Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5537_Библиотеки_им_академика_М_И_Перельмана.pdf
The Kidney
As noted earlier in our discussion of the rennin–angiotensin system, renal
involvement is common in malignant hypertension, but can be highly
variable in presentation. Proteinuria and elevated creatinine are common,
but often in the nonnephrotic ranges
2
; however, malignant nephroclerosis
is possible. Furthermore, renal artery stenosis may be the precipitating
factor in the oversecretion of renin and subsequently the onset of malignant hypertension.
10
Hematological Changes
As erythrocytes travel through the damaged vasculature, they tend to lyse,
resulting in microangiopathic hemolytic anemia. Hypokalemia is possible
due to aldosterone oversecretion and while renin levels can be reduced fairly
quickly, aldosterone levels may remain elevated for some time, presenting in
subsequent weeks as what appears to be primary hyperaldosteronism.
2
Clinical Evaluation (Table 2)
Treatment
When treating severely elevated BP, the distinction between a hypertensive emergency and a hypertensive urgency becomes very important.
Hypertensive Urgency (Table 3)
If no end organ damage can be detected, the patient is considered to
have presented with a hypertensive urgency. Antihypertensive medication should be administered orally, initially at very low doses with incremental increases to avoid excessive BP reduction. The goal of treatment
is to lower the BP by 25% to around 160/100 mmHg within 24 hr. After
the initial administration, the patient should be monitored for several
hours and discharged. A followup examination should be done within
the next 1–2 days.
2,7
264
A.Harris and M. Kim
265
Malignant Hypertension
Table 2.
2,7
Focused Physican Exam Elements and Laboratory Tests in the
Evaluation of Malignant Hypertension
History Physical Laboratory Testing
• Current hypertensive • BP should be measured • Renal function: serum
condition. in both arms (a large electrolyte, blood
difference is suggestive of urea nitrogen and
aortic dissection) and in creatinine levels
the supine and standing should be assessed, as
positions (orthostatic well as performing a
hypotension is indicative urinalysis and urine
of volume depletion). sediment examination.
• Cardiovascular history. • Fundoscopic examination • Hematological
• Baseline BP and should be performed to condition: a complete
previous organ damage identify retinopathy blood count and smear
• Medications, particularly characteristic of malignant to identify potential
antihypertensive hypertension. microangiopathic
prescription and • Cardiovascular examination hemolytic anemia.
compliance — cessation should aim to identify new • Cardiovascular
of β-blockers or central murmurs which may indicate condition: an
sympatholytic agents recent myocardial ischemia. electrocar diogram
may have resulted in • Pulmonary rales suggest should be obtained
rebound hypertension. heart failure. for all patients
• Abdominal bruits, particularly presenting with severe
in patients with a history of hypertension to reveal
atherosclerotic plaque in any possible myocardial
vasculature, can indicate renal ischemia/infarct and
artery stenosis, a possible possible leftunderlying cause of their ventricular hypertrophy
hypertensive emergency. resulting from
• A careful neurological underlying chronic
examination is of paramount hypertension. Also,
importance. Hypertensive a chest X-ray to evaluate
encephalopathy presents with pulmonary congestion
flapping tremor, delirium, and mediastinum
nausea and headache, widening suggestive
and must be ruled out. of aortic dissection.
• Neurologic condition: a
CT scan of the head
without contrast (to
avoid precipitating acute
renal failure) should
be performed in any
patient with neurological
symptoms.
Hypertensive Emergency (Table 4)
If end organ damage is detected, it is a hypertensive emergency. The
patient should be admitted to intensive care and have an arterial line placed
for accurate BP reading.
1
Parenteral drug administration should begin
immediately, with the goal of reducing the mean arterial pressure by 10%
during the first hour and an additional 15% within the next 2–3 hr to a diastolic pressure of approximately 100mmHg. The initial fall in the BP should
not exceed 25%.
7
Because many patients presenting with malignant hypertension have profound volume depletion, vasodilatation can result in a very
rapid reduction in the BP, leading to cardiac and cerebrovascular hypotension. Thus, patients with volume depletion should be placed on an intravenous saline regimen to restore blood volume and decrease RAAS
266
A.Harris and M. Kim
Table 3.7Specific Drugs for Hypertensive Urgencies
Dosage (until
Mechanism of Onset/Peak desired BP is Adverse
Drug Action Effect achieved) Effects
Captopril Angiotensin- 15–30 min/ 25 mg initial oral Cough, hypotension,
converting 30–90 min dose, incremental hyperkalemia,
enzyme doses of 50–100 mg angioedema,
(ACE) every 90–120 min contraindicated in
inhibitor bilateral renal
artery stenosis
Nicardipine Calcium ½–2 hr 30 mg oral dose, Palpitations,
channel every 8 hr flushing,
blocker dizziness,
constipation
Labetalol α1- and β- 1–2 hr 200 mg oral Nausea dizziness
adrenergic dose, every 3–4 hr
antagonists
Clonidine α2-adrenergic 15–30 min/ 0.1–0.2 mg initial oral Sedation, orthostatic
receptor 2–4 hr dose, 0.05–0.1 mg hypotension
agonist every hour,
maximum dose
of 0.7 mg
267
Malignant Hypertension
p
Table 4.7Specific Drugs for Hypertensive Emergencies
Dosage (until desired
Drug Mechanism Onset/Duration BP is achieved) Side Effects Notes
Sodium nitroprusside Nitric oxide Immediate/2–3 min 0.25–5 µg/kg/min IV Nausea, vomiting, Due to rapidity of onset
compound cyanide intoxication, and direct dilation of
increased intracranial both arteries and
pressure, veins, nitroprusside
methemoglobinemia is considered to be
the first-line drug
for most hypertensive
emergencies.
4
Fenoldopam Dopamine-1 <5 min/30 min Initial dose Headache, flushing, Unique in its ability to
mesylate receptor 0.1 mcg/kg tachycardia, ST-T increase renal
agonist per min; titrate at wave abnormalities perfusion, and thus is
15 min intervals (Primarily T-wave recommended in
depending upon the inversion) patients with renal
blood pressure hypokalemia failure. Contraindicated
response in patients with
glaucoma.
5
Nitroglycerin Nitric oxide 2–5 min/5–10 min 5–100 µg/min IV Headache, tachycardia, Used primarily in
compound (requires special flushing, tachyphylaxis, patients with acute
delivery system due methemoglobinemia coronary syndrome or
(Continued )
268
A.Harris and M. Kim
p
Table 4.7(Continued)
Dosage (until desired
Drug Mechanism Onset/Duration BP is achieved) Side Effects Notes
to drug binding to pulmonary edema,
tubing) otherwise not
considered to be
first-line therapy.
12
Enalaprilat ACE inhibitor <30 min/12–24 hr 0625–2.5 mg Cough, hypotension, Active form of
every 6 hr IV angioedema, taste enalapril, therefore
changes, hyperkalemia contraindicated in
pregnancy and
bilateral renal artery
stenosis. Due to
variability in patient
volume status and
renin activity,
may be response
unpredictable.
6
Hydralazine Direct 10 min/1–4 hr 5–20 mg IV bolus Tachycardia, flushing, Use is limited primarily
vasodilator, every 4–6 hr headache, sodium to pregnancy
arterial only and water retention, (pre-eclampsia) due to
increased intracranial unpredictability of
pressure, aggravation response. Administer
(Continued )
269
Malignant Hypertension
p
Table 4.7(Continued)
Dosage (until desired
Drug Mechanism Onset/Duration BP is achieved) Side Effects Notes
of angina with β -blocker to
prevent reflex
sympathetic discharge.
12
Nicardipine Calcium 5–15min/4–6 hr 5 mg/hr, increasing Tachycardia, Has been shown to
channel by 2.5 mg/hr every headache, flushing, increase myocardial
blocker 5 min to a maximum local phlebitis perfusion and stroke
of 15 mg/hr volume. Also
recommended
treatment for ischemic
stroke in patients with
BP>220 mmHg
systolic or 120 mmHg
diastolic.
12
Esmolol β-adrenergic 1–2 min/10–30 min 500 µ g/kg bolus Hypotension, nausea, Ultrashort-acting, but
blocker injection IV; bronchoconstriction, metabolized by RBCs
50–100 µ g/kg/min first-degree and therefore anemic pts
by infusion. May atrioventricular block will have longer
repeat bolus after half-life. Particularly
5 min or increase useful in postoperative
infusion rate; patients to prevent
hemodynamic
instability.
12
(Continued )
270
A.Harris and M. Kim
p
Table 4.7(Continued)
Dosage (until desired
Drug Mechanism Onset/Duration BP is achieved) Side Effects Notes
Labetalol α-, β-adrenergic 5–10 min/3—6 hr 20–80 mg IV bolus Bronchoconstriction,
blocker every 10 min; heart block, vomiting,
0.5–2.0 mg/min exacerbation of heart
IV infusion failure
Phentolamine α-adrenergic 1–2 min/10–30 min 5–15 mg IV bolus Tachycardia, flushing,
receptor headache
blocker
Clevidipine Arterial 2–4 min/5–15 min Initial dose IV Dizziness, drowsiness, Does not reduce
calcium infusion of 1–2 mg/hr headache; nausea, cardiac filling
channel maintenance dose vomiting, severe pressures or reflex
blocker 4–6 mg/hr allergic reactions tachychardia.
12
ECG = electrocardiogram; IM - intramuscular; IV = intravenous; RBCs = red blood cells; BP = blood pressure.
activation. Drug choice and subsequent therapy for patients presenting
with malignant hypertension are dependent on specific end organ damage.
Traditionally, in the absence of specific comorbidities, the most commonly
used drugs for hypertensive emergencies are IV labetolol and nicardipine.
However, recently, clevidipine, a fast acting calcium channel blocker, has
become the drug of choice for most practitioners. Clevidipine is metabolized by esterases in blood and extravascular tissue. Its clearance will
therefore be unaffected by renal or hepatic failure, which may be present
during hypertensive emergencies. Furthermore, because it is selective for
arterial calcium channels, it preserves cardiac function while reducing cardiac afterload and maintaining preload. When the BP is under control, the
patient should be switched to oral therapy and treated on an outpatient
basis with the goal of reducing the diastolic pressure gradually to approximately 90 mmHg over 1–3 months. Finally, secondary causes should be
investigated, particularly in young patients.
2
Specific Situations (Table 5)
Acute kidney failure. This may be the cause or effect of malignant hypertension. Given that there is potential for renal recovery, immediate antihypertensive therapy is of paramount importance in patients presenting
with acute renal failure. While lowering BP is paramount, one must be
careful to maintain euvolemia so as to avoid ischemic damage. In order to
provide the best chance for renal recovery, patients should be placed on
dialysis and have their BP kept under control. Fenoldopam is generally
used in acute kidney failure because it has been shown to maintain or
increase renal perfusion while lowering BP.
7
Hypertensive encephalopathy. Patients presenting with hypertensive
encephalopathy require rapid reduction in BP. Therefore, the mean BP
should be lowered by 20% or to 100–110 mmHg diastolic pressure within
the first hour.
1
Special care must be taken in elderly patients and patients
with essential hypertension, as they are more prone to hypoperfusion at
lower pressures.
2
In the case of patients who present with seizures, the use
271
Malignant Hypertension
of anticonvulsants is reasonable and will itself help to lower the BP.
7
Hypertensive encephalopathy is a rapidly reversible condition if treated in
a timely fashion. If symptoms do not abate within 6–12 hr of normalization of the BP, other causes for the encephalopathy should be investigated.
Aortic dissection. This is the most rapidly fatal complication of malignant
hypertension. BP should be reduced rapidly and aggressively, to a systolic
pressure of 100–110 mmHg. The therapeutic goal is to reduce shear stress
on the aortic wall by lowering both the BP and the heart rate.
1
This can be
accomplished by using a combination of β-blockers and vasodilators like
sodium nitroprusside. β-blockers should be administered first.
2
References
1. Vaughan CJ, Delanty N. (2000) Seminar: hypertensive emergencies.
The Lancet 356: 411–17.
2. Kitiyakara C, Guzman NJ. (1998) Malignant hypertension and hyper-
tensive emergencies. J. Am. Soc. Nephrol. 9: 133–142.
272
A.Harris and M. Kim
Table 5.
7,12
Drug of Choice for Specific Hypertensive Complications
Type of Emergency First-Line Drug Second-Line Drug
Subarachnoid Nimodipine Labetalol
hemorrhage
Cerebral vascular event Nicardipine Nitroprusside, enalaprilat
Acute renal failure Fenoldopam Nicardipine
Aortic dissection α-blocker + nitroprusside Labetalol, trimethaphan
Pulmonary edema Nitroglycerin (β blockers Nitroprusside ± ACE
and other drugs that inhibitor
decrease cardiac output
should be avoided)
Cardiac ischemia Nitroglycerin ±β-blocker Nitroprusside, labetalol
Pre-eclampsia Methyldopa magnesium Hydralazine ± β-blocker
sulfate (do not use with
calcium channel blocker)
Pheochromocytoma Phentolamine Nitroprusside +β-blocker
3. Flemin S. (2000) Malignant hypertension — the role of paracrine
rennin — angiotensin system. 192: 135–139.
4. Archer SL, Huang JM, Hampl V, et al. (1994) Nitric oxide and cGMP
cause vasorelaxation by activation of a charybdotoxin-sensitive
K channel by cGMP-dependent protein kinase. Proc. Nat. Acad. Sci.;
91(16): 7583.
5. Murphy MB, Murray C, Shorten GD. (2001) Fenoldopam: a selective
peripheral dopamine-receptor agonist for the treatment of severe
hypertension. N Engl J Med 345(21): 1548.
6. Hirschl MM, Binder M, Bur A, et al. (1995) Clinical evaluation of
different doses of intravenous enalaprilat in patients with hypertensive crises. Arch Intern Med 155(20): 2217.
7. Vaidya CK, Ouelette JR. (2007) Hypertensive urgency and emergency. Hospital Physician, Resident Grand Rounds 43: 43–50.
8. Edmunds E, Beevers DG. (2000) What has happened to malignant
hypertension? A disease no longer vanishing. J. Hum. Hypertens. 14:
159–161.
9. Kumar V, Abbas AK, Fausto N, Aster J. (2009) Robbins and Cotran
Pathologic Basis of Disease, 8th ed. WB Saunders, Philadelphia, PA.
10. Izzo JL Jr, Sica DA, Black HR. (2008) in the essentials of high blood
pressure. Hypertensive Primer 4th ed. Lippincott Williams and
Wilkins, Philadelphia, PA.
11. Bennett NM, Shea S. (1988) Hypertensive emergency: Case criteria,
sociodemographic profile, and previous care of 100 cases. Am J Public
Health 78: 636–40.
12. Varon J (2008) Treatment of acute severe hypertension: current and
newer agents. Drugs 68(3): 283.
273
Malignant Hypertension