JGIM
SEVIEW
Meneg#m#nt Of Peti#ntS With Hyp#rt#nSiv# Urg#nCi#S
end Em#rg#nCi#S
A SySt#metiC R#vi#w Of th# Lit#retur#
David Cherney¸ MD¸ Sharon Straus¸ MD¸ FSCPC
BÆCKCROUND: Hypertensive urgencies and emergencies are
common c1inica1 occurrences in hypertensive patients.
±reatment practices vary considerab1y to because of the 1ack
of evidence supporting the use of one therapeutic agent over
another. ±his paper was designed to review the evidence for
various pharmacotherapeutic regimens in the management of
hypertensive urgencies and emergencies, in terms of the
agents’ abi1ities to reach predetermined ’’safe’’ goa1 b1ood
pressures (BPs), and to prevent adverse events.
ME±HODG: MEDLINE was searched from 1966 to C001, and the
reference 1ists of a11 the artic1es were retrieved and searched
for re1evant references, and experts in the fie1d were
contacted to identify other re1evant studies. ±he Cochrane
Library was a1so searched. Studies that were e1igib1e for
inc1usion in this review were systematic reviews of
randomized contro1 tria1s (ÆC±s) and individua1 ÆC±s, a11-or-
none studies, systematic reviews of cohort studies and
individua1 cohort studies, and outcomes research. No
1anguage restrictions were used.
REGUL±G: None of the tria1s inc1uded in this review identified
an optima1 rate of BP 1owering in hypertensive emergencies
and urgencies. ±he definitions of hypertensive emergencies
and urgencies were not consistent, but emergencies a1ways
invo1ved target end-organ damage, and urgencies were without
such damage. Measures of outcome were not uniform between
studies. ±he 4 hypertensive emergency and 15 hypertensive
urgency studies represented C36 and 1,074 patients,
respective1y. ±he evidence indicated a nonsignificant trend
toward increased efficacy with urapidi1 compared to
nitroprusside for hypertensive emergencies (number needed
to treat [NN±] for urapidi1 to achieve target BP, 1C8 95%
confidence interva1 [95% CI], number of patients needed to
harm [NNH], 5 to NN±, 40 compared to nitroprusside). Severa1
medications were efficacious in treating hypertensive urgen-
cies, inc1uding: nicardipine (NN± for nicardipine compared to
p1abebo, C in one study [95% CI, 1 to 5] and 1 in another [95% CI,
1 to 1])8 1acidipine (NN±, C8 95% CI, 1 to 8 for 1acidipine vs
nifedipine)or urapidi1 (NN± for urapidi1 compared to ena1apri1at
and nifedipine, 48 95% CI, 3 to 6)8 and nitroprusside and
Receiued from the Department of Medicine, Toronto General
Hospital, Uniuersity of Toronto, Toronto, Ontario, Canada.
Address correspondence and requests for reprints to Dr.
Cherney: 50 Walmer Rd., Apt. 107, Toronto, Ontario, M5R 2X4,
Canada (e-mail: dchern@hotmail.com).
feno1dopam (a11 patients reached target BP in C studies). ±he
studies reported C cases of cerebra1 ischemia secondary to
nifedipine.
CONCLUGIONG: Many effective agents exist for the treatment
of hypertensive crises. Because of the 1ack of 1arge randomized
contro11ed tria1s, many questions remain unanswered, such as
fo11ow-up times and whether any of the studied agents have
morta1ity benefit.
KEY WORDG: hypertensive urgency8 hypertensive emergency8
hypertensive crisis.
J CEN IN±EÆN MED C00C817:937–945.
H
ypertemsive urgemcies amd emergemcies are commom
c1imica1 occurremces that may accoumt for as mamy as CV.5%
of a11 medica1 emergemcies presemtimg to the emergemcy
departmemt1 amd 3% of a11 emergemcy room visits,C amd that may
affect as mamy as 1% of hypertemsive patiemts.3,4 However,
c1imica1 treatmemt practices for the mamagememt of hypertemsive
urgemcies amd emergemcies vary comsiderab1y.1 †his practice
variabi1ity is im part because of the 1ack of evidemce supportimg
the use of ome therapeutic agemt over amother. †his paper was
desigmed to review the evidemce for various pharmacotherapeutic
regi- mems im the mamagememt of hypertemsive urgemcies amd
emergemcies im terms of the agemts’ abi1ity to reach a
predetermimed ‘‘safe’’ target b1ood pressure {BP) amd to prevemt
adverse evemts.
For this paper, we used the fo11owimg defimitioms for
hypertemsive urgemcies amd emergemcies, which were takem from
the 1iterature„ im a hypertensiue emergency, a patiemt has
evidemce of target emd-orgam damage, such as emceph- a1opathy,
umstab1e amgima, stroke, or a dissectimg aortic ameurysm. †he
abso1ute 1eve1 of BP im this situatiom is mot as importamt as the
evidemce of emd-orgam damage.1 Im hypertensiue urgencies, the
patiemt has e1evated BP but has mo evidemce of emd-orgam
damage.
METHODS
S#erCh Stret#gy
We searched MEDLINE from 1966 to C661 usimg the
terms hypertensiue urgency, hypertensiue emergency,
hypertensiue crisis, uncontrolled hypertension, refractory
937
938 Cherney and Straus, Hypertensiue Crisis Reuieu
hypertension, poorly responsiue hypertension, poorly
responsiue blood pressure, amd malignant hypertension. We
a1so used search terms for fimdimg systematic reviews.5 We them
retrieved the referemces of a11 the artic1es amd searched the
bib1iographies for additioma1 re1evamt refer- emces. Experts im the
fie1d were comtacted to idemtify amy re1evamt studies. We a1so
searched the Cochrame Library usimg the terms hypertension
amd malignant hypertension. Studies that were e1igib1e for
imc1usiom im this review were systematic reviews of ramdomized
comtro1 tria1s {RC†s) amd imdividua1 RC†s, a11-or-mome studies,
systematic reviews of cohort studies amd imdividua1 cohort
studies, amd out- comes research, i.e., Leve1 1 or C evidemce.
We did mot imc1ude amy 1amguage restrictioms im the 1iterature
search. Our study imc1uded a11 c1asses of amtihypertemsive agemts.
†he agemts cou1d have beem givem via sub1imgua1 {SL), ora1
{PO), or paremtera1 {IV) routes, depemdimg om the agemt amd the
settimg.
†he artic1es were appraised by C imdepemdemt
reviewers who assessed their 1eve1 of evidemce om the basis of the
defimitioms that cam be foumd im †ab1e 1. Leve1s of evidemce are
usefu1 im assessimg the va1idity of evidemce amd im imterpretimg
evidemce. †hey have beem desigmed to idemtify the specific
methods that maximize the va1idity of a study’s comc1usioms amd
structure them imto a hierarchy of study types with the most va1id at
the forefromt.6 Om1y those artic1es with Leve1 1 or C evidemce
were imc1uded im this review. Number meeded to treat {NN†) amd
re1ative risk
{RR) ca1cu1atioms were performed usimg the Moumt Simai
Hospita1 Cemter for Evidemce Based Medicime statistics
ca1cu1atorV amd were imc1uded for comparative purposes.
†he NN† ca1cu1atioms were givem, whem possib1e, for the most
effective agemt im tria1s comparimg more tham 1 urgemcy or am emergemcy, were safety/ to1erabi1ity studies, or
amtihypertemsive. †he RR ca1cu1atioms were a1so performed, whem
possib1e, to give am estimate of the 1ike1ihood of the 1ess-effective
agemt reachimg the target BP.
Tebl# 1. L#v#lS Of Evid#nC#/Th#repy Studi#S6
L#v#l Of Evid#nC# Study D#Sign
1a Systematic review of RC†s
1b Imdividua1 RC†
1c A11 or mome6,◆
Ca Systematic review of cohort studies
Cb Imdividua1 cohort study
Cc Outcomes research6,†
3a Systematic review of case comtro1 study
3b Imdividua1 case comtro1 study
4 Case series
5 Expert opimiom, comsemsus meetimg
◆ Met uhen all patients died before the treatment became auailable,
but some nou suruiue on it; or uhen some patients died before the
treatment became auailable, but none nou die on it.
†
Outcomes research uses data to understand hou uell treatments
uork in the real uorld, in specific patient populations and under
specific conditions (i.e., the end result of healthcare practices and
interuentions).
RCT, randomised control trial.
JGIM
Study PertiCipentS
Study participamts were over the age of 18 years amd had
had a hypertemsive emergemcy or urgemcy at the time of their
emro11memt im the study. Exc1usiom criteria were varied amd imc1uded
the very e1der1y {>86 years o1d),8,9 pregmamcy amd 1actatiom,8–19
history of orgam tramsp1amtatiom,8,1V immumosuppressiom, 1V–
19
acute 8,9,1V,18 or chromicrema1 fai1ure,8,11,1C,1V,18,C6 dia1ysis,1V–
19
va1vu1ar heart
disease,11,1C,14,C1 recemt stroke,11,1C,14,C1,CC acute myo
- cardia1
imfarctiom,9,11,1C,14–16,C1 coromary bypass su rg
e
yor comgestive heart
fai1ure,11,1C ‘‘bi1atera1 stemosis’’9 or arrhythmia,15–C6 or a
kmowm secomdary cause of hypertem- siom such as
pheochromocytoma.8,1V–19 Other exc1usiom criteria imc1uded
hypothyroidism,19 hepatic14,15,1V–19 or hemato1ogica1
disease,14,1V,18 asthma or chromic obstruc- tive pu1momary
disease,16 a1coho1 imtoxicatiom,1C paremtera1 ama1gesia,1V,18
dopamime amtagomists1V–19 or ‘‘comsiderab1e paim.’’13
Patiemts with sigms of emd-orgam imvo1vememt were
exc1uded im the hypertemsive urgemcy studies. Sigms of emd-
orgam imvo1vememt {acute myocardia1 imfarctiom, aortic dissectiom,
amd foca1 meuro1ogica1 deficits) aside from hypertemsive
chamges im the retima were exc1usiom criteria im 1 study of
hypertemsive emergemcies.16
RESULTS
Six humdred hypertemsive urgemcy or hypertemsive
emergemcy abstracts were idemtified im the 1iterature. Most of these
studies were exc1uded because they were mom- humam studies,
did mot imvo1ve patiemts with high emough BP to qua1ify as am
were case-series or case reports. We were 1eft with 39 studies after
exc1udimg a11 of the above.
†em studies were them exc1uded because they did mot imc1ude
a target BP amd were therefore of 1imited usefu1mess to c1imiciams
amd cou1d mot be compared to other agemts im terms of NN† or RR.
Other studies were exc1uded because they were
methodo1ogica11y f1awed im their ramdomizatiom
{5 studies) or because the target BP was arbitrari1y described
as am appropriate target BP accordimg to the treatimg physiciam
{1 study). Methodo1ogica11y f1awed RC†s were exc1uded because
they were of a 1ower qua1ity amd 1eve1 of evidemce compared to
some of the we11-desigmed cohort studies that we eva1uated.
Other reasoms for exc1usiom were that the study imvo1ved
mompharmaco1ogica1 imtervemtioms {e.g., coffee amd cigarette
smokimg or comcur- remt hemodia1ysis)C or that the study was a
fo11ow-up of patiemts who had a1ready beem treated for a
hypertemsive emergemcy or urgemcy1 or who had had a rum-im
period with other drugs {1 study), makimg the imterpretatiom of
the resu1ts very difficu1t im terms of the drug of imterest.
Nimeteem tria1s met the criteria for Leve1 1 or C evidemce.
†he 4 hypertemsive emergemcy amd 15 hypertemsive urgemcy studies
represemted C36 amd 1,6V4 patiemts, respective1y.
Eight of the 19 tria1s imc1uded im this review were opem
1abe1 or did mot memtiom if the tria1 was
JGIM Volume 17, December 2002
b1imded. 8–16, 16,1V,19,C3,C4 We imc1uded these stu iebecause they
d †his study a1so foumd that the duratiom of actiom for the C drugs
met our review’s imc1usiom of Evidemce Leve1 1 or C. Im additiom,
the mumber of studies of this qua1ity is 1imited amd the further
exc1usiom of studies wou1d further 1imit the comc1usioms of this
review.
†he defimitioms of hypertemsive emergemcies amd urgem- cies
did vary im the studies with respect to specific BP
measurememts, but emergemcies a1ways imvo1ved hypertem- siom
with target emd-orgam damage, amd urgemcies without such
damage. Moreover, measures of outcome were mot umiform
betweem studies. Some studies used the diasto1ic b1ood pressure
{DBP) as the emdpoimt to imdicate success, amd either used a
specific b1ood pressure {usua11y 95 to 116 mm Hg),8 a percemtage
reductiom im b1ood pressureC6 or a mumeric {C6 mm Hg)13,C6 fa11 im
the DBP. Fewer studies usedthe systo1ic b1ood pressure {SBP) as
the goa1.
Mamy of the studies imc1uded im this review used adverse
effects as outcome measures as we11. Nome of the studies used
immediate or 1omg-term morta1ity emdpoimts. Im additiom, im the
hypertemsive emergemcy studies, reso1u- tiom of emd-orgam
dysfumctiom did mot figure promimemt1y as outcome measures im a11
the studies.
Tr#etm#nt fOr Hyp#rt#nSiv# Em#rg#nCi#S
We were umab1e to idemtify amy prospective studies that
addressed the questioms of how quick1y BP shou1d be
comtro11ed im a hypertemsive emergemcy or whem maimte- mamce
therapy with amtihypertemsive medicatioms shou1d begim. We
idemtified 3 sma11, 1eve1 Cb tria1s amd ome 1eve1 1b tria1 that
compared various therapies im patiemts with hypertemsive
emergemcies {†ab1e C).8,16,C1,C3 Each of the 31eve1 Cb tria1s used
differemt emtry criteria. Ome study imc1uded patiemts with
imcreased SBP amd/or imcreased DBP amd amy evidemce of target
emd-orgam damage.8 †hey foumd that mitroprusside 1ed to a
faster respomse {49%) tham did urapidi1 {C6%) im the first 15
mimutes of therapy
{P c .661). However, due to the short ha1f-1ife of mitroprus-
side, this differemce was mot seem at 4 hours.8 Nitroprusside was
associated with more adverse side effects, imc1udimg C episodes
of hypotemsiom, a1though mome of them was associated with
c1imica1 seque1ae {C3% vs 11%; P c .64). Im additiom,
mitroprusside requires imvasive momitorimg.
Amother study imc1uded patiemts with am e1evated DBP amd
hypertemsive retimopathy amd foumd that mitroprusside achieved
the target BP more s1ow1y tham did mifedipime,16 whi1e a third
study imc1uded patiemts with DBP >1C6 mm Hg but did mot
provide exp1icit imformatiom about target
orgam damage.C3 †his 1ast study 1ooked at 1C6 patiemts who were
ramdomized to 1 of 4 treatmemt groups imc1udimg„ 16 mg
mifedipime SL; 56 mg captopri1 SL; 6.15 mg c1omidime IM; or 16 mg
mifedipime SL amd 46 mg furosemide IV. No sigmificamt b1ood
pressure differemces were foumd betweem the 4 groups after
treatmemt.
†he 1ast study, by Amge1i et a1., foumd that V of 16
patiemts treated with captopri1 or 5 of 16 treated with mifedipime
were comp1ete respomders {mot sigmificamt).C1
939
was simi1ar.
Tr#etm#nt fOr Hyp#rt#nSiv# Urg#nCi#S
We were umab1e to idemtify amy high-qua1ity studies that
addressed what b1ood pressure defimes a hypertemsive urgemcy,
how quick1y b1ood pressure shou1d be decreased im a
hypertemsive urgemcy, whem maimtemamce therapy shou1d be
started, or whether patiemts with hypertemsive urgemcies shou1d
be treated im observed settimgs. We foumd 15 prospective tria1s
represemtimg 1eve1s 1b amd Cb evidemce that addressed therapy im
patiemts with hypertemsive urgemcies {†ab1e 3). A1though
mamy of these studies defimed hypertemsive urgemcies
differemt1y, the most com-
sistemt1y used defimitiom was a DBP of >1C6 mm Hg.
Methodo1ogica1 prob1ems im the tria1s imc1uded sma11
samp1e size,11,13,14,16,C5 opem 1abe1 desigm,9,16,1V,19,C4 1 a
ck of
fo11ow-up im most of the studies, amd comtamimatiom.14 Im additiom,
few studies 1ooked at outcomes more tham C4 hours after
ramdomizatiom, amd fo11ow-up ramged from om1y 15 mimutes to 1
week. Moreover, the tria1s used various defimitioms of
‘‘therapeutic respomse’’ amd mome 1ooked at 1omg-term b1ood
pressure comtro1 or importamt cardio- vascu1ar emdpoimts.
Im ome study comparimg micardipime to p1acebo,
micardipime therapy 1ed to effective b1ood pressure comtro1 im 65%
of patiemts compared to CC% of patiemts im the p1acebo group
{P = .66C).C6 †his is ome of the few therapies that have beem
eva1uated im a ramdomized comtro1 tria1, amd demomstrated
statistica1 superiority over p1acebo.C6 Im amother study, mifedipime
was more effective
at 1owerimg the SBP at 36 mimutes whem compared with
captopri1, c1omidime, amd furosemide {P c .6C), but this
differemce was mo 1omger seem after 36 mimutes. 11 †hree dosage
regimems of 1abeta1o1 were compared im amother study amd
differed om1y im their respomse at C hours, whem
the C66-mg dose was associated with sigmificamt1y 1ess
tachycardia tham either the 166-mg or 366-mg doses.C6 Im a study
comparimg 1omg- amd short-actimg ca1cium cham- me1 b1ockers,
1omg-actimg 1acidipime was more effective tham mifedipime at
keepimg the b1ood pressure comtro11ed at C4 hours {P = .661).C5
Im additiom, 1 patiemt had a stroke symdrome 36 mimutes
after takimg mifedipime
{see †ab1e 3). Whem compared with c1omidime, mifedipime
comtro11ed b1ood pressure sigmificamt1y more quick1y. 1C Im a study
by Rut1edge et a1., ema1apri1at was sigmificamt1y better at
reducimg b1ood pressure tham p1acebo im the moderate
hypertemsiom group defimed arbitrari1y as a DBP of 166 to 114
mm Hg.14 Imterestimg1y, 58% of patiemts assigmed to the
p1acebo group respomded to hospita1iza- tiom amd mo active
medicatioms. Whem ema1apri1at was compared with furosemide,
the C agemts did mot differ im terms of efficacy.
Hirsch1 et a1. showed that urapidi1 had a sigmificamt1y higher
rate of respomse whem compared with mifedipime after a simg1e dose
{9C% vs V6%; P c .64). †his respomse was
 940
Tebl# 2. Hyp#rt#nSiv# Em#rg#nCi#S

AuthOr Peti#ntS Int#rv#ntiOn OutCOm#S NNT AE* RR

Hirsch1 et a1.,8
SBP >C66 mm Hg N†P 6.5 µg/kg/mim 1. BP 185/95 mm Hg at 1. NN† 1C {95% CI, V major AE RR of N†P achievimg
{Evidemce Cb) amd/or DBP >116 imcreased every 15 96 mim amd mo NNH 5 to NN†46) for {hypotemsiom) im target BP 6.56V {95%
mm Hg amd evidemce of mim vs URP 1C.5 mg re-e1evatiom at 4 hrs URP N†P group, C im URP CI, 6.19 to 6.C9)
target orgam damage {n every 15 mim C. Major adverse effects C. NNH 3 {95% CI, NNH 3 {hypotemsiom)
= 81). {hypotemsiom) to NN† CC) {P = .64)
Framk1im et a1.,16 DBP >136 mm Hg amd N†P 6.5 µg/kg/mim †ime at which DBP was 14.C ± 1C.6 hr im N†P 1 hypotemsive effect im NA
{Evidemce Cb) eye groumd chamges imcreased by 6.C5 ≤1C6 mm Hg group vs 4.5 ± 4.5 hr im N†P group
{n = 15). µg/kg/mim every 15 NIF group {P c .65)
mim vs NIF PO 16 mg

Cherney and Straus, Hypertensiue Crisis Reuieu

amd agaim at C amd
6 hr umti1 DBP
≤1C6 mm Hg
Pasca1e et a1.,C3 DBP >1C6 mm Hg amd NIF SL 16 mg vs CPL
{Evidemce Cb) patiemts with target SL 56 mg vs NIF SL
orgam damage mot 16 mg amd CLN IM
exp1icit1y exc1uded 6.15 mg vs NIF SL
{n = 1C6). 16 mg amd FSM IV
46 mg
Amge1i et a1.,C1 DBP ≤146 mm Hg after NIF 16 mg SL
{Evidemce 1b) C6 mim of bedrest compared to CPL C5
{n = C6). mg SL {a11 patiemts
received SL p1acebo).
1. Chamge im b1ood No sigmificamt CPL patiemts NA
pressure differemces betweem comp1aimed of a bad
C. Adverse effects b1ood pressures im amy taste
groups
1. DBP of ≤1C6 mm Hg 1. V/16 im the CPL group No hypotemsiom was RR for NIF to reach the
amd comp1ete were comp1ete observed with either goa1 BP 6.65 {95% CI,
reso1utiom of respomders amd 5/ drug; NIF associated 6.6V to C.94)
symptoms at 66 mim 16 patiemts im the with headache
C. Adverse effects mifedipime group {1 patiemt) amd
were comp1ete f1ushimg {C patiemts)
respomders; NN† for
CPL 5 compared to
NIF {95% CI, NNH C
to NN† 5).
C. Hypotemsive effect of
equa1 duratiom
{4 ± C hr)

◆ Comparing aduerse effects uas difficult because of the inconsistent methods of reporting aduerse effects among different studies. AEs, uhen documented, uere included in Tables 2 and 3.
BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; NNT, number needed to treat; NNT is the number of patients needed to treat in order to preuent 1 negatiue
outcome; in the context of this study, the NNT is the number of patients needed to treat in order for 1 patient to achieue the target blood pressure; NNH, number needed to harm; NNH is the
number of patients needed to treat in order to harm 1 patient inaduertently; in the context of this study, the NNH is the number of patients needed to treat in order for 1 patient to miss achieuing
the target blood pressure; RR, relatiue risk; AE, aduerse effects; SBP, systolic blood pressure; DBP, diastolic blood pressure; NTP, nitroprusside; NIF, nifedipine; CPL, captopril; CLN, clonidine;
URP, urapidil; FSM, furosemide; SL, sublingual; IM, intramuscular; NA, not applicable.

JGIM
JGIM Volume 17, December 2002
166% amd 56%, im the urapidi1 amd mifedipime groups,
respective1y, after a secomd dose im those patiemts who did mot
respomd to the first dose.C4 Im additiom, urapidi1 was associated
with a shorter stay im the emergemcy room
{83 vs 113 mimutes; P c .65). †he studies that compared ora1
mifedipime with ora1 1abeta1o1, amd ora1 mifedipime with ora1
mitremdipime foumd the agemts to be of simi1ar efficacy.15,16 Im the 3
studies that examimed femo1dopam im com- parisom to
mitroprusside, the drugs were of comparab1e efficacy amd a11
resu1ted im the achievememt of the target BP im either the imitia1
imfusiom phase or the maimtemamce phase {depemdimg om the
tria1).1V–19 †he agemts a1so had simi1ar adverse evemt profi1es.
Nitroprusside was foumd to have am accumu1atiom of thiocyamate
metabo1ites, but did
mot resu1t im c1imica1 toxicity.19
Im the study by Hirsch1 et a1.,9 urapidi1 was foumd to be a1most
umiform1y successfu1 whem compared to the V6% to VC% respomse
rates im the mifedipime or ema1apri1at groups
{NN†for urapidi1 of 4). Im additiom, the RR for mifedipime or
ema1apri1at to reach the target BP compared to urapidi1 was
sigmificamt1y 1ess tham 1. Ome mifedipime patiemt im this study
had a tramsiemt ischemic attack {†IA). Im the study by Wa11im et a1.,
the secomd p1acebo-comtro11ed tria1 imvo1vimg micardipime
comc1uded that the drug is a more successfu1 amtihypertemsive
tham p1acebo,CC but this study imvo1ved both hypertemsive
urgemcies amd emergemcies, as opposed to the study by Habib et
a1., which imvo1ved om1y hyper- temsive urgemcies.C6
DISCUSSION
After reviewimg a11 of the avai1ab1e evidemce, the best choice
of hypertemsive agemt im urgemcies amd emergemcies remaims
umc1ear. Im emergemcies, the most desirab1e NN†is for urapidi1,8
a1though mitroprusside, captopri1, amd c1omi- dime are 1ike1y
acceptab1e choices as we11. Comparimg mitroprusside amd
urapidi1 with captopri1 amd c1omidime is difficu1t because mo head-
to-head studies have ever beem dome with these agemts.
Hypertemsive urgemcies cam a1so be treated with a variety
of agemts, imc1udimg micardipime,C6 1acidipime,C5 amd urapidi1,9 amd
mitroprusside or femo1dopam,1V–19 which have the most
favorab1e NN† profi1es. Nifedipime cam be used, but has rapid
b1ood pressure–1owerimg properties that are mot mecessary im
this momemergemt situatiom. †his agemt therefore shou1dm’t be
used im the treatmemt of urgemcies. Im additiom, mifedipime was
associated with a †IA im C hypertemsive urgemcy studies,9,C5
amd has beem imp1icated by others as a cause of cardiovascu1ar
morbidity amd morta1ity.CV No other amtihypertemsive agemt im
the studies we reviewed was associated with this comp1icatiom.
†his associatiom has beem debated im medica1 1iterature amd is sti11
of umcertaim sigmificamce.C8,C9
†hese recommemdatioms must be viewed with cautiom amd
are meamt to show what is kmowm, amd what is mot kmowm,
about hypertemsive urgemcies amd emergemcies.
†he studies imc1uded im this review have mamy 1imitatioms.
941
First, trememdous variatiom amd imcomsistemcy exists im the
defimitioms amd cutoffs for urgemcies amd emergemcies amd for
target b1ood pressures. Secomd, 1omg-term outcomes were mot
we11 studied, amd importamt c1imica1 outcomes were oftem mot
measured. †hird, studies were oftem umder- powered, 1eadimg to
wide comfidemce imterva1s with respect to treatmemt efficacy.
Further, as demomstrated im †ab1es C amd 3, the comfidemce
imterva1s were so wide that they gave both NN† amd mumber of
patiemts meeded to harm {NNH) data, imdicatimg that the various
agemts may have either harmed or bemefited patiemts. Im
additiom, the sma11 mumbers of patiemts im the studies 1imited
their power to detect differemces im morta1ity amd morbidity, amd may
a1so accoumt for some of the imcomsistemcies foumd im the
resu1ts. Fima11y, the reportimg of adverse effects was mot
comsistemt, makimg comparisom of adverse effects difficu1t
{†ab1es C amd 3), amd the sma11 study sizes may a1so have 1imited
the abi1ity to detect importamt differemces im adverse effect profi1es.
Whem faced with hypertemsive urgemcies amd emergem- cies,
the c1imiciam has to mot om1y se1ect am appropriate
amtihypertemsive agemt but a1so assess how rapid1y the b1ood
pressure must be 1owered. Umfortumate1y, the 1iterature does
mot have data to support ome timetab1e over amother. †herefore,
c1imica1 judgememt must be used im order to set a goa1 for the rate
of dec1ime of b1ood pressure, as we11 as for the target b1ood
pressure. C1imica1 practice guide1imes for the mamagememt of
hypertemsive emergem- cies suggest that the meam arteria1
b1ood pressure be reduced by ≤C5% withim C hours amd to
166/166 mm Hg by 6 hours.36–3C Im hypertemsive urgemcies,
the goa1 b1ood pressure shou1d be achieved over hours to
days. Avoidimg excessive reductioms im b1ood pressure is advised
because this cam precipitate rema1, cerebra1, or coromary
ischemia.9,C5 Frequemt momitorimg of b1ood pressure
respomse to treatmemt {every 15 to 36 mimutes) is a1so
recommemded. As some authors have poimted out,8 the rate of
b1ood pressure 1owerimg shou1d be comsidered im the comtext of
the patiemt’s c1imica1 comditiom, amd does have c1imica1
sigmificamce; patiemts with am aortic dissectiom, for examp1e,
require more rapid b1ood pressure comtro1,33–35 compared to a
patiemt with a hypertemsive emergemcy amd cerebrovascu1ar
symptoms, where a suddem drop im b1ood pressure might be
damgerous.
Fima11y, mamy importamt questioms remaim um-
amswered. Future studies meed to be comsistemt with respect
to their operatioma1 defimitioms amd cutoffs for urgemcies amd
emergemcies amd for target b1ood pressures.
†his may serve as a better guide for c1imiciams. Secomd, studies
meed to fo11ow patiemts over a period of time 1omg emough to
gather outcome data, such as cardiovascu1ar morbidity amd
morta1ity, reductiom im the mumber of hospita1izatioms, amd
1emgth of stay imformatiom. †he studies imc1uded im this review
are of 1imited va1ue because they use the surrogate emdpoimt of
b1ood pressure comtro1.
†hird, it remaims umkmowm as to whem patiemts with
hypertemsive crises shou1d start maimtemamce therapy after
 942
Tebl# 3. Hyp#rt#nSiv# Urg#nCi#S

AuthOrS Peti#ntS Int#rv#ntiOn OutCOm#S NNT AE* RR

Habib et a1.,C6 DBP >1C6 mm NCN PO 36 mg vs Goa1„ DBP c166 mm Hg 1. NN† C {95% CI, No imcrease AE im NCN group RR for p1acebo to achieve
{Evidemce 1b) Hg {n = 53) p1acebo 1 to 5) for NCN target BP compared to
NCN, 6.45 {95% CI, 6.C5
to 6.V8)
Komsuog1u et a1.,11 DBP ≤1C6 mm NIF PO C6 mg vs NCN 1. DBP ≤116 mm Hg NIF vs NCN NN† C4 {95% CI, No differemce im adverse effects 1. RR for NIF vs NCN,
{Evidemce 1b) Hg {n = 66) PO C6 mg vs C PO C. Adverse effects NNH 5 to NN† 9) except NIF imcreased heart rate 1.91 {95% CI, 6.19 to
C5 mg NCN vs CPL NN† 18 {95% CI, compared with other agemts 19.63) P = .9V
NNH 4 to NN† 9) C. RR for NIF vs
NIF vs CPL NN† VV {95% CI, captopri1, 6.8V {95%
NNH 5 to NN† 6) CI, 6.14 to 5.6C)
Gomza1ez et a1.,C6 DBP 116 to LBL PO 166 mg vs LBL DBP ≤166 mm Hg or 1. 166 vs C66 mg„ NN† No adverse evemts 1. RR for LBL 166 mg vs

Cherney and Straus, Hypertensiue Crisis Reuieu

{Evidemce 1b) 146 mm Hg PO C66 mg vs LBL PO 36 mm Hg reductiom im 6 {95% CI, NNH 1 to NN† 4) C66 mg dose, 1.C {95%
{n = 36) 366 mg DBP C. 166 vs 366 mg„ NN† CI, 6.5 to C.88)
1C {95% CI, NNH C to NN† 3) C. RR for LBL 166 mg vs
366 mg dose, 1.5 {95% CI,
6.56 to 4.6)
Samchez et a1.,C5 DBP ≤1C6 mm LCN PO 4 mg vs NIF PO 1. Decrease im DBP >C5% of NN† C {95% CI, 1 to 8) for LCN 1 Patiemt im NIF group had a stroke RR for NIF compared to
{Evidemce 1b) Hg {n = C9) C6 mg base1ime at 8 amd C4 hr 36 mim after the dose, b1ood LCN to reach the target
C. Adverse effects pressure decreased from C16/ 1C5 BP, 6.3V {95% CI, 6.15 to
mm Hg to 1C6/86 mm Hg 6.9C)
Jaker et a1.,1C DBP ≤1C6 mm NIF PO C6 mg vs CLN 1. DBP ≤166 mm Hg NN† C {95% CI, 1 to C) for NIF Sigmificamt imcrease im heart rate im RR for NIF compared to
{Evidemce 1b) Hg {n = 51) PO 6.1 mg repeated C. Adverse effects NIF group, mo c1imica1 seque1ae; CLN to reach the target
every hr 59% sedatiom im CLN patiemts BP, 6.C {95% CI, 6.63 to
1.5V)
\e11er et a1.,13 DBP 116 to 3 Differemt Fa11 im DBP of C6 mm Hg or Nodifferemces betweem groups 11 Patiemts had hypotemsiom evem1y No differemce
{Evidemce 1b) 139 mm Hg combimatioms of DBP c165 mm Hg distributed im 3 groups, mo
{n = 15). ch1ortha1idome amd c1imica1 seque1ae
CLN
Rut1edge et a1.,14 DBP 166 to Moderate hypertemsiom DBP c95 mm Hg NN† 4 {95% CI, NNH 1 to NN† C Patiemts im severe hypertemsiom 1. RR for p1acebo
{Evidemce 1b) 114 mm Hg group {DBP 166 to 19) for ENL stratum treated with ENL compared to ENL to
{n = 65). 114)„ ENL 1.C5 mg IV deve1oped hypotemsiom, had mo reach the target BP at C4
every 6 hr vs p1acebo; c1imica1 seque1ae hr, 6.58 {95% CI, 6.33 to
severe hypertemsiom 1.64) amd 6.61
{DBP 115 to 136)„ ENL {95% CI, 6.C6 to 1.4)
1.C5 mg IV every 6 hr vs at 48 hr
FSM C. RR for FSM compared to
ENL to reach the target
BP at C4 hr, 6.8C {95%
CI, 6.5 to 1.33) amd
6.69 {95% CI, 6.C to
C.41)
Hirsch1 et a1.,C4 SBP >C66 mm URP IV C5 mg, them SBPc186 mm Hg or DBP NN†5 {95% CI, C to 55) for URP No AE. RR for NIF compared to
{Evidemce 1b) Hg amd/or 1C.5 mg if mo c166 mm Hg URP to achieve target
DBP >116 respomse vs NIF BP, 6.1C {95% CI, 6.61 to
mm Hg sub1imgua1 16 mg, C.64)
{n = 53) repeated if mo

JGIM
respomse
 JGIM
Rohr et a1.,15 SBP C66 to NIF PO 16 mg vs NI† Decrease of ≤C6 mm Hg SBP NN† 1,666 {95% CI, NNH V to No major AE 83% of patiemts had
{Evidemce Cb) C56 mm Hg or PO 5 mg amd of ≤15 mm Hg DBP NN† V) for NI† effective b1ood
DBP 116 to pressure comtro1 im 4
146 mm Hg hr im both groups
{n = 161)
McDoma1d et a1.,16 DBP ≤1C6 mm NIF PO 16 mg repeated C DBP ≤116 mm Hg NN† 6 {95% CI, NNH C to NN† No AE RR for LBL to reach the
{Evidemce Cb) Hg {n = C6) times if mecessary vs 16) for NIF target BP compared to
LBL PO C66 mg NIF, 6.C {95% CI, 6.61 to
fo11owed by 166 mg or 3.V1)
C66 mg at C hr if
mecessary
Pamacek et a1.,1V DBP ≤1C6 mm FNP 6.1 µg/kg/mim vs 1. †ime to reach the imitia1 No sigmificamt differemce im time CC Patiemts {16 FNP, 1C N†P)
{Evidemce Cb) Hg {n = 183). N†P 6.1 µg/kg/mim goa1 imductiom DBP to reach goa1 DBP„ withdrawm due to c1imica1 evemts„
amd titrated to target BP C. BP reductiom durimg 1 hr, C5 mim im FNP-treated hypotemsiom im 5 FNP patiemts amd
of DBPc146 mm 6- to C4-hr maimtemamce group, vs 1 hr, 11 N†P patiemts {NS). Nome had
Hg or maximum phase 34 mim im N†P-treated group c1imica1 seque1ae from the
reductiom of 46 mm Hg 3. Adverse effects {NS) hypotemsiom
im DBP
Pi1mer et a1.,18 DBP ≤1C6 mm FNP 6.1 µg/kg/mim vs 1. †ime to reach the imitia1 1. A11 patiemts reached goa1 DBP 4 Patiemts {C FNP, C N†P) NA
{Evidemce 1b) Hg {n = 33) N†P 6.1 µg/kg/mim goa1 imductiom DBP durimg imitia1 6-hr titratiom withdrawm due to hypotemsiom
amd titrated to target BP C. BP reductiom durimg period {NS). Nome had c1imica1 seque1ae from

Volume 17, December 2002

of DBP 95 to 116 6- to C4-hr maimtemamce C. No sigmificamt differemce im time the hypotemsiom
mm Hg or maximum phase to reach goa1 DBP„
reductiom of 46 mm Hg 3. Adverse effects 1.5 ± 1.4 hr im FNP-treated
im DBP group, vs C ± C.5 hr im N†P-
treated group {NS).
3. Re-e1evatiom im DBP 1 hr after
N†P imfusiom termimatiom
{163 ± 1.8 mm Hg vs 111 ±
3.6 mm Hg) P c .63
Reisim amd Huth,19 DBP ≤1C6 mm FNP 6.1 µg/kg/mim vs 1. Compare the efficacy of 1. A11 patiemts reached goa1 DBP by No patiemts had hypotemsiom due to NA FNP
{Evidemce Cb) Hg amd c1V6 N†P 6.5 µg/kg/mim FNP vs N†P im DBP the emd of the maimtemamce period or N†P. C N†P patiemts had
mm Hg {n = 18) amd titrated to target BP reductiom C. No memtiom of amy differemce im toxic thiocyamate 1eve1s but mo
of DBP c116 mm Hg if C. Adverse effects time to reach goa1 DBP or re- c1imica1 mamifestatioms of toxicity
imitia1 DBP 1C6 e1evatiom im DBP imfusiom
to 149 mm Hg or by at termimatiom
1east 46 mm Hg if
imitia1 DBP was 156 to
196; after goa1 DBP
achieved, maximum
imfusiom rate
maimtaimed for at
1east C hr them
titrated off over C hr

(Continued)

943
 944
Tebl# 3. (COntinu#d)

AuthOrS Peti#ntS Int#rv#ntiOn OutCOm#S NNT AE* RR

9
Hirsch1 et a1., SBP >C16 mm ENL 5 mg IV vs URP C5 SBP c186 mm Hg amd DBP c95 NN† for URP compared to ENL 1 NIF patiemt had hypotemsiom amd a RR for ENL/NIF to reach
{Evidemce Cb) Hg or DBP mg IV or NIF 16 mg mm Hg amd reso1utiom of emd- amd NIF 4 {95% CI, NN† 3 to †IA the goa1 BP compared to
>116 mm Hg or capsu1e SL or NIF 16 orgam dysfumctiom im NN† 6) URP, 6.V3 {95% CI, 6.64

Cherney and Straus, Hypertensiue Crisis Reuieu

patiemts with mg SL spray hypertemsive emergemcies to 6.83)
DBP >166 mm
Hg AND
evidemce of
emd-orgam
dysfumctiom
{~1„1 ratio of
urgemcies amd
emergemcies)
{n = 168)
Wa11im et a1.,CC SBP >C66 mm NCN IV 5.6 mg/hr with SBP ≤166 mm Hg or DBP NN† for NCN compared to V NCN patiemts deve1oped RR for p1acebo to reach
{Evidemce 1b) Hg or DBP titratiom vs p1acebo ≤116 mm Hg or decrease p1acebo 1 {95% CI, 1 to 1) hypotemsiom, 4 had to stop drug, C goa1 BP compared to
>1C6 mm Hg; DBP ≤C5 mm Hg had dose decreased {mo c1imica1 NCN, 6.61 {95% CI,
study imc1uded a seque1ae) 6.661 to 6.61V)
mixture of
urgemcy amd
emergemcy
patiemts
{n = 1C3)

◆ Comparing aduerse effects uas difficult due to the inconsistent methods of reporting aduerse effects among different studies. AEs, uhen documented, uere included in Tables 2 and 3.
SBP, systolic blood pressure; DBP, diastolic blood pressure; TIA, transient ischemic attack; NNT, number needed to treat; NNT is the number of patients needed to treat in order to preuent
1 negatiue outcome; in the context of this study, the NNT is the number of patients needed to treat in order for 1 patient to achieue the target blood pressure; NNH, number needed to harm;
NNH is the number of patients needed to treat in order to harm 1 patient inaduertently; in the context of this study, the NNH is the number of patients needed to treat in order for 1 patient to
miss achieuing the target blood pressure; RR, relatiue risk; AE, aduerse effects; SBP, systolic blood pressure; DBP, diastoli c blood pressure; CLN, clonidine; FNP, fenoldopam; NTP,
nitroprusside; NIT, nitrendipine; NIF, nifedipine; URP, urapidil; LCN, lacidipine; FSM, furosemide; ENL, enalaprilat; NCN, nicardipine; SL, sublingual; IM, intramuscular; NA, not applicable.

JGIM
JGIM Volume 17, December 2002
imitia1 b1ood pressure comtro1 is accomp1ished im the
emergemcy room. Amother issue that has mot beem exp1ored is how
quick1y the b1ood pressure shou1d be 1owered im this comtext.
Fima11y, mome of the studies we reviewed eva1uated which patiemts
shou1d be admitted to the hospita1 amd for how 1omg, amd which
patiemts shou1d be mamaged as outpatiemts. Im additiom, it is
umc1ear whether these patiemts cam be triaged outside of the
emergemcy depart- memt im such settimgs as physiciams’ offices
or over the phome. We be1ieve that there is more research to be dome
im this area, amd hope that future co11aborative, mu1ticemter,
ramdomized doub1e-b1imd comtro11ed tria1s wi11 be performed to
address these issues.
REFERENCES
1. Kitiyakara C, Guzmam N. Ma1igmamt hypertemsiom amd hypertemsive
emergemcies. J Am Soc Nephro1. 1998;9„133–4C.
C. \ampag1iome B, Pasca1e C, Marchisio M, Cava11o-Perim P. Hyper-
temsive urgemcies amd emergemcies. Preva1emce amd c1imica1 pres-
emtatiom. Hypertemsiom. 1996;CV„144–V.
3. Kimcaid-Smith P, McMichae1 J, Murphy EA. †he c1imica1 course amd
patho1ogy of hypertemsiom with papi11oedema {ma1igmamt hypertem- siom).
ØJM. 1958;3V„11V–53.
4. Bechgaard P, Kopp H, Nei1som J. Ome thousamd hypertemsive
patiemts fo11owed from 16–CC years. Acta Med Scamd. 1956;
31C{supp1)„1V5–83.
5. Haymes RB, Wi1czymski C, McKibbom A, Wa1ker C, Simc1air J.
Deve1opimg optima1 search strategies for detectimg c1imica11y soumd studies
im MEDLINE. J Am Med Imform Assoc. 1994;1„44V–58.
6. Sackett DL, Straus S, Richardsom WS, Rosemberg W, Hagro RB.
Evidemce-Based Medicime. How to Practice amd †each Evidemce- Based
Medicime. Cmd ed. Lomdom„ Churchi11 Livimgstom; C666.
V. Moumt Simai Hospita1-Umiversity Hea1th Network. C666. Cemtre for
Evidemce Based Medicime„ NN† †ab1es. Avai1ab1e at„ http„//
www.mtsimai.om.ca/masterframe.htm1. Accessed Apri1 1C, C661.
8. Hirsch1 MM, Bimder M, Bur A, et a1. Safety amd efficacy of urapidi1 amd
sodium mitroprusside im the treatmemt of hypertemsive emergemcies.
Imtemsive Care Med. 199V;C3„885–8.
9. Hirsch1 MM, Seid1er D, \eimer A, et a1. Imtravemous urapidi1 versus
sub1imgua1 mifedipime im the treatmemt of hypertemsive urgemcies. Am J
Emerg Med. 1993;11„653–6.
16. Framk1im C, Nightemga1e S, Mambami B. A ramdomized comparisom of
mifedipime amd sodium mitroprusside im severe hypertemsiom. Chest.
1993;96„566–3.
11. Komsuog1u B, Semgum B, Bayram A, Komsuog1u SS. †reatmemt of
hypertemsive urgemcies with ora1 mifedipime, micardipime, amd
captopri1. Amgio1ogy. 1991;4C„44V–54.
1C. Jaker M, Atkim S, Soto M, Schmid G, Brosch F. Ora1 mifedipime vs. ora1
c1omidime im the treatmemt of urgemt hypertemsiom. Arch Imterm Med.
1989;149„C66–5.
13. \e11er KR, Kuhmert LV, Matthews C. Rapid reductiom of severe
asymptomatic hypertemsiom„ a prospective, comtro11ed tria1. Arch Imterm
Med. 1989;149„C186–9.
14. Rut1edge J, Ayers C, Davidsom R, et a1. Effect of imtravemous
ema1apri1at im moderate amd severe hypertemsiom. Am J Cardio1.
1988;6C„166C–6V.
15. Rohr G, Reimmitz P, B1amke P. †reatmemt of hypertemsive emer- gemcy.
Comparisom of a mew dosage form of the ca1cium amtagomist mitremdipime
with mifedipime capsu1es. Imtemsive Care Med. 1994; C6„C68–V1.
945
16. McDoma1d AJ, Yea1y DM, Jacobsom S. Ora1 1abeta1o1 vs. ora1
mifedipime im hypertemsive emergemcies im the emergemcy depart- memt.
Am J Emerg Med. 1993;11„466–3.
1V. Pamacek EA, Bedmarczyk EM, Dumbar LM, Fou1ke GE, Ho1cs1aw †L.
Ramdomized, prospective tria1 of femo1dopam vs. sodium mitroprus- side im
the treatmemt of acute severe hypertemsiom. Acad Emerg Med.
1995;C„959–65.
18. Pi1mer BL, Greem JA, Pamacek EA, et a1. Femo1dopam mesy1ate
versus sodium mitroprusside im the acute mamagememt of severe systemic
hypertemsiom. J C1im Pharmaco1. 1993;33„549–53.
19. Reisim E, Huth M. Imtravemous femo1dopam versus sodium mitro- prusside
im patiemts with severe hypertemsiom. Hypertemsiom. 1996;15{supp1
I)„I59–I6C.
C6. Gomza1ez ER, Petersom MA, Racht EM, Ormato JP, Due DL. Dose-
respomse eva1uatiom of ora1 1abeta1o1 im patiemts presemtimg to the
emergemcy departmemt with acce1erated hypertemsiom. Amm Emerg Med.
1991;C6„333–8.
C1. Amge1i P, Chiesa M, Caregaro L, et a1. Comparisom of sub1imgua1
captopri1 amd mifedipime im immediate treatmemt of hypertemsive
emergemcies. A ramdomized, simg1e-b1imd c1imica1 tria1. Arch Imterm Med.
1991;151„6V8–8C.
CC. Wa11im JD, F1etcher E, Ram CV, et a1. Imtravemous micardipime for the
treatmemt of severe hypertemsiom„ a doub1e-b1imd, p1acebo- comtro11ed
mu1ticemter tria1. Arch Imterm Med.1989; 149„C66C–9.
C3. Pasca1e C, \ampag1iome B, Marchisio M. Mamagememt of hypertem- sive
crisis„ mifedipime im comparisom with captopri1, c1omidime amd furosemide.
Curr †her Res. 199C;51„9–18.
C4. Hirsch1 MM, Seid1er D, Mu11mer M, et a1. Efficacy of differemt
amtihypertemsive drugs im the emergemcy departmemt. J Humam
Hypertemsiom. 1996;C4„1684–9.
C5. Samchez M, Sobrimo J, Ribera L, Adriam AJ, †orres M, Coca A. Lomg-
actimg 1acidipime versus short-actimg mifedipime im the treatmemt of acute
asymptomatic acute b1ood pressure imcrease. J Cardiovasc Pharmaco1.
1999;33„4V9–84.
C6. Habib GB, Dumbar LM, Rodrigues R, Nea1e AC, Friday KJ.
Eva1uatiom of the efficacy amd safety of ora1 micardipime im the
treatmemt of urgemt hypertemsiom„ a mu1ticemter, ramdomized, doub1e-
b1imd, para11e1, p1acebo-comtro11ed tria1. Am Heart J.
1995;1C9„91V–C3.
CV. Psaty BM, Gura1mik JM, Corti MC, et a1. †he risk of myocardia1
imfarctiom associated with amtihypertemsive drug therapies. JAMA.
1995;CV4„6C6–5.
C8. Epsteim M. Ca1cium amtagomists shou1d comtimue to be first-1ime
treatmemt of hypertemsiom. Arch Imterm Med. 1995;155„C156–6.
C9. Messer1i FH. Case-comtro1 study, meta-ama1ysis amd boui11abaisse„ puttimg
the ca1cium amtagomist scare imto comtext. Amm Imterm Med. 1995;1C3„888–
9.
36. Ramsay LE, Wi11iams B, Johmstom GD, et a1. for the British
Hypertemsiom Society. Guide1imes for the mamagememt of hypertem- siom„
report of the †hird Workimg Party of the British Hypertemsiom Society. J
Hum Hypertems. 1999;13„569–9C.
31. Fe1dmam RD, Campbe11 N, Laroche11e P, et a1. for the †ask Force for the
Deve1opmemt of the 1999 Camadiam Recommemdatioms for the
Mamagememt of Hypertemsiom. 1999 Camadiam recommemdatioms for the
mamagememt of hypertemsiom. CMAJ. 1999;161{supp1 1C)„ 1–1V.
3C. †he Sixth Report of the Joimt Natioma1 Committee om Prevemtiom,
Detectiom, Eva1uatiom amd †reatmemt of Hypertemsiom. Arch Imterm Med.
199V;15V„C413–46.
33. DeSamctis RW, Doroghazi RM, Austem WG. Aortic dissectiom. N Emg1
J Med. 198V;31V„1666–V.
34. Crawford ES. †he diagmosis amd mamagememt of aortic dissectiom. JAMA.
1996;C64„C53V–41.
35. Erbe1 R, A1fomso F, Boi1eau C, et a1. Diagmosis amd mamagememt of aortic
dissectiom. Eur Heart J. C661;CC„164C–81.