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

Treatment in Selected Co-Morbidities

ConditionBP GoalPreferred Agents
Acute aortic dissectionSBP < 120 mmHg within 20 minEsmolol, Labetalol, Nicardipine, Nitroprusside
Eclampsia or PreeclampsiaSBP < 140 mmHg within 1 hourNicardipine, Labetalol, Hydralazine
Pheochromocytoma (catecholamine excess)SBP < 140 mmHg within 1 hourNicardipine, Phentolamine*
Intracranial hemorrhageSBP < 160 mmHg within 6 hoursNicardipine, Labetalol
Acute ischemic strokePre-alteplase: < 185/110 mmHg; Post-alteplase: < 180/105 for 24 hours; No thrombolytic: SBP reduced 15% in 24 hours**Nicardipine, Labetalol

*Phentolamine currently unavailable due to nationwide shortage
**Permissive hypertension may be reasonable; maintain SBP < 220 mmHg or DBP < 120 mmHg

Intravenous Antihypertensives

MedicationClassOnsetDurationDosingClinical Pearls
NicardipineCa channel blockerIV: 5-10 minIV: 2-6 hoursInitial: 5 mg/hr
Titration: 2.5 mg/hr every 15 min
Maximum: 15 mg/hr		No dose adjustments in elderly patients
EsmololBeta-blockerIV: 1-2 minIV: 10-20 minBolus: 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
LabetalolBeta-blocker / Alpha-1 antagonistIV: 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
Phentolamine*Non-selective alpha antagonistIV: SecondsIV: 15 minInitial: 5 mg IV push
May repeat every 10 min PRN		Useful in catecholamine excess and clonidine withdrawal
NitroglycerinNO-dependent vasodilatorIV: 2-5 minIV: 5-10 minACS:
Initial: 5 mcg/min
Titration: 5 mcg/min every 3-5 min
Maximum: 20 mcg/min
Pulmonary edema:
Initial: 100-200 mcg/min
Titration: 50 mcg/min every 3-5 min
Maximum: 400 mcg/min		Indicated in ACS or pulmonary edema
Use caution in volume-depleted patients
Sodium nitroprussideNO-dependent vasodilatorIV: SecondsIV: 1-2 minInitial: 0.3-0.5 mcg/kg/min
Titration: 0.5 mcg/kg/min every 1 min
Maximum: 10 mcg/kg/min		Requires intra-arterial BP monitoring
Tachyphylaxis and cyanide toxicity with prolonged use – Limit treatment duration
HydralazineDirect vasodilatorIV: 10 min
IM: 20 min		IV: 1-4 hours
IM: 2-6 hours		Initial: 10-20 mg IV push
Repeat every 4-6 hours PRN		Not available as an IV infusion
EnalaprilatACE inhibitorIV: 15-30 minIV: 12-24 hoursInitial: 1.25 mg IV over 5 min
Titration: increase by 5 mg every 6 hours as needed		Slow onset (~15 min)
Contraindications:
– Pregnancy
– MI
– Bilateral renal stenosis

*Phentolamine currently unavailable due to nationwide shortage

Evidence

Overview of Evidence

Author (Title), YearDesignPurposeOutcome
Anderson (INTERACT), 2008RCT (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), 2016RCT (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), 2011RCT (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, 2004Prospective 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

Source PDF

HTN Emergency FINAL 12.17.20.pdf