Preoperative Amlodipine Is Efficacious in Preventing Intraoperative HDI in Pheochromocytoma: Pilot RCT

Abstract

Background Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aimed to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin GITS (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP<60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings The median (IQR) episodes (2 [1-3] vs. 0 [0-1], p 0·002) and duration of hypertension (19 [14-42] min vs. 0 [0-3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68–32·14%, p 0·002) were significantly higher in the prazosin GITS arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Interpretation Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.

Management of Patients with Treatment of Pheochromocytoma: A Critical Appraisal

“…They can control blood pressure and have benefits such as cardio and renal protection [ 3 ]. Calcium channel blockers and alpha blockers have been found to have the same impact on the incidence and severity of intraoperative hemodynamic instability episodes [ 43 , 44 ]. Magnesium has been shown to decrease the release of the catecholamine surge with better control of adrenergic control during surgery for pheochromocytoma [ 45 ].…”

Perioperative Management of Pheochromocytomas and Sympathetic Paragangliomas

“…Calcium channel blockers are the most preferred add-on class of agent in PPGL patients with uncontrolled hypertension on α-blockers [ 51 ]. Calcium channel blockers therapy should be added in patients on α-blockers without blood pressure control or with side effects related to α-blockers, such as postural hypotension [ 6 , 9 ].…”

“…Calcium channel antagonists inhibit norepinephrine-mediated transmembrane calcium influx in vascular smooth muscles [ 9 ]. Few studies with small cohorts demonstrated similar intraoperative hemodynamic stability when comparing calcium channel blockers to α-blockers in monotherapy for perioperative PPGL management [ 51-53 ]. However, only small cohorts of PPGLs with less severe hypertension were studied.…”

Controversies about the systematic preoperative pharmacological treatment before pheochromocytoma or paraganglioma surgery

“…One monocentric, pilot, open-label, randomized-controlled trial with the objective of comparing the efficacy of calcium channel blockers (CCB) and α-blockers on intraoperative HDI has been recently published. However, the results did not reach statistical significance as the authors initially decided to include 26 patients 'based on feasibility' and finally, only included 23 patients and analyzed the data from 20 patients (15). Moreover, the study protocol cannot be found in the clinicaltrials.gov database.…”