Le emergenze ipertensive: cosa fare e cosa non fare?

Maria Lorenza Muiesan

Università di Brescia

ASST Spedali Civili di Brescia

n engl j med 381;19 nejm.org November 7, 2019

A 58-year-old woman with known hypertension comes to the ED and reports headaches and blurred vision for the past 3 days. Her prescribed medications are amlodipine, HCTZ, and lisinopril, spotty adherence (no drugs in previous 3 weeks. She is anxious but comfortable. The average of multiple seated BP is 242/134 mm Hg, HR is 68 b/minFunduscopy shows arteriolar narrowing, bilateral flame hemorrhages, cotton-wool spots, and papilledema; auscultation reveals a fourth heart sound. ECG = left ventricular hypertrophy.Other laboratory tests and chest radiography are normal. Emergency computed CT of the head shows heterogeneous hypoattenuation of subcortical white matter in the posterior parieto-occipital regions bilaterally but no hemorrhage or infarction.

How would you further evaluate and treat this patient?

van den Born BH et al, Eur Heart J Cardiovasc Pharmacother. 2018

Abandon the term «hypertensive crisis»

Simplified stratification system: Hypertensive Emergency

DEFINITION OF HYPERTENSIVE EMERGENCIES

➢ Very high BP values associated with acute hypertension-mediated organ damage

➢ Key target organs: heart, retina, brain, kidneys, and large arteries

➢ Immediate BP reduction required to limit extension or promote regression of target organ damage

➢ The type of target organ damage is the principal determinant of the choice of treatment, target BP, and timeframe by which BP should be lowered

P van den Born et al. Management of hypertensive emergencies. European Heart Journal - Cardiovascular Pharmacotherapy 2018

An Italian survey: progetto GEAR (Gestione dell’Emergenza e urgenza in ARea critica)

European Journal Intern Med 2019

667 questionnaires

Trends in the Incidence of Hypertensive Emergencies in US Emergency Departments From 2006 to 2013

J Am Heart Assoc. 2016;5:e004511

incidence of 1640 per million adult ED visits in 2013, yielding an estimated rate increase of 13.9% per year

35%

Hospital Admissions for Hypertensive Emergencies and Urgencies

<Pinna et al , 2014

Prospective analysis

N = 1551

2.2% of admission to the ED

1551 (90%)

20%

80%

Emergencies

Urgencies

Age 70 ± 14 yrs,

range 18-102

M 44 %; F 56 %

Salvetti M et al J Hypertens 2019

N =1214

1.75 % of admission to the ED

Update 2019

STRATIFICATION OF HYPERTENSIVE EMERGENCIES ACCORDING TO THE CONDITION OR TARGET ORGAN INVOLVED

P van den Born et al. Management of hypertensive emergencies. European Heart Journal - Cardiovascular Pharmacotherapy 2018

advanced retinopathy, acute renal failure, and/or thrombotic microangiopathy (TMA)

Stratification of hypertensive emergencies according

to the condition or target organ involved

van den Born BH et al, Eur Heart J Cardiovasc Pharmacother. 2018

Acute and severe increases in BP can be precipitated by pheochromocytoma or by ingestion of sympathomimetics (meta-amphetamine or cocaine.) This can result in a hypertension emergency when there is evidence of acute HMOD

Adelaide Conti, Anna Paini, Chiara Rossetti, Marzia Bernini, Maria Lorenza Muiesan, Massimo Salvetti

The American Journal of Medicine, Vol 131, No 5, May 2018

A 25-year-old man was found unconscious by his wife in the bathroom of his apartment. She called emergency services and cardiopulmonary resuscitation was promptly initiated within a few minutes. The patient was intubated, transferred to the Emergency Department (ED) of a local hospital, and after 1 hour of advanced cardiac life support he was pronounced dead. His relatives reported a history of cocaine abuse; he had complained of epigastric discomfort during the previous 2 days

Table 30 Diagnostic workup for patients with a suspectedhypertension emergency

ESH ESC 2018 Hypertension Guidelines

diagnostic studies in patients with

suspected hypertensive emergency

In a patient admitted to the emergency department for acute hypertension,

a funduscopic examination may particularly helpful in identifying the

presence of exudates, haemorrages and/or papilledema.

The detection of these retinal changes indicates the presence of acute

organ damage and allows the diagnosis of hypertensive emergency and

of malignant hypertension

Traditional ophtalmoscope Smartphone small optical device (D-Eye, Si14 S.p.A.)

Muiesan Ml et al J Hypertens 2017

2 observers (1 trained not expert, 1 expert ophtalmologist )

BP lowering target/timing in hypertensive emergency

AHA/ACC , 2017• For adults with a compelling condition (i.e., aortic dissection,

severe preeclampsia or eclampsia, or pheochromocytomacrisis), SBP should be reduced to less than 140 mm Hg during the first hour and to less than 120 mm Hg in aortic dissection.

• For adults without a compelling condition, SBP should be reduced by no more than 25% within the first hour; then, if stable, to 160/100 mm Hg within the next 2 to 6 hours; and then cautiously to normal during the following 24 to 48 hours.

• In adults with a hypertensive emergency, admission to an intensive care unit is recommended for continuous monitoring of BP and target organ damage and for parenteral administration of an appropriate agent

Hypertension emergencies are situations in which severe hypertension (grade 3) is associated with acute HMOD, which is often lifethreatening and requires immediate but careful intervention to lower BP, usually with intravenous(i.v.) therapy.

•ESH/ESC guidelines 2018 and ESC/ESH position paper Eur Heart J Cardiovasc Pharmacother. 2018

DRUG CHOICE ACCORDING THE CAUSE AND MECHANISM OF THE HTN EMERGENCY

Stroke. 2019;50:e•••–e•••.

2019 Guidelines for Management of Acute Ischemic Stroke

Anderson C et al Lancet 2019; 393: 877–88

✓Fewer patients in the intensive group(160 [14·8%] of 1081) than in theguideline group (209 [18·7%] of 1115)had any intracranial haemorrhage (OR0·75, 0·60–0·94, p=0·0137).

Drug choice according the cause and mechanism of the HTN Emergency

- nitroglycerin, oxygen, aspirin,benzodiazepines, or calciumantagonists, alpha blockers

- Beta-blockers should beadministered with caution, sincetheir use may worsen vasospasm byallowing unopposed stimulation ofalpha receptors.

New England Journal of Medicine, 348;6

Treatment

“…A review of the literature revealed reports of serious adverse effects

such as cerebrovascular ischemia, stroke, numerous instances of

severe hypotension, acute myocardial infarction, conduction

disturbances, fetal distress, and death. Sublingual absorption of nifedipine

has been found to be poor; most of the drug is absorbed by the intestinal

mucosa. Given the seriousness of the reported adverse events and the lack

of any clinical documentation attesting to a benefit, the use of nifedipine

capsules for hypertensive emergencies and pseudoemergencies

should be abandoned”

JAMA 1996

An Italian survey: progetto GEAR (Gestione dell’Emergenza e urgenza in ARea critica)

European Journal Intern Med 2019

Need for a follow-up

• patients with hypertensive emergencies may have this condition because they are not adherent to their medications

• follow-up will allow for educating the patient about home BP monitoring that may improve hypertension control

• medications may not be enough to improve BP

• some patients with acute hypertensive emergencies may have a secondary cause for hypertension and an investigation for secondary hypertension is needed

Event-rate in emergencies and urgencies

(events/100pts/yrs)

14,5

11,8

7,5

42,7

4,33,5

0

5

10

15

Emergencies

4,53,6

1,9 1,7 0,9 1,7 2,3 2,380,9

0

5

10

15

Urgencies

Clinica Medica Università di Brescia & DEA Spedali Civili di Brescia, Muiesan et al ESH 2011

Cardiovascular event-rate during FU

Kumar N et al Hypertension. 2019;73:60-67.

Among patients with initial hospitalization for acute hypertensive emergency 17,8 % were hospitalized again within 30 days of the index admission.

Two prevalent conditions: acute HF, CKD

An Italian survey: progetto GEAR (Gestione dell’Emergenza e urgenza in ARea critica)

Are you aware of a protocol

for the management of

hypertensive

emergencies/urgencies ?

Are you using a fast-track for short

term re-evaluation of patients with

hypertensive emergencies/urgencies by

an hypertension specialist in your

hospital?

Yes No I don’t know Yes No

Eur Journal Intern Med 2019 Submitted

n engl j med 381;19 nejm.org November 7, 2019

The patient had acute severe hypertension complicated by PRES ie an hypertensiveemergency precipitated by nonadherence to antihypertensive therapy. She should be admitted to the intensive care unit and immediately begin IV nicardipine (given the relatively low HR) therapy guided by invasive intraarterial blood-pressure monitoring. BP was lowered by approximately 20 to 25% in the first hour, aiming for a blood pressure of approximately 160/100 mm Hg by 6 hours. Then, amlodipine and lisinopril were restsrted and her diuretic was restarted the following day, if needed. Nicerdipine was weaned over a period of 18 to 36 hours, although the timingshould be guided by close blood-pressure monitoring.Dischanrge when BP is controlled for at least 24 hours without the use of intravenous therapy, and arrangements for a follow-up office appointment within 1 week.

Do you agree ?

Asymptomatic uncontrolled hypertensionSBP or DBP >180 or >110 mmHg, respectively, in which OD is excluded

van den Born BH et al, Eur Heart J Cardiovasc Pharmacother. 2018

Acute BP increase (>180/110)

Absence of organ damage Presence of organ damage

Author NCV risk/ year

(approximated)

Vlcek M, 2008 384 6 %

Merlo C, 2012 50 6 %

Patel KK, 2016 58.535 1,8 %

Guiga H, 2017 285 8,9%

Author NCV risk/ year

(approximated)

Keith NM, 1939 200 78%

Guiga H, 2017 385 39%

Cardiovascular events*

Follow up (days)

Log Rank (Mantel-Cox) p<0.001

Emergencies

Urgencies

Emergencies

Urgencies

Log Rank (Mantel-Cox) p<0.0001

* Acute coronary syndromes, cerebrovascular events or hospitalizations for heart failure

0

4

8

12

16

20

Urgencies Emergencies

Events/100 patients/years

Muiesan et al, J Hypertens 2011 (abst)

• Male, 37 years, indian. • No previous diseases, no treatment• Left sided body weakness and numbness• BP 165/100 HR 70 bpm SpO2 98% AA. • Admitted to the Stroke Unit

• 4 hours after admission in the Stroke Unit chest pain

• BP 210/110 mmHg

• At echocardiography “ hypokinetic IV septum EF 55%”;

troponin I normal.

• Administration of IV nitroprussiate.

• 100% medium IVA occlusion with collaterals (Cdx).

• Occlusion 80 % LP Cdx

• Tubular stenosis 60% Cfx

• No PTCA because of recent ischemic stroke

• Patients moved from the Stroke Unit to the UTIC

100%

80%

60%

• Unstable angina

during hypertensive

crisis

• Coronary artery

disease

• Ischemic stroke

• Resistant

hypertension

• Diabetes mellitus

• Dyslipidemia

drug dosage

Ticagrelor 90 mg

+ASA 100mg

Amlodipine 10 mg 1cp x 2

Carvedilol 25mg Carvedilolo 25mg x 2

Ramipril 10mg 1cp

Doxazosin 4mg 1cp x 3

Candesartan 32 mg 1cp

Canrenone 100mg 1cp

NTG TTS 15 8→20

Aliskiren 150 mg 1cp x 2

Insulin lispro +

glargine

According to glycemia

Atorvastatin 40mg 1cp

Nitroprussiato ev During hypertensive

crisis with chest pain

In UTIC , despite treatment, BP values are still elevated;- PTCA is not performed because of fever and diarrhea (acute gastroenteritis).- Aorta and renal arteries angio-CT performed with the indication to evaluate elegibility for renal arteries denervation)

Moved from UTIC to Internal Medicine “Urgency Unit”

• Aorta + renal arteries Angio CT + adrenal CT : normal

• 24 hrs urinary metanephrine , PRA and palsma aldosterone , cortisol and TSH (all normal)

• Toxicology = negative

• No nocturnal SO2 desaturation (OSAS absent )

• Fundus oculi (II KW grade hypertensive retinopathy, no

diabetic retinopathy)

• Creatinine : 0.8 mg/dL

• Albumine/creatinine ratio 43,6 mg/g.

• Carotid Doppler US: IM Thickening and small plaques

• Unusual changes in BP when ev therapy (NTG +

labetalol) is stopped and changed to oral drugs

(ACE-I + CCB)

-20

20

60

100

140

180

220

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

PAS

PAD

EV EV EV

Event-rate in emergencies and urgencies

(events/100pts/yrs)

14,5

11,8

7,5

42,7

4,33,5

0

5

10

15

Emergencies

4.53.6

1.9 1.70.9

1.7 2.3

0

5

10

15

Urgencies

Clinica Medica Università di Brescia & DEA Spedali Civili di Brescia, Muiesan et al ESH 2011

Cardiovascular event-rate during FU

The term ‘hypertension urgency’ has also been used to describe severe hypertension in patients presenting to the emergency department in whom there is no clinical evidence of acute HMOD. Whilst these patients require BP reduction, they do not usually require admission to hospital,and BP reduction is best achieved with oral medication according to the drug treatment algorithm. However, these patients will require urgent outpatient review to ensure that their BP is coming under control

Park SK et al, J Hypertens 2017;35:1474-1480

CLINICAL EFFICACY OF RESTING VS ANTI-HYPERTENSIVE

TREATMENT IN HYPERTENSIVE URGENCIES

N.138 patients with hypertensive urgency randomized to resting vs resting + telmisartan 80 mg

EPISTASSI

✓60% della popolazione

✓PRIMARIE / SECONDARIE

✓Anteriori / posteriori

American Journal of the Medical Sciences: July 1930 - Volume 180 - Issue 1 - ppg 47-58

Epistaxis and hypertension

Kikidis D et al Eur Arch Otorhinolaryngol 2014;271(2):237-43.

Studies evaluation the relationship between epistaxis and hypertension

BP and epistaxis

Systolic BP Diastolic BP

*

126 subjects (84 M, age range 15-93 yrs march 2014-february 2015

Personal data, 2015

Conclusions The presence of high arterial blood pressure during the actual episode of nasal bleeding cannot establish a causative relationship with epistaxis, because of confounding stress and possible white coat phenomenon, but may lead to initial diagnosis of an already installed arterial hypertension.

Cerebral edema consequenceof an acute hyperperfusion

Symptoms : severe hypertensionseizures, lethargy, cortical blindness and coma, in the absence of an alternative explanation

Histopathological changes :cerebral oedema, microscopichaemorrhages and infarctionsPosterior reversible encephalopathysyndrome (PRES)

Hypertensive encephalopathy

10 % patients with malignant hypertension

Uncontrolled hypertension (>180/110)

Absence of organ damage Presence of organ damage

Author NCV risk/ year

(approximated)

Vlcek M, 2008 384 6 %

Merlo C, 2012 50 6 %

Patel KK, 2016 58.535 1,8 %

Guiga H, 2017 285 8,9%

Author NCV risk/ year

(approximated)

Keith NM, 1939 200 78%

Guiga H, 2017 385 39%

Shah M et al. Am J Hypertens. 2016

Trends in hospitalization for hypertensive emergency

2002–2012 nationwide inpatient sample database to identify patients with HTNE129,914 admissions, 630 (0.48%) patients died during their hospital stay

Presence of acute cardiorespiratory failure, stroke/TIA, chest pain, and aortic dissection were most predictive of higher hospital mortality.

The optimum therapy, treatment is dictated by consensus on the basis of:- particular presentation of the clinical situation- end-organ complications

-not on the absolute value of blood pressure

van den Born BH et al, Eur Heart J Cardiovasc Pharmacother. 2018

ULTIMA DIAPOSITIVA

Treatment aspects of hypertensive emergencies and urgencies vary widely according to a patient’s clinical conditions and are largely based on consensus from clinical experience , observations and comparisons of intermediate outcomes

Further research is needed to assess the impact of acute hypertension-mediated organ damage on future cardiovascular risk and its therapeutic consequences in these patients

Flow chart for acute BP elevation

[

]

Muiesan ML et al ESH Manual of Hypertension 2018

Treatment aspects of hypertensive emergencies and urgencies vary widely according to a patient’s clinical conditions and are largely based on consensus from clinical experience , observations and comparisons of intermediate outcomes

Further research is needed to assess the impact of acute hypertension-mediated organ damage on future cardiovascular risk and its therapeutic consequences in these patients

Conclusions

•

• Which of the following is used to define a hypertensive emergency?

– The velocity of acute rise in blood pressure

– The presence of clinical organ damage

– The presence of comorbidities

– The sympathetic nervous system activation

•

• Among the following diagnostic examinations, which one is useful for the diagnosis of a hypertensive emergency ?

• Blood pressure monitoring

• Fundus oculi examination

• Kidney ultrasound

• Abdominal ultrasound

•

• Among the following , which drug is more likely used for the treatment of a patient with an hypertensive emergency ?

• Oral Captopril

• Intravenous nitrate

• Transdermal nitrate

• Sublingual nifedipine

•

• Which drug is less indicated for the treatment of cocaine induced acute coronary syndrome?

• ASA

• Beta-blockers

• Heparin

• benzodiazepines

•

• In a patient with hypertensive encephalopathy the time line and BP target are

• Minutes, < 90 mmHg

• Minutes , - 20-25 % MAP

• Hours , < 140 mmHg

• Several hours, < 120 mmHg

A 58-year-old woman with known hypertension comes to the emergency department

and reports headaches and blurred vision for the past 3 days. Her prescribed medications

include amlodipine, hydrochlorothiazide, and lisinopril, but she acknowledges

spotty adherence and has not taken any of the drugs in approximately 3 weeks. On

examination, she is anxious but comfortable. The average of multiple seated bloodpressure

measurements is 242/134 mm Hg, and the heart rate is 68 beats per minute.

Funduscopy shows arteriolar narrowing, bilateral flame hemorrhages, cotton-wool

spots, and papilledema; auscultation reveals a fourth heart sound. The remainder of

the examination is normal. The electrocardiogram shows left ventricular hypertrophy.

Other laboratory tests and chest radiography are normal. Emergency computed

tomography of the head shows heterogeneous hypoattenuation of subcortical white

matter in the posterior parieto-occipital regions bilaterally but no hemorrhage or

infarction. How would you further evaluate and treat this patient?

Massimo Salvetti Medicina Interna & 2a Medicina

Università di Brescia-ASST Spedali Civili di Brescia

Le emergenze ipertensive:

il trattamento delle forme più comuni

Donna 42 aa

- Ipertensione arteriosa nota da almeno 7 anniTerapia solo per alcuni mesi, autosospesa dalla paziente per benessere soggettivo

- Familiarità per ipertensione arteriosa

- Da un mese circa riferisce dispnea da sforzo, ortopnea

Accesso in PS per:

- improvviso peggioramento della dispnea a riposo

- comparsa di ortopnea

- cefalea pulsante

- Non dolore toracico

✓ Dispnoica; PA 260/145 mmHg (dx=sn); FC 120 r ; SatO2 88% in aa, T 36C°

✓ Rantoli crepitanti bilaterali campi medi e basi polmonari

Emocromo: nella normaCreatininemia 0,7 mg/dlLieve incremento AST e ALTTroponina I 0,02 ng/mL; CK-MB normaliCoagulazione: normaleD-dimero: negativoEAB arterioso : lieve ipossiemia

Tachicardia sinusale; IVS; sovraccarico VS

• RX Torace

In DEA: Labetalolo ev 75 mg

PA 170/120 mmHg

Ricoverata UTIC: PA 180/130 mmHg; Fc 80 bpm (r)

Ecocardiogramma:

- Marcata ipertrofia VS concentrica

- Sezioni destre nella norma

- Conservata funzione sistolica globale e regionale (EF 57%)

- IM ++; IT ++ PAPs 64 mmHg

- VCI congesta

- Disfunzione diastolica VS (E/e’ 15)

Inizia infusione con nitroprussiato ev e boli di furosemide evMetoprololo ev

In circa 3 ore

PA 260/145 mmHg → 170/120 mmHg→ PA 140/90 mmHg

Trasferita presso la nostra Divisione (sezione Medicina d’Urgenza)

Netta regressione della dispneaComparsa di “discomfort” retrosternaleComparsa di alterazioni della ripolarizzazione all’ECG (T negative)Troponina I sempre negativa

→ PA 120-130/80-85 mmHg in 20 ore

Sospeso nitroprussiato ev

Prosegue con Furosemide boli ev

Shift a terapia per os:- Bisoprololo- Amlodipina- Doxazosina

Medicina d’Urgenza C/O Clinica Medica/2 Medicina Spedali Civili BS

Angio-TAC

“… coronarie pervie…”

Alterazioni ECG durante la prima fase di trattamento (rapida-brusca riduzione dei valori di PA)

Pz con spiccata ipertrofia VS e valori di PA elevati:

M.Pepi, M.Alimento, D.Guazzi, Eur Heart J 1988

la rapida riduzione dei valori di PA (terapia e.v.)

In ipertrofia VS da ipertensione arteriosa Alterata riserva coronarica Alterato rapporto media:lume nei vasi di resistenza (ipertrofia della media)→Elevati valori di PA necessari per adeguata perfusione coronarica→ rapida riduzione PA (→ “furto coronarico”)→ sofferenza subendocardio

→ alterazioni ECG suggestive per sofferenza miocardio (T neg.) in parallelo alle modificazioni dei valori di PA

2015 ESC Heart Failure Guidelines, European Heart Journal 2016

J Cardiac Fail 2016;22:618–627

“…Hypertensive acute heart failure (H-AHF) isdefined as the rapid onset of pulmonarycongestion in the setting of a systolic bloodpressure >140 mm Hg, and often >160 mm Hg…”

Presentations of Hypertensive Acute Heart

Failure Darling et al J Cardiovasc Dis Diagn. 2017

four historical, cross-sectional cohorts with AHF who were admitted to tertiary care medical centres in the North-eastern USA in 1995, 2000, 2006, and 2011–13.

Hypertensive Acute HF

Aortic dissection

Stroke

37%

79 % ischemic

21% hemorrhagic37.5%

Acute Heart Failure

Acute Coronary Syndrome

25%

0,5 %

Journal of Hypertension 2019

✓ Acute heart failure precipitated by rapid andexcessive increase in arterial blood pressuretypically manifests as acute pulmonary oedema.

✓ A prompt reduction in blood pressure should beconsidered as a primary therapeutic target andinitiated as soon as possible.

✓ Aggressive blood pressure reduction (in the rangeof 25% during the first few hours and cautiouslythereafter) with i.v. vasodilators in combinationwith loop diuretics is recommended.

ESC Heart Failure Guidelines, European Heart Journal 2016

Indication Drugs Goal of treatment BP goal Adverse effects

Acute heart

failure

Systolic dysf

Nitroglycerin,

sodium nitroprusside,

furosemide, nesiritide (for

improvement of dyspnea)

Reduce peripheral

resistance and

cardiac workload,

without affecting

cardiac contractility

Reduce 15 % of

baseline BP, until

resolution of acute

pulmonary edema

Non invasive

ventilation may induce

a rapid BP ↓

Avoid SBP ↓ < 110

mmHg

Acute heart

failure

Diastolic dysf

Nitroglycerin, sodium

nitroprusside,

furosemide, betablockers

or nonDHPD CCB

Reduce peripheral

resistance and

cardiac workload

(heart rate)

Reduce 15 % of

baseline BP, until

resolution of acute

pulmonary edema

Non invasive

ventilation may induce

a rapid decrease of BP

Muiesan ML et al J Cardiovasc Med 2015

Peackock FW et al Am Heart J 2014;167:529-36

Clevidipine in acute heart failureBlood Pressure Control in Acute Heart Failure

A Pilot Study (PRONTO)

Serious adverse events (24% vs 19%) and 30-day mortality (3 vs 2) were similar between clevidipine and SOC, respectively, and there were no deaths during study drug administration

Aortic dissection

Stroke

37%

79 % ischemic

21% hemorrhagic37.5%

Acute Heart Failure

Acute Coronary Syndrome

25%

0,5 %

Journal of Hypertension 2019

Higher BP

Myocardial stress and oxygen needs

Muiesan ML et al J Cardiovasc Med 2015

European Heart Journal 2016

Indication Drugs Goal of treatment BP goal

Acute coronary

syndrome + HT

Emergency

Nitroglycerin, (sodium nitroprusside),

labetalol, metoprolol, esmolol,

nicardipine

Reduce cardiac

workload and improve

coronary perfusion

Reduce 25 % of

baseline BP in 3-4

hours

5.1 Pharmacological treatment of ischaemia5.1.1 General supportive measuresThe goal of pharmacological anti-ischaemic therapyis to decrease myocardial oxygen demand(secondary to a decrease in heart rate,blood pressure, preload or myocardial contractility)or to increase myocardial oxygen supply (byadministration of oxygen or throughcoronary vasodilation)

“…A review of the literature revealed reports of serious adverse effects

such as cerebrovascular ischemia, stroke, numerous instances of

severe hypotension, acute myocardial infarction, conduction

disturbances, fetal distress, and death. Sublingual absorption of nifedipine

has been found to be poor; most of the drug is absorbed by the intestinal

mucosa. Given the seriousness of the reported adverse events and the lack

of any clinical documentation attesting to a benefit, the use of nifedipine

capsules for hypertensive emergencies and pseudoemergencies

should be abandoned”

JAMA 1996

Adelaide Conti, Anna Paini, Chiara Rossetti, Marzia Bernini, Maria Lorenza Muiesan, Massimo Salvetti

The American Journal of Medicine, Vol 131, No 5, May 2018

A 25-year-old man was found unconscious by his wife in the bathroom of his apartment. She called emergency services and cardiopulmonary resuscitation was promptly initiated within a few minutes. The patient was intubated, transferred to the Emergency Department (ED) of a local hospital, and after 1 hour of advanced cardiac life support he was pronounced dead. His relatives reported a history of cocaine abuse; he had complained of epigastric discomfort during the previous 2 days

“…The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter…” Circulation. 1999

- nitroglycerin, oxygen, aspirin,benzodiazepines, or calciumantagonists, alpha blockers

- Beta-blockers should beadministered with caution, sincetheir use may worsen vasospasm byallowing unopposed stimulation ofalpha receptors.

New England Journal of Medicine, 348;6

Treatment

“…Beta-blockers should not be administered inpatients with symptoms possibly related tocoronary vasospasm or cocaine use, as theymight favour spasm by leaving alpha-mediatedvasoconstriction unopposed by beta-mediatedvasodilation…”

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Aortic dissection

Stroke

37%

21% hemorrhagic

79 % ischemic37.5%

Acute Heart Failure

Acute Coronary Syndrome

25%

0,5 %

Journal of Hypertension 2019

✓ incidence of 24.6 per100.000 person-years

✓ 10 to 20% of all strokes inCaucasians

✓ Mortality:40% at 1 month55% at 1 year

✓ only 18 to 39% of patientsliving independently at 1year

Intracerebral hemorrhage

✓ High BP is associated with increased risk of death, disability or neurological deterioration in patients with hemorrhagic stroke

✓ Hematoma volumes > 30 ml are related to increased mortality rates (60%-90%) at 1 month after ICH

✓ Increased BP is related to hematoma growth and formation of cerebral edema

✓ Hematoma expansion is a frequent complication of ICH, occurring in 30% of patients (mainly in the first 24 hours)

✓ for each 1 ml increase in hematoma expansion, the risk of death and dependency will increase by 5%

Prevalence of Elevated Blood Pressure in 563,704 Adult Patients Presenting to the Emergency Department with Stroke in USA

Qureshi AI et al Am J Emerg Med. 2007; 25(1): 32–38.

SBP > 140 mmHg- ICH 75%- SAH 100%

Mortality rate according to admission BP (all strokes)

Journal of Internal Medicine 2004

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100

Mortality at one month in hemorrhagic stroke (%)

SBP DBP

The already compromised cerebral blood flow (CBF) in

the perihematomal area due to the compression of

small arteries by the hematoma and the associated

edema might be further reduced by aggressive BP

lessening and might led to perihematomal ischemia

Theroretical risks associated with BP lowering in acute stroke

Linear regression indicated no relationship between the absolute change in systolic bloodpressure (BP) and perihematoma relative cerebral blood flow (rCBF) in the <150 mm Hg (R=0.00005; 95% CI, −0.001 to 0.001) or <180 mm Hg target groups (R=0.000; 95% CI, −0.001 to 0.001).

Conclusions—Rapid BP lowering after a moderate volume of ICH does not reduce perihematoma CBF. These physiological data indicate that acute BP reduction does not precipitate cerebral ischemia in ICH patients.

ICH ADAPT Investigators, Stroke 2013

n=75

INTERACT2 Investigators, N Engl J Med 2013

- We randomly assigned 2839 patients who had had a spontaneous intracerebralhemorrhage within the previous 6 hours and who had elevated systolic bloodpressure to receive intensive treatment to lower their BP (with a target SBP of <140mm Hg within 1 hour) or guideline-recommended treatment (with a target SBP of<180 mm Hg) with the use of agents of the physician’s choosing.

Intensive BP treatment was safe and associated with significantly better health-related quality of life than standard BP treatment. The two groups did not differ significantly in terms of all-cause mortality and hematoma expansion.

(Baseline hematoma vol 11, IQ range 6-20)

2015 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

RecommendationIn acute ICH within 6 h of onset, intensive blood pressure reduction (systolic target <140 mmHg in <1 h) is safe and may be superior to a systolic target <180 mmHg. No specific agent can be recommended. Quality of evidence: ModerateStrength of recommendation: Weak

2014 European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

Recommendations1. For ICH patients presenting with SBP between 150 and 220 mm Hg and without

contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe (Class I; Level of Evidence A) and can be effective for improving functional outcome (Class IIa; Level of Evidence B). (Revised from the previous guideline)

2. For ICH patients presenting with SBP >220 mm Hg, it may be reasonable to consideraggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring (Class IIb; Level of Evidence C). (New recommendation)

1.000 participants with intracerebral hemorrhage (volume, <60 cm3) and a Glasgow ComaScale score of 5 or more to a SBP target of 110 to 139 mm Hg (intensive treatment) or atarget of 140 to 179 mm Hg (standard treatment); intravenous nicardipine to lower bloodpressure was administered within 4.5 hours after symptom onset (+ labetalol if needed)Enrollment was stopped because of futility after a prespecified interim analysis

The mean minimum systolic blood pressure during the first 2 hours was 128.9±16 mm Hg in the intensive treatment

- 141.1±14.8 mm Hg in the standard-treatment

ATACH-2 Trial Investigators

Carandini et al, Intern Emerg Med 2017

- six studies for a total of 4385 patients (mean age 62 years, 62.3% men)

ESC Council on hypertension position document on the management of hypertensive emergencies

European Heart Journal - Cardiovascular Pharmacotherapy 2018

Lowering blood pressure after acute intracerebral haemorrhage:protocol for a systematic review and meta-analysis using individualpatient data from randomised controlled trials participating in theBlood Pressure in Acute Stroke Collaboration (BASC)

BMJ Open 2019

✓ Introduction Conflicting results from multiple randomized trials indicate that themethods and effects of blood pressure (BP) reduction after acute intracerebralhaemorrhage (ICH) are complex.

✓ The Blood pressure in Acute Stroke Collaboration is an international collaboration, whichaims to determine the optimal management of BP after acute stroke including ICH.

✓ The primary outcome will be functional outcome according to the modified RankinScale.

✓ Safety outcomes will be early neurological deterioration, symptomatic hypotension and✓ serious adverse events.✓ Secondary outcomes will include death and neuroradiological and haemodynamic

variables.

Aortic dissection

Stroke

37%

21% hemorrhagic

79 % ischemic37.5%

Acute Heart Failure

Acute Coronary Syndrome

25%

0,5 %

Journal of Hypertension 2019

Prevalence of Elevated Blood Pressure in 563,704 Adult Patients Presenting to the Emergency Department with Stroke in USA

Qureshi AI et al Am J Emerg Med. 2007; 25(1): 32–38.

SBP > 140 mmHg: In > 75 % of pts

Bangalore et al, European Heart Journal (2017) 38, 2827–2835

✓ Patients in the Get With The Guidelines-Stroke registry with acute ischaemic stroke were included (n= 309 611 )

collateral flow by

loss of autoregulation due to

ischemia, increasing

infarction size

cerebral edema,

hemorrhagic transformation

favour long term BP control

Early BP lowering in ischemic stroke

Lee M et al. Stroke. 2015;46:1883-1889.

Effect of Blood Pressure Lowering in Early Ischemic Stroke

Relative risk with 95% confidence interval (CI) estimates

for death or dependency (early blood pressure lowering vs control)

at 3 months or at trial end point among patients with ischemic stroke.

2018 AHA/ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke

✓ Nine studies were included, for a total of 1037 patients.

✓ The heterogeneity in findings with respect to BP monitoring and studied parameters precluded a

meta-analysis

Stroke. 2019;50:00-00

✓ We recommend that systolic blood pressure should be maintained >140

mm Hg (fluids and vasopressors) and <180 mm Hg (with or without IV tPA),

and diastolic blood pressure <105 mm Hg (class IIa, level of evidenceB).

✓ We also recommend that blood pressure targets may be adjusted (lowered) in

communication with the neurointerventionalists and neurologists following

successful recanalization of occluded vessel(s) (class IIb, level of evidence

C), as reperfused brain often lacks autoregulation leading to high risk of

hyperperfusion leading potentially to hemorrhagic conversion.

Society for Neuroscience in Anesthesiology and Critical Care Expert Consensus Statement:

Anesthetic Management of Endovascular Treatment for Acute Ischemic Stroke

Stroke. 2014;45:e138-e150

Recommendations for Periprocedural Hemodynamic Management

Indication Drugs Goal of

treatmentBP goal

Adverse

effects

Acute ischemic

stroke

Labetalol, esmolol,

nicardipine, clevidipine*,

nitroglycerin, urapidil,

sodium nitroprusside (only if

DBP > 140 mmHg)

Avoid hemorrhagic

conversion and

enlargement of ischemic

penumbra

Reduce 15 % of

baseline BP (if

>220/115) in 2-3 hours

Acute but gentle BP

reduction indicated only if

fibrinolysis is planned

(BP < 185/110 mmHg)

Hypertensive

encephalopathy

Labetalol, nicardipine,

esmolol

Reduce intracranial

pressure

Reduce 25 % of

baseline BP in 2-3

hours

Muiesan ML et al J Cardiovasc Med 2015

Lancet 2019

Prehospital treatment withtransdermal GTN does not seem toimprove functional outcome inpatients with presumed stroke

✓ 1149 adults with presumed stroke within 4 h of onset, systolic blood pressure 120 mmHg or higher.

✓ Randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; theGTN group) or a similar sham dressing (the sham group) in Ukbased ambulances byparamedics

✓ 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109(9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the finaldiagnosis of the index event.

✓ In the GTN group, SBP was lowered by 5·8 mm Hg compared with the sham group(p<0·0001), and DBP was lowered by 2·6 mm Hg (p=0·0026) at hospital admission.

Distribution of mRS score at day 90

Methods - In 2005, AIS cases were ascertained at all 16 hospitals in Greater Cincinnati. BP wasrecorded at emergency department presentation and before and after antihypertensivetreatment. Hypertension was defined as BP 220/120 mm Hg.

Results - A total of 1739 patients with AIS met inclusion criteria. Median age was 72 yearswith 43% male and 25% black.

Conclusions - Only one third of patients with acute ischemic stroke treated withantihypertensives met American Heart Association recommended treatment criteria, andthe rate of change of BP was frequently greater than recommended. Further studies arewarranted to determine the impact of practice patterns on AIS outcomes.

(Stroke. 2012;43:557-559.)

•ESH/ESC guidelines 2018 and ESC/ESH position paper Eur Heart J Cardiovasc Pharmacother. 2018

San Sebastiano, Antonello da Messina (1478)

Grazie

Patients with a hypertensive emergency should be

admitted for close monitoring and, in most cases, treated

with intravenous blood pressure lowering agents to

reach the recommended BP target in the designated

time-frame

ESC Council on hypertension position document on the management of hypertensive emergencies Eur Heart Journal 2018

Management

Place two large bore IVs; monitor heart rate and blood pressure continuously,

preferably using an arterial line.

Control heart rate and blood pressureΔ. Maintain heart rate <60 BPM and systolic

blood pressure between 100 and 120 mmHg.

Administer esmolol (250 to 500 mcg/kg IV loading dose, then infuse at 25 to 50

mcg/kg/minute; titrate to maximum dose of 300 mcg/kg/minute) or labetalol (20 mg

IV initially, followed by either 20 to 80 mg IV boluses every 10 minutes to a

maximal dose of 300 mg, or an infusion of 0.5 to 2 mg/minute IV). If beta blockers

are not tolerated, alternatives are verapamil or diltiazem.

Once heart rate is consistently <60 BPM, give vasodilator therapy. IF the systolic

blood pressure remains above 120 mmHg, initiate nitroprusside infusion (0.25 to

0.5 mcg/kg/minute titrated to a maximum of 10 mcg/kg/minute) or nicardipine

infusion (2.5 to 5 mg/hour titrated to a maximum of 15 mg/hour). Vasodilator

therapy (eg, nitroprusside, nicardipine) should not be used without first

controlling heart rate with beta blockade.

Give IV opioids for analgesia (eg, fentanyl).

Place Foley catheter for assessment of urine output and kidney perfusion.

Blood pressure control in aortic dissection

Clinical features and evaluation

Acute onset of severe, sharp, or knife-like pain in the anterior chest, with radiation to the

neck, back, or abdomen. Pain may be migratory.

Assess risk factors for TAAD*.

Palpate carotid, subclavian, and femoral pulses; note any significant differences between

sides. Obtain blood pressure in both arms.

Auscultate for diastolic cardiac murmur of aortic regurgitation; assess for tamponade

(muffled heart sounds, jugular venous distention, pulsus paradoxus).

Evaluate for signs of ischemic stroke, spinal cord ischemia, ischemic neuropathy, hypoxic

encephalopathy.

Findings suggesting involvement of the ascending aorta include back pain, anterior chest

pain, hemodynamic instability, diastolic cardiac murmur, tamponade, syncope or stroke

(persistent or transient¶; right hemispheric stroke is most common, but bilateral can occur),

Horner syndrome (typically partial with ptosis/miosis), weak or absent carotid or subclavian

pulse, upper extremity pain/paresthesia/motor deficit.

Findings suggesting involvement of the descending aorta include back pain, chest pain,

abdominal pain, weak or absent femoral pulses, lower extremity pain/paresthesia/motor

deficit, acute paraplegia.

Aortic dissection

Findings on initial studies

Obtain ECG. Look for signs of ACS; extension of type A dissection to coronary ostia can cause coronary

ischemia (right coronary artery most commonly affected).

Obtain D-dimer, CBC, basic electrolytes, LDH, cardiac markers, coagulation parameters, and type and

crossmatch. D-dimer <500 ng/dL is less likely to be aortic dissection.

Chest radiograph: Widened mediastinum and/or unexplained pleural effusion are consistent with

dissection, particularly if unilateral.

Vascular imaging

For hemodynamically stable patient without suspicion for ascending aortic involvement: Obtain thoracic

CT angiography or MR angiography, depending upon resources and speed of acquisition. Dissection is

confirmed by presence of intimal flap separating true and false lumen. If these are not readily available or

there is a contraindication, obtain transesophageal echocardiogram.

For hemodynamically unstable patient or for strong suspicion of ascending aortic involvement: Obtain

transesophageal echocardiogram. If not immediately available, obtain CT angiography.

Transthoracic echocardiography may be useful for identifying complications of ascending aortic

dissection (eg, aortic valve regurgitation, hemopericardium, inferior ischemia) but is not sensitive for

identification of dissection.

Aortic dissection