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Neonatal Hypertension Treatment & Management

  • Author: Joseph Flynn, MD, MS; Chief Editor: Ted Rosenkrantz, MD  more...
 
Updated: Jan 03, 2016
 

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.[16]

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[12] (Open Table in a new window)

Drug Class Intravenous (IV) Dosage Comments
Esmolol Beta blocker 100-300 mcg/kg/min IV infusion Very short acting; constant IV infusion necessary
Hydralazine Vasodilator (arteriolar) 0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusion Tachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
Labetalol Alpha blocker and beta blocker 0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion Heart failure, bronchopulmonary dysplasia (BPD), relative contraindications
Nicardipine Calcium channel blocker 1-5 mcg/kg/min IV constant infusion May cause reflex tachycardia
Sodium nitroprusside Vasodilator (arteriolar and venous) 0.5-10 mcg/kg/min IV constant infusion Thiocyanate 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[12] (Open Table in a new window)

Drug Class Oral Dosage Comments
Captopril Angiotensin-converting enzyme (ACE) inhibitor Under 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
Clonidine Central agonist 0.05-0.1 mg/dose 2-3 times daily Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
Enalapril ACE inhibitor 0.08-0.6 mg/kg/day, given once or twice daily Monitor serum creatinine and potassium levels
Hydralazine Vasodilator (arteriolar) 0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/day Suspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
Isradipine Calcium channel blocker 0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/day Suspension may be compounded; useful for both acute and chronic hypertension
Amlodipine Calcium channel blocker 0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/d Less likely to cause sudden hypotension than isradipine
Minoxidil Vasodilator (arteriolar) 0.1-0.2 mg/kg/dose 2-3 times daily Most potent oral vasodilator; excellent for refractory hypertension
Propranolol Beta-blocker 0.5-1 mg/kg/dose 3 times daily Maximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
Labetalol Alpha and beta blocker 1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/d Monitor heart rate; avoid in infants with BPD
Spironolactone Aldosterone antagonist 0.5-1.5 mg/kg/dose twice daily Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
Hydrochlorothiazide Thiazide diuretic 2-3 mg/kg/d orally every day or divided twice daily Monitor electrolytes
Chlorothiazide Thiazide diuretic 5-15 mg/kg/dose twice daily Monitor 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 Chief, 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, Phi Beta Kappa

Disclosure: Received consulting fee from Pfizer, Inc for review panel membership; Received royalty from UpToDate, Inc. for author; Received royalty from Spronger, Inc for authoring.

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 Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

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
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  2. Friedman AL, Hustead VA. Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up. Pediatr Nephrol. 1987 Jan. 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. 2011 Sep 17. [Medline].

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

  5. Abman SH, Warady BA, Lum GM, Koops BL. Systemic hypertension in infants with bronchopulmonary dysplasia. J Pediatr. 1984 Jun. 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. 1998 Jan. 15(1):3-8. [Medline].

  7. Sahu R, Pannu H, Yu R, Shete S, Bricker JT, Gupta-Malhotra M. Systemic hypertension requiring treatment in the neonatal intensive care unit. J Pediatr. 2013 Jul. 163(1):84-8. [Medline].

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

  9. 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. 1995 Nov-Dec. 15(6):470-9. [Medline].

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

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

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

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

  14. 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. 1987 Jan. 79(1):1-25. [Medline].

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

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

  17. Batisky DL. Neonatal hypertension. Clin Perinatol. 2014 Sep. 41(3):529-42. [Medline].

  18. Nickavar A, Assadi F. Managing hypertension in the newborn infants. Int J Prev Med. 2014 Mar. 5(Suppl 1):S39-43. [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 Age 50th Percentile 95th Percentile 99th Percentile
44 weeks      
SBP 88 105 110
DBP 50 68 73
MAP 63 80 85
42 weeks      
SBP 85 98 102
DBP 50 65 70
MAP 62 76 81
40 weeks      
SBP 80 95 100
DBP 50 65 70
MAP 60 75 80
38 weeks      
SBP 77 92 97
DBP 50 65 70
MAP 59 74 79
36 weeks      
SBP 72 87 92
DBP 50 65 70
MAP 57 72 77
34 weeks      
SBP 70 85 90
DBP 40 55 60
MAP 50 65 70
32 weeks      
SBP 68 83 88
DBP 40 55 60
MAP 49 64 69
30 weeks      
SBP 65 80 85
DBP 40 55 60
MAP 48 63 68
28 weeks      
SBP 60 75 80
DBP 38 50 54
MAP 45 58 63
26 weeks      
SBP 55 72 77
DBP 30 50 56
MAP 38 57 63
Table 2. Intravenous Drugs for Severe Hypertension in Neonates [12]
Drug Class Intravenous (IV) Dosage Comments
Esmolol Beta blocker 100-300 mcg/kg/min IV infusion Very short acting; constant IV infusion necessary
Hydralazine Vasodilator (arteriolar) 0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusion Tachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
Labetalol Alpha blocker and beta blocker 0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion Heart failure, bronchopulmonary dysplasia (BPD), relative contraindications
Nicardipine Calcium channel blocker 1-5 mcg/kg/min IV constant infusion May cause reflex tachycardia
Sodium nitroprusside Vasodilator (arteriolar and venous) 0.5-10 mcg/kg/min IV constant infusion Thiocyanate 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 [12]
Drug Class Oral Dosage Comments
Captopril Angiotensin-converting enzyme (ACE) inhibitor Under 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
Clonidine Central agonist 0.05-0.1 mg/dose 2-3 times daily Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
Enalapril ACE inhibitor 0.08-0.6 mg/kg/day, given once or twice daily Monitor serum creatinine and potassium levels
Hydralazine Vasodilator (arteriolar) 0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/day Suspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
Isradipine Calcium channel blocker 0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/day Suspension may be compounded; useful for both acute and chronic hypertension
Amlodipine Calcium channel blocker 0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/d Less likely to cause sudden hypotension than isradipine
Minoxidil Vasodilator (arteriolar) 0.1-0.2 mg/kg/dose 2-3 times daily Most potent oral vasodilator; excellent for refractory hypertension
Propranolol Beta-blocker 0.5-1 mg/kg/dose 3 times daily Maximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
Labetalol Alpha and beta blocker 1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/d Monitor heart rate; avoid in infants with BPD
Spironolactone Aldosterone antagonist 0.5-1.5 mg/kg/dose twice daily Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
Hydrochlorothiazide Thiazide diuretic 2-3 mg/kg/d orally every day or divided twice daily Monitor electrolytes
Chlorothiazide Thiazide diuretic 5-15 mg/kg/dose twice daily Monitor electrolytes
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