Neonatal Hypertension Treatment & Management

  • Author: Joseph Flynn, MD, MS; Chief Editor: Ted Rosenkrantz, MD   more...
 
Updated: Jan 3, 2012
 

Approach Considerations

Tailor treatment decisions, which may include intravenous therapy, oral therapy, or both, to the severity of the hypertension. Hypertension resolves in most infants over time, although a small number of infants may have persistent blood pressure elevation throughout childhood.

Numerous medications are available that may be used in the treatment of neonatal hypertension. Assess the clinical status of the infant and correct any easily correctable iatrogenic causes of hypertension (eg, infusions of inotropic agents, volume overload, pain) prior to instituting drug therapy. Next, choose an antihypertensive agent that is most appropriate for the specific clinical situation.[15]

Few medications are approved for use in treating hypertension in neonates; therefore, all such use must be considered off label.

Transfer

Occasionally, infants may need to be transferred to specialized centers for advanced diagnostic or therapeutic procedures, such as angiography or vascular surgery.

Diet

A low-sodium diet may assist in treatment of infants with persistent hypertension; however, because most infant formula is relatively low in sodium content, no special dietary modifications are usually necessary in the neonatal period.

Consultations

Consultation with a cardiologist may be indicated for performance of echocardiography and/or evaluation of congestive heart failure. Nephrologist consultation may be needed if parenchymal renal disease is diagnosed. Consultation with an interventional radiologist may also be needed in some cases for performance of renal angiography.

Deterrence and prevention

Although several studies have examined the role of placement of umbilical artery catheters (ie, low versus high lines), no definitive proof has emerged that changes in catheter placement can prevent thromboembolism and the subsequent development of hypertension.

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Intravenous Antihypertensive Infusions

Usually, continuous intravenous infusions are the most appropriate initial therapy, especially in acutely ill infants with severe hypertension. The advantages of intravenous infusions are numerous, most importantly including the ability to quickly increase or decrease the rate of infusion to achieve the desired blood pressure (BP). In patients of any age with malignant hypertension, take care to avoid too rapid a reduction in BP, in order to avoid cerebral ischemia and hemorrhage; premature infants in particular are already at an increased risk because of the immaturity of their periventricular circulation.

Because of the paucity of available data regarding the use of intravenous antihypertensive infusions in newborns, the choice of agent depends on the individual clinician's experience.

Currently available drugs for continuous infusion include sodium nitroprusside, labetalol, esmolol, fenoldopam and nicardipine (see Table 1, below). Nicardipine, which is a dihydropyridine calcium channel blocker, has been reported to be effective most often in neonates; it appears to have some advantages compared with older drugs that may make it the drug of choice in the neonatal population.

Regardless of the drug chosen, continuously monitor BP via an indwelling arterial catheter or by frequently repeated (every 10-15min) cuff readings so that the rate of infusion can be titrated to achieve the desired degree of BP control.

Table 2. Intravenous Drugs for Severe Hypertension in Neonates[11] (Open Table in a new window)

DrugClassIntravenous (IV) DosageComments
EsmololBeta blocker100-300 mcg/kg/min IV infusionVery short acting; constant IV infusion necessary
HydralazineVasodilator (arteriolar)0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusionTachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
LabetalolAlpha blocker and beta blocker0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusionHeart failure, bronchopulmonary dysplasia (BPD), relative contraindications
NicardipineCalcium channel blocker1-5 mcg/kg/min IV constant infusionMay cause reflex tachycardia
Sodium nitroprussideVasodilator (arteriolar and venous)0.5-10 mcg/kg/min IV constant infusionThiocyanate toxicity can occur with prolonged use (>72 h) or in renal failure; usual maintenance dose is below 2 mcg/kg/min; may use 10 mcg/kg/min for short duration (ie, < 10-15 min)
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Intermittently Administered IV Antihypertensive Agents

For some infants, intermittently administered intravenous agents have a role in therapy (see Table 1, above). Hydralazine and labetalol, in particular, may be useful in infants with mild to moderate hypertension who are not yet candidates for oral therapy because of gastrointestinal (GI) dysfunction. Enalaprilat, the intravenous angiotensin-converting enzyme (ACE) inhibitor, has also been reported to be useful in the treatment of neonatal renovascular hypertension; however, it should be used with great caution. No study has been performed to determine a safe and effective pediatric dose; furthermore, even doses at the lower end of published ranges may lead to significant prolonged hypotension and oliguric acute renal failure.

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Oral Antihypertensive Agents

Oral antihypertensive agents (see Table 2, below) are best reserved for infants with less severe hypertension or infants whose acute hypertension has been controlled with intravenous drugs and who are ready to be converted to long-term therapy. Although captopril had once been considered by many authorities to be the oral drug of choice for neonatal hypertension, this has come under question because of the possibility of adverse effects on renal development, particularly in premature infants. It is probably acceptable for use in infants with a postconceptual age of 44 weeks and above.

Beta-blockers may need to be avoided in long-term antihypertensive therapy in infants with bronchopulmonary dysplasia (BPD). In such infants, diuretics may have a beneficial effect not only in controlling blood pressure (BP), but also in improving pulmonary function. Other drugs that may be useful in some infants include vasodilators, such as hydralazine and minoxidil (because it can be compounded into a stable suspension), and the calcium channel blocker isradipine, which may be superior to the older agents.

Nifedipine is a poor choice for long-term therapy because of the difficulty in administering small doses and because of the rapid, profound, and short-lived drops in BP that are typically produced by this agent.

Table 3. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension[11] (Open Table in a new window)

DrugClassOral DosageComments
CaptoprilAngiotensin-converting enzyme (ACE) inhibitorUnder age 3 months: 0.01-0.5 mg/kg/dose 3 times daily; not to exceed 2 mg/kg/day



At or above age 3 months: 0.15-0.3 mg/kg/dose 3 times daily; not to exceed 6 mg/kg/day



Monitor serum creatinine and potassium levels
ClonidineCentral agonist0.05-0.1 mg/dose 2-3 times dailyAdverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
EnalaprilACE inhibitor0.08-0.6 mg/kg/day, given once or twice dailyMonitor serum creatinine and potassium levels
HydralazineVasodilator (arteriolar)0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/daySuspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
IsradipineCalcium channel blocker0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/daySuspension may be compounded; useful for both acute and chronic hypertension
AmlodipineCalcium channel blocker0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/dLess likely to cause sudden hypotension than isradipine
MinoxidilVasodilator (arteriolar)0.1-0.2 mg/kg/dose 2-3 times dailyMost potent oral vasodilator; excellent for refractory hypertension
PropranololBeta-blocker0.5-1 mg/kg/dose 3 times dailyMaximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
LabetalolAlpha and beta blocker1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/dMonitor heart rate; avoid in infants with BPD
SpironolactoneAldosterone antagonist0.5-1.5 mg/kg/dose twice dailyPotassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
HydrochlorothiazideThiazide diuretic2-3 mg/kg/d orally every day or divided twice dailyMonitor electrolytes
ChlorothiazideThiazide diuretic5-15 mg/kg/dose twice dailyMonitor electrolytes
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Surgical Care

Surgery is rarely indicated for the treatment of neonatal hypertension, except for specific diagnoses, such as ureteral obstruction, aortic coarctation, or certain tumors. Unilateral renal venous thrombosis is commonly treated with nephrectomy to avoid the need for long-term drug therapy.

For infants with renal arterial stenosis, managing the infant medically may be necessary until the patient’s growth is sufficient for the child to undergo definitive repair of the vascular abnormalities. Infants with malignant hypertension secondary to polycystic kidney disease may require bilateral nephrectomy. Fortunately, such severely affected infants are quite rare.

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Monitoring

Monitor blood pressure (BP) regularly in neonates with hypertension until the infant is ready for discharge from the NICU. Infants treated with angiotensin-converting enzyme (ACE) inhibitors or diuretics should have electrolyte levels and renal function monitored periodically until discharge.

Arrangements for home BP monitoring should be part of the discharge plan for any infant sent home on antihypertensive therapy. The optimal device for home BP measurements in an infant is a Dinamap device or a similar oscillometric device. A second choice is a Doppler device: however, this only measures systolic BP and is difficult to teach parents to use. Therefore, oscillometric devices should be prescribed.

Include BP measurement at all follow-up visits for infants with neonatal hypertension. In addition, monitor infants with bronchopulmonary dysplasia at discharge and those who had complicated NICU courses for the development of hypertension following discharge.

Ultrasonography should be obtained 6-12 months after discharge in infants with hypertension to ensure that the kidneys are growing normally.

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Contributor Information and Disclosures
Author

Joseph Flynn, MD, MS  Director of Pediatric Hypertension Program, Division of Nephrology, Seattle Children's Hospital; Professor, Department of Pediatrics, University of Washington School of Medicine

Joseph Flynn, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American Heart Association, American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Novartis Pharmaceuticals Consulting fee Consulting; Pfizer, Inc Consulting fee Review panel membership

Chief Editor

Ted Rosenkrantz, MD  Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

References
  1. Singh HP, Hurley RM, Myers TF. Neonatal hypertension. Incidence and risk factors. Am J Hypertens. Feb 1992;5(2):51-5. [Medline].

  2. Friedman AL, Hustead VA. Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up. Pediatr Nephrol. Jan 1987;1(1):30-4. [Medline].

  3. Blowey DL, Duda PJ, Stokes P, Hall M. Incidence and treatment of hypertension in the neonatal intensive care unit. J Am Soc Hypertens. Sep 17 2011;[Medline].

  4. Neal WA, Reynolds JW, Jarvis CW, Williams HJ. Umbilical artery catheterization: demonstration of arterial thrombosis by aortography. Pediatrics. Jul 1972;50(1):6-13. [Medline].

  5. Abman SH, Warady BA, Lum GM, Koops BL. Systemic hypertension in infants with bronchopulmonary dysplasia. J Pediatr. Jun 1984;104(6):928-31. [Medline].

  6. Alagappan A, Malloy MH. Systemic hypertension in very low-birth weight infants with bronchopulmonary dysplasia: incidence and risk factors. Am J Perinatol. Jan 1998;15(1):3-8. [Medline].

  7. Seliem WA, Falk MC, Shadbolt B, Kent AL. Antenatal and postnatal risk factors for neonatal hypertension and infant follow-up. Pediatr Nephrol. Dec 2007;22(12):2081-7. [Medline].

  8. Zubrow AB, Hulman S, Kushner H, Falkner B. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group. J Perinatol. Nov-Dec 1995;15(6):470-9. [Medline].

  9. Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in non-critically ill preterm and full-term neonates. Pediatr Nephrol. Feb 2007;22(2):249-57. [Medline].

  10. Kent AL, Kecskes Z, Shadbolt B, Falk MC. Normative blood pressure data in the early neonatal period. Pediatr Nephrol. Sep 2007;22(9):1335-41. [Medline].

  11. Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. Jan 2012;27(1):17-32. [Medline].

  12. Dionne JM, Abitbol CL, Flynn JT. Erratum to: Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. Jan 2012;27(1):159-60. [Medline].

  13. Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children--1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics. Jan 1987;79(1):1-25. [Medline].

  14. Crossland DS, Furness JC, Abu-Harb M, et al. Variability of four limb blood pressure in normal neonates. Arch Dis Child Fetal Neonatal Ed. Jul 2004;89(4):F325-7. [Medline].

  15. Brierley J, Marks SD. Treating the causes of paediatric hypertension using non-invasive physiological parameters. Med Hypotheses. May 3 2010;[Medline].

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Normal blood pressure percentile curves for older infants. From the Second (1987) Task Force on Blood Pressure Control in Childhood; National Heart, Lung, and Blood Institute.
Table 1. Neonatal Blood Pressures and Potential Treatment Parameters. Adapted from Dionne et al.*
Postconceptual Age50th Percentile95th Percentile99th Percentile
44 weeks
SBP88105110
DBP506873
MAP638085
42 weeks
SBP8598102
DBP506570
MAP627681
40 weeks
SBP8095100
DBP506570
MAP607580
38 weeks
SBP779297
DBP506570
MAP597479
36 weeks
SBP728792
DBP506570
MAP577277
34 weeks
SBP708590
DBP405560
MAP506570
32 weeks
SBP688388
DBP405560
MAP496469
30 weeks
SBP658085
DBP405560
MAP486368
28 weeks
SBP607580
DBP385054
MAP455863
26 weeks
SBP557277
DBP305056
MAP385763
Table 2. Intravenous Drugs for Severe Hypertension in Neonates[11]
DrugClassIntravenous (IV) DosageComments
EsmololBeta blocker100-300 mcg/kg/min IV infusionVery short acting; constant IV infusion necessary
HydralazineVasodilator (arteriolar)0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusionTachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
LabetalolAlpha blocker and beta blocker0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusionHeart failure, bronchopulmonary dysplasia (BPD), relative contraindications
NicardipineCalcium channel blocker1-5 mcg/kg/min IV constant infusionMay cause reflex tachycardia
Sodium nitroprussideVasodilator (arteriolar and venous)0.5-10 mcg/kg/min IV constant infusionThiocyanate toxicity can occur with prolonged use (>72 h) or in renal failure; usual maintenance dose is below 2 mcg/kg/min; may use 10 mcg/kg/min for short duration (ie, < 10-15 min)
Table 3. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension[11]
DrugClassOral DosageComments
CaptoprilAngiotensin-converting enzyme (ACE) inhibitorUnder age 3 months: 0.01-0.5 mg/kg/dose 3 times daily; not to exceed 2 mg/kg/day



At or above age 3 months: 0.15-0.3 mg/kg/dose 3 times daily; not to exceed 6 mg/kg/day



Monitor serum creatinine and potassium levels
ClonidineCentral agonist0.05-0.1 mg/dose 2-3 times dailyAdverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
EnalaprilACE inhibitor0.08-0.6 mg/kg/day, given once or twice dailyMonitor serum creatinine and potassium levels
HydralazineVasodilator (arteriolar)0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/daySuspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
IsradipineCalcium channel blocker0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/daySuspension may be compounded; useful for both acute and chronic hypertension
AmlodipineCalcium channel blocker0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/dLess likely to cause sudden hypotension than isradipine
MinoxidilVasodilator (arteriolar)0.1-0.2 mg/kg/dose 2-3 times dailyMost potent oral vasodilator; excellent for refractory hypertension
PropranololBeta-blocker0.5-1 mg/kg/dose 3 times dailyMaximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
LabetalolAlpha and beta blocker1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/dMonitor heart rate; avoid in infants with BPD
SpironolactoneAldosterone antagonist0.5-1.5 mg/kg/dose twice dailyPotassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
HydrochlorothiazideThiazide diuretic2-3 mg/kg/d orally every day or divided twice dailyMonitor electrolytes
ChlorothiazideThiazide diuretic5-15 mg/kg/dose twice dailyMonitor electrolytes
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