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Neonatal Hypertension Medication

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

Medication Summary

Most medications discussed in this article have not been specifically studied in newborns; however, through the empiric use of these medications, reasonable clinical experience has been accumulated.

As previously stated, 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]

A study by Blowey et al[3] assessing pharmacologic treatment in neonates with hypertension (excluding patients with congenial cardiac disorders) demonstrated that multiple drugs are commonly prescribed for hypertensive neonates; the distribution of medication classes used was as follows:

  • Vasodilators - 64.2% of patients
  • Angiotensin-converting enzyme (ACE) inhibitors - 50.8% of patients
  • Calcium channel blockers - 24% of patients
  • Alpha and beta blockers - 18.4% of patients

The authors also determined that more than 1 antihypertensive agent was used in 45% of the neonates with hypertension.

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Vasodilators

Class Summary

These agents relax blood vessels, thereby decreasing peripheral vascular resistance.

Hydralazine

 

Hydralazine decreases systemic resistance through direct vasodilation of arterioles.

Sodium nitroprusside (Nitropress)

 

Sodium nitroprusside produces vasodilation and increases inotropic activity of the heart.

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Calcium Channel Blockers

Class Summary

These agents block calcium channels in vascular smooth muscle, which leads to vasodilatation.

Amlodipine (Norvasc)

 

Amlodipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. This agent is a good choice for long-term outpatient treatment. It may be compounded into a stable suspension (1mg/mL).

Isradipine (DynaCirc CR)

 

Isradipine is a dihydropyridine calcium channel blocker. It binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and smooth muscle. The resultant effect is arteriole dilation, which reduces systemic resistance and blood pressure, with a small increase in resting heart rate. Isradipine has a rapid onset of action. It may be compounded into a stable suspension.

Nicardipine (Cardene)

 

Nicardipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery and reduces myocardial oxygen consumption. Intravenous nicardipine is the drug of choice for initial management of severe neonatal hypertension.

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Cardiovascular, Other

Class Summary

These agents decrease heart rate and cardiac output.

Labetalol (Normodyne, Trandate)

 

Labetalol blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites, decreasing blood pressure.

Propranolol (Inderal, InnoPran XL)

 

Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions.

It is not suitable for the emergency treatment of hypertension. Do not administer propranolol intravenously in hypertensive emergencies.

Esmolol (Brevibloc)

 

Esmolol is an excellent drug for use in patients at risk for experiencing complications from beta blockade, particularly individuals with reactive airway disease, mild to moderate left ventricular dysfunction, and/or peripheral vascular disease. Its short half-life of 8 minutes allows for titration to the desired effect and quick discontinuation if needed.

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ACE Inhibitors

Class Summary

These agents inhibit the conversion of angiotensin I to angiotensin II.

Captopril

 

Captopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and reduces aldosterone secretion.

Enalapril (Vasotec)

 

Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, decreasing aldosterone secretion.

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Diuretics, Other

Class Summary

These agents decrease plasma volume and promote excretion of water and electrolytes by the kidneys. They may be used as monotherapy or combination therapy to treat hypertension.

Chlorothiazide (Diuril)

 

Chlorothiazide inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.

Hydrochlorothiazide (Microzide)

 

Hydrochlorothiazide inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions. It is a good second agent to add to angiotensin-converting enzyme (ACE) ̶ inhibitor or vasodilator therapy.

Spironolactone (Aldactone)

 

Spironolactone is a potassium-sparing diuretic that is used for the management of hypertension. It may block the effects of aldosterone on arteriolar smooth muscles.

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Alpha2 Agonists, Central-Acting

Class Summary

These agents decrease central adrenergic output.

Clonidine (Catapres)

 

Clonidine stimulates alpha2-adrenoreceptors in the brain stem, activating an inhibitory neuron, which, in turn, results in reduced sympathetic outflow. These effects produce a decrease in vasomotor tone and heart rate.

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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
  1. Singh HP, Hurley RM, Myers TF. Neonatal hypertension. Incidence and risk factors. Am J Hypertens. 1992 Feb. 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. 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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