Nicardipine is superior to esmolol for the management of postcraniotomy emergence hypertension: a randomized open-label study.

BACKGROUND

Emergence hypertension after craniotomy is a well-documented phenomenon for which natural history is poorly understood. Most clinicians attribute this phenomenon to an acute and transient increase in catecholamine release, but other mechanisms such as neurogenic hypertension or activation of the renin-angiotensin-aldosterone system have also been proposed. In this open-label study, we compared the monotherapeutic antihypertensive efficacy of the 2 most titratable drugs used to treat postcraniotomy emergence hypertension: nicardipine and esmolol. We also investigated the effect of preoperative hypertension on postcraniotomy hypertension and the natural history of postcraniotomy hypertension in the early postoperative period.

METHODS

Fifty-two subjects were prospectively randomized to receive either nicardipine or esmolol as the sole drug for treatment of emergence hypertension at the conclusion of brain tumor resection (40 subjects finally analyzed). After a uniform anesthetic, standardized protocols of these antihypertensive medications were administered for the treatment of systolic blood pressure (SBP) >130, with the goal of maintaining SBP <140 throughout the first postoperative day. In the event of study medication "failure," a "rescue" antihypertensive (labetalol or hydralazine) was used. The O'Brien-Fleming Spending Function was used to calculate the appropriate α value for each interim analysis of the primary outcome; univariate analysis was performed otherwise, with a 2-sided P<0.05 considered statistically significant.

RESULTS

The incidence of nicardipine failure (5%, 95% confidence interval [CI] 0.1%-24.9%) was significantly less than that of esmolol (55%, 95% CI 31.5%-76.9%) as a sole drug in controlling SBP after brain tumor resection (difference 99% CI 13.8%-75.7%, P = 0.0012). The presence of preoperative hypertension or the approach to surgery (open craniotomy versus endonasal transsphenoidal) had no significant effect on the incidence of failure of the antihypertensive regimen used. We did not observe a difference in the need for opioid therapy for postcraniotomy pain between drug groups (99% CI difference -39.2%-30.2%). Failure of the study drug predicted the need for rescue drug therapy in the initial 12 hours after discharge from the recovery room (difference success versus failure = -41.7%, 99% CI difference -72.3% to -1.8%, P = 0.0336) but not during the period 12 to 24 hours after discharge from the recovery room (difference success versus failure = -27.4%, 99% CI difference -63.8%-9.2%, P = 0.143). However, in those patients carrying a preoperative diagnosis of hypertension, the need for rescue medication was only different during the period 12 to 24 hours after discharge from the recovery room (difference normotensive versus hypertensive = -35.4%, 99% CI difference -66.9% to -0.3%, P = 0.0254).

CONCLUSIONS

Nicardipine is superior to esmolol for the treatment of postcraniotomy emergence hypertension. This type of hypertension is thought to be a transient phenomenon not solely related to sympathetic activation and catecholamine surge but also possibly encompassing other physiologic factors. For treating postcraniotomy emergence hypertension, nicardipine is a relatively effective sole drug, whereas if esmolol is used, rescue antihypertensive medications should be readily available.