Ug ix-2-3 pm htn emg 05-09-2014

Hypertension in Children (Hypertensive Emergency)

Dr. R Ramesh KumarMD, DNB, FPCC, DM (Ped Crit Care), MNAMSAssistant ProfessorPediatric Critical Care UnitsDepartment of pediatricsJIPMER, Puducherry 605 006

Overview

• Case based discussion

• Work-up

• Initial management and algorithm

Pre-hospital h/o

S y m p t o m a t I c1 2 3 4 5 6 m o n t h s

Developmentally normalImmunized for ageFirst episode of major illnessNo family h/o of similar illness

Abdominal pain - 6monthsPeri-umbilical & left upper regionColicky, intermittent. Constipation

Head ache - 6monthsFrontal region, throbbing naturealternate with pain abdomenrelieved with medication

Worsening symptoms 2monthsBlurring of visionPoor appetite and loss of weight(5kgs)Polyuria and Polydipsia

Admitted for 18days144 / 96 mmHg

Ref to Higher Centre

Pediatric Emergency:

AppearanceNormal / Abnormal

Work of breathingNormal / Increased / decreased

Skin circulationNormal / Abnormal

Stable : Non-Life threatening

Primary Assessment (ABCDE): Assessment Pentagon

Airway:Open & stable

Breathing:RR 26/minEfforts: NormalAir entry: NormalAuscultation: NoneSpO2 (room air) :100%

Circulation:HR : 100/minCFT : 2 SecBP : 140/104 mmHg (116)Central pulse: GoodPeripheral pulse: GoodSkin temp: CoolRhythm: Regular

Disability:GCS 15/15Pupils –3mm RLActivity: Normal & symmetricalBlood sugar : 156mg/dl

Exposure: Temp: 37 CColour: NormalSurface finding: - - -

Pediatric emergency:

Final physiological impression

Stable

Respiratory Distress

Respiratory Failure

Compensated Shock

Hypotensive Shock

Cardiopulmonary failure

Primary brain/systemic dysfunction

Triage classification

Level 1 (resuscitation)

Level 2 (emergent)

Level 3 (urgent)

Level 4 (less urgent)

Level 5 (non-urgent)

Immediate concern

• Is it hypertension ? { definition }

• Is it hypertensive crisis ? { classify }

• End organ damage ? { asses the severity }

• Immediate goal of the Rx ? { target of therapy }

Investigations ? { underlying cause }

Immediate concern : Is it hypertension ? { definition }

Task Force on High Blood Pressure in Children and Adolescents(The fourth report). Pediatrics 2004.

• systolic blood pressure (SBP) and/or diastolic blood pressure(DBP) ≥ 95th percentile for age, height, and sex on repeatedmeasurement.

based on severity-

• stage I

between the 95th and 99th percentile plus 5mmHg.

• stage II

blood pressure >99th percentile plus 5mmHg.

Immediate concern : Is it hypertension ? { definition }

ESH/ESC guidelines 2007. J Hypertens 2009.

• term prehypertension has been changed to ‘high-normal’.

• ≥ 90th to ≤ 95th

• ≥ 120/80 even if below 90th percentile in adolescents.

• patient age =10yrs, height = 140cms, sex=male.

MABP = 101 mmHg

Immediate concern : Is it hypertensive crisis ? { classify }

• hypertensive emergencies

• hypertensive urgencies

• they exceed stage II hypertension in severity.

• require prompt pharmacologic intervention .

• however, they differ based upon clinical presentation.▫ with symptomatic end-organ dysfunction --> emergencies

▫ without symptomatic end-organ dysfunction -- > urgencies

• whether both definitions are absolutely necessary ? ? ?▫ both diagnoses require emergent therapy.

- Pediatr Nephrol 2009 - Pediatr Drugs 2011

hypertensive crises

Immediate concern : Is it hypertensive crisis ? { classify }

CNS :

GCS 15/15

Pupil –3 mm RL

Tone – N

DTR- N

Plantar : flexor

Meningeal signs: -ve

No focal deficits

Funds- papilloedema

with hypertensive

retinopathy (Grade - IV)

CVS:

S1 S2

apex at 5th ICS -MCL

soft systolic murmur present in

left parasternal area (AA)

RS :

NVBS

No added sound

P/A:

No tenderness, lump, bruit

Soft , BS+

Wt: 23kgs L- 140cms

hypertensive emergencies

Immediate concern: End organ damage? { asses the severity }

• the presentation depends on▫ underlying medical conditions▫ baseline systemic BP▫ rate of rise and degree of BP elevation▫ effects on end organs

• common Sequelae of End-Organ Damage▫ Encephalopathy▫ Acute left ventricular failure▫ Myocardial infarction & Unstable angina▫ Pulmonary edema▫ Eclampsia▫ Stroke & Head trauma▫ Life-threatening bleeding▫ Aortic dissection

Immediate concern: End organ damage? { asses the severity }

• on physical exam: findings of accelerated hypertension(papilledema, CCF, pulmonary edema)

• usually only seen in hypertensive emergencies.- Pediatr Nephrol 2009

• retinopathy : pattern of lesion related to the onset.- Clin Pediatr (Phila) 2009

• recent significant increases in BP▫ focal arteriolar narrowing & retinal hemorrhages

▫ Microaneurysms & cotton-wool spots

• long-standing systemic HTN▫ generalized arteriolar narrowing & arteriovenous nicking

-N Engl J Med 2004

Grade 1Generalised arteriolar constriction - seen as `silver wiring` and Vascular tortuosities.Grade 2+ irregularly located, tight constrictions - `AV nicking` or `AV Nipping`Grade 3+ with cotton wool spots and flame-haemorrhagesGrade 4+ with swelling of the optic disk (papillodema)

only 8.6% had evidence of retinopathy diagnosed with an ophthalmoscope

Immediate concern : End organ damage?{ asses the severity }

• strongest link between HTN and retinal changes with theirrelationship with stroke risk.

• retinal blood flow shares embryologic, anatomic, andphysiologic attributes with the cerebral circulation.

• left ventricular hypertrophy (LVH)

• correlation is lower when casual BP measurements are used.

• occurs more frequently in Hispanic and African American.

• eight percent experienced CCF with pulmonary edema.

- Pediatrics 2004 - J Pediatr 2008

Immediate concern : End organ damage?{ asses the severity }

• evidence of renal damage

• the degree of proteinuria can be correlated with the severity.

• Clinically, elevated sr creatinine and BUN levels

▫ segmental glomerular fibrinoid necrosis.

▫ prominent fibrinoid necrosis of afferent and efferent arterioles.-Arch Pathol Lab Med 2007

Immediate concern : Immediate goal of the Rx ? { target of therapy }

• Task Force on High Blood Pressure in Children andAdolescents (The fourth report). Pediatrics 2004.

• controlled antihypertensive therapy

• gradual BP decrease of ≤ 25% within the first 8 hours.

• deliberate and gradual lowering of over the next 40 hours.

• 25% first 8–12 h, 25% next 8–12 h, final 50% 24 h after that.- AIIMS protocal -Pediatr Nephrol (2009)

• MABP should be lowered no > 25% within the first hour.


• Task Force on High Blood Pressure in Children andAdolescents (The fourth report). Pediatrics 2004.

• controlled antihypertensive therapy

• Final targets

• BP ≤ 90th percentile for sex, age, and height

if end-organ damage or underlying co-morbidities such diabetes.

• All other should have their BP decreased to ≤ 95th percentile.


• autoregulation of cerebral blood flow

• autoregulation of renal blood flow

Initial management

• i.v NTG 0.25 to 0.35 µg /kg /min

target MABP 1st 8hours not < 75mmHgat 48hours 93mmHg

85

90

95

100

105

110

115

1 2 3 4 5 6 7 8 9

MA

BP

mm

Hg

Time in hour

• Proparanlol 3.8 mg /kg/ day ÷2doses

• Prazocin 277 µg /kg / day ÷4 doses

• Phenoxybenzamine 4.7 mg /kg/day ÷ 3doses

Resistant Arterial Hypertension

• defined as BP above the target range set by current guidelines despite the concurrent use of ≥ 3 antihypertensive drugs of different classes, including a diuretic, at their maximum or highest tolerated doses.

• primary aldosteronism, pheochromocytoma & Cushing's syn.• acromegaly, hyper or hypothyroidism, hyperparathyroidism and

mineralocorticoid hypertension (e.g. apparent mineralocorticoid excess, Liddle's syndrome).

• first step in evaluation is to exclude other secondary causes, particularly renal disorders.

Endocrine hypertension

- European Journal of Internal Medicine 2011

Causes of Hypertension

Mechanism of Hypertensive crisis

Investigations – Initial

• Complete blood count

• Basic metabolic panel including magnesium and phosphate

• Serum uric acid

• Fasting lipid profile

• Fasting blood glucose

• Urine analysis/culture

• Urine electrolytes, creatinine, protein

• Chest X-ray

• EKG and echocardiogram

• Renal ultrasound with doppler

Investigations ?

For end-organ damage For underlying cause

- Fundus- Neuroimaging - Carotid doppler- CXR- 12 lead ECG- ECHO- USG abdomen- Urine R/E & C/S- Hemogram

- Angiography - Nuclear scan- Hormonal study- Lipid profile

Initial investigations

• SERFTSr.Na 144, K- 4.5, Urea- 19, Cr-0.4

• Hemogram Hb-9.7, TLC-9400 (56,44,5,2),platelets- 7.85lakhs, PS-normal

• USG abdomen• Urine analysis - normal

• CXR (CT ratio 53%)

• ECG

• ECHOMild LVH and mild LV dysfunction (EF 42%)

• CPK-MB- 69U/L• CT Chest -angio

Biochemical Diagnosis of Pheochromocytoma

• Epinephrine 4.16 (<8.66)

1.69 µg / g creat (1-15)

• Nor epinephrine 147.58 (5-50)

414.57 µg / g creat (20-73)

• Dpamine 1363.84(51-474)

3831µg / g creat (164-749)

• VMA- random -HPLC 62.55 µg / g creat (1.5-5.1)

(72hours before: tea, coffee, banana, vanilla, chocolate )

Catecholamine Producing Tumors

Neural Crest

Sympathoadrenal Progenitor Cell(Neuroblasts)

Chromaffin Cell Sympathetic Ganglion Cell

Intra-adrenal Extra-adrenalPheochromocytoma

Ganglioneuroma

Neuroblastoma

Catecholamine synthesis and metabolism & Tumor Secretion

• Large Pheo: more metabolites

(metabolized within tumor before release)

• Small Pheo: more catecholamines

• Sporadic Pheo: Norepi > Epi

• Familial Pheo: Epi > Norepi

• Malignant Pheo: Dopamine, HVA

• Paraganglioma: Norepi

• Cheodectoma, glomus jugulare: Norepi

• Gangioneuroma: Norepi

• Neuroblastoma: Dopamine, HVA

{ left side }

Size cut-off - ≥ 8cms ≤

{ right side }

Urine catecholamines in paediatrics

Do I need to do 24 h collection or is a single, spot sample good enough?

• a 24 h collection on an infant or young child is difficult.

• diurnal variation in metabolite excretion.(well documented in the setting of phaeochromocytoma)

• negative spot samples are also negative on 24 h collections.

Clinical bottom line

• Untimed (random or spot), urine collection methods are as effective as 24 h collections and far more practical.

- Arch Dis Child Educ Pract Ed (2011)

Patient – random – urine sample – HPLC - positive

Urine catecholamines in paediatrics

Can I use the test to rule out phaeochromocytoma?

• higher index of suspicion is warranted.

• triad of hypertension, sweating and tremors.

• in practice, it is almost never the cause of isolated HTN.

• sensitivity of 86% and specificity of 88%.

Clinical bottom line

• Without strong clinical suspicion, urine catecholamine testing does not provide useful diagnostic information.

- Arch Dis Child Educ Pract Ed (2011)

Biochemical Diagnosis : Which Test Is Best?

• Sensitivitiesplasma free metanephrines 99% [95% CI,96%-100%]

urinary fractionated metanephrines 97% [95% CI, 92%-99%]

• Specificityurinary vanillylmandelic acid 95% [95% CI, 93%-97%]

urinary total metanephrines 93% [95% CI, 89%-97%]

plasma free metanephrines 89% [95% CI, 87%-92%]

urinary catecholamines 88% [95% CI, 85%-91%]

plasma catecholamines 81% [95% CI, 78%-84%]

urinary fractionated metanephrines 69% [95% CI, 64%-72%]

• Combinatin tests did not improve the diagnostic yield.Clinical bottom linePlasma free metanephrines provide the best test for excluding or confirming pheo

Should be the test of first choice for diagnosis of the tumor. -JAMA. 2002

Phaeochromocytoma in children - Review

• thought to be responsible for ,1% of childhood hypertension.

• benign - 0.11 & malignant - 0.02 per million.

Functioning

PhaeochromocytomasExtraadrenal sympathetic

paragangliomas

Non-functioning

Parasympatheticparagangliomas

of head and neck

-Arch Dis Child (2008)

Phaeochromocytoma in children - Review

• more common in older children.

• male preponderance in childhood. (female reproductive yr).

• overall equal sex incidence.

rule of 10

• 10% extra-adrenal (closer to 15%)

• 10% occur in children

• 10% familial (59% - 70%)

• 10% bilateral or multiple (more if familial)

• 10% recur (12% more if extra-adrenal)

• 10% malignant

• 10% discovered incidentally

Plan for definitive producer: Step -1 Localisation of tumour

• Successful management depends on- high-quality imaging to accurately localize the tumor and stage

the extent of disease.

• The choice of imaging modality depends on - the level of suspicion determined by biochemical evidence,

- previous history of a phaeochromocytoma

- inherited predisposition

• Ultrasound - initial investigation in those who are symptomatic.

• abdominal MRI or CT scan

• whole-body metaiodobenzylguanidine (MIBG)


• spiral CT: - high sensitivity (93% and 100% for adrenal gland and 90% for

extra-adrenal disease- Lesions 0.5 cm or larger can routinely be detected- iodinated contrast is related to hypertensive crises

• MRI- sensitivity 90% for extra-adrenal disease- absence of fat in pheochromocytomas (ct. benign adenomas)- superior to CT in the assessment of the relationship between the

tumor and the surrounding vessels.

• they lack specificity.

-Hematol Oncol Clin N Am (2007)


• 123 (131) -I-MIBG scintigraphy

- may lack sensitivity (80–90%), but high specificity (98%).- it is a physiologic and not anatomic study.- False negative scan

- Labetalol, reserpine, TCAs, phenothiazines (stop 4-6 wk prior)

• 111-Indium-penotreotide (somatostatin receptors)• 18F-fluorodeoxyglucose (FDG) & 6-[18F]-fluorodopamine

• Benign vs malignant (invasion of adjacent organs or metastatic disease)

• no single investigation can reliably predict malignancy before surgery.

Plan for definitive producer: Step -2 pharmacologic blockade

• manipulation of tumor can cause massive outpouring catech- hypertensive crisis, stroke,

- arrhythmias, myocardial infarction

• Before the introduction of adrenergic blockade- surgical mortality rates ranged from 24% to 50%.

• Extended release prazosin (4 times/day)- provides round the clock control of blood pressure.

- very effective in controlling paroxysms and adequate α blockade.

-HK Ganesh et al ,Indian J Pediatr 2009

• Kocak et al found that prazosin given in 3-4 divided doses- much more effective in BP control than a single daily dose.

- Int Surg 2002Normal targeted BP or development of orthostatic hypotension

Plan for definitive producer: Step -2 pharmacologic blockade

Target 90th centile

Achieved 90-95th centile

Phenoxy

Pr

az

os

in

Prazosin

Phenoxy

Ph

en

ox

y

Propranolol

liberal salt and fluid intake

Plan for definitive producer: Step -3 Pre-operative plan

• BP control 90-95th centile

• Pre-anasethetic order

• N.P.O & i.v fluid (100%)

• Stop phenoxybenzamine dose

• Shift to O.T at 6am

• Anticipated complication

• intraoperative hypertension --- hypotension

• postoperative ventilation & hypotension

• electrolyte abnormality

Plan for definitive producer: Step -4 operative & post-op

• 14 huors in O.T ( bilateral adrenalectomy)-inherited pheochromocytoma, cortical-sparing adrenalectomy

• triple-lumen IJV, intra-arterial line.

• GA & epidural (induced with thiopentone ---- fentanyl,lignocaine, vecur)

• After clamping of adrenal vessel hydrocortisone was given.

• 4 liter of fluid (colloid , crystalloids )

• Dopamine, NE, epi, dobutamine

• Shifted to PICU at 8 pm

• P-SIMV for 6hours--- spont 2hours– extubated---n-CPAP

In O.T

Plan for definitive producer: Step -4 post-op

• Sedo-analgesia (midazolam, fentanyl).

• Ceftriaxone, amikacine – 5days.

• N.P.O for 7days

• MABP 90-95th centile

• Vasoactive therapy gradually trapped off over 48hours.

• Electrolytes and RBS - Sr.Na:140----147---144---137---142---137-----131----137

- Sr.K: 4.8----3.2----4.7----3.6----3.4-----3.5-----3.4-----4.7

- RBS:107----132---85----131---151----118----125---120

• Hydrocortisone 100mg/m2/d-48hrs - tapered to 20mg/m2/day.

Proposed algorithm for the management of hypertensive crisis

Medication

Follow-up plan

• lifelong steroid hormone replacement therapy.- risk of acute adrenal insufficiency(25% to 33%).

-Hematol Oncol Clin N Am (2007)

• 1st urinary catecholamines after 1 – 2 w.

• initial - 6-monthly measurement of BP and urinary catecholamines.

• if a second or recurrent phaeochromocytoma is identified- investigation is as for the initial presentation.

- ture recurrence 12%.

• annual follow-up for life-long.

r e c a p • Contrary to traditional teaching

an identifiable germline mutation in up to 59% - 70%.

• Endocrine hypertensionprimary aldosteronism, pheochromocytoma & Cushing's syndrome.

to exclude other secondary causes, particularly renal disorders.

• Random urine collection are as effective as 24 h sample.British Society of Paediatric Endocrinology and Diabetes

raised 24 h urinary metanephrines and catecholamines on twooccasions.

• Preoperative preparation is essentialpharmacologic blockade of catecholamine

thank you

Ug ix-2-3 pm htn emg 05-09-2014

Health & Medicine

Transcript of Ug ix-2-3 pm htn emg 05-09-2014