emDOCs Videocast: EBM Update – IV BP Meds in NV Emergencies

EBM Update: IV BP Meds in NV Emergencies

Background:

• There is no one agent that is recommended over others for reducing elevated BP in those with neurovascular emergencies.
• Several agents are available including labetalol, clevidipine, nicardipine, nitroprusside.
• Delaying treatment of elevated BP in patients may lead to worse outcomes, and an optimal IV antihypertensive medication will reach the BP goal rapidly while avoiding hypotension and causing end organ injury.
• Is there one IV antihypertensive that is best?

Paper:

• Brown CS, Oliveira J E Silva L, Mattson AE, et al. Comparison of Intravenous Antihypertensives on Blood Pressure Control in Acute Neurovascular Emergencies: A Systematic Review. Neurocrit Care. 2022;37(2):435-446.

Clinical question:  

• In patients presenting with acute neurovascular emergencies requiring blood pressure control, is one agent more efficient and safe than the rest?

Design: 

• Systematic review of literature databases from inception up to August 2020 seeking to identify superiority (efficacy and safety) with one anti-hypertensive agent over another in patients presenting with acute neurovascular emergencies.
• Authors used PRISMA guidelines.
• Initial search revealed 3878 titles. Authors included 183 for complete article review, and they ultimately included 10 studies (2 of those were RCTs).
• Study inclusion criteria:
  • RCT or nonrandomized comparative observational studies
  • Neurologic emergencies defined as:
    • Hypertensive encephalopathy
    • Ischemic stroke
    • Hemorrhagic stroke
    • Subarachnoid hemorrhage
    • TBI
  • Anti-hypertensive agents included nicardipine, clevidipine, labetalol, and nitroprusside.
• Exclusion criteria:
  • BP control for non-neurologic disease (e.g., aortic dissection)
  • No control group
• Outcomes: Mortality, functional outcome, BP variability, time to goal BP, time within goal BP, hypotension, need for rescue antihypertensives.
• Authors extracted proportions dichotomous outcomes (in-hospital mortality) and calculated risk ratios. For continuous outcomes (time to reach blood pressure goal), they calculated mean differences with standard deviations.

Results:

• Nicardipine vs Labetalol
  • 5 studies with 1 RCT, 413 patients
  • Poor quality of evidence was graded as poor, high levels of bias.
  • Dichotomous outcomes:
    • In-hospital mortality no different in 1 RCT.
    • Functional outcome was similar for this comparison group.
  • BP-related outcomes
    • 2/5 studies showed lower BP variability within the nicardipine groups, while the remaining three showed similar variability.
    • Nicardipine had higher time within BP goal range than labetalol in 2/5 studies, no difference in 2 other studies.
    • Nicardipine was associated with quicker time to blood pressure control and was faster than labetalol.
    • Nicardipine was associated with fewer rescue anti-hypertensive measures being needed in 3 of the 5 studies.
•  Nicardipine vs Clevidipine
  • Three observational studies, 386 patients
  • Low quality, high risk of bias.
  • None of the studies evaluated functional outcomes.
  • One study reported in-hospital mortality with similar mortality rates across both groups (20% nicardipine vs 15.7% clevidipine).
  • BP-related outcomes:
    • BP variability remained similar in the one study that reported it.
    • Similar time to BP control and time within goal but estimates favored clevidipine.
    • Similar rescure interventions.
    • 2/3 studies showed less hypotension with nicardipine.
•  Nicardipine vs Nitroprusside
  • Two studies (1 RCT), 1563 patients
  • In-hospital mortality:
    • Observational study reported lower in-hospital mortality in the nicardipine group compared to the nitroprusside group.
  • BP-related goals:
    • No difference across either group on time within goal BP and hypotension.

Considerations:

• Asks important question and followed PRISMA guidelines.
• However, the systematic review included both RCT and observational studies.
• High risk of bias, high heterogeneity, poor data quality.

Conclusions from Systematic Review

• In patients with neurologic emergency and HTN, you have options. Pick a drug, and know how to use it.
• Nicardipine is easy to use, cheap, reliable, and titratable; avoid nitroprusside.

• Guideline recommendations incorporate two large RCTs: INTERACT2 and ATACH-2.
• Anderson CS, Heeley E, Huang Y, et al; INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013 Jun 20;368(25):2355-65.
  • Randomized, multi-center, partially blinded trial comparing intensive BP control (target SBP <140 within 1 hour) to guideline recommended care (target SBP <180) in 2794 adult patients with ICH within the last 6 hours. No difference in 90-day disability or death. Improved secondary outcome ordinal analysis in strict SBP control group.
• Qureshi AI, Palesch YY, Barsan WG, et al; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43.
  • Randomized, multi-center, open-label trial comparing intensive BP management (target SBP 110-139) to standard BP management (target SBP 140-179) in 1000 patients with acute ICH. No difference in 90-day disability or death.

Greenberg SM, Ziai WC, Cordonnier C, et al; American Heart Association/American Stroke Association. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 May 17:101161STR0000000000000407. doi: 10.1161/STR.0000000000000407.

Recommendations for Acute BP Lowering:

• In patients with spontaneous ICH requiring acute BP lowering, careful titration to ensure continuous smooth and sustained control of BP, avoiding peaks and large variability in SBP, can be beneficial for improving functional outcomes. COR 2a, LOE B-NR
• In patients with spontaneous ICH in whom acute BP lowering is considered, initiating treatment within 2 hours of ICH onset and reaching target within 1 hour can be beneficial to reduce the risk of HE and improve functional outcome. COR 2a, LOE C-LD
• In patients with spontaneous ICH of mild to moderate severity presenting with SBP between 150 and 220 mm Hg, acute lowering of SBP to a target of 140 mm Hg with the goal of maintaining in the range of 130 to 150 mm Hg is safe and may be reasonable for improving functional outcomes. COR 2b, LOE B-R
• HARM: In patients with spontaneous ICH of mild to moderate severity presenting with SBP >150 mm Hg, acute lowering of SBP to <130 mm Hg is potentially harmful. COR 3, LOE B-R

Consideration: The guideline recommends a range between 130-150 for a BP target in those with a presenting BP between 150-220, while avoiding drops less than 130.  For those with higher BPs, decrease that BP by 20% in the first hour. If you drop these patients by too much and too rapidly, end organ injury can occur (ie, renal injury), and cerebral perfusion pressure will also decrease.  The key is a steady, early decrease in BP. Most of the studies incorporated in the guideline included patients where BP treatment was initiated at least 3 hours after onset of the ICH (ATACH-2, INTERACT). Decreasing BP within the first hour can improve patient outcomes. Use a reliable antihypertensive infusion such as nicardipine or clevidipine.  An arterial line can be helpful in these critical patients, but if this is not feasible, make sure the blood pressure cuff is routinely recycled (less than every 10 minutes).