Conversely, although not evaluated in this analysis, several conditions exist for which calcium channel blockers are not recommended as first-line agents. This is not necessarily because of a direct contraindication, but rather that other agents have clinical or theoretical advantages. This includes kinase inhibitor Veliparib myocardial infarction, where oral beta blockers confer a mortality reduction benefit, and in the setting of aortic dissection where the negative inotropic effect of beta blockers is desirable to decrease shear forces in the false lumen of the dissection. In fact, labetalol has been specifically recommended for use in patients with aortic dissection because it has both alpha and beta blockade effects.Overall, iatrogenic complications were rare in both treatment cohorts.

Overshoot of BP below the specified range occurred in less than 15% with either nicardipine or labetalol. This may have been a function of the relatively short duration of therapy of this study, and a longer period may demonstrate different outcomes. The potential for significant overshoot represents a serious limitation in the use of any IV antihypertensive agent. Excessive overshoot, resulting in iatrogenic hypotension, may contribute to increased morbidity risk (e.g., hypoperfusion in watershed regions of the brain, resulting in acute CVA). Agents with this potential thus require close hemodynamic monitoring, which may impart an undue burden on ED nursing staff. Moreover, excessively labile anti-hypertensives have ED disposition consequences, such as requiring ICU admission rather than a step-down unit.

Our study is not without limitations. First, it was unblinded and how this may have impacted outcomes is unclear. Additionally, although most (63%) CLUE patients had symptoms consistent with a hypertensive emergency, some had elevated BP without evidence of end-organ damage. In this later group it could be argued acute BP control could have been deferred or managed with oral agents. However, our primary objective was to determine which agent was most effective at BP control for use in the ED patient population. This strictly numerical outcome requires initially hypertensive patients, but not necessarily those with end-organ injury, and makes feasible a study with much smaller numbers than would be required to power for clinical outcomes. Brefeldin_A Also, the use of this model provides valuable data to determine the most effective BP management agent while deferring the ethical conflict of treating critical patients with a potentially inferior agent.Secondly, the separation of effect curves between nicardipine and labetalol occur after 15 minutes. This time period encompasses the period of re-dosing for labetalol, and re-dosing was at the discretion of the treating physician.