947CHAPTER 78 Acute Severe Hypertension South Korea that likely reflects the patient population seen in most tertiary centers 17 Severe fluid overload in dialysis patients or noncompliance with antihy[.]
CHAPTER 78 Acute Severe Hypertension • Box 78.2 Causes of Severe Hypertension in Children and Adolescents Renal Disease Malignancy Glomerulonephritis (GN), especially membranoproliferative GN Reflux nephropathy Obstructive uropathy Acute kidney injury Polycystic kidney disease Hemolytic-uremic syndrome End-stage renal disease at presentation Pheochromocytoma Wilms tumor Neuroblastoma Other Medication noncompliance in a patient with known hypertension Drug-induced (see Box 78.1) Primary hypertension (rare) Vascular Aortic coarctation (thoracic, abdominal) Renal artery stenosis Vasculitis South Korea that likely reflects the patient population seen in most tertiary centers.17 Severe fluid overload in dialysis patients or noncompliance with antihypertensive therapy in patients with established HTN of any cause may also result in severe, symptomatic HTN requiring immediate treatment This was clearly demonstrated in a case series of adults presenting to the emergency department of a teaching hospital in the United States.18 In that study, 90% of patients requiring intervention for a hypertensive urgency had a known diagnosis of HTN; the most common contributing factors to the severe BP elevation included running out of prescribed medications and medication noncompliance While no similar pediatric data exist, anecdotal experience suggests that similar acute presentations with severe HTN may occur in chronically hypertensive children and adolescents followed at referral centers Finally, abrupt withdrawal of either clonidine or a beta-adrenergic blocker may result in severe “rebound” HTN that may require prompt intervention Pathophysiology The mechanisms responsible for generating and maintaining acute severe HTN continue to be elucidated What seems plausible in many cases is that there is a triggering event that precipitates a dramatic increase in BP over a short time period in a patient who is hypertensive at baseline This event then leads to further arteriolar damage that prolongs the hypertensive state Mean arterial pressure (MAP) is approximately equal to the product of cardiac output (CO) and systemic vascular resistance (SVR), as expressed mathematically as MAP CO SVR (Central venous pressure should be subtracted from the MAP in this equation but is usually so small it can be ignored.) Thus, factors that increase either CO or SVR lead to elevated BP if the other does not decrease proportionally In addition, chronically, these factors have an interdependent interaction that is still poorly understood For example, while the initiating event leading to HTN may cause a rise in CO, a compensatory rise in peripheral vascular resistance often develops that may persist even after CO returns to baseline.19 Endothelial Homeostasis The endothelium seems to play a crucial role in the development of severe symptomatic HTN The endothelium is on the receiving 947 end of the excessive pressures and shear stress generated from high blood flows along with concomitant increased resistance imparted by the vascular architectural scaffolding and surrounding smooth muscle cells (see also Chapter 23) Aside from structural trauma, endothelial cell function is also affected For instance, the stressed endothelial cell increases intracellular levels of nuclear factor-kB (NF-kB) In turn, NF-kB leads to generation of inflammatory mediators that lead to endothelial dysfunction and vascular injury.20,21 Adults with primary HTN who experienced acute severe HTN demonstrated a significant decline in BP when given l-arginine (a precursor of nitric oxide [NO]) compared with patients who also had primary HTN but had not experienced a similar event This observation underscores the importance of the endothelium in the pathogenesis of acute severe HTN because an intact functional endothelial cell surface is necessary to respond to l-arginine.22 Von Willebrand factor (an endothelial cell surface marker), P-selectin (platelet activation), and fibrinogen serum levels were all increased in hypertensive adult patients with acute severe HTN compared with control hypertensive subjects, suggesting that alterations in the homeostasis of the endothelial and/or the coagulation system occur during an episode of acute severe HTN.23 Sympathetic Nervous System Activation A common cause of increased CO in hypertensive individuals is sympathetic nervous system (SNS) activation,24 often in concert with an increase in intravascular volume At the same time, SNS activation further increases SVR, exacerbating the rise in BP The therapeutic approach to HTN depends on reducing SVR and often suppressing or reducing SNS activation Without the latter being suppressed, the drop in SVR mediated by a vasodilator may be compensated by an increase in sympathetic activation, with a resultant increase in CO and no net reduction in BP The SNS can also be the cause of severe HTN This is particularly seen in children with pheochromocytomas and other tumors that produce vasoactive substances, including neuroblastoma.25 End-stage kidney disease is characterized by SNS activation,24 which can contribute to a substantial increase in catecholamines and renin, which then can contribute to HTN.26 Increased SNS activity can worsen severe HTN in several conditions, including renovascular HTN and polycystic kidney disease, and seems to be unrelated to the level of kidney function Renal ischemia triggered by these diseases seems to cause the systemic overactivation.27 Activation of the SNS leading to systemic vasoconstriction is generally accepted as the mechanism of severe postoperative HTN.28 Renin-Angiotensin-Aldosterone System The renin-angiotensin-aldosterone system (RAAS) plays a prominent role in many patients with acute severe HTN.21,29 Renin is a proteolytic enzyme synthesized in the juxtaglomerular cells of the afferent renal arterioles that cleaves angiotensinogen (an a2-globulin synthesized in the liver) to create angiotensin I (a decapeptide) In turn, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II (an octapeptide), which acts at the angiotensin type receptor (a Gcoupled receptor found in renal afferent and efferent arterioles) to cause vasoconstriction, increased aldosterone release, and enhanced sodium and water reabsorption.19 S E C T I O N V I I Pediatric Critical Care: Renal Increased serum renin levels can reflect a primary condition, such as renovascular disease, or can be secondary to renal parenchymal ischemia, hypotension, hypovolemia, increased sympathetic effects, b-adrenergic agonists, or a combination of these factors.19,30 Ultimately, increased renin levels raise BP through a number of mechanisms primarily mediated through angiotensin II Aside from its vasoconstrictive properties, angiotensin II increases the expression of aldosterone that leads to increased renal sodium and water retention, thus augmenting CO by increasing intravascular volume Angiotensin II also induces the expression of interleukin-6 and NF-kB; this, in turn, leads to elevated levels of tumor necrosis factor-a and increases nicotinamide adenine dinucleotide phosphate oxidase activity The latter initiates generation of reactive oxygen species, promoting oxidative stress, and inhibits the cytokine-mediated activation of inducible-nitric oxide synthase (iNOS) that attenuates vasodilation.19 Over time, the collective result of these processes is enhanced and sustained endothelial cell trauma, vascular dysfunction, and ultimately, end-organ damage Nitric Oxide NO, now recognized as a ubiquitous biological effector, is a labile, short-lived chemical produced from arginine via NO synthases.31 These synthases are distinguished by cellular distribution and by the requirement for calcium as a cofactor The constitutive isoform of NOS is believed most responsible for basal vasomotor tone, although iNOS may have a role NO is released continuously from arteries and arterioles but not from veins In addition, other mediators function through the NO system For instance, bradykinin stimulates the release of NO to produce vasodilation NO diffuses from the endothelium to the vascular smooth muscle cell, where it produces its vasodilatory effect in part by increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP) through stimulation of soluble guanylate cyclase NO that diffuses from the local endothelial environment reacts with hemoglobin, forming nitrosohemoglobin and methemoglobin Thus, HTN need not be attributed only to a direct vasoconstrictor effect but also may be related to loss of basal NO vasodilation Antihypertensive drugs used in acute severe HTN, such as sodium nitroprusside and nitroglycerin, produce their systemic vasodilator action by stimulating NO production (see HTN management section that follows) Volume Overload An acute increase in intravascular volume is a frequent cause of acute decompensation of BP control in a patient with chronic HTN, particularly in the setting of stimuli that increase SNS and/ or RAAS activation Volume overload is the most common mechanism leading to HTN in children with renal diseases It is often caused by AKI with oliguria or anuria in those without preexisting renal disease Although volume overload is a common cause of acute severe HTN, pressure diuresis may render some patients relatively hypovolemic, producing hemoconcentration and further marked activation of the RAAS.29 Further volume depletion may actually worsen HTN by stimulating a further increase in SVR with the potential for organ ischemia Thus, diuretics and fluid restriction are not standard therapy for most patients who present with acute severe HTN; they are reserved for patients with clinically apparent fluid overload.29,32 One patient population in whom fluid overload is probably the most important contributing factor to episodes of severe HTN are children and adolescents on dialysis Fluid overload in dialysis patients most often results from poor adherence to dietary sodium and fluid restriction Chronic underdialysis and failure to consistently reach “dry weight” may lead to gradual fluid accumulation that can be clinically imperceptible until the child presents with acute severe HTN This may happen even in the best dialysis center due to the difficulty in assessment of fluid status in children and because differences in body weight may be attributed to growth instead of to fluid accumulation.33 Clinical Presentation The presentation of a patient with acute severe HTN depends on underlying medical conditions, baseline systemic BP, rate of rise and degree of BP elevation, and effects on end organs Headache, dizziness, and nausea/vomiting are common presenting complaints in patients with acute severe HTN, as was recently demonstrated in two pediatric case series of patients with acute severe HTN.17,34 Visual impairment is another common presenting complaint in patients with acute severe HTN and may signal the presence of CNS involvement.35 A small number of severely hypertensive children may manifest isolated abdominal pain with or without vomiting.36 Although exceedingly rare in the pediatric age group, aortic dissection may present with severe HTN along with the abrupt onset of chest or back pain.37 Neurologic manifestations of acute severe HTN are probably most common in children Symptoms may include seizures, lethargy, confusion, headache, and visual disturbances, especially cortical blindness Hypertensive encephalopathy (increased blood flow with pressures exceeding the autoregulatory range) typically presents as a severe headache with dizziness and changes in mental status ultimately culminating as seizures Other reported symptoms include facial palsies and visual changes that may lead to blindness and coma.14,38,39 Hypertensive encephalopathy may occur with a MAP below 200 mm Hg in the normotensive individual, but it may require a much higher MAP in patients who have sustained HTN (Fig 78.1) Cardiac manifestations of severe acute HTN can also be seen in children, although not as often as in adults These may include asymptomatic left ventricular hypertrophy, acute congestive heart failure with pulmonary edema, and myocardial ischemia.40,41 In two case series of children with severe HTN from the Great Ormond Street Hospital, the incidence of left ventricular hypertrophy ranged from 13% to 66%, and the incidence of congestive heart failure was 9%.14,42 Clearly, a high index of suspicion for an 140 Cerebral blood flow (mL 100 g–1 min–1) 948 Cerebral hyperperfusion Vasoconstriction 70 Vasodilation Autoregulation failure 60 120 160 Mean arterial pressure (mm Hg) • Fig 78.1 Altered cerebral blood flow autoregulation in chronic hypertension CHAPTER 78 Acute Severe Hypertension underlying cause of HTN should be maintained in a patient who presents acutely with cardiac symptoms and severe HTN and appropriate investigation initiated Severely hypertensive children can also exhibit evidence of AKI, such as hematuria, albuminuria, and azotemia However, in many cases, attempts to determine the acute renal effects of severe HTN may be complicated by the frequent association of renal parenchymal and/or renovascular disease with systemic HTN in children Moreover, hypertensive pathology is not usually limited to a single organ like the kidney; other end-organ abnormalities usually can be seen, such as left ventricular hypertrophy and neurologic sequelae (such as mental status changes, seizures, and cerebrovascular accidents) Nevertheless, children with severe HTN resulting from vasculitis have been found to have nephrotic range proteinuria, microscopic hematuria, elevated serum creatinine levels, and diminished glomerular filtration rates.43–45 Patient Evaluation and Monitoring Blood Pressure Measurement and Other Monitoring The most critical component of identifying and monitoring patients with acute severe HTN is accurately measuring BP Both noninvasive and invasive techniques may be used in the ICU setting and are commonly used together The main techniques available to determine BP in the ICU are the auscultatory method, oscillometric method, Doppler method, and invasive hemodynamic monitoring Auscultatory, oscillometric, and Doppler BP methods are noninvasive techniques that are based on the return of blood flow through a major artery after compression by an inflatable cuff Auscultatory methods require the observer to listen to the Korotkoff sounds generated as the sphygmomanometer cuff deflates Korotkoff sounds and should be used to represent systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively It should be noted that the current pediatric normative BP values were generated using this technique over the brachial artery; therefore, it is the preferred site of BP measurement in children and adolescents.4 To obtain accurate measurements, it is important that an appropriately sized cuff size be used, which should cover 80% to 100% of the upper arm circumference Although auscultation can be time-consuming,46 it can be helpful to confirm BP values obtained by other methods Oscillometric techniques use a similar technique except that the MAP is first determined from oscillometric wave forms generated as blood flow returns through the artery SBP and DBP are then calculated using a proprietary formula specific to the brand of monitor Oscillometric methods are known to overestimate both SBP and DBP,47 but since the devices can be programmed to take repeated BP measurements at regular intervals, they can provide vital information regarding BP trends Doppler devices use changes in ultrasound frequency to infer velocity of blood flow The Doppler shift corresponds to the turbulent flow, as signified by the Korotkoff sounds, that diminishes as laminar flow predominates.48 As with the auscultatory method, selection of an appropriate cuff size is paramount for both the oscillometric and Doppler BP methods Invasive arterial lines are fluid-filled tubes attached to a pressure transducer—a device consisting of a thin, flexible diaphragm connected to a strain gauge and capable of converting the pressure transmitted to an electrical signal (see Chapter 26) The most common source of inaccuracy is the influence of electrical damping on reported BP An overdamped signal underestimates 949 both SBP and DBP, although MAP may be accurate On the other hand, an underdamped system overestimates SBP, especially with a hyperdynamic circulation, but does not affect MAP This phenomenon is recognized as a narrow-peaked pressure wave and wide pulse pressure Moreover, invasive BP measured in the lower extremity is higher than in the upper extremities because of the nature of BP wave transmission, which results in an increase in SBP reading the farther away from the heart it is measured Generally, children with acute severe HTN need to be closely monitored in a controlled setting, such as the ICU, and the ideal way to continuously follow BPs is with the aid of an indwelling arterial catheter Arterial lines can be placed in a variety of locations, but usually they are placed in peripheral arteries that supply areas with robust collateral blood flow Common sites include the radial, dorsalis pedis, and posterior tibial arteries Continuous intraarterial BP monitoring is generally preferred for patients with acute severe HTN because of the lability of BP when continuous infusions of IV medications are used However, using noninvasive techniques to confirm that transduced values are accurate is a quite common practice because electrical damping of the transduced signal can cause inaccuracies in SBP and DBP, although MAP is likely to be less affected Additionally, as mentioned previously, modern oscillometric devices can be programmed to take repeated measurements of BP at short intervals Therefore, they may sometimes be acceptable for short time periods or for patients without life-threatening symptoms Other important aspects of monitoring the patient with acute severe HTN include pulse oximetry and frequent neurologic assessment Appropriate IV access should be established; ideally, there should be an IV line placed that is used only for administration of antihypertensive medications Monitoring of central venous pressure may also be helpful in selected patients, especially when volume status is otherwise difficult to assess A central line may also be needed for administration of intravenous antihypertensive medications, such as nicardipine Finally, an indwelling Foley catheter may be needed for urine output monitoring, especially in severely hypertensive patients with known or suspected acute or chronic kidney disease Diagnostic Evaluation Evaluation should be targeted at identifying underlying etiology and potential signs of injury to the cardiovascular, nervous, renal, and ocular systems A detailed history and review of systems should be obtained for all patients, with special care paid to symptoms suggestive of an underlying hypertensive disorder or targetorgan damage (Table 78.2) Signs and symptoms often reflect severity and rapidity of onset of HTN Chronic HTN is more commonly asymptomatic or characterized by low-grade generalized symptoms such as fatigue and recurrent headaches As already discussed, acutely hypertensive patients may present with a wide range of symptoms, with headache, nausea, seizures, and other neurologic complaints among the most common Physical examination should include BP measurements in all four extremities (or at least both arms and one leg) as a screening for coarctation of the aorta, which should be suspected if upper extremity pressures are higher than lower extremity pressures and lower extremity pulses are weak or absent Special attention also should be paid to heart rate because HTN with associated bradycardia is suggestive of increased intracranial pressure (ICP) Rapidly lowering BP in this setting could lead to decreased cerebral perfusion and its associated sequelae A thorough cardiac examination 950 S E C T I O N V I I Pediatric Critical Care: Renal TABLE History and Physical Examination Findings in Hypertension 78.2 Finding Possible Significance Historical Findings Complaint/Review of Systems Finding Possible Significance Head and Neck Moon facies Cushing disease Elfin facies Williams syndrome Proptosis/goiter Hyperthyroidism Web neck Turner syndrome Adenotonsillar hypertrophy Sleep disorders Underlying renal disease Fundal changes Chronic or severe HTN Joint pains/swelling, edema, rashes Autoimmune-mediated disease/ glomerulonephritis Friction rub Systemic lupus erythematosus, collagen vascular disease, uremia Weight loss, sweating, flushing, palpitations Pheochromocytoma or hyperthyroidism Apical heave Left ventricular hypertrophy Muscle cramps, weakness, constipation Hypokalemia associated with hyperaldosteronism Disparity in pulses Coarctation Delayed puberty Congenital adrenal hyperplasia Snoring Sleep apnea Prescription, over-the-counter, or illicit drug use Drug-induced HTN Headaches, dizziness, epistaxis, visual changes Nonspecific with respect to etiology of HTN Abdominal/flank pain with hematuria Renal artery or vein thrombosis Hematuria, swelling, decreased urine output Acute glomerulonephritis Dysuria, frequency, urgency, nocturia, enuresis Cardiovascular Medical History Umbilical artery catheterization Renal artery thrombosis/renal embolus Previous urinary tract infections Renal scarring Thyroid cancer, neurofibromatosis, von Hippel Lindau disease Pheochromocytoma Heart failure Abdomen Masses Obstructive nephropathy, Wilms tumor, neuroblastoma, pheochromocytoma, polycystic kidney disease Hepatomegaly Heart failure Bruit Renal artery stenosis, abdominal coarctation Genitalia Ambiguous, virilized Congenital adrenal hyperplasia Extremities Family History HTN Lungs Crackles/rales Inherited forms of HTN (AME, Gordon syndrome, Liddle syndrome, GRA), essential HTN Renal disease Polycystic kidney disease, Alport syndrome Tumors Familial pheochromocytoma, multiple endocrine neoplasia type II Physical Examination Findings Vital Signs Tachycardia Hyperthyroidism, pheochromocytoma, neuroblastoma, primary HTN Bradycardia Increased ICP (tumor, hydrocephalus) Drop in BP from upper to lower extremities Coarctation of aorta General Edema Underlying kidney disease Joint swelling Autoimmune disease Rickettsial changes Chronic kidney disease Dermatologic Neurofibromas Neurofibromatosis Tubers, ash leaf spots, adenoma sebaceum Tuberous sclerosis Bronzed skin Excessive adrenocorticotropic hormone Acanthosis nigricans Insulin resistance/metabolic syndrome Striae, acne Cushing disease Rashes Vasculitis/nephritis Needle tracks Drug-induced HTN Neurologic Growth retardation Chronic kidney disease Mental status changes Severe HTN Truncal obesity Cushing disease, insulin resistance Cranial nerve palsy Severe HTN AME, Apparent mineralocorticoid excess; BP, blood pressure; GRA, glucocorticoid-remediable aldosteronism; HTN, hypertension; ICP, intracranial pressure CHAPTER 78 Acute Severe Hypertension to identify signs of heart failure, a search for carotid or abdominal bruits, a fundoscopic examination, evaluation of cutaneous lesions, and a neurologic examination also are essential in the initial evaluation of patients with severe HTN With respect to the fundoscopic examination, evidence indicates that the pattern of retinal lesions can offer some information related to the onset of HTN For instance, generalized arteriolar narrowing and arteriovenous nicking were associated with longstanding systemic HTN, whereas focal arteriolar narrowing, retinal hemorrhages, microaneurysms, and cotton-wool spots were indicative of recent significant increases in BP.49 Papilledema may also be present in some patients As with any hypertensive child or adolescent, the remainder of the physical examination should be focused on identifying clues to underlying secondary causes of HTN, such as renal disease or a genetic syndrome Specific examples can be found in Table 78.2 Initial laboratory studies for all patients with acute severe HTN should include electrolytes, blood urea nitrogen, creatinine, complete blood cell count with peripheral smear, and urinalysis Many of these values may already be available if the patient has been in the ICU for any length of time Renal disease is the most common cause of secondary HTN in children; both chronic and acute renal conditions may present with acute severe HTN Anemia associated with chronic disease or a microangiopathic anemia resulting from disseminated activation of the coagulation system or hemolytic uremic syndrome may be seen as well Finally, a hypokalemic metabolic alkalosis may develop with volume depletion and secondary hyperaldosteronism Similar laboratory findings may be seen in children with inherited monogenic forms of HTN.50 Further laboratory evaluation for the cause of HTN should be targeted based on the history and physical examination findings In selected patients, thyroid studies, a drug screen, cortisol concentrations, and plasma or urinary catecholamines/metanephrines may help elicit the cause of elevated BP Given the high likelihood of underlying renal disease, nephrology consultation should be obtained in most patients with acute severe HTN to assist with patient evaluation Renal ultrasonography is indicated for most patients to evaluate for renal parenchymal lesions such as small scarred kidneys, polycystic kidney disease, obstruction, or other structural anomalies Doppler evaluation of blood flow to the kidneys also should be performed, although this evaluation is less sensitive than in adults at identifying subtle renal artery stenosis in smaller children and therefore is not always helpful if negative.51 Although both computed tomography (CT) and magnetic resonance (MR) angiography have shown some promise as a screening tool for renal artery stenosis, renal arteriography, sometimes in conjunction with renal vein renin sampling, remains the gold standard for identifying this lesion.51–53 Further renal imaging, such as a dimethylsuccinic acid scan, may be indicated in children who are suspected of having renal scarring These advanced imaging studies can often be deferred until after the patient’s BP has been stabilized A chest radiograph and echocardiogram should be obtained at presentation to look for signs of heart failure and evidence of ventricular hypertrophy An echocardiogram is also useful to assess for congenital anomalies, such as a coarctation of the aorta Electrocardiography may be helpful to assess for abnormalities of cardiac conduction but is not recommended as an assessment for left ventricular hypertrophy in the pediatric age group.4 A head CT scan or MR imaging (MRI) should be done in patients with concern for increased ICP In children with cerebral edema or increased ICP, increased BP may develop as a strategy to 951 preserve cerebral perfusion due to the increased resistance to cerebral blood flow Initially, a child with traumatic brain injury will often maintain sufficient cerebral blood flow over a range of BPs because of the brain’s capacity for autoregulation, as depicted in Fig 78.1 However, if the resistance to cerebral blood flow increases, such as when ICP rises from cerebral edema, then the patient may compensate through cerebral vasodilation or increased CO to meet the metabolic needs of the brain Cerebral vasodilation, however, will only increase ICP further To attempt to maintain adequate cerebral blood flow, the perfusion pressure must increase, as noted in the following mathematical relationship: Cerebral perfusion pressure Mean arterial pressure (MAP) ICP In such situations, it is prudent to undertake measures to control brain edema through hyperosmolar therapy, judicious sedation/analgesia, and avoiding maneuvers that might inadvertently increase ICP while cautiously securing the airway to control oxygenation and ventilation Efforts to directly lower systemic BP can undermine the patient’s ability to support injured but viable cerebral tissue MRI of the brain should be obtained for patients with other neurologic symptoms The most common brain-associated finding in children with acute severe HTN has been termed posterior reversible encephalopathy syndrome (PRES) PRES is characterized by the sudden onset of severe HTN, headaches, altered mental status, seizures, visual loss, and even cortical blindness.35,54,55 Neuroimaging studies during PRES typically demonstrate cerebral edema affecting the white matter in a parieto-occipital distribution.35 PRES is associated with immunosuppressive therapy (especially cyclosporine and tacrolimus), acute glomerulonephritis, eclampsia of pregnancy, and hypertensive encephalopathy (Fig 78.2).56,57 Hypertensive emergencies and tonic-clonic seizures were presenting features in 59% of renal transplant patients who were found to have PRES on further workup.58 In addition, nearly half of the patients with PRES had no history of uncontrolled chronic HTN This constellation of symptoms and pathology, which has also been called reversible posterior leukoencephalopathy, typically resolves once the HTN is treated, but it may take weeks to months for the imaging abnormalities to normalize.35,58 Pharmacologic Therapy General Considerations The therapeutic strategy for patients with acute severe HTN depends on the clinical context of the BP elevation Hypertensive children returning from surgery need to be adequately sedated and given sufficient analgesia postoperatively for comfort and to control sympathetic activation It is not uncommon for children to return to recovery areas, general care floors, and ICUs with variable levels of anesthetics still circulating that can permit pain, anxiety, and emergence phenomena that could be accompanied by elevated BPs This situation by no means minimizes the potential detrimental effects of severely elevated SBPs or DBPs if they are inadequately treated or ignored It is prudent to ascertain the patient’s volume status while determining the best management approach Some clinical situations, such as the presence of pulmonary edema and AKI, clearly identify the child with probable fluid overload On the other hand, other children with significant HTN may exhibit a pressure-induced diuresis associated with secondary activation of the ... increasing intravascular volume Angiotensin II also induces the expression of interleukin-6 and NF-kB; this, in turn, leads to elevated levels of tumor necrosis factor-a and increases nicotinamide adenine... accumulation that can be clinically imperceptible until the child presents with acute severe HTN This may happen even in the best dialysis center due to the difficulty in assessment of fluid status... respectively It should be noted that the current pediatric normative BP values were generated using this technique over the brachial artery; therefore, it is the preferred site of BP measurement in