HYPERTENSIONNEONATAL HYPERTENSIONMohammad Ilyas, M.D.

Assistant Clinical Professor

University of Florida / Health Sciences Center

Jacksonville, Florida USA

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Outline

1. Definition, Regulation and Pathophysiology

2. Measurement of Blood Pressure, Staging of Hypertension and Ambulatory Blood Pressure Monitoring

3. Evaluation of Primary Versus Secondary

4. Sequel of Hypertension and Hypertension Emergencies

5. Management of Hypertension (Non-Pharmacology versus Drug Therapy)

6. The Relation Between Hypertension: Obesity, Drugs, Stress and Sleep Disorders.

7. Hypertension in Renal diseases and Pregnancies

8. Pediatric, Neonatal and Genetic Hypertension

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QUESTIONS TO BE ANSWERED

1. What is the proper way of obtaining BP in the neonate?

2. Does the device used in getting the BP matters?

3. What is the primary determinant of BP in both Term and Preterm infants?

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QUESTIONS TO BE ANSWERED

1. What are the common causes of Hypertension among the neonates?

2. Does catheter tip placement play a role in the incidence of Hypertension among the neonates?

3. What are the “RED FLAGS” in history and PE that points to neonatal hypertension?

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QUESTIONS TO BE ANSWERED

1. What initial laboratory studies are important?

2. Who should receive treatment ?

3. How do we choose a suitable agent?

4. Are there any medications to avoid?

5. Long term outcome and prognosis depend on which factor?

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DEFINITION

Systolic and/or diastolic BP >/= 95%

(> 2 SD above the mean) Stage 1 : BP at 95 to < 99 % + 5 mm

Hg Stage 2 : BP >/= 99% + 5 mm Hg

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BLOOD PRESSURE MEASUREMENT

Nwankwo et al LBW and PT infants

BP is significantly lower in the prone

than supine position

First reading is significantly higher than

the third reading.

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BLOOD PRESSURE MEASUREMENT

STANDARDIZED PROTOCOL Check blood pressure 1.5 hours

after the last feeding or intervention

Apply appropriately sized cuff 2/3 the length of the limb segment 75% of the limb circumference

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BLOOD PRESSURE MEASUREMENT

Wait 15 minutes or more of stillness

3 successive readings at 2-minute interval.

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BLOOD PRESSURE MEASUREMENT

Intra-arterial catheters most accurate technique placed in aorta or radial artery continuous readings Oscillometric

devices non-invasive ; continuous measure systolic and mean and

calculate diastolic pressure.

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BLOOD PRESSURE MEASUREMENT

INTRA-ARTERIAL CATHETERS VS. OSCILLOMETRIC DEVICES

Low et al (study on 31 newborns) Average oscillometric pressures

significantly

lower than intra-arterial pressures. Systolic lower by 1 mm HG Mean pressure lower by 5.3 mm Hg Diastolic pressure lower by 4.6 mm HG

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BLOOD PRESSURE MEASUREMENT

Leg pressures are higher than arm pressures

Normal BP increases with gestational age, post-conceptual age and birth weight.

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BLOOD PRESSURE MEASUREMENT

Zubrow et al (695 PT infant) Day one Systolic and Diastolic

correlate strongly with BW and GA First 5 days after birth

Systolic increase by 2.2-2.7 mm Hg/day

Diastolic increase by 1.6-2 mm Hg/day regardless of BW and GA

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BLOOD PRESSURE MEASUREMENT

Zubrow et al (695 PT infant)

After 5th Day – more gradual

increments Systolic – 0.24-0.27 mm Hg/day Diastolic – 0 – 0.15 mm Hg/day

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BLOOD PRESSURE MEASUREMENT

Zubrow et al (695 PT infant generated standard curves for mean BP + upper and lower 95% confidence limits regression lines developed based on Birth weight Gestational age Post conceptual age

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BLOOD PRESSURE MEASUREMENT

Post conceptual age, Postmenstrual age (GA + postnatal age) – primary determinant of BP in this population

RECOMMENDATION BP consistently > 95% confidence

limit by ZUBROW CURVES.

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THE ZUBROW CURVE

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INCIDENCE

General NICU population .08% (26/3,179)

NICU admissions 2% ( 20/988) 0.7 to 3 % in three studies

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INCIDENCE

More common in patients with certain diagnoses :

BPD – 6 % PDA – 3 % IV hemorrhage – 3 % Umbilical catheterization – 9 %

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CAUSES OF NEONATAL HYPERTENSION

RENOVASCULAR most common

thromboembolism umbilical artery catheters as theoretical sources

of thomboembolic events

studies established an association between local thrombi and development of hypertension

renal artery stenosis

renal venous thrombosis

compression of renal artery

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CAUSES OF NEONATAL HYPERTENSION

THROMBOEMBOLISM COCHRANE STUDY

analysis of 11 randomized clinical trials

one study using alternate assignments

To compare the incidence of

morbidity and mortality for HIGH Vs. LOW catheter tip placement.

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CAUSES OF NEONATAL HYPERTENSION

HIGH – in the descending aorta above the diaphragm (T6 and T9)

LOW – above the bifurcation but below the renal arteries (L3 and L5)

CONCLUSION High catheter positions caused fewer

ischemic complications and possibly decreased the frequency of aortic thrombosis

Hypertension appears with equal frequency

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CAUSES OF NEONATAL HYPERTENSION

RENAL ARTERY STENOSIS caused by fibromuscular

dysplasia if present there also may be mid-

aortic coarctation and cerebral

vascular stenosis may be due to congenital rubella

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CAUSES OF NEONATAL HYPERTENSION

RENAL VEIN THROMBOSIS Hypertension Gross hematuria Abdominal/flank mass Thrombocytopenia

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CAUSES OF NEONATAL HYPERTENSION

CONGENITAL RENAL DISEASE Polycystic kidney disease

autosomal dominant and recessive enlarged kidney and hypertension

Multicystic-dysplastic kidney disease non-functional

Ureteropelvic junction obstruction Activation of Renin-angiotensin system

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CAUSES OF NEONATAL HYPERTENSION

ACQUIRED RENAL DISEASE ATN/Interstitial nephritis/cortical

necrosis due to volume overload & hyper-

reninemia

HUS Obstruction by a tumor

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CAUSES OF NEONATAL HYPERTENSION

BRONCHOPULMONARY DYSPLASIA 13- 43% of infants develop systemic

hypertension cause unclear : chronic hypoxia severity (greater need for diuretics) of BPD

related to likelihood of developing increased BP.

sickest infant require the closest monitoring

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CAUSES OF NEONATAL HYPERTENSION

COARCTATION OF THE AORTA early repair improves the long

term

outcome hypertension may persist even

after surgical repair

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CAUSES OF NEONATAL HYPERTENSION

ENDOCRINE seizures and increased intracranial

pressure are common causes of

episodic hypertension CAH HYPERALDOSTERONISM HYPERTHYROIDISM

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CAUSES OF NEONATAL HYPERTENSION

IATROGENIC NICU meds

Dexamethasone Theophylline Caffeine Pancuronium Phenylephrine

Prolonged TPN lead to salt and water overload/ hypercalcemia

Under treatment of pain

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CAUSES OF NEONATAL HYPERTENSION

MATERNAL CAUSES Cocaine use

harm the developing kidneys

Heroine use with neonatal withdrawal

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CAUSES OF NEONATAL HYPERTENSION

NEOPLASMS from compression of renal vessels

and ureters production of vasoactive substances

Neuroblastoma Wilm’s tumor Mesoblastic nephroma

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CAUSES OF NEONATAL HYPERTENSION

MISCELLANEOUS CAUSES closure of abdominal wall defect adrenal hemorrhage hypercalcemia ECMO birth asphyxia

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EVALUATION

Life-threatening presentation CHF Cardiogenic shock Seizures

Presentation of less ill infants feeding difficulties unexplained tachypnea lethargy, apnea, irritability mottling of the skin

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EVALUATION

RED FLAGS IN THE HISTORY prenatal exposures to heroin and

cocaine predisposing conditions – BPD, CNS

disorders, PDA, hypervolemia (post BT)

Medications/ Umbilical artery

catheterizations

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EVALUATION

RED FLAGS IN THE PHYSICAL EXAMINATION

BP in lower extremities/non-palpable

femoral pulses – CoA dysmorphic features – CAH/Turner Sy Flank mass – UPJ obstruction Epigastric bruit – renal artery stenosis

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EVALUATION

RED FLAGS IN THE PHYSICAL EXAMINATION

Abdominal distention – obstructive

uropathy, PKD, tumors Peripheral thrombi – UAC related HTN Tachycardia/flushing/LBW -

hyperthyroidism Ambiguous genitalia - CAH

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LABORATORY EXAMINATIONS

Urinalysis CBC Electrolytes, BUN, Crea, Ca Urine culture if UTI is suspected Plasma renin level – significantly

elevated level indicates renovascular disease

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LABORATORY EXAMINATIONS

Additional tests Thyroid studies VMA/Homovanillic acid Aldosterone Cortisol

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IMAGING STUDIES

CX Ray/2D echo – CHF US of genitourinary tract

should be performed in all hypertensive infant to rule out UPJ obstruction, renal vein thrombo.

Doppler flow studies Abdominal/pelvic US VCUG

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IMAGING STUDIES

Radionuclide imaging - Abnormal kidney displays: decreased effective renal plasma flow decreased urine flow rate increased isotope concentration

MRA – gold standard for diagnosis of reno vascular hypertension must be 3 kg

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MANAGEMENT

optimal management uncertain threshold for starting antihypertensive

has not been well defined idiosyncratic responses to certain

drugs due to developmental immaturity of liver and kidney function.

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MANAGEMENT

RECOMMENDATION Asymptomatic /Mild Hypertension (Systolic 95th to < 99th %)

observation resolves in time

Moderate to Severe (Systolic >/= 99th %)

antihypertensive therapy

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MANAGEMENT

Address correctible causes of

hypertension treat pain correct volume overload wean inotropic infusion

Choose a suitable agent depends on specific clinical situation

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TREATMENT

ACUTELY ILL INFANTS continuous IV infusion

intermittently administered agents cause wide fluctuation in BP

PT are at increased risk for cerebral

ischemia and hemorrhage from rapidly falling BP’s.

allows titration for desired effect

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TREATMENT

ACUTELY ILL INFANTS continuous IV infusion

Nicardipine - DOC Nitroprusside Labetalol – cathecholamine and CNS

mediated hypertension

- avoid in BPD

monitor BP Q 10-15 minutes

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TREATMENT

NICARDIPINE calcium channel blocker peripheral vasodilator short half life : 10-15 minutes IV infusion 0.5 mcg/kg/min if normal BP not achieved in 15 minutes increase infusion to max of 3 mcg/kg/min. If still elevated, add Sodium nitroprusside then stop Nicardipine.

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TREATMENT

NITROPRUSSIDE potent vasodilator rapid onset of action short duration of

effect complications : hypotension and

thiocyanate toxicity.

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TREATMENT

LABETALOL combined alpha-1 and beta-blocker rapid onset of action duration of action : 2-3 hours do not cause tachycardia, cerebral

vasodilatation or changes in

intracranial pressure.

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TREATMENT(NeoReviews)

LESS SEVERE HYPERTENSION NOT READY FOR ORAL

Intermittent IV agents Hydralazine Labetalol

sometimes doses at lower end of

recommended range cause significant

hypotension

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TREATMENT

HYDRALAZINE peripheral vasodilator relaxes vascular smooth muscle

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TREATMENT(NeoReviews)

INFANT READY TO BE WEANED FROM IV / READY FOR ORAL

ORAL ANTIHYPERTENSIVE AGENTS Captopril

Diuretic - can be added if captopril is ineffective

B Blocker – should be avoided (BPD)

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TREATMENT

CAPTOPRIL Drug of choice ACE inhibitor 0.017 mg/kg/dose PO BID –TID Extremely low doses (0.01mg/kg/dose

or 0.03 mg/kg/day) may be effective in newborns

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TREATMENT

CAPTOPRIL more potent in newborns

than older children because of

higher renal vascular resistance longer duration of action

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TREATMENT

BETA BLOCKER effective in newborns side effects uncommon avoided in infants with BPD

because of bronchoconstriction

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TREATMENT

DIURETICS reduce extracellular and plasma

volume use in newborns limited to mild

hypertension resulting from fluid

overload or as an adjunctive

medication.

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TREATMENT(UPTODATE)

IV Enalapril IV administered ACE inhibitor effective in renovascular hypertension has been used successfully in

newborns lowest dose should be tried first

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TREATMENT(NeoReviews)

IV Enalapril avoided because of it’s unpredictable

antihypertensive efficacy and potential to cause oligoanuria via blockade of the renin-angiotensin axis.

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TREATMENT

Surgical correction CoA UPJ obstruction

Medical management + surgery Renal artery stenosis

Nephrectomy Polycystic kidney disease

Chemotherapy + surgery Wilm’s tumor and Neuroblastoma

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PROGNOSIS

depends on the cause often resolves over time persistent

polycystic kidney disease renal parenchymal disease renal vein thrombosis – require nephrectomy

recurrent restenosis of renal artery stenosis or

CoA after repair

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REFERENCES

1. Ettinger, Leigh et al : Neoreviews Vol 3 No.8. 2002

2. Fanaroff, Jonathan, et al. Blood pressure disorders in the Neonate : Hypotension and Hypertension.

3. Seminars in Fetal and Neonatal Medicine Vol 11. No. 3, June 2006, 174-181.

4. Ettinger, Leigh et al : Neoreviews. Vol 3 No. 8, 2002

5. Neonatal Hypertension : Uptodate.2006

6. Neonatal Hypertension : Emedicine. August 29, 2006

7. Sondheimer, Judith M. (editor) : Current Pediatric Diagnosis and Treatment. 16th ed. McGraw-Hill Companies,2003

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THANK YOU62