e1 References 1 Dreisbach AW The influence of chronic renal failure on drug me tabolism and transport Clin Pharmacol Ther 2009;86(5) 553 556 2 Lalande L, Charpiat B, Leboucher G, Tod M Consequences of[.]
e1 References Dreisbach AW The influence of chronic renal failure on drug metabolism and transport Clin Pharmacol Ther 2009;86(5):553-556 Lalande L, Charpiat B, Leboucher G, Tod M Consequences of renal failure on non-renal clearance of drugs Clin Pharmacokinet 2014;53(6):521-532 Miners JO, Yang X, Knights KM, Zhang L The role of the kidney in drug elimination: transport, metabolism, and the impact of kidney disease on drug clearance Clin Pharmacol Ther 2017;102(3): 436-449 Rodieux F, Wilbaux M, Van den Anker JN, Pfister M Effect of kidney function on drug kinetics and dosing in neonates, infants, and children Clin Pharmacokinet 2015;54(12):1183-1204 Matalová P, Urbánek K, Anzenbacher P Specific features of pharmacokinetics in children Drug Metab Rev 2016;48(1):70-79 Zachwieja K, Korohoda P, Kwinta-rybicka J, et al Modification of the Schwartz equations for children increases their accuracy at eGFR 60 mL/min/1.73 m2 Ren Fail 2016;38(5):787-798 Pasala S, Carmody JB How to use… serum creatinine, cystatin C and GFR Arch Dis Child Educ Pract Ed 2017;102(1):37-43 Barreto EF, Rule AD, Murad MH, et al Prediction of the renal elimination of drugs with Cystatin C vs Creatinine: a systematic review Mayo Clin Proc 2019;94(3):500-514 Assadi F, Sharbaf FG Practical considerations to drug dosing in children with acute kidney injury J Clin Pharmacol 2016;56(4): 399-407 10 Ostermann M, Chawla LS, Forni LG, et al Drug management in acute kidney disease - Report of the Acute Disease Quality Initiative XVI meeting Br J Clin Pharmacol 2018;84(2):396-403 11 Matzke GR, Aronoff GR, Atkinson AJ, et al Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Int 2011;80(11):1122-1137 12 Vilay AM Antibiotic dosing in chronic kidney disease and end-stage renal disease: a focus on contemporary challenges Adv Chronic Kidney Dis 2019;26(1):61-71 13 Schetz M Drug dosing in continuous renal replacement therapy: general rules Curr Opin Crit Care 2007;13(6):645-651 14 Bridges BC, Askenazi DJ, Smith J, Goldstein SL Pediatric renal replacement therapy in the intensive care unit Blood Purif 2012;34(2):138-148 15 Stitt G, Morris J, Schmees L, Angelo J, Akcan arikan A Cefepime pharmacokinetics in critically ill pediatric patients receiving continuous renal replacement therapy Antimicrob Agents Chemother 2019;63(4) 16 Rizkalla NA, Feudtner C, Dai D, Zuppa AF Patterns of medication exposures in hospitalized pediatric patients with acute renal failure requiring intermittent or continuous hemodialysis Pediatr Crit Care Med 2013;14(9):e394-e403 17 Veltri MA, Neu AM, Fivush BA, Parekh RS, Furth SL Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients Paediatr Drugs 2004;6(1):45-65 18 Fissell WH Antimicrobial dosing in acute renal replacement Adv Chronic Kidney Dis 2013;20(1):85-93 19 Cefepime Pediatric and Neonatal Lexi-Drugs Hudson, OH: Lexicomp; 2019 Available at: http://online.lexi.com/ 20 Qavi AH, Kamal R, Schrier RW Clinical use of diuretics in heart failure, cirrhosis, and nephrotic syndrome Int J Nephrol 2015;2015: 975934 21 Rossi S, Picetti E, Zoerle T, Carbonara M, Zanier ER, Stocchetti N Fluid management in acute brain injury Curr Neurol Neurosci Rep 2018;18(11):74 22 Pacifici GM Clinical pharmacology of furosemide in neonates: a review Pharmaceuticals (Basel) 2013;6(9):1094-1129 23 Ellison DH Clinical pharmacology in diuretic use Clin J Am Soc Nephrol 2019;14(8):1248-1257 24 Strom BL, Schinnar R, Apter AJ, et al Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics N Engl J Med 2003;349(17):1628-1635 25 Johnson KK, Green DL, Rife JP, Limon L Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39(2):290-301 26 Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari ET, Goudevenos J, Elisaf MS Hypomagnesemia and concurrent acidbase and electrolyte abnormalities in patients with congestive heart failure Eur J Heart Fail 2002;4(2):167-173 27 Blaine J, Chonchol M, Levi M Renal control of calcium, phosphate, and magnesium homeostasis Clin J Am Soc Nephrol 2015;10(7): 1257-1272 28 Alexander RT, Dimke H Effect of diuretics on renal tubular transport of calcium and magnesium Am J Physiol Renal Physiol 2017;312(6):F998-F1015 29 Matlaga BR, Shah OD, Assimos DG Drug-induced urinary calculi Rev Urol 2003;5(4):227-231 30 Heo JH, Rascati KL, Lopez KN, Moffett BS Increased fracture risk with furosemide use in children with congenital heart disease J Pediatr 2018;199:92-98.e10 31 Bernstein PL, Ellison DH Diuretics and salt transport along the nephron Semin Nephrol 2011;31(6):475-482 32 Hoorn EJ, Ellison DH Diuretic resistance Am J Kidney Dis 2017;69(1):136-142 33 Ding D, Liu H, Qi W, et al Ototoxic effects and mechanisms of loop diuretics J Otol 2016;11(4):145-156 34 Hirose K, Li SZ, Ohlemiller KK, Ransohoff RM Systemic lipopolysaccharide induces cochlear inflammation and exacerbates the synergistic ototoxicity of kanamycin and furosemide J Assoc Res Otolaryngol 2014;15(4):555-570 35 Michael Z, Spyropoulos F, Ghanta S, Christou H Bronchopulmonary dysplasia: an update of current pharmacologic therapies and new approaches Clin Med Insights Pediatr 2018;12: 1179556518817322 36 Jentzer JC, Dewald TA, Hernandez AF Combination of loop diuretics with thiazide-type diuretics in heart failure J Am Coll Cardiol 2010;56(19):1527-1534 37 Tume SC, Goldberg J, Molossi S, Bronicki RA Pharmacologic approach to heart failure in children Curr Cardiol Rev 2016;12(2): 117-120 38 Kao LC, Durand DJ, Mccrea RC, Birch M, Powers RJ, Nickerson BG Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia J Pediatr 1994; 124(5 Pt 1):772-781 39 Higashi K, Murakami T, Ishikawa Y, et al Efficacy and safety of tolvaptan for pediatric patients with congestive heart failure Multicenter survey in the working group of the Japanese Society of Pediatric Circulation and Hemodynamics (J-SPECH) Int J Cardiol 2016;205:37-42 40 Bonilla-felix M Development of water transport in the collecting duct Am J Physiol Renal Physiol 2004;287(6):F1093-101 41 Aditya S, Rattan A Vaptans: A new option in the management of hyponatremia Int J Appl Basic Med Res 2012;2(2):77-83 42 Kobayashi S, Clemmons D, Nogami H, et al Tubular hypertrophy due to work load induced by furosemide is associated with increases of IGF-1 and IGFBP-1 Kidney Int 1995;47:818-828 43 Loon N, Wilcox C, Unwin R Mechanisms of impaired natriuretic response to furosemide during prolonged therapy Kidney Int 1989;36:682-689 44 Shah N, Madanieh R, Alkan M, Dogar MU, Kosmas CE, Vittorio TJ A perspective on diuretic resistance in chronic congestive heart failure Ther Adv Cardiovasc Dis 2017;11(10):271-278 45 Van der Vorst M, Ruys-Dudok van Heel I, Kist-van Holthe J, et al Continuous intravenous furosemide in haemodynamically unstable children after cardiac surgery Intensive Care Med 2001;27: 711-715 46 Alqahtani F, Koulouridis I, Susantitaphong P, Dahal K, Jaber BL A meta-analysis of continuous vs intermittent infusion of loop diuretics in hospitalized patients J Crit Care 2014;29(1):10-17 e2 47 Kim S, Byun Y Comparison of renal function indicators according to hydration volume in patients receiving intravenous acyclovir with CNS infection Biol Res Nurs 2015;17(1):55-61 48 Richelsen RKB, Jensen SB, Nielsen H Incidence and predictors of intravenous acyclovir-induced nephrotoxicity Eur J Clin Microbiol Infect Dis 2018;37(10):1965-1971 49 Yildiz C, Ozsurekci Y, Gucer S, Cengiz AB, Topaloglu R Acute kidney injury due to acyclovir CEN Case Rep 2013;2(1):38-40 50 Vora SB, Brothers AW, Englund JA Renal toxicity in pediatric patients receiving cidofovir for the treatment of adenovirus infection J Pediatric Infect Dis Soc 2017;6(4):399-402 51 Izzedine H, Launay-vacher V, Deray G Renal tubular transporters and antiviral drugs: an update AIDS 2005;19(5):455-462 52 Lash LH, Lee CA, Wilker C, Shah V Transporter-dependent cytotoxicity of antiviral drugs in primary cultures of human proximal tubular cells Toxicology 2018;404-405:10-24 53 Townsend DR, Bagshaw SM New insights on intravenous fluids, diuretics and acute kidney injury Nephron Clin Pract 2008; 109(4):c206-16 54 Nadeau-fredette AC, Bouchard J Fluid management and use of diuretics in acute kidney injury Adv Chronic Kidney Dis 2013;20(1): 45-55 e3 Abstract: The kidney plays an important role in fluid management, as a drug target, and as a primary elimination pathway for medications and endogenous substances Understanding medication dosing in patients with impaired renal function and in patients on renal replacement therapy is imperative to avoid therapeutic failure or medication toxicity Diuretics are used in the pediatric intensive care unit for a variety of indications Evaluating diuretic site of action, pharmacodynamics, and pharmacokinetics is critical in optimizing therapeutic goals for managing fluid and electrolyte homeostasis for pediatric critically ill patients Key words: kidney, drug dosing, diuretics, diuretic resistance, renal replacement therapy, glomerular filtration rate 78 Acute Severe Hypertension JOSEPH T FLYNN PEARLS • • • Acute severe hypertension, defined as significant blood pressure (BP) elevation with or without evidence of acute hypertensive target-organ damage, requires prompt therapy to prevent and/or ameliorate further target-organ damage The most common causes of acute severe hypertension in children are renal and cardiac conditions The central nervous system is the most commonly affected target organ Mechanisms of acute severe hypertension may include volume overload with or without renal dysfunction and/or activation of the renin-angiotensin-aldosterone system Primary (sometimes referred to as essential) hypertension (HTN) is a relatively uncommon condition in children and adolescents, with an estimated prevalence of 3% to 5%.1–3 The prevalence has increased over the past decades as a consequence of the childhood obesity epidemic and is likely to be diagnosed more often because of recent changes in the normative data used to define childhood HTN (see later discussion) While most hypertensive patients in the pediatric intensive care unit (PICU) will have secondary HTN (i.e., HTN because of another underlying condition), the increasing prevalence of pediatric primary HTN may ultimately increase the frequency that such patients present to the PICU Several questions are commonly posed to the intensivist when managing a patient with acute severe HTN What constitutes acute severe HTN in the PICU? Is this level of HTN dangerous? Does the HTN represent a transient acute response or is there an underlying chronic process to be uncovered? Is it important to manage the high blood pressure (BP) at this moment? How aggressively should it be managed? This chapter promotes understanding of the deleterious effects of severe HTN, recognition of when invasive versus noninvasive monitoring is warranted, and development of a prompt but cautious approach to management Terminology The most recent clinical practice guidelines for diagnosing and managing HTN in children and adolescents were published in 2017 by the American Academy of Pediatrics (AAP).4 They were designed to align with adult guidelines from the American Heart Association and American College of Cardiology, which were also released in 2017.5 By using a statistical definition based on the • • Treatment of acute severe hypertension requires continuous monitoring of BP and administration of intravenous antihypertensive medication(s), most commonly labetalol or nicardipine Mean arterial pressure in patients with acute severe hypertension and significant target-organ involvement should be lowered no more than 25% within the first hours to prevent harm from dropping BP and thus organ perfusion too rapidly (e.g., cerebral, coronary, or renal ischemia) distribution of BP values in the pediatric population, HTN in children and adolescents is defined as sustained systolic and/or diastolic BP elevation greater than or equal to the 95th percentile for age, gender, and height, with adult BP cutpoints used in adolescents aged 13 years or older.4 Its severity can be further classified according to the scheme in Table 78.1 Of note, the 2017 AAP guideline calls out BP readings greater than 30 mm Hg above the 95th percentile as being potentially associated with a risk of development of acute complications of HTN Severe HTN, however, has not been as rigorously defined, which has led to some confusion with respect to terminology The clinical state of a “malignant sclerosis” or “bösartig hypertension” was first reported by Volhard and Fahr in 1914 in patients with HTN and “hypernephrosclerosis.”6 In 1928, Keith et al described 81 cases of what was termed “the malignant hypertension syndrome,” which was a diagnosis made before end-stage damage of retinal, cerebral, cardiac, or renal function occurred.7,8 It was also the first description of pediatric patients with significantly uncontrolled HTN Subsequently, the terms hypertensive crisis and hypertensive emergency have appeared interchangeably in the literature, usually to denote a rapidly elevated level of either systolic or diastolic BP that is associated with end-organ damage A preferred term, acute severe hypertension, denotes this potentially dangerous condition; the terms hypertensive emergency and hypertensive urgency may be used to differentiate between levels of target-organ involvement (see later discussion) Acute severe HTN can be defined as an acute BP elevation that fulfills (and usually exceeds) the definition of stage HTN and that is accompanied by severe symptoms Physical examination and/or laboratory findings of accelerated HTN are frequently also present.9 945 946 S E C T I O N V I I Pediatric Critical Care: Renal TABLE Classification of Blood Pressure Levels in Children and Adolescents 78.1 Blood Pressure Classification Children and Adolescents ,13 Years Adolescents 13 Years Normal SBP and DBP ,90th percentile SBP ,120 mm Hg and DBP ,80 mm Hg Elevated blood pressure SBP or DBP 90th–95th percentile, or if BP is 120/80 to ,95th percentile SBP 120–129 mm Hg and DBP ,80 mm Hg Stage hypertension SBP or DBP 95th–95th percentile plus 12 mm Hg, or if BP is 130/80 to 139/89 mm Hg SBP 130–139 mm Hg or DBP 80–89 mm Hg Stage hypertension SBP or DBP 95th percentile plus 12 mm Hg, or if BP is #140/90 SBP 140 mm Hg or DBP 90 mm Hg DBP, Diastolic blood pressure; SBP, systolic blood pressure Modified from 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 Organs commonly affected by acute severe HTN include the central nervous system (CNS) (hypertensive encephalopathy, retinal vasculopathy–induced visual changes, cerebral infarction, and hemorrhage); the cardiovascular system (congestive heart failure, myocardial ischemia, aortic dissection); and the kidneys (proteinuria, hematuria, and acute renal insufficiency) Traditionally, severe HTN has been divided into hypertensive emergencies and hypertensive urgencies, the former associated with life-threatening symptoms and/or target-organ injury and the latter associated with less significant symptoms and no targetorgan injury.9,10 For example, an adolescent with seizures and hypertensive encephalopathy would be considered to be experiencing a hypertensive emergency, whereas a hypertensive child with nausea and vomiting would be classified as a hypertensive urgency This distinction is not absolute and depends on clinical judgment • Box 78.1 Drug-Induced Hypertension Drug withdrawal (narcotic, benzodiazepine)a Cyclosporine and tacrolimusa Erythropoietin Glucocorticoids and mineralocorticoids Heavy metals Maternal drug use (cocaine, heroin) 3,4-methylenedioxymethamphetamine (“ecstasy”)a Nonsteroidal antiinflammatory agents Oral contraceptive agents Rebound after withdrawal of antihypertensives (especially clonidine, methyldopa, and b-blockers)a • Sympathomimetic drugs (amphetamines, cocaine, ephedrine, lysergic acid diethylamide, phenylephrine)a • Theophylline/caffeine • • • • • • • • • • a More likely to present acutely Etiology HTN may be either primary (essential) or secondary to another underlying medical condition Children with primary HTN are frequently overweight and have positive family histories for HTN and cardiovascular disease.11 The prevalence of primary pediatric HTN increases progressively with increasing body mass index, with approximately 30% of overweight children (body mass index 95th percentile) exhibiting HTN.12 That said, although the frequency of primary HTN has been increasing,4 it is unusual in the PICU, with almost all cases of acute severe HTN being secondary to another condition.9 Secondary causes of HTN can either be transient or sustained The most common reasons for transiently elevated BP in a critical care unit are inadequately treated pain and agitation Without a high degree of suspicion, this can be difficult to detect, particularly if neuromuscular blockade is administered Tachycardia and eye tearing with noxious interventions are two useful clues to this condition Drug-induced HTN is also common in the critical care setting, especially when high-dose corticosteroids are administered to patients with organ transplantation and other immunologic conditions A number of other drugs associated with elevated BP are listed in Box 78.1 Reviewing all medications taken by the patient and considering the possibility of illicit drug use is therefore necessary in all patients with a significantly elevated BP A patient’s fluid balance should also be reviewed when HTN develops while in the ICU Apparently innocuous daily discrepancies between input and output can cumulatively produce significant fluid overload after several days, although this alone is not typically enough to cause acute severe HTN in the absence of other renal, cardiovascular, or CNS problems Finally, postoperative HTN is common in the ICU setting, occurring in up to 75% of patients Initially, factors such as hypoxia, hypercarbia (through its sympathomimetic effects), and pain should be promptly and adequately addressed.13 Afterward, pharmacologic therapy is indicated if HTN is refractory or sustained despite adequate ventilation, sedation, and analgesia Renal disease predominates in most pediatric case series of acute severe HTN (Box 78.2) Deal et al., from Great Ormond Street Hospital, retrospectively reviewed their experience with severe HTN in children in 1992.14 The most common causes of severe HTN in their series included reflux nephropathy, glomerular disease, renovascular disease, obstructive uropathy, and hemolytic-uremic syndrome, which together accounted for 76% of the cases In a relatively large series of children with severe HTN treated with intravenous (IV) nicardipine,15 causes included complications of organ transplantation, multiorgan failure, renovascular disease, and acute kidney injury (AKI) Renal disease accounted for 48% of patients included in a more recent case series focusing on the use of IV labetalol in severely hypertensive infants.16 Cancer complications and renal disease were the most common conditions associated with hypertensive crisis in a case series from ... uncovered? Is it important to manage the high blood pressure (BP) at this moment? How aggressively should it be managed? This chapter promotes understanding of the deleterious effects of severe... of suspicion, this can be difficult to detect, particularly if neuromuscular blockade is administered Tachycardia and eye tearing with noxious interventions are two useful clues to this condition... severe hypertension and significant target-organ involvement should be lowered no more than 25% within the first hours to prevent harm from dropping BP and thus organ perfusion too rapidly (e.g.,