resonance imaging (MRI) using T-2 weighted images which demonstrate edema in the white matter of the parieto-occipital regions of the brain.

Once the child is stabilized, a more thorough evaluation including a renal ultrasound should be conducted. Please see the chapter on pediatric hypertension for the full work up of a child with hypertension (link HTN).

If you are able to confirm that the patient has hypertensive crisis, what treatment should be initiated?

After ruling out conditions in which it would be contraindicated to decrease the blood pressure (increased intracranial pressure, coarctation of the aorta), prompt treatment is indicated.

If the etiology of the hypertensive urgency or emergency is related to severe pain, appropriate pain control should be the first goal of therapy. If the child remains hypertensive despite adequate analgesia, then anti-hypertensive agents should be considered.

In cases where the etiology is related to the ingestion of sympathomimetic agents, appropriate initial treatment should be focused on treating the intoxication (i.e. benzodiazepine and phentolamine administration for a child who has overdosed on cocaine). If hypertension persists despite this, treatment with an antihypertensive is warranted.

Initial therapy may vary depending on if the child presents with target organ damage.

Children presenting with hypertensive urgency should have their blood pressure lowered, but there is no clear consensus as to how quickly to lower their blood pressure. Particularly, in asymptomatic children with severely elevated blood pressure, there is no proven benefit to rapid reduction of blood pressure.

For children who have a history of chronic hypertension, increasing the dose of their chronic antihypertensive medication, or adding a new antihypertensive to their home regimen, is a standard approach. In chronically hypertensive patients who have been non-compliant in taking their prescribed medication, restarting these medications is the preferred course of action.

Hypertensive children with end stage renal disease who are on dialysis can be treated with increased fluid removal via hemodialysis or peritoneal dialysis.

Children who are newly diagnosed with hypertension presenting with a hypertensive urgency can be treated either with intravenous or oral antihypertensive medications, depending on the presence/absence of symptoms. In situations where the blood pressure elevation occurred over a short period of time and is related to an acute process such as post-infectious glomerulonephritis, intravenous therapy is appropriate. Oral medications are most appropriate in children who have experiences a more gradual increase in their blood pressure due to a chronic disease, such as chronic kidney disease (See Table II).

n

However, a child with a hypertensive emergency who does not have increased intracranial pressure or coarctation of the aorta should have emergent reduction in his or her blood pressure with an intravenous antihypertensive medication.

When initiating antihypertensive therapy for a child in hypertensive crisis, the goal should be to reduce the blood pressure by no more than 25% of the planned blood pressure reduction over the first 8 hours. The rationale for this gradual reduction in blood pressure is to avoid tissue hypoperfusion that may occur due to autoregulation. Dropping the blood pressure below the lower limit of this “autoregulatory zone” could lead to cerebral infarct and/or underperfusion of other vital organs leading to a myocardial infarction, visual defects or renal failure.

After initiation of this therapy in the emergency department, the child should be cared for in the intensive care unit where he or she can be closely observed and managed. Over the next 8-12 hours, the blood pressure should be lowered further by 25% of the planned reduction, with goal of complete normalization over the next 24 hours.

The intravenous route is preferred for this initial therapy because it is easier to titrate the dose. Usual therapy consists of an IV bolus of labetalol or hydralazine, followed by a continuous intravenous infusion of an antihypertensive medication (See Table II). In children who are severely symptomatic, intraarterial blood pressure monitoring is indicated.

Once the blood pressure has normalized, often the child will need to be either started on an antihypertensive medication or have their current antihypertensive regimen intensified. There are many agents available for the chronic outpatient treatment of hypertension; please refer to the chapter on pediatric hypertension for a comprehensive list and description of these agents.

What are the possible outcomes of hypertensive crisis?

The prognosis of children presenting in hypertensive crisis is intrinsically linked to the underlying diagnosis that led to the severe blood pressure elevation. In some instances, it is possible that the child’s blood pressure will return to normal without the need for chronic antihypertensive medications (post-infectious glomerulonephritis, drug intoxication, renal artery stenosis) once the cause itself resolves or is corrected. In other instances, the hypertensive crisis unmasks a more serious disease or condition (intrinsic kidney disease, malignancy, urologic disease, see Table III) that requires long-term antihypertensive therapy, as well as additional therapy to treat the underlying condition.

Table III.n

Children requiring chronic antihypertensive therapy should be followed by a specialist who is comfortable managing hypertension and screening for end-organ damage which can develop over time when blood pressure is not well controlled.

What causes this disease and how frequent is it?

Over the last 35 years, the prevalence of pediatric hypertension has increased from 0.3-1.2% to now 3.2-4.5%. Despite this increasing prevalence, hypertensive urgencies and emergencies remain rare in children, occurring in less than 1% of Emergency Department visits.

While overall primary hypertension appears to on the rise, children presenting in hypertensive crisis will almost always have secondary hypertension. The most common secondary causes are related to the kidney: reflux nephropathy, glomerular disease, renovascular disease, obstructive uropathy, and hemolytic-uremic syndrome being some examples. Other common causes are related to solid organ transplantation, medication non-adherence, or fluid overload (in children receiving chronic dialysis).

Children with hypertensive emergency most often present with hypertensive encephalopathy, in the form of altered mental status or seizure. Less commonly (approximately 25% of the time) they will present with hypertensive retinopathy.

See Table III. Diseases and Conditions associated with severe blood pressure elevation.

Additionally, there are several rare genetic disorders that cause hypertension, and are often associated with electrolyte disorders: Liddle’s syndrome, Pseudohypoaldosteronism type 2 (Gordon’s syndrome), Glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type I), Congenital adrenal hyperplasia (due to 11ß-hydroxylase deficiency), and syndrome of apparent mineralocorticoid excess. For detailed descriptions of these monogenic forms of hypertension, please refer to the chapter on pediatric hypertension.

What complications might you expect from the disease or treatment of the disease?

Children with unrecognized hypertensive emergencies, or those who experience a delay in treatment, may suffer from irreversible end-organ damage. Further, children who have their blood pressure reduced too quickly can also suffer irreversible end-organ damage as rapid reduction can override the autoregulatory mechanisms needed to maintain blood flow to vital organs. Some examples of this irreversible injury include: cerebrovascular accidents, visual impairment or defects, myocardial infarction, and kidney injury.

How can hypertensive crisis be prevented?

Hypertensive crises can only be prevented if children have a known prior diagnosis of hypertension. In these cases, detailed counseling and anticipatory guidance are important in educating children and families on the need for strict adherence to chronic antihypertensive therapy, particularly when prescribed medications that can cause rebound hypertension when abruptly discontinued.

Often, children who present with severely elevated blood pressure had no prior diagnosis of hypertension. This may be related to a myriad of things including recent onset of an acute illness or condition leading to the severe blood pressure elevation, access to care or provider under-recognition of blood pressure elevation, as some examples. Provider adherence to recommended guidelines of measuring blood pressure at each physician visit may help to improve recognition which may lead to earlier diagnosis and treatment.

What is the evidence?

“The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents”. Pediatrics. vol. 114. 2004. pp. 555-76. (This comprehensive report developed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents details the recent evidence leading to the current recommendations regarding hypertension in children. These recommendations for diagnosis, evaluation, and treatment of pediatric hypertension are also provided in this important report.)

Flynn, JT, Tullus, K. “Severe hypertension in children and adolescents: pathophysiology and treatment”. Pediatr Nephrol. vol. 24. 2009. pp. 1101-12. (This comprehensive review provides a summary of the underlying causes and pathophysiology of hypertensive crises in children and discusses various options for pharmacological treatment. It also provides a succinct and clinically useful approach to managing children in hypertensive crisis.)

Baracco, R, Mattoo, TK. “Pediatric Hypertensive Emergencies”. Curr Hypertens Rep. vol. 16. 2014. pp. 456(Another review of hypertensive crises in children that complements the Flynn and Tullus Review, incorporating more recent published data.)

“Harriet Lane Handbook: A Manual for Pediatric House Officers”. 2009. (This important pediatric resource provides additional information regarding dosing, side effects and monitoring of anti-hypertensive therapy.)

Flynn, JT, Bradford, MC, Harvey, EM. “Intravenous Hydralazine in Hospitalized Children and Adolescents with Hypertension”. Journal of Pediatrics. 2015.

Flynn, JT, Ingelfinger, J, Portman, R. Pediatric Hypertension. 2013.

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