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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