All Pharmacy Pearls

Introduction

  • 1.

    • Hypertensive emergency is characterized by systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) >

    120 mmHg with evidence of target organ damage.

  • 2.

    • Rapid blood pressure lowering with intravenous antihypertensives is warranted to prevent further organ damage.

  • 3.

    • Patients presenting with intracranial hemorrhage, aortic dissection, preeclampsia, or pheochromocytoma crisis should

    achieve target blood pressure within one hour of presentation.

  • 4.

    • Current literature lacks evidence of mortality benefit with any one antihypertensive drug. Selection of a medication should

    consider target organ(s) affected, underlying disease states, and time to target blood pressure.

    Treatment in Selected Co-Morbidities

    Condition

    BP Goal

    Preferred Agents

    Acute aortic dissection

    SBP < 120 mmHg

    within 20 min

    Esmolol

    Labetalol

    Nicardipine

    Nitroprusside

Pharmacology

First-line Agents
Medication
Class
Onset
Duration
Dosing
Clinical Pearls
Nicardipine
Ca channel
blocker
IV: 5-10 min
IV: 2-6 hours
Initial: 5 mg/hr
Titration: 2.5 mg/hr every
15 min
Maximum: 15 mg/hr
No dose adjustments
in elderly patients
Esmolol
Beta-blocker
IV: 1-2 min
IV: 10-20 min
Bolus: 500-1,000 mcg/kg
Initial: 50 mcg/kg/min
Titration: repeat bolus
dose, then increase by
50 mcg/kg/
min every 10 min
Maximum: 200
mcg/kg/min
Contraindications:
- Bradycardia
- Decompensated
HF
Labetalol
Beta-blocker
Alpha-1
antagonist
IV: 2-5 min
Peak: 5-15
min
IV: 2-6 hours
Peak: 18 hours
Bolus: 10-20 mg IV
push every 10 min
IV infusion: 0.5 - 10
mg/min titrated 1-2
mg/min every 2 hours
Maximum: 300 mg total
Precaution:
- Second-/third-
degree heart block
- Bradycardia
- Heart failure
Second-line Agents
Phentolamine*
Non-selective
alpha
antagonist
IV: Seconds
IV: 15 min
Initial: 5 mg IV push
May repeat every 10 min
PRN
Useful in cate-
cholamine excess and
clonidine withdrawal
Nitroglycerin
NO-
dependent
vasodilator
IV: 2-5 min
IV: 5-10 min
ACS:
Initial: 5 mcg/min
Titration: 5 mcg/
min every 3-5 min
Maximum: 20 mcg/min
Pulmonary edema:
Initial: 100-200 mcg/min

Evidence

Author
(Title), Year
Design
Purpose
Outcome
Anderson
(INTERACT),
2008
RCT
(N=404)
Comparison of BP goals
(SBP < 140 vs SBP < 180)
in patients with acute ICH
- Mean hematoma expansion was smaller in the
intensive group (13.7% vs 36.3%)
- No difference in death or disability at 3 months (48%
vs 49%)
- Limitation: included patients with SBP > 150 mmHg,
over 30% of patients were treated with oral
antihypertensive therapy
Quereshi
(ATACH-2),
2016
RCT
(N=1,000)
Comparison of BP goals
(SBP 110-139 vs SBP 179-140)
in patients with acute ICH
- All patients received nicardipine infusion
- No difference between death or disability at 3
months (38.7% vs 37.7%)
- Increased renal adverse events within 24 hours in
the intensive group (9.0% vs 4.0%)
- Limitation: mean SBP differed by only 10 mmHg
between groups 2 hours post-randomization (129
mmHg vs 141 mmHg)
Peacock
(CLUE),
2011
RCT
(N=226)
Nicardipine IV infusion versus
labetalol IV bolus for
management of hypertensive
emergency
- Patients receiving nicardipine were more likely to
reach target BP within 30 min (91.7% vs 82.5%)
- Rescue antihypertensive use did not differ
significantly between groups within first 6 hours
- Limitation: only 63.3% of patients had evidence of
target organ damage at randomization
Yang,
2004
Prospective cohort
(N=40)
Nitroprusside IV versus
nicardipine IV for hypertensive
emergency with pulmonary
edema
- No significant difference between blood pressure
readings across groups at any time point
- No adverse events reported in either group
- Limitation: nicardipine dosing started at 3
mcg/kg/min (12.5 mg/hr in a 70 kg patient)

Conclusions

  • 1.

    • Selection of a first-line antihypertensive should consider compelling indications and acute blood pressure goals, as robust

    literature comparing long-term outcomes across drug classes is lacking for most indications.

  • 2.

    • Nicardipine may provide more consistent blood pressure control than labetalol. This is particularly important in patients

    with acute stroke, as large fluctuations in blood pressure are believed to negatively impact cerebral perfusion.

  • 3.

    • Aggressive lowering of SBP less than 140 mmHg in patients with acute ICH has not been shown to improve long-term

    outcomes and may negatively impact renal perfusion.

  • 4.

    • Nicardipine has been shown to provide similar blood pressure control to nitroprusside. In patients with acute ICH,

    nitroprusside use within 24-hours of presentation was associated with higher in-hospital mortality.

References

1.
Whelton, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation,
and Management of High Blood Pressure in Adults. J Amer Heart Assoc 2018;71(6):e13-e115.
2.
Benken ST. Hypertensive emergencies. CCSAP 2018;1:7-30.
3.
Anderson, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet
Neurol 2008;7:391-9.
4.
Quereshi, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. New Engl J Med 2016;375(11):1033-43.
5.
Peacock WF, et al. CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency
department. Critical Care 2011;15(R157):1-8.
6.
Yang HJ, Kim JG, Lim YS, et al. Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies. J Int Med
Res 2004;32:118-23.
Tags: SBP > 180 DBP > 120 target organ damage intravenous antihypertensives

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HTN Emergency FINAL 12.17.20.pdf