An approach to hypertensive

crisis in children and

adolescents

Mark Mitsnefes, M.D., M.S.

Division of Nephrology and Hypertension

Cincinnati Children’s Hospital Medical Center

University of Cincinnati

Definition: terminology

• Hypertensive Crisis: sudden and abrupt severe

elevation in blood pressure from baseline, life-threatening

with the potential to cause rapid end-organ damage

Hypertensive emergency Hypertensive urgency

Similar elevation in blood pressure

With end-organ damage Without end-organ damage

Hypertensive Crisis

n=55

9/46

Young et al, BMC Pediatrics 2012

11.1 Acute Severe Hypertension 2017 AAP CPG

Definition: severe? • Adults: 180/120 = 50% above 120/80 (~50th percentile)

• Children:

– 20 mmHg above 95th percentile

– “well-above 99th percentile” (US 4th Task Force)

– Stage 2 HTN: 95th percentile + 12 mmHg

– 20% above stage 2 HTN (2016 EHS)

Flynn and Tullus, 2009 Pediatric Nephrology

2017 CPG

Definition : severe? BP %

HTN

Height Percentile Height Percentile

5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th

50th 101 101 102 104 106 108 109 61 62 62 62 62 63 64

90th 113 114 115 117 119 121 122 75 75 75 75 75 76 76

95th 116 117 118 121 124 126 128 78 78 78 78 78 79 79

95th+ 12 128 129 130 133 136 138 140 90 90 90 90 90 91 91

20 mmHg > 95th %tile: >141/98

>133/90 Stage 2 (> 95th %tile +12): 50% > 50th percentile: >156/93

12-year old boy

20% > stage 2 HTN: >160/108

2017 CPG: 30mm Hg > 95th %tile - 151/108

For ≥ 13 y old using 30 mmHg > 95th percentile

13y: 155/108

14y: 160/111

15y: 162/113

16y: 164/114

17y: 165/115

For ≥ 13 y old using adult definition: 180/120

30 mmHg > stage 1 HTN: 160/110

How often is hypertensive crisis?

• Deal et al (Arch Dis Child, 1992) - London – Severe HTN (>99th %tile): 1975-1985: 110 among 453 children (24%)

referred for HTN

• McNiece et al (J. Pediatrics, 2007) - Houston – >Stage 2 HTN: 0.6% (or 19% of patients diagnosed with HTN)

• Wu et al (Arch Dis Child, 2012) – Taiwan – > Stage 2 HTN: 1995-2010: 110 cases among 202 children

diagnosed with HTN (54%) seen in ED

– Overall prevalence: 110/531,400 cases (0.021%) seen in ED

• Young et al (BMC Pediatrics 2012) - Changhua – > Stage 2 HTN: 2000-2007: 55 hypertensive crisis cases among 110

(50%) children presented in ED for HTN

Prevalence of hypertensive emergencies is

difficult to estimate because there has been no

uniform definition and methodological approach

• A 12-year-old boy presented to ER in status epilepticus

BP: 165/100

• A 12-year-old boy presented to ER with migraine headache, blurred vision, nausea, 1 vomiting episode at home

BP: 165/100

• A 12-year-old boy presented to ER with bloody urine, peripheral edema and history of sore throat 2 weeks ago

BP: 165/100

• A 12-year-old boy presented in pediatrician office for routine annual

evaluation

BP: 165/100

Does it really matter?

Flynn and Tullus, 2009 Ped Nephrology

“Careful assessment”

Major goals

• Recognize the difference between urgency and

emergency

• Prevent progression of hypertensive urgency to

emergency and development of end-organ damage

• Minimize end-organ damage in case of

hypertensive emergency

Hypertensive urgencies

• Severe hypertension without end-organ damage

– Asymptomatic

– Headache

– Nausea

– Vomiting

– Blurred vision

– Anxiety attack

Hypertensive emergency

• Hypertension which requires immediate BP reduction to prevent or limit acute end-organ damage: – Cerebral infarction

– Hypertensive encephalopathy

– Cerebral hemorrhage

– Bilateral retinal hemorrhage

– Papilledema

– CHF/Pulmonary edema

– AKI

Brain

Eyes

Heart

Kidneys

Differential diagnosis of hypertensive

encephalopathy

• Intracranial hemorrhage

• Cerebral thrombosis and infarction

• Uremia with encephalopathy

• Rapidly growing brain tumor

• Anxiety of hysterical states

• Encephalitis

• Pseudotumor cerebri

PRES: posterior reversible

encephalopathy syndrome

• Headaches

• Visual disturbances

• Confusion or altered

mental status

• Seizure

Stevens and Heran, The British Journal of Radiology, 2012

Hypertensive emergency: Neonates

• Irritability

• Feeding problems

• Failure to thrive

• Tachypnea

• Congestive heart failure

• Lethargy

• Seizures

Malignant hypertension

• Acute increase in blood pressure with or without

previous history of hypertension

• Retinopathy stages 3 or 4

• Involvement of at least 3 different target organs

• Microangiopathic hemolytic anemia

Stage 4 hypertensive retinopathy

Clinical manifestation (single–center data)

Young et al, BMC Pediatrics 2012

!!! Most frequent

Etiology

Flynn and Tullus, 2009

Stein and Ferguson, 2012

, 2012

Patel et al, 2012

Lee et al, 2016

Young et al, 2012

Renal

Malignancies

Cardiovascular

Endocrine

Neurologic

Medications/Toxins

Monogenic HTN

Mechanical stress

Fibrinoid arteriolar necrosis

Subintimal cellular proliferation

Abnormal autoregulation to maintain adequate cerebral circulation

Luminal occlusion

Ischemia

Medications that might cause

severe HTN

• Amphetamines

• Anabolic steroids

• Caffeine (newborns)

• Calcineurin inhibitors

• Cocaine

• Corticosteroids

• Erythropoietin

• Phenylephrine eye drops (newborns)

• Phenylpropanolamine (cough syrups-prescription only)

• Pseudoephedrine

• Theophylline (newborns)

Initial Evaluation

• Look for evidence of end-organ damage and possible cause:

– Brief history: known HTN, pre-existing conditions?

– Brief physical exam: to assess volume status, neurological and cardiac status, abdominal mass (?)

– Laboratory and Radiology (don’t wait for results to initiate immediate treatment)

Stein and Ferguson, Integrated BP Control 2016

What is really important:

Initial Management

The main aim of treatment

• Prevention or treatment of life-threatening complications

of hypertension-induced organ dysfunction

• Children with hypertensive crisis necessitate immediate

intervention to effectively but safely lower the BP and

should be treated in an intensive care unit (ICU)

Seeman, Hamdani, Mitsnefes. Pediatric Nephrology 2018

ICU admission will ensure:

• Intravenous access for application of IV drugs, especially prompt delivery and titration of antihypertensive medications

• Intra-arterial access for invasive BP monitoring

• Monitoring of the vital organs including neurological (e.g., Glasgow coma scale), cardiac (ECG, cardiac telemetry), and kidney status ( monitor AKI)

• Supportive therapy for possible life-threatening complications (e.g., anticonvulsives and cardiotropics)

Seeman, Hamdani, Mitsnefes. Pediatric Nephrology 2018

Decisions before starting treatment

should be made

• Which route of administration should be the

antihypertensive drug given?

• Which drug should be used?

• How fast should the BP be lowered?

• What should be treatment BP target?

Seeman, Hamdani, Mitsnefes. Pediatric Nephrology 2018

Treatment strategy

• Immediate goal: reduce BP towards mild hypertension

• Do NOT reduce BP towards normotension – threat of hypoperfusion of vital

organs, mainly brain (seizures, stroke), eyes (visual loss), heart (heart attack,

heart failure), kidney (acute kidney injury/failure)

• Phase 1: reduce BP by no more than ¼ of the planned BP reduction over

the first ¼ day (6 hours)

• Phase 2: further gradual BP reduction over the next 24-48 hours

• Phase 3: Decrease BP <95th percentile after 48 hours

0

2

4

6

8

MAP

Faster normalization of severe HTN should be avoided

as this can cause more harm than severe HTN itself

CPG 2017

15 year old adolescent with SBP 190 mmHg

1st phase: (6 hours, ¼ of planned reduction) • ¼ of 60 is 15 mm Hg: 190 – 15 = 175

Reduce BP to 175 mmHg over first 6 hours

2nd phase: (6 – 48 hours) • further gradual reduction over the next 24-48 hours to 130mmHg

3rd phase: (> 48 hours) • reduce BP below 95th percentile

Overall planned reduction to ̴ 130 (95th %):

190 -130 = 60 mmHg

• Two groups: 1) bolus treatment vs 2) continuous infusion

Current recommendations on slow BP

reduction are likely based on this table

Deal et al, Arch Dis Child 1992

Questions

• Have you seen permanent damage secondary to treatment of acute hypertension?

• Do you follow recommendations outlined previously (phase 1 and phase 2 treatment)

• How successful are you in following these recommendations?

• Can you predict the response by using IV bolus medications or short-acting oral medications?

A 15-year old male with a rare form of sarcoma (on ambulatory

treatment) developed severe headache and was seen in ED

• BP: 190/110

• Normal mental status

• Headache slightly improved with ibuprofen at home

• Kidney function test, U/A, kidney U/S and head CT

are ordered

Treatment Oral or IV?

Hydralazine IV

Minoxidil PO

Isradipine PO

Clonidine PO

Nicardipine PO

Labetalol IV 145/90 (one hour after the dose)

Guidelines: 25% of desired reduction over 6-8 hours: 175 mmHg

Pazopanib (Multityrosine Kinase Inhibitor)

A 16-year old female came to HTN clinic for ABPM placement. At time of ABPM

placement she was found to have BP 184/118. She is completely asymptomatic.

Normal physical exam. Transferred to ED for observation and further management.

Clonidine PO

Labetalol IV bolus

24%

43%

35%

• 520 nifedipine doses in 117 patients with severe HTN

J Pediatrics, 2001

Short-acting nifedipine PO? Short-acting oral nifedipine is not recommended in

children due to difficulties with dosing, prolonged and

unpredictable action, risk of hypotension, and rebound

hypertension UpToDate

J Hypertension, 2016

• A 17-year old female with SLE and no kidney disease (normal function,

normal U/A, normal kidney U/S)

• Presented to ED with severe headache and BP 262/149 mmHg. On arrival, she

had a 3-min seizure episode, spontaneously resolved with no medications

• Her SLE medications: CellCept, Prednisone and Plaquenil

• Controlled hypertension on Nifedipine XL

• Admits not taking BP medications for two week

A few weeks prior, she was prescribed a high

dose of steroids due to increased disease activity

Labetalol continuous IV infusion

Nicardipine continuous IV infusion

Esmolol continuous IV infusion

Nitroprusside continuous IV infusion

How to treat ???

Choice of drug

• Hydralazine IV bolus

• Labetalol IV bolus

• Labetalol continuous IV infusion

• Nicardipine continuous IV infusion

• Nitroprusside continuous IV infusion

Flynn, UpToDate

BP 262/149 and PRES

Start nicardipine continuous IV infusion in ED

Transfer to ICU to continue/titrate nicardipine

BP 170-180 in 6-8 hours

Restart home BP medications

Weaned off nicardipine

(over next 12 hours)

• Well-controlled BP on ACEI, CCB, and diuretics

• One year later: ED with BP 220/130

• Admits not taking BP medications for one month

Conclusion

• Almost always secondary causes

• Renal disease, TMA (e.g. post BMT), medications are

the most common causes

• This is a real medical emergency that requires

immediate treatment!!!

• Multiple treatment options are available

• Permanent end-organ damage is rare if treated on time