an approach to hypertensive crisis in children and...
TRANSCRIPT
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