NEONATAL HYPERTENSION

MARIFI DE JESUS U. CABALUNA, MD PL-2 NOVEMBER 28, 2006

QUESTIONS TO BE ANSWERED
What is the proper way of obtaining BP in the neonate? Does the device used in getting the BP matters? What is the primary determinant of BP in both Term and Preterm infants?

QUESTIONS TO BE ANSWERED
What are the common causes of Hypertension among the neonates? Does catheter tip placement play a role in the incidence of Hypertension among the neonates? What are the RED FLAGS in history and PE that points to neonatal hypertension?

QUESTIONS TO BE ANSWERED
What initial laboratory studies are important? Who should receive treatment ? How do we choose a suitable agent? Are there any medications to avoid? Long term outcome and prognosis depend on which factor?

DEFINITION
Systolic and/or diastolic BP >/= 95% (> 2 SD above the mean) Stage 1 : BP at 95 to < 99 % Stage 2 : BP >/= 99% + 5 mm Hg

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.

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

BLOOD PRESSURE MEASUREMENT

Wait 15 minutes or more of stillness 3 successive readings at 2-minute interval.

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.

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

BLOOD PRESSURE MEASUREMENT

Leg pressures are higher than arm pressures
Normal BP increases with gestational age, post-conceptual age and birthweight.

BLOOD PRESSURE MEASUREMENT

Zubrow et al (695 PT infant) D1 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

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

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
Birthweight Gestational age Postconceptual age

BLOOD PRESSURE MEASUREMENT

Postconceptual age/Postmenstrual age (GA + postnatal age) primary determinant of BP in this population
RECOMMENDATION BP consistently > 95% confidence limit by ZUBROW CURVES.

THE ZUBROW CURVE

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

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

INCIDENCE
More common in patients with certain diagnoses : BPD 6 % PDA 3 % IV hemorrhage 3 % Umbilical catheterization 9 %

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

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.

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

CAUSES OF NEONATAL HYPERTENSION

RENAL ARTERY STENOSIS caused by fibromuscular dysplasia if present there also may be midaortic coarctation and cerebral vascular stenosis may be due to congenital rubella

CAUSES OF NEONATAL HYPERTENSION

RENAL VEIN THROMBOSIS Hypertension gross hematuria abdominal/flank mass thrombocytopenia

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

CAUSES OF NEONATAL HYPERTENSION

ACQUIRED RENAL DISEASE ATN/Interstitial nephritis/cortical necrosis
due to volume overload/hyperreninemia

HUS Obstruction by a tumor

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

CAUSES OF NEONATAL HYPERTENSION

COARCTATION OF THE AORTA early repair improves the long term outcome hypertension may persist even after surgical repair

CAUSES OF NEONATAL HYPERTENSION

ENDOCRINE seizures and increased intracranial pressure are common causes of episodic hypertension CAH HYPERALDOSTERONISM HYPERTHYROIDISM

CAUSES OF NEONATAL HYPERTENSION

IATROGENIC NICU meds
Dexamethasone Theophylline Caffeine Pancuronium Phenylephrine

Prolonged TPN

Under treatment of pain

lead to salt and water overload/hypercalcemia

CAUSES OF NEONATAL HYPERTENSION

MATERNAL CAUSES Cocaine use
harm the developing kidneys

Heroine use
with neonatal withdrawal

CAUSES OF NEONATAL HYPERTENSION

NEOPLASMS
from compression of renal vessels and ureters production of vasoactive substances

Neuroblastoma Wilms tumor Mesoblastic nephroma

CAUSES OF NEONATAL HYPERTENSION

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

EVALUATION
Life-threatening presentation
CHF Cardiogenic shock Seizures

Presentation of less ill infants

feeding difficulties unexplained tachypnea lethargy, apnea, irritability mottling of the skin

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

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

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

LABORATORY EXAMINATIONS
Urinalysis CBC Electrolytes, BUN, Crea, Ca Urine culture if UTI is suspected Plasma renin level significantly elevated level indicates renovascular disease

LABORATORY EXAMINATIONS
Additional tests Thyroid studies VMA/Homovanillic acid Aldosterone Cortisol

IMAGING STUDIES
CXRay/2D echo CHF US of genitourinary tract
should be performed in all hypertensive infants to rule out UPJ obstruction, renal vein thrombosis

Doppler flow studies Abdominal/pelvic US VCUG

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

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.

MANAGEMENT
RECOMMENDATION Asymptomatic /Mild Hypertension (Systolic 95th to < 99th %)
observation resolves in time

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

antihypertensive therapy

MANAGEMENT
Address correctible causes of hypertension
treat pain correct volume overload wean inotropic infusion

Choose a suitable agent

depends on specific clinical situation

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 BPs. allows titration for desired effect

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

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.

TREATMENT
NITROPRUSSIDE potent vasodilator rapid onset of action short duration of effect complications : hypotension and thiocyanate toxicity.

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.

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

TREATMENT
HYDRALAZINE peripheral vasodilator relaxes vascular smooth muscle

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)

TREATMENT CAPTOPRIL
Drug of choice

ACE inhibitor .017 mg/kg/dose PO BID TID Extremely low doses (0.01 mg/kg/dose or 0.03 mg/kg/day) may be effective in newborns

TREATMENT CAPTOPRIL
more potent in newborns than older children because of higher renal vascular resistance longer duration of action

TREATMENT
BETA BLOCKER
effective in newborns side effects uncommon avoided in infants with BPD because of bronchoconstriction

TREATMENT
DIURETICS reduce extracellular and plasma volume use in newborns limited to mild hypertension resulting from fluid overload or as an adjunctive medication.

TREATMENT (UPTODATE)
IV Enalapril IV administered ACE inhibitor effective in renovascular hypertension has been used successfully in newborns lowest dose should be tried first

TREATMENT (NeoReviews)
IV Enalapril avoided because of its unpredictable antihypertensive efficacy and potential to cause oligoanuria via blockade of the renin-angiotensin axis.

TREATMENT
Surgical correction
CoA UPJ obstruction

Medical management + surgery

Renal artery stenosis

Nephrectomy
Polycystic kidney disease

Chemotherapy + surgery
Wilms tumor and Neuroblastoma

PROGNOSIS
depends on the cause often resolves over time persistent

recurrent

polycystic kidney disease renal parenchymal disease renal vein thrombosis require nephrectomy restenosis of renal artery stenosis or CoA after repair

REFERENCES
Ettinger, Leigh et al : Neoreviews Vol 3 No.8. 2002 Fanaroff, Jonathan, et al. Blood pressure disorders in the Neonate : Hypotension and Hypertension. Seminars in Fetal and Neonatal Medicine Vol 11. No. 3, June 2006, 174-181. Ettinger, Leigh et al : Neoreviews. Vol 3 No. 8, 2002 Neonatal Hypertension : Uptodate.2006 Neonatal Hypertension : Emedicine. August 29, 2006 Sondheimer, Judith M. (editor) : Current Pediatric Diagnosis and Treatment. 16th ed. McGraw-Hill Companies,2003

THANK YOU AND GOOD MORNING