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Charleston, SC

jimmy@pharmacyfridaypeals.com

Management of Hypertensive Emergency

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 
ConditionBP GoalPreferred Agents
Acute aortic dissection  SBP < 120 mmHg within 20 minEsmolol Labetalol Nicardipine Nitroprusside
Eclampsia or Preeclampsia  SBP < 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

 Pharmacology: Intravenous Antihypertensives 
 First-line Agents 
MedicationClassOnsetDurationDosingClinical Pearls
Nicardipine    Ca channel blocker IV: 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 
Esmolol            Beta-blocker IV: 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 
Labetalol    Beta-blocker  Alpha-1 antagonistIV: 2-5 min Peak: 5-15 minIV: 2-6 hours Peak: 18 hoursBolus: 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-/thirddegree heart block Bradycardia Heart failure
 Second-line Agents 
Phentolamine*Non-selective alpha antagonistIV: SecondsIV: 15 min  Initial: 5 mg IV push  May repeat every 10 min PRN  Useful in catecholamine excess and clonidine withdrawal 
  Nitroglycerin        NOdependent 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/minIndicated in ACS or pulmonary edema  Use caution in volume-depleted patients 
Sodium nitroprusside    NOdependent 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
Hydralazine  Direct vasodilatorIV: 10 min IM: 20 minIV: 1-4 hours IM: 2-6 hoursInitial: 10-20 mg IV push  Repeat every 4-6 hours PRN Not available as an IV infusion 
Enalaprilat        ACE 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

  Overview of Evidence
Author (Title), Year DesignPurposeOutcome
Anderson (INTERACT), 2008RCT (N=404)Comparison of BP goals  (SBP < 140 vs SBP < 180)  in patients with acute ICHMean 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 ICHAll 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 emergencyPatients 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 edemaNo 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. 

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