Advertisement

Pediatric Nephrology

, 24:1101 | Cite as

Severe hypertension in children and adolescents: pathophysiology and treatment

  • Joseph T. FlynnEmail author
  • Kjell Tullus
Review

Abstract

Severe, symptomatic hypertension occurs uncommonly in children, usually only in those with underlying congenital or acquired renal disease. If such hypertension has been long-standing, then rapid blood pressure reduction may be risky due to altered cerebral hemodynamics. While many drugs are available for the treatment of severe hypertension in adults, few have been studied in children. Despite the lack of scientific studies, some agents, particularly continuous intravenous infusions of nicardipine and labetalol, are preferred in many centers. These agents generally provide the ability to control the magnitude and rapidity of blood pressure reduction and should—in conjunction with careful patient monitoring—allow the safe reduction of blood pressure and the avoidance of complications. This review provides a summary of the underlying causes and pathophysiology of acute severe hypertension in childhood as well as a detailed discussion of drug treatment and the optimal clinical approach to managing children and adolescents with acute severe hypertension.

Keywords

Children Clonidine Esmolol Hydralazine Hypertension Kidney disease Labetalol Nicardipine 

Notes

Statement of Disclosure

Joseph Flynn is a consultant to Boehringer Ingelheim Pharmaceuticals, Novartis Pharmaceuticals, and Pfizer, Inc. Kjell Tullus has no consulting relationships to disclose.

References

  1. 1.
    National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2005) The Fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Institute of Health publication 05:5267. Bethesda, MD, National Heart, Lung, and Blood InstituteGoogle Scholar
  2. 2.
    Marik PE, Varon J (2007) Hypertensive crises: Challenges and management. Chest 131:1949–1962PubMedCrossRefGoogle Scholar
  3. 3.
    Haas CE, LeBlanc JM (2004) Acute postoperative hypertension: a review of therapeutic options. Am J Health Syst Pharm 61:1661–1673PubMedGoogle Scholar
  4. 4.
    Flynn JT (2005) Hypertension in childhood and adolescence. In: Kaplan NM (ed) Kaplan’s clinical hypertension, 9th edn. Lippincott-Williams and Wilkins, Philadelphia, pp 465–488Google Scholar
  5. 5.
    Deal JE, Barratt TM, Dillon MJ (1992) Management of hypertensive emergencies. Arch Dis Child 67:1089–1092PubMedCrossRefGoogle Scholar
  6. 6.
    Flynn JT, Mottes TA, Brophy PB, Kershaw DB, Smoyer WE, Bunchman TE (2001) Intravenous nicardipine for treatment of severe hypertension in children. J Pediatr 139:38–43PubMedCrossRefGoogle Scholar
  7. 7.
    Bender SR, Fong MW, Heitz S, Bisognano JD (2006) Characteristics and management of patients presenting to the emergency department with hypertensive urgency. J Clin Hypertens 8:12–18CrossRefGoogle Scholar
  8. 8.
    Rose JC, Mayer SA (2004) Optimizing blood pressure in neurological emergencies. Neurocrit Care 1:287–299PubMedCrossRefGoogle Scholar
  9. 9.
    Shroff R, Roebuck DJ, Gordon I, Davies R, Stephens S, Marks S, Chan M, Barkovics M, McLaren CA, Shah V, Dillon MJ, Tullus K (2006) Angioplasty for renovascular hypertension in children: 20-year experience. Pediatrics 118:268–275PubMedCrossRefGoogle Scholar
  10. 10.
    Vaughan CJ, Delanty N (2000) Hypertensive emergencies. Lancet 356:411–417PubMedCrossRefGoogle Scholar
  11. 11.
    Schwartz RB, Jones KM, Kalina P, Bajakian RL, Mantello MT, Garada B, Holman BL (1992) Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases. AJR Am J Roentgenol 159:379–383PubMedGoogle Scholar
  12. 12.
    Flynn JT, Woroniecki RP (2003) Pathophysiology of hypertension. In: Avner E, Harmon W, Niaudet P (eds) Pediatric nephrology, 5th edn. Lippincott Williams and Wilkins, Philadelphia, pp 1153–1178Google Scholar
  13. 13.
    Funakoshi Y, Ichiki T, Ito K, Takeshita A (1999) Induction of interleukin-6 expression by angiotensin II in rat vascular smooth vascular cells. Hypertension 34:118–125PubMedGoogle Scholar
  14. 14.
    Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harboring the mouse Ren-2 gene. Nature 344:541–544PubMedCrossRefGoogle Scholar
  15. 15.
    Montgomery HE, Kiernan LA, Whitworth CE, Fleming S, Unger T, Gohlke P, Mullins JJ, McEwan JR (1998) Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27. J Hypertens 16:635–643PubMedCrossRefGoogle Scholar
  16. 16.
    Padfield PL, Brown JJ, Lever AF, Morton JJ, Robertson JI (1981) Blood pressure in acute and chronic vasopressin excess: studies of malignant hypertension and the syndrome of inappropriate antidiuretic hormone secretion. N Engl J Med 304:1067–1070PubMedGoogle Scholar
  17. 17.
    Brouwers FM, Eisenhofer G, Lenders JW, Pacak K (2006) Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma. Endocrinol Metab Clin North Am 35:699–724PubMedCrossRefGoogle Scholar
  18. 18.
    Rauth W, Hund E, Sohl G, Rascher W, Mehls O, Scharer K (1983) Vasoactive hormones in children with chronic renal failure. Kidney Int Suppl 15:S27–S33Google Scholar
  19. 19.
    Faber JE, Brody MA (1985) Afferent renal nerve-dependent hypertension following acute renal artery stenosis in the conscious rat. Circ Res 57:676–688PubMedGoogle Scholar
  20. 20.
    Whitworth CE, Veniant MM, Firth JD, Cumming AD, Mullins JJ (1995) Endothelin in the kidney in malignant phase hypertension. Hypertension 26:925–931PubMedGoogle Scholar
  21. 21.
    Vaziri ND, Ni Z, Wang XQ, Oveisi F, Zhou XJ (1998) Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol 274:F642–F649PubMedGoogle Scholar
  22. 22.
    Endemann DH, Schiffrin EL (2004) Endothelial dysfunction. J Am Soc Nephrol 15:1983–1992PubMedCrossRefGoogle Scholar
  23. 23.
    Patel H, Mitsnefes M (2005) Advances in the pathogenesis and management of hypertensive crisis. Curr Opin Pediatr 17:210–214PubMedCrossRefGoogle Scholar
  24. 24.
    Muller DN, Dechend R, Mervaala EMA, Park J-K, Schmidt F, Fiebler A, Theuer J, Ganten D, Haller H, Luft FC (2000) NF-κB inhibition ameliorates angotensin II induce inflammatory damage in rats. Hypertension 35:193–201PubMedGoogle Scholar
  25. 25.
    Lip GYH, Edmunds E, Hee FL, Blann AD, Beevers DG (2001) A cross-sectional, diurnal, and follow-up study of platelet activation and endothelial dysfunction in malignant phase hypertension. Am J Hypertens 14:627–631PubMedCrossRefGoogle Scholar
  26. 26.
    Seeman T (2007) Hypertension after renal transplantation. Pediatr Nephrol doi: 10.1007/s00467-007-0627-7
  27. 27.
    Grossman E, Messerli FH (2008) Secondary hypertension: interfering substances. J Clin Hypertens (Greenwich) 10:556–566CrossRefGoogle Scholar
  28. 28.
    U.S. Food and Drug Administration. Summaries of medical and clinical pharmacology reviews of pediatric studies. Available at: http://www.fda.gov/cder/pediatric/Summaryreview.htm. Accessed 3 June 2008
  29. 29.
    Treluyer JM, Hubert P, Jouvet P, Couderc S, Cloup M (1993) Intravenous nicardipine in hypertensive children. Eur J Pediatr 152:712–714PubMedCrossRefGoogle Scholar
  30. 30.
    Michael J, Groshong T, Tobias JD (1998) Nicardipine for hypertensive emergencies in children with renal disease. Pediatr Nephrol 12:40–42PubMedCrossRefGoogle Scholar
  31. 31.
    Tenney F, Sakarcan A (2000) Nicardipine is a safe and effective agent in pediatric hypertensive emergencies. Am J Kidney Dis 35:E20PubMedCrossRefGoogle Scholar
  32. 32.
    Nakagawa TA, Sartori SC, Morris A, Schneider DS (2004) Intravenous nicardipine for treatment of postcoarctectomy hypertension in children. Pediatr Cardiol 25:26–30PubMedCrossRefGoogle Scholar
  33. 33.
    Flynn JT (2003) Successes and shortcomings of the FDA Modernization Act. Am J Hypertens 16:889–891PubMedCrossRefGoogle Scholar
  34. 34.
    Dunne J (2007) The European Regulation on medicines for paediatric use. Paediatr Respir Rev 8:177–183PubMedCrossRefGoogle Scholar
  35. 35.
    Public law 107–109. Best Pharmaceuticals for Children Act. Enacted January 4, 2002. Available at: http://www.fda.gov/opacom/laws/pharmkids/contents.html. Accessed 3 June 2008
  36. 36.
    Rocco TP, Fang JC (2006) Pharmacotherapy of congestive heart failure. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York, pp 869–898Google Scholar
  37. 37.
    Goa KL, Benfield P, Sorkin EM (1989) Labetalol. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in hypertension and ischaemic heart disease. Drugs 37:583–627PubMedCrossRefGoogle Scholar
  38. 38.
    Bunchman TE, Lynch RE, Wood EG (1992) Intravenously administered labetalol for treatment of hypertension in children. J Pediatr 120:140–144PubMedCrossRefGoogle Scholar
  39. 39.
    Flynn JT, Pasko DA (2000) Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension. Pediatr Nephrol 15:302–316PubMedCrossRefGoogle Scholar
  40. 40.
    Wallin JD, Bienvenu GS, Cook E, Laddu A, Turlapaty P, Clifton GG (1990) Nicardipine in severe hypertension: oral therapy following intravenous treatment. Int J Clin Pharmacol Ther Toxicol 28:14–19PubMedGoogle Scholar
  41. 41.
    Hoffman BB (2006) Therapy of hypertension. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York, pp 845–868Google Scholar
  42. 42.
    Alexander KS, Pudipeddi M, Parker GA (1993) Stability of hydralazine hydrochloride syrup compounded from tablets. Am J Hosp Pharm 50:683–686PubMedGoogle Scholar
  43. 43.
    Kirsten R, Nelson K, Kirsten D, Heintz B (1998) Clinical pharmacokinetics of vasodilators. Part I. Clin Pharmacokinet 34:457–482PubMedCrossRefGoogle Scholar
  44. 44.
    McCrory WW, Kohaut EC, Lewy JE, Lieberman E, Travis LB (1979) Safety of intravenous diazoxide in children with severe hypertension. Clin Pediatr 18:661–667, 671CrossRefGoogle Scholar
  45. 45.
    Grossman E, Ironi AN, Messerli FH (1998) Comparative tolerability profile of hypertensive crisis treatments. Drug Saf 19:99–122PubMedCrossRefGoogle Scholar
  46. 46.
    Adamson PC, Rhodes LA, Saul JP, Dick M 2nd, Epstein MR, Moate P, Boston R, Schreiner MS (2006) The pharmacokinetics of esmolol in pediatric subjects with supraventricular arrhythmias. Pediatr Cardiol 27:420–427PubMedCrossRefGoogle Scholar
  47. 47.
    Wells TG, Bunchman TE, Kearns GL (1990) Treatment of neonatal hypertension with enalaprilat. J Pediatr 117:664–667PubMedCrossRefGoogle Scholar
  48. 48.
    Sica DA (2007) Centrally acting antihypertensive agents: An update. J Clin Hypertens (Greenwich) 9:399–405CrossRefGoogle Scholar
  49. 49.
    Falkner B, Onesti G, Lowenthal DT, Affrime MB (1983) The use of clonidine monotherapy in adolescent hypertension. Chest 83(Suppl 2):425–427PubMedCrossRefGoogle Scholar
  50. 50.
    MacDonald JL, Johnson CE, Jacobson P (1994) Stability of isradipine in an extemporaneously compounded oral liquid. Am J Hosp Pharm 51:2409–2411PubMedGoogle Scholar
  51. 51.
    Strauser LM, Groshong T, Tobias JD (2000) Initial experience with isradipine for the treatment of hypertension in children. South Med J 93:287–293PubMedGoogle Scholar
  52. 52.
    Flynn JT, Warnick SJ (2002) Isradipine treatment of hypertension in children: a single-center experience. Pediatr Nephrol 17:748–753PubMedCrossRefGoogle Scholar
  53. 53.
    Saragoça MA, Portela JE, Plavnik F, Ventura RP, Lotaif L, Ramos OL (1992) Isradipine in the treatment of hypertensive crisis in ambulatory patients. J Cardiovasc Pharmacol 19(Suppl 3):S76–S78PubMedGoogle Scholar
  54. 54.
    Pennisi AJ, Takahashi M, Bernstein BH, Singsen BH, Uittenbogaart C, Ettenger RB, Malekzadeh MH, Hanson V, Fine RN (1977) Minoxidil therapy in children with severe hypertension. J Pediatr 90:813–819PubMedCrossRefGoogle Scholar
  55. 55.
    Strife CF, Quinlan M, Waldo FB, Fryer CJ, Jackson EC, Welch TR, McEnery PT, West CD (1986) Minoxidil for control of acute blood pressure elevation in chronically hypertensive children. Pediatrics 78:861–865PubMedGoogle Scholar
  56. 56.
    Murphy MB, Murray C, Shorten GD (2001) Fenoldopam – a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N Engl J Med 345:1548–1557PubMedCrossRefGoogle Scholar
  57. 57.
    Nordlander M, Sjöquist P-O, Ericsson H, Rydén L (2004) Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev 22:227–250PubMedGoogle Scholar
  58. 58.
    Powroznyk AVV, Vuylsteke A, Naughton C, Misso SL, Holloway J, Jolin-Mellgård Å, Latimer RD, Nordlander M, Feneck RO (2003) Comparison of clevidipine with sodium nitroprusside in the control of blood pressure after coronary artery surgery. Eur J Anaesthesiol 20:697–703PubMedCrossRefGoogle Scholar
  59. 59.
    Dooley M, Goa KL (1998) Urapidil. A reappraisal of its use in the management of hypertension. Drugs 56:929–955PubMedCrossRefGoogle Scholar
  60. 60.
    Woisetschläger C, Bur A, Vlcek M, Derhaschnig U, Laggner AN, Hirschl MM (2006) Comparison of intravenous urapidil and oral captopril in patients with hypertensive urgencies. J Hum Hypertens 20:707–709PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2008

Authors and Affiliations

  1. 1.Pediatric Hypertension Program, Department of PediatricsUniversity of Washington School of MedicineSeattleUSA
  2. 2.Division of Nephrology, A-7931Children’s Hospital & Regional Medical CenterSeattleUSA
  3. 3.Great Ormond Street Hospital for ChildrenLondonUK

Personalised recommendations