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TREATMENT OF SEVERE HYPERTENSION
IN LOW RESOURCE SETTING
Brian Rayner,
Division of Hypertension, University of Cape Town
Cardiovascular Mortality Risk Doubles with Each 20/10 mmHg
Increment in Systolic/Diastolic Blood Pressure*
CV mortality risk
8
8X
risk
6
4
4X
risk
2
0
1X risk
2X
risk
115/75
135/85
155/95
175/105
Systolic BP/Diastolic BP (mmHg)
*Individuals aged 40–69 years
Lewington et al. Lancet 2002;360:1903-1913.
TABLE 3 Definitions and classification of office blood pressure
levels (mmHg)
Copyright © 2013 Journal of Hypertension. Published by Lippincott Williams & Wilkins.
Mancia, GiuseppeJournal of Hypertension. 31(7):1281-1357, July 2013.
DEFINITIONS
• Asymptomatic severe
• Hypertensive urgency*
• Hypertensive emergency*
• * BP usually > 220/120
• * Frequent in young black men without
obvious risk factors
Definitions
• Urgency
– Severe hypertension with symptoms
• Emergency (impending or progressive OD)
–
–
–
–
–
–
–
hypertensive encephalopathy
cerebral infarction
intracranial haemorrhage
acute pulmonary oedema
aortic dissection
renal failure
eclampsia
Epidemiology
• The syndrome of hypertensive emergency was first described by
Volhard and Fahr in 1914
• In 1939 the1-year mortality of 79% and a median survival of 10.5
months
• Approximately 1% of patients with hypertension will develop a
hypertensive crises at some point during their lives. 7% before BP
treatment
• Parallels the distribution of essential hypertension in the
community, being much higher among African-Americans and the
elderly; however, men are affected two times more frequently than
are women
• Most previously been diagnosed as hypertensive and many have
been prescribed antihypertensive therapy with inadequate blood
pressure control
• Illicit drug use has also been reported to be a major risk factor for
the development of hypertensive emergency
CAUSES
• Most in Africans is primary hypertension
• Risks are related to the severity of the underlying hypertension
• Mechanical stress on the vessel wall appears to be critical in its
pathogenesis
• Vicious cycle of further vascular injury, tissue ischemia, and release
of vasoconstrictor substances especially from the kidney
• Volume depletion that results from pressure natriuresis further
simulates the release of vasoconstrictor substances from the kidney
• Activation of the RAAS has been strongly implicated in the initiation
and perpetuation of the vascular injury
• Vasopressin, endothelin and catecholamines are also implicated
Also eye and brain
Causes
•
•
•
Severe HT
DM
Stiff arteries
KEY ASSESSMENTS
• Adherence to medication
• Symptoms – headache, chest pain, SOB
• Consider secondary causes e.g. pulses, bruits,
symptoms of phaeo
• JVP, basal crackles
• Fundi
• Oliguria
• Urine – blood and/or protein – settles with
treatment
FUNDI
INVESTIGATIONS
• ECG – LVH plus RCs
• CXR – heart size, ULVD, pulmonary oedema,
dissection
• K+ - often low due to secondary hyperaldosteronism (primary aldo seldom causes
hypertensive emergency)
• Creatinine – often elevated and continues to rise
• FBC –  Hb due to micro-angiopathic haemolytic
anaemia, ↑LDH
R in AvL > 11
Cornel – (S in V3 + R in aVL + 6 in females) x QRS duration > 2440
>35 – Sokolow-Lyon)
Harbinger of death
ASYMPTOMATIC SEVERE
• No symptoms, no impending or progressive
TOD
• Start any 2 of first line drugs in combination
– ACE or ARB
– CCB
– Thiazide or thiazide like diuretic
• Review within 1 week and escalate as needed
URGENCY/EMERGENCY – KEY ISSUES
• Loss or marked shift of autoregulation in eye, kidney, brain
• Excessive lowering of BP can lead to stroke, visual loss and
worsening kidney failure
• ICU admission
• Intra-arterial monitoring
• Recommended 25% lowering in first few hours with
intravenous therapy - labetalol, Na nitroprusside (avoid if
AKI), or nitroglycerin (preferred if ischaemia) by titration
• Furosemide if pulmonary oedema, possibly acute dialysis
• Thereafter institution of long term oral treatment once
stabilised
LOW RESOURCE CENTRE
• Often treated in the emergency unit or
general ward
• Intensive monitoring not feasible
• Oral treatment often only option
• Potential for excessive drops in BP that can’t
be detected early or easily reversed easily
SAHS 2014
ACE INHIBITORS
• Hypertensive emergencies are often
association with volume contraction
• Marked activation of RAAS
• Hence propensity to cause profound drops in
BP
• Preferably used once patient is more stable
Nifedipine Dosing
Clinical features
Loading dose
Maintenance
BP > 130 mmHg
20mg PO or SL
10 every 30 min until
target BP
BP 115-130
10mg PO or SL
5-10 mg
BP < 115
5-10 mg PO or SL
5mg
Elderly, CAD, prior
CVA, volume
depletion, anti HPT
drugs
5mg PO or SL
5mg
Nifedipine Advantages
• Rapid consistent BP lowering
• Admission to hospital not always required
• Reflex tachycardia common, but angina and
MI uncommon
• Improvement in CCF
• Numerous dosage forms
• Side effects minor and frequent
Disadvantages
•
•
•
•
Potential for hypotension and stroke
Worsening of renal function
Possible cerebral oedema (theoretical)
Negligible buccal absorbtion
Effect of Nifedipine Formulation on Concentration Time Profiles: Hypertensive Patients
200
Nifedipine Capsule (20mg)
plasma conc (ng/ml)
150
100
Nifedipine Retard (20mg)
50
Nifedipine GITS (60mg)
0
0
4
8
12
Time (h)
16
20
24
Meredith & Elliott 2004
Effect of Nifedipine Formulation on Heart Rate
Responses – Placebo-Corrected : Hypertensive Patients
50
Nifedipine Capsule (20mg)
Heart Rate (beats/min)
40
30
20
Nifedipine Retard (20mg)
10
0
Nifedipine GITS (60mg)
-10
0
4
8
12
Time (h)
16
20
24
Meredith & Elliott 2004
Effect of Nifedipine Formulation on Systolic BP
Responses – Placebo-Corrected : Hypertensive Patients
5
Nifedipine Capsule (20mg)
Systolic BP (mmHg)
0
-5
Nifedipine Retard (20mg)
-10
-15
Nifedipine GITS (60mg)
-20
-25
-30
0
4
8
12
Time (h)
16
20
24
Meredith & Elliott 2004
• Nifedipine not been approved by the FDAQ for labelling for
treatment of hypertensive emergencies or of any other form of
hypertension because of lack of outcome data
• 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.
APPROACH
• History, examination
• Basic tests, ECG, Na, K, creatinine, Dipsticks, CXR
• Best to admit to ward or clinic area where patient
can be monitored
• Half hourly pulse and BP
• Labetalol 20mg IVI repeated at 10 min intervals
up to maximum of 80mg
• or Start single oral drug
MEDICATION
• Furosemide if CCF or pulmonary oedema
• Start nifedipine GITs 30 mg stat, do not chew or
crush
• Monitor BP, urine output, and neurological status
• If poor response, take another 30mg
• Continue to monitor ½ hourly BP
• If BP drops > 25% consider giving fluids, elevate
foot of bed especially if patient shows clinical
deterioration
Following Day
• Check elecs and renal function
• Monitor vital signs and clinical status
• 25% lowering achieved continue nifedipine 30-60
mg
• Not achieved – add second drug (diuretic/beta
blocker)
• After 48 hours aim to achieve BP closer to target
• Consider ACE inhibitor
• Monitor as out patient
CONCLUSIONS
• Treatment of severe hypertension is not based
on RCTs and is largely observational
• Treatment in low resource setting is even less
well documented
• A practical approach is given based largely on
my personal perspective