50 Years Ago in TheJournalofPediatrics: The Search for Safe and Effective Treatment of Acute Severe Hypertension in Childhood

Abstract

McLaine PN, Drummond KN. Intravenous diazoxide for severe hypertension in childhood. J Pediatr 1971;79:829-32. Children with acute presentations of severe hypertension require prompt therapy to avoid end-organ effects of uncontrolled hypertension such as hypertensive encephalopathy. Usually, an intravenous antihypertensive agent is preferred, given their more rapid onset of action compared with oral medications. No matter what agent is chosen, a major concern in treating such patients is to avoid rapid hypotension, which can lead to cerebral ischemia, especially in those with chronic hypertension. McLaine and Drummond provide one of the first descriptions of using an intravenously administered drug for children with acute severe hypertension. They gave bolus doses of diazoxide, a potassium channel activator, to 16 children aged 16 days to 16 years with severe hypertension, defined as blood pressure (BP) >140/90 mm Hg. The children all had hypertension secondary to kidney disease, and many were receiving other antihypertensive agents. Reduction of mean arterial pressure occurred within 10 minutes, with reductions of 25%-35% or more of pretreatment BP levels. Although this effect would be considered excessive according to current recommendations,1Seeman T. Hamdani G. Mitsnefes M. Hypertensive crisis in children and adolescents.Pediatr Nephrol. 2019; 34: 2523-2537Crossref PubMed Scopus (25) Google Scholar the authors reported no side effects, even though in 3 patients, the diastolic BP briefly dropped to zero! Today, intravenous diazoxide is no longer in use for the treatment of acute severe hypertension—clinicians have recognized that its use is riskier than other agents such as labetalol or hydralazine. However, even these agents have safety concerns. For example, in our analysis of the use of intravenous hydralazine in hospitalized children with acute hypertension,2Flynn J.T. Bradford M.C. Harvey E.M. Intravenous hydralazine in hospitalized children and adolescents with hypertension.J Pediatr. 2016; 168: 88-92Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar approximately 30% of doses resulted in drops of mean arterial pressure that exceeded the current recommendation of no greater than a 25% reduction.1Seeman T. Hamdani G. Mitsnefes M. Hypertensive crisis in children and adolescents.Pediatr Nephrol. 2019; 34: 2523-2537Crossref PubMed Scopus (25) Google Scholar So, the search for safe and effective treatment of acute severe hypertension in childhood continues. In the absence of prospective clinical trials in this patient population, we can at least apply the findings of pioneers like McLaine and Drummond to improve patient safety and avoid untoward outcomes.