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.
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 mid- aortic 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 • lead to salt and water overload/hypercalcemia • Under treatment of pain
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 • Wilm’s 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 BP’s. • 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