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

NEONATAL NEONATAL HYPERTENSIONHYPERTENSION

MARIFI DE JESUS U. CABALUNA, MDMARIFI DE JESUS U. CABALUNA, MD

PL-2PL-2

NOVEMBER 28, 2006NOVEMBER 28, 2006

QUESTIONS TO BE QUESTIONS TO BE ANSWEREDANSWERED

What is the proper way of obtaining What is the proper way of obtaining

BP in the neonate?BP in the neonate? Does the device used in getting the Does the device used in getting the

BP matters?BP matters? What is the primary determinant of What is the primary determinant of

BP in both Term and Preterm infants? BP in both Term and Preterm infants?


What are the common causes of What are the common causes of

Hypertension among the neonates?Hypertension among the neonates? Does catheter tip placement play a Does catheter tip placement play a

role in the incidence of Hypertensionrole in the incidence of Hypertension

among the neonates?among the neonates? What are the “RED FLAGS” in historyWhat are the “RED FLAGS” in history

and PE that points to neonatal and PE that points to neonatal

hypertension?hypertension?


What initial laboratory studies are What initial laboratory studies are

important?important? Who should receive treatment ?Who should receive treatment ? How do we choose a suitable agent?How do we choose a suitable agent? Are there any medications to avoid?Are there any medications to avoid? Long term outcome and prognosis Long term outcome and prognosis

depend on which factor?depend on which factor?

DEFINITIONDEFINITION

Systolic and/or diastolic BP >/= Systolic and/or diastolic BP >/= 95%95%

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

HgHg

BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT

Nwankwo et alNwankwo et al LBW and PT infantsLBW and PT infants

BP is significantly lower in the BP is significantly lower in the proneprone than than supine supine positionposition

First reading is significantly First reading is significantly higherhigher than than

the third reading.the third reading.


STANDARDIZED PROTOCOLSTANDARDIZED PROTOCOL Check blood pressure 1.5 hours Check blood pressure 1.5 hours

after after

the last feeding or interventionthe last feeding or intervention

Apply appropriately sized cuff Apply appropriately sized cuff 2/3 the length of the limb segment2/3 the length of the limb segment 75% of the limb circumference75% of the limb circumference


Wait 15 minutes or more of Wait 15 minutes or more of stillnessstillness

3 successive readings at 2-3 successive readings at 2-minuteminute

interval.interval.


Intra-arterial catheters Intra-arterial catheters most accurate techniquemost accurate technique placed in aorta or radial arteryplaced in aorta or radial artery continuous readingscontinuous readings

Oscillometric devicesOscillometric devices non-invasive ; continuousnon-invasive ; continuous measure systolic and mean and calculate measure systolic and mean and calculate

diastolic pressure.diastolic pressure.


INTRA-ARTERIAL CATHETERS VS. INTRA-ARTERIAL CATHETERS VS.

OSCILLOMETRIC DEVICESOSCILLOMETRIC DEVICES

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

significantly significantly

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


Leg pressures are higher than armLeg pressures are higher than arm

pressurespressures

Normal BP increases with Normal BP increases with gestationalgestational

age, post-conceptual age and age, post-conceptual age and

birthweight.birthweight.


Zubrow et al (695 PT infant)Zubrow et al (695 PT infant) D1 – Systolic and Diastolic correlateD1 – Systolic and Diastolic correlate

strongly with BW and GAstrongly with BW and GA First 5 days after birth – First 5 days after birth –

Systolic increase by 2.2-2.7 mm Hg/day Systolic increase by 2.2-2.7 mm Hg/day Diastolic increase by 1.6-2 mm Hg/ Diastolic increase by 1.6-2 mm Hg/

day regardless of BW and GA day regardless of BW and GA


Zubrow et al (695 PT infant)Zubrow et al (695 PT infant)

After 5After 5thth Day – more gradual Day – more gradual

incrementsincrements Systolic – 0.24-0.27 mm Hg/daySystolic – 0.24-0.27 mm Hg/day Diastolic – 0 – 0.15 mm Hg/dayDiastolic – 0 – 0.15 mm Hg/day


Zubrow et al (695 PT infant )Zubrow et al (695 PT infant ) generated standard curves for mean generated standard curves for mean BP + upper and lower 95%BP + upper and lower 95% confidence limitsconfidence limits regression lines developed based on regression lines developed based on

BirthweightBirthweight Gestational ageGestational age Postconceptual agePostconceptual age


Postconceptual age/Postmenstrual Postconceptual age/Postmenstrual

age (GA + postnatal age) – age (GA + postnatal age) – primary primary

determinantdeterminant of BP in this population of BP in this population

RECOMMENDATIONRECOMMENDATION BP consistently > 95% confidence BP consistently > 95% confidence

limit by ZUBROW CURVES.limit by ZUBROW CURVES.

THE ZUBROW CURVE

INCIDENCEINCIDENCE

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

NICU admissionsNICU admissions 2% ( 20/988)2% ( 20/988) 0.7 to 3 % in three studies0.7 to 3 % in three studies

INCIDENCEINCIDENCE

More common in patients with More common in patients with certain certain

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

CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION

RENOVASCULARRENOVASCULAR most commonmost common

thromboembolismthromboembolism umbilical artery catheters as theoretical sources umbilical artery catheters as theoretical sources

of of

thomboembolic events thomboembolic events studies established an association between local studies established an association between local

thrombi and development of hypertensionthrombi and development of hypertension

renal artery stenosisrenal artery stenosis renal venous thrombosisrenal venous thrombosis compression of renal arterycompression of renal artery


THROMBOEMBOLISMTHROMBOEMBOLISM COCHRANE STUDYCOCHRANE STUDY

analysis of 11 randomized clinical trialsanalysis of 11 randomized clinical trials one study using alternate assignments one study using alternate assignments

To compare the incidence ofTo compare the incidence of

morbidity and mortality for HIGH Vs. morbidity and mortality for HIGH Vs.

LOW catheter tip placement.LOW catheter tip placement.


HIGH – in the descending aortaHIGH – in the descending aorta above the diaphragm (T6 and T9)above the diaphragm (T6 and T9) LOW – above the bifurcation but below the renal LOW – above the bifurcation but below the renal arteries (L3 and L5)arteries (L3 and L5)

CONCLUSIONCONCLUSION High catheter positions caused fewer High catheter positions caused fewer ischemic complications and possibly decreased ischemic complications and possibly decreased

the the frequency of aortic thrombosis frequency of aortic thrombosis

Hypertension appears with equal frequencyHypertension appears with equal frequency


RENAL ARTERY STENOSISRENAL ARTERY STENOSIS caused by fibromuscular caused by fibromuscular

dysplasiadysplasia if present there also may be mid- if present there also may be mid-

aortic coarctation and cerebral aortic coarctation and cerebral

vascular stenosisvascular stenosis may be due to congenital rubellamay be due to congenital rubella


RENAL VEIN THROMBOSISRENAL VEIN THROMBOSIS HypertensionHypertension gross hematuriagross hematuria abdominal/flank massabdominal/flank mass thrombocytopeniathrombocytopenia


CONGENITAL RENAL DISEASECONGENITAL RENAL DISEASE Polycystic kidney diseasePolycystic kidney disease

autosomal dominant and recessiveautosomal dominant and recessive enlarged kidney and hypertensionenlarged kidney and hypertension

multicystic-dysplastic kidney multicystic-dysplastic kidney diseasedisease non-functionalnon-functional

ureteropelvic junction obstructionureteropelvic junction obstructionActivation of Renin-angiotensin systemActivation of Renin-angiotensin system


ACQUIRED RENAL DISEASEACQUIRED RENAL DISEASE ATN/Interstitial nephritis/cortical ATN/Interstitial nephritis/cortical

necrosisnecrosis due to volume due to volume

overload/hyperreninemiaoverload/hyperreninemia HUSHUS Obstruction by a tumorObstruction by a tumor


BRONCHOPULMONARY DYSPLASIABRONCHOPULMONARY DYSPLASIA 13- 43% of infants develop systemic 13- 43% of infants develop systemic

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

related to likelihood of developing related to likelihood of developing

increased BP.increased BP. sickest infant require the closest monitoringsickest infant require the closest monitoring


COARCTATION OF THE AORTACOARCTATION OF THE AORTA early repair improves the long early repair improves the long

term term

outcome outcome hypertension may persist even hypertension may persist even

after after

surgical repairsurgical repair


ENDOCRINEENDOCRINE seizures and increased seizures and increased

intracranialintracranial

pressure are common causes of pressure are common causes of

episodic hypertensionepisodic hypertension CAHCAH HYPERALDOSTERONISMHYPERALDOSTERONISM HYPERTHYROIDISM HYPERTHYROIDISM


IATROGENICIATROGENIC NICU medsNICU meds

DexamethasoneDexamethasone TheophyllineTheophylline CaffeineCaffeine PancuroniumPancuronium PhenylephrinePhenylephrine

Prolonged TPNProlonged TPN lead to salt and water lead to salt and water

overload/hypercalcemiaoverload/hypercalcemiaUnder treatment of painUnder treatment of pain


MATERNAL CAUSESMATERNAL CAUSES Cocaine useCocaine use

harm the developing kidneysharm the developing kidneys Heroine useHeroine use

with neonatal withdrawalwith neonatal withdrawal


NEOPLASMSNEOPLASMS from compression of renal vessels from compression of renal vessels

and and uretersureters production of vasoactive production of vasoactive

substancessubstances NeuroblastomaNeuroblastoma Wilm’s tumorWilm’s tumor Mesoblastic nephromaMesoblastic nephroma


MISCELLANEOUS CAUSESMISCELLANEOUS CAUSES closure of abdominal wall defectclosure of abdominal wall defect adrenal hemorrhageadrenal hemorrhage hypercalcemiahypercalcemia ECMOECMO birth asphyxiabirth asphyxia

EVALUATIONEVALUATION

Life-threatening presentationLife-threatening presentation CHFCHF Cardiogenic shockCardiogenic shock SeizuresSeizures

Presentation of less ill infantsPresentation of less ill infants feeding difficultiesfeeding difficulties unexplained tachypneaunexplained tachypnea lethargy, apnea, irritabilitylethargy, apnea, irritability mottling of the skinmottling of the skin


RED FLAGS IN THE HISTORYRED FLAGS IN THE HISTORY prenatal exposures to heroin and prenatal exposures to heroin and

cocainecocaine predisposing conditions – BPD, CNSpredisposing conditions – BPD, CNS

disorders, PDA, hypervolemia (post disorders, PDA, hypervolemia (post

BT)BT) Medications/ Umbilical artery Medications/ Umbilical artery

catheterizationscatheterizations


RED FLAGS IN THE PHYSICAL RED FLAGS IN THE PHYSICAL

EXAMINATIONEXAMINATION BP in lower extremities/non-palpable BP in lower extremities/non-palpable

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

stenosisstenosis


RED FLAGS IN THE PHYSICAL RED FLAGS IN THE PHYSICAL

EXAMINATIONEXAMINATION Abdominal distention – obstructive Abdominal distention – obstructive

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

hyperthyroidismhyperthyroidism Ambiguous genitalia - CAHAmbiguous genitalia - CAH

LABORATORY LABORATORY EXAMINATIONSEXAMINATIONS

UrinalysisUrinalysis CBCCBC Electrolytes, BUN, Crea, CaElectrolytes, BUN, Crea, Ca Urine culture if UTI is suspectedUrine culture if UTI is suspected Plasma renin level – significantly Plasma renin level – significantly

elevated level indicates elevated level indicates renovascular renovascular

diseasedisease

LABORATORY LABORATORY EXAMINATIONSEXAMINATIONS

Additional testsAdditional tests Thyroid studiesThyroid studies VMA/Homovanillic acidVMA/Homovanillic acid AldosteroneAldosterone CortisolCortisol

IMAGING STUDIESIMAGING STUDIES

CXRay/2D echo – CHFCXRay/2D echo – CHF US of genitourinary tract US of genitourinary tract

should be performed in all hypertensive should be performed in all hypertensive infantsinfants

to rule out UPJ obstruction, renal veinto rule out UPJ obstruction, renal vein

thrombosis thrombosis

Doppler flow studies Doppler flow studies Abdominal/pelvic US Abdominal/pelvic US VCUGVCUG

IMAGING STUDIESIMAGING STUDIES

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

MRA – gold standard for diagnosis of MRA – gold standard for diagnosis of

reno vascular hypertensionreno vascular hypertension must be 3 kgmust be 3 kg

MANAGEMENTMANAGEMENT

optimal management uncertainoptimal management uncertain threshold for starting threshold for starting

antihypertensive antihypertensive

has not been well definedhas not been well defined idiosyncratic responses to certain idiosyncratic responses to certain

drugs due to developmental drugs due to developmental

immaturity of liver and kidney immaturity of liver and kidney

function.function.


RECOMMENDATIONRECOMMENDATION Asymptomatic /Mild HypertensionAsymptomatic /Mild Hypertension (Systolic 95(Systolic 95thth to < 99 to < 99thth %) %)

observationobservation resolves in timeresolves in time

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

antihypertensive therapyantihypertensive therapy


Address correctible causes ofAddress correctible causes of

hypertensionhypertension treat paintreat pain correct volume overloadcorrect volume overload wean inotropic infusionwean inotropic infusion

Choose a suitable agentChoose a suitable agent depends on specific clinical depends on specific clinical

situationsituation

TREATMENTTREATMENT

ACUTELY ILL INFANTSACUTELY ILL INFANTS continuous IV infusioncontinuous IV infusion

intermittently administered agents intermittently administered agents cause cause

wide fluctuation in BP wide fluctuation in BP PT are at increased risk for cerebral PT are at increased risk for cerebral

ischemia and hemorrhage from rapidly ischemia and hemorrhage from rapidly falling BP’s.falling BP’s. allows titration for desired effectallows titration for desired effect

TREATMENTTREATMENT

ACUTELY ILL INFANTSACUTELY ILL INFANTS continuous IV infusioncontinuous IV infusion

Nicardipine - DOCNicardipine - DOC Nitroprusside Nitroprusside Labetalol – cathecholamine and CNS Labetalol – cathecholamine and CNS mediated hypertensionmediated hypertension - avoid in BPD- avoid in BPD

monitor BP Q 10-15 minutesmonitor BP Q 10-15 minutes

TREATMENTTREATMENT

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

TREATMENTTREATMENT

NITROPRUSSIDENITROPRUSSIDE potent vasodilator potent vasodilator rapid onset of action short rapid onset of action short

duration ofduration of

effect effect complications : hypotension and complications : hypotension and

thiocyanate toxicity.thiocyanate toxicity.

TREATMENTTREATMENT

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

vasodilatation or changes in vasodilatation or changes in

intracranial pressure.intracranial pressure.

TREATMENTTREATMENT(NeoReviews)(NeoReviews)

LESS SEVERE HYPERTENSION NOT LESS SEVERE HYPERTENSION NOT READY FOR ORALREADY FOR ORAL

Intermittent IV agentsIntermittent IV agents HydralazineHydralazine LabetalolLabetalol

sometimes doses at lower end of sometimes doses at lower end of recommended range cause recommended range cause

significant significant hypotensionhypotension

TREATMENTTREATMENT

HYDRALAZINEHYDRALAZINE peripheral vasodilatorperipheral vasodilator relaxes vascular smooth musclerelaxes vascular smooth muscle


INFANT READY TO BE WEANED INFANT READY TO BE WEANED FROM IV / READY FOR ORALFROM IV / READY FOR ORAL

ORAL ANTIHYPERTENSIVE AGENTSORAL ANTIHYPERTENSIVE AGENTS CaptoprilCaptopril Diuretic - can be added if captopril is Diuretic - can be added if captopril is

ineffectiveineffective B Blocker – should be avoided (BPD)B Blocker – should be avoided (BPD)

TREATMENTTREATMENT

CAPTOPRIL CAPTOPRIL Drug of choiceDrug of choice ACE inhibitorACE inhibitor .017 mg/kg/dose PO BID –TID.017 mg/kg/dose PO BID –TID Extremely low doses (0.01 Extremely low doses (0.01 mg/kg/dose or 0.03 mg/kg/dose or 0.03

mg/kg/day)mg/kg/day) may be effective in newbornsmay be effective in newborns

TREATMENTTREATMENT

CAPTOPRIL CAPTOPRIL more potent in newborns more potent in newborns

than older children because of than older children because of

higher renal vascular higher renal vascular resistanceresistance

longer duration of actionlonger duration of action

TREATMENTTREATMENT

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

because of because of bronchoconstrictionbronchoconstriction

TREATMENTTREATMENT

DIURETICSDIURETICS reduce extracellular and plasma reduce extracellular and plasma

volumevolume use in newborns limited to mild use in newborns limited to mild

hypertension resulting from fluid hypertension resulting from fluid

overload or as an adjunctive overload or as an adjunctive

medication. medication.

TREATMENTTREATMENT(UPTODATE)(UPTODATE)

IV EnalaprilIV Enalapril IV administered ACE inhibitor IV administered ACE inhibitor effective in renovascular effective in renovascular

hypertensionhypertension has been used successfully in has been used successfully in

newbornsnewborns lowest dose should be tried firstlowest dose should be tried first


IV EnalaprilIV Enalapril avoided because of it’s avoided because of it’s

unpredictable unpredictable

antihypertensive efficacy andantihypertensive efficacy and

potential to cause oligoanuria via potential to cause oligoanuria via

blockade of the renin-angiotensin blockade of the renin-angiotensin

axis.axis.

TREATMENTTREATMENT

Surgical correctionSurgical correction CoACoA UPJ obstructionUPJ obstruction

Medical management + surgeryMedical management + surgery Renal artery stenosis Renal artery stenosis

Nephrectomy Nephrectomy Polycystic kidney diseasePolycystic kidney disease

Chemotherapy + surgeryChemotherapy + surgery Wilm’s tumor and NeuroblastomaWilm’s tumor and Neuroblastoma

PROGNOSISPROGNOSIS

depends on the causedepends on the cause often resolves over timeoften resolves over time persistentpersistent

polycystic kidney diseasepolycystic kidney disease renal parenchymal diseaserenal parenchymal disease renal vein thrombosis – require renal vein thrombosis – require nephrectomynephrectomy

recurrentrecurrent restenosis of renal artery stenosis or CoArestenosis of renal artery stenosis or CoA after repairafter repair

REFERENCESREFERENCES

Ettinger, Leigh et al : Ettinger, Leigh et al : Neoreviews Neoreviews Vol 3 Vol 3 No.8. 2002No.8. 2002 Fanaroff, Jonathan, et al. Fanaroff, Jonathan, et al. Blood pressure disorders in Blood pressure disorders in

the Neonate : Hypotension and Hypertensionthe Neonate : Hypotension and Hypertension. . Seminars in Fetal and Neonatal Medicine Vol 11. No. Seminars in Fetal and Neonatal Medicine Vol 11. No. 3, June 2006, 174-181.3, June 2006, 174-181.

Ettinger, Leigh et al : Ettinger, Leigh et al : Neoreviews. Neoreviews. Vol 3 Vol 3 No. 8, 2002No. 8, 2002 Neonatal Hypertension : Neonatal Hypertension : Uptodate.2006Uptodate.2006 Neonatal Hypertension : Neonatal Hypertension : EmedicineEmedicine. August . August 29, 200629, 2006 Sondheimer, Judith M. (editor) : Sondheimer, Judith M. (editor) : CurrentCurrent Pediatric Diagnosis and TreatmentPediatric Diagnosis and Treatment. 16. 16thth ed. ed. McGraw-Hill Companies,2003McGraw-Hill Companies,2003

THANK YOU THANK YOU AND AND

GOOD MORNINGGOOD MORNING

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