957CHAPTER 78 Acute Severe Hypertension to increase fluid intake; no increase in serum creatinine levels or adverse hemodynamic effects were observed 112 Like other drugs that act through adrenergic r[.]
CHAPTER 78 Acute Severe Hypertension to increase fluid intake; no increase in serum creatinine levels or adverse hemodynamic effects were observed.112 Like other drugs that act through adrenergic receptor stimulation, tolerance develops in patients who take fenoldopam for longer than 48 hours Fenoldopam has the potential to increase intraocular pressure and is known to cause dose-dependent tachycardia.107,111 Minoxidil is a direct vasodilator that opens potassium channels in smooth muscle cells, causing potassium efflux, which, in turn, leads to hyperpolarization and relaxation.113 It acts primarily on arterioles and does not produce venous dilation Minoxidil generally acts within hour and its effects may last as long as to 12 hours It is renally excreted and easily removed by dialysis Therefore, dose adjustment may be needed in patients with severe renal insufficiency, and it should be dosed after dialysis.113 Minoxidil has been shown to be effective in children with severe chronic HTN refractory to other oral agents114 and in children with chronic HTN experiencing acute BP elevations.115 It has well-known side effects of hirsutism and fluid retention that are primarily seen with chronic use; thus, these should not be a significant consideration in the acutely hypertensive patient Short-acting nifedipine was previously used for acute severe HTN and may still be available in some centers but is no longer recommended One retrospective case series showed that a significant proportion of patients administered short-acting nifedi pine had BP reductions greater than 25% after the initial dose.62 Other adverse effects of short-acting nifedipine have been reported, including arrhythmia.116 The drug itself is a gelatin capsule containing an oil-based liquid with drug concentrations of either 20 mg/mL or 30 mg/mL depending on manufacturer that cannot be compounded into a stable suspension This makes accurate administration to young patients extremely difficult Since more stable and more easily administered alternatives are available, short-acting nifedipine use should be avoided in patients with acute severe HTN.117 Nitroglycerin is principally a venodilator, although arteriolar dilation occurs at higher doses Once nitroglycerin is converted to NO, it activates guanylate cyclase within smooth muscle (similar to nitroprusside) and stimulates the production of cGMP The result is increased venous capacitance with a predictable decrease in myocardial preload.118 In volume-depleted patients, reduction of myocardial preload reduces CO and is undesirable, especially in patients with compromised myocardial, cerebral, or renal perfusion.119 Onset of action of IV nitroglycerin is to minutes, with a duration of action of to minutes.120 Common adverse effects include headache, orthostatic hypotension, nausea, palpitations, and flushing The hemodynamic effects of nitroglycerin may be deleterious in patients with anatomically restrictive cardiac lesions, such as aortic stenosis or other left-sided obstructive cardiac lesions Furthermore, nitroglycerin should be avoided in patients with increased ICP because of its cerebral vasodilatory properties Special Situations Preeclampsia Pregnancy associated with preeclampsia also must be considered in female adolescents experiencing acute severe HTN Preeclampsia is a state of hypertensive proteinuria in a pregnant woman who is at greater than 20 weeks’ gestation.121 Clinically, the classic triad 957 of preeclampsia consists of HTN, proteinuria, and edema, although now it is accepted that edema should no longer be considered a prerequisite for making the diagnosis of preeclampsia Under these circumstances, an elevated BP separated by a minimum of hours (maximum days) is considered adequate for making a diagnosis for HTN (.140/90 mm Hg) or severe HTN (.160/100 mm Hg) Proteinuria is considered significant when two random urine samples collected at least hours (but ,7 days) apart have a level of 30 mg/dL or higher (11) or 300 mg or more of protein are present in a 24-hour urine collection.121 In the absence of proteinuria, pregnancy-induced HTN, gestational HTN, or chronic HTN must be considered The goal of managing preeclampsia is to meticulously control the BP in order to protect the fetus from insufficient placentaluterine blood flow via overly aggressive antihypertensive therapy and to avoid development of eclampsia (the condition characterized by tonic-clonic seizure activity culminating in coma) IV antihypertensives that are commonly used for acute severe HTN in pregnancy include labetalol and hydralazine However, other drugs—including esmolol and nicardipine—have been safely used.122 Pheochromocytoma Although rare as a cause of HTN in childhood,123 pheochromocytomas present a unique set of management challenges to the intensivist Many children with pheochromocytomas initially present with severe, symptomatic HTN of unknown etiology.124 Such children require careful immediate stabilization and gradual BP reduction as described in the preceding sections until the necessary studies can be obtained to establish the diagnosis Although, theoretically, the a- and b-adrenergic blocker labetalol may seem uniquely well suited for treatment of HTN caused by a pheochromocytoma, in practice a continuous infusion of any of the IV antihypertensives listed in Table 78.3 could be used for initial BP management Phentolamine has also been advocated in such patients, although pediatric experience with this agent is extremely limited Once the diagnosis of pheochromocytoma has been made, the child’s BP should be stabilized with oral antihypertensives until the tumor can be surgically removed Phenoxybenzamine, a potent a-adrenergic blocker, is usually recommended as the primary agent for this phase of management, although there has been a recent trend toward use of the long-acting peripheral a-adrenergic antagonist doxazosin for a-blockade.125 b-adrenergic blockade is frequently advocated as adjunctive therapy to counter tachycardia in patients treated with phenoxybenzamine In the ICU setting, it is likely that these oral agents will need to be overlapped with IV therapy followed by gradual discontinuation of IV therapy Goal BP does not need to be reached prior to patient transfer out of the ICU, but the BP should be sufficiently controlled so that the patient is no longer experiencing symptoms of severe HTN The patient with pheochromocytoma may present back to the ICU following surgical removal of the tumor, usually for a brief period to ensure that the BP has stabilized Intraoperatively, BP surges and arrhythmias may occur due to manipulation of the tumor These complications are typically treated with use of rapidly acting IV antihypertensive agents and beta-adrenergic blockade Volume resuscitation may be required immediately following removal of the tumor, but postoperative volume overload is not a significant concern 958 S E C T I O N V I I Pediatric Critical Care: Renal Summary Severe HTN is a potential medical emergency that needs to be addressed immediately After a brief evaluation of the possible etiology, antihypertensive treatment should be initiated This is mostly done with IV agents A number of options exist, albeit many not well studied in children The intensivist needs a heightened awareness for factors that predispose children to severe hypertensive events as well as an understanding of the clinical symptoms that may reflect end-organ damage from critically high BPs Key References Blumenfeld JD, Laragh JH Management of hypertensive crises: the scientific basis for treatment decisions Am J Hypertens 2001;14:1154-1167 Brouwers FM, Eisenhofer G, Lenders JW, Pacak K Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma Endocrinol Metab Clin North Am 2006;35:699-724 Curran MP, Robinson DM, Keating GM Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indications Drugs 2006;66:1755-1782 Flynn JT, Bradford MC, Harvey EM Intravenous hydralazine in hypertensive children and adolescents J Pediatr 2016;168:88-92 Flynn JT, Kaelber DC, Baker-Smith CM, et al Clinical practice guideline for screening and management of high blood pressure in children and adolescents Pediatrics 2017;140:e20171904 Flynn JT, Pasko DA Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension Pediatr Nephrol 2000;15: 302-316 Flynn JT, Tullus K Severe hypertension in children and adolescents: pathophysiology and treatment Pediatr Nephrol 2009;24:11011112 Ishikura K, Hamasaki Y, Sakai T, et al Posterior reversible encephalopathy syndrome in children with kidney diseases Pediatr Nephrol 2012;27:375-384 Jain A, Baracco R, Kapur G Pheochromocytoma and paraganglioma-an update on diagnosis, evaluation, and management Pediatr Nephrol 2020;35:581-594 Lee GH, Lee IR, Park SJ, et al Hypertensive crisis in children: an experience in a single tertiary care 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prophylaxis... diagnosis of renovascular hypertension Pediatr Nephrol 2017;32:495-502 The full reference list for this chapter is available at ExpertConsult.com e1 References Flynn JT The changing face of pediatric... hypertension in children and adolescents Curr Hypertens Rep 2012;14:591-595 52 Shahdadpuri J, Frank R, Gauthier BG, et al Yield of renal arteriography in the evaluation of pediatric hypertension Pediatr