Endocrine Abstracts (2018) 56 OC7.5 | DOI: 10.1530/endoabs.56.OC7.5

Randomized trial comparing phenoxybenzamine and doxazosine for preoperative treatment of patients with a pheochromocytoma (PRESCRIPT)

E Buitenwerf1, TE Osinga1, HJLM Timmers2, JWM Lenders2,3, RA Feelders4, EMW Eekhoff5, HR Haak6,7,8, EPM Corssmit9, PHLT Bisschop10, GD Valk11, R GrooteVeldman12, RPF Dullaart1, TP Links1, MF Voogd13, JKG Wietasch13 & MN Kerstens1


1Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; 2Department of Internal Medicine, Section of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands; 3Department of Medicine III, Technische Universität Dresden, Dresden, Germany; 4Department of Endocrinology, Erasmus Medical Center, Rotterdam, Netherlands; 5Department of Internal Medicine, Endocrinology Section, VU University Medical Center, Amsterdam, Netherlands; 6Department of Internal Medicine, Máxima Medical Center, Eindhoven, Netherlands; 7Division of General Internal Medicine, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands; 8CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University, Maastricht, Netherlands; 9Department of Endocrinology, Leiden University Medical Center, Leiden, Netherlands; 10Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands; 11Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, Netherlands; 12Department of Internal Medicine, Medical Spectrum Twente, Enschede, Netherlands; 13Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.


Background: Administration of α-adrenergic receptor antagonists is recommended before resection of a pheochromocytoma (PCC) in order to prevent perioperative cardiovascular complications. For this purpose either phenoxybenzamine (PXB) or doxazosin (DOX) is commonly prescribed. We conducted the first randomized controlled trial comparing the efficacy of PXB and DOX in controlling perioperative hemodynamics in patients undergoing PCC resection (ClinicalTrials.gov:NCT01379898).

Methods: Patients ≥18 years with benign PCC were randomized to pretreatment with PXB or DOX. Preoperative BP targets were: <130/80 mmHg (supine) and systolic BP 90–110 mmHg (upright). β-blockers were added if heart rate was >80/min (supine) or >100/min (upright). Anesthetic procedures were standardized. Primary endpoint was the percentage of intraoperative time outside the BP target range (i.e. MAP<60 mmHg and systolic BP>160 mmHg). Size of the study population was calculated at 134 patients. Data are presented as mean ± S.D. or median (IQR). Two-sided P-values <0.05 were considered significant.

Results: One hundred and thirty four patients were included (52% female), aged 54±15 years. Pretreatment with DOX (n=68) or PXB (n=66) was administered in a dose of 40 (32–48) mg and 120 (78–140) mg, respectively. BP values and heart rate just before anesthesia were not different between groups. β-receptor antagonists were initiated in 66 and 89% of the patients on DOX or PXB, respectively (P=0.002). Intraoperative time outside BP target range was 12 (5–20) % in the DOX group and 11 (4–21) % in the PXB group (P=0.75). The number of intraoperatively administered vasodilating agents was 0, 1 or >2 among 21, 34 and 45% in the DOX group, respectively. Respective percentages in the PXB group were 45, 32 and 23% (P=0.02). Cumulative intravenous dose of magnesium sulphate was 3 (0–4) grams in the DOX group and 0 (0–3) grams in the PXB group (P=0.005). The number of intraoperatively administered inotropic/vasopressive agents was 0, 1 or ≥2 among 18, 40 and 42% in the DOX group, respectively. Respective percentages in the PXB group were 26, 36 and 38% (P=0.38). Cumulative intravenous dose of phenylephrine and norepinephrine was 0 (0–300) μg and 137 (0–580) μg in the DOX group and 0 (0–425) μg, 55 (0–660) μg in the PXB group, respectively (P=0.98 and P=0.59).

Conclusions: The results of this RCT demonstrate an equal efficacy of DOX- and PXB-pretreatment in intraoperative hemodynamic control during PCC resection. Patients pretreated with PXB required more b-blockers preoperatively, presumably via enhanced reflex tachycardia, but fewer vasodilating agents during surgery.