Doxazosin and Phenoxybenzamine Both Effective For Haemodynamic Control During Pheochromocytoma and Sympathetic Paraganglioma Resection: Presented at ECE

By Chris Berrie

BARCELONA, Spain -- May 24, 2018 -- Alpha-blockers doxazosin and phenoxybenzamine demonstrate similar efficacies when administered preoperatively for intraoperative haemodynamic control during resection of a pheochromocytoma and sympathetic paraganglioma, according to results from the open-label, phase 4 PRESCRIPT study presented here on May 21 at the 20th European Congress of Endocrinology (ECE).

Phenoxybenzamine requires greater beta-blocker use preoperatively, but less vasodilator use during surgery.

“Surgery is the treatment of choice for patients with pheochromocytoma and sympathetic paraganglioma, but it is also considered to be a potentially hazardous procedure,” explained lead author Edward Buitenwerf, MD, University Medical Centre Groningen, Groningen, The Netherlands.

Following routine diagnostic work-up, Dr. Buitenwerf and colleagues randomised 134 adults (52% female; mean age, 54 years) with benign pheochromocytoma or sympathetic paraganglioma to receive preoperative doxazosin 8 to 48 mg daily (n = 68) or phenoxybenzamine 20 to 140 mg daily (n = 66).
All subjects demonstrated similar baseline characteristics.

The target systolic blood pressure (SBP) / diastolic blood pressures were: supine, <130/80 mmHg, with heart rate <80 bpm; upright, SBP 90 to 110 mmHg, with heart rate <100 bpm. If these targets were not reached, nifedipine 30-90 mg daily was added, with metoprolol 50-200 mg daily for tachycardia.

Similar levels of patients reached the supine (46% vs 42%) and upright (25% vs 24%) targets across the preoperative doxazosin and phenoxybenzamine treatments, although Dr. Buitenwerf noted significantly greater beta-blocker use with phenoxybenzamine (66% vs 89%; P = .002), and at higher doses (metoprolol, 50 vs 100 mg; P = .007). The researchers observed no significant difference for nifedipine use.

Following hospital admission, the patients received 2 litres of sodium chloride 0.9% intravenously prior to surgery. Under anaesthesia during surgery, standardised haemodynamic management was followed, with targets of SBP <160 mmHg, mean arterial pressure >60 mmHg, and heart rate <100 beats per minute (bpm), with preferential vasoactive agents used. There were no significant differences in surgical procedures across the preoperative treatments.

The primary endpoint was percentage of intraoperative time outside the predefined blood-pressure targets, with no significant differences observed (14% vs 14%). Preoperative doxazosin showed significantly greater hypertension (SBP >160 mmHg; P = .005), however, and significantly greater maximum SBP (P = .005).

Intraoperative use of the number of vasodilators was significantly greater for preoperative doxazosin (P = .017), and significantly greater for magnesium sulphate use (3 vs 0 g; P = .005). The researchers observed no significant differences in the intraoperative use of number of vasoconstrictors, norepinephrine and phenylepinephrine, or fluid therapy.

Postoperatively, Dr. Buitenwerf indicated no significant differences between those who received doxazosin and those who received phenoxybenzamine.

Funding for this study was provided by an unrestricted research grant from Ipsen Bioscience Inc., Cambridge, Massachusetts.

[Presentation title: Randomized Trial Comparing Phenoxybenzamine and Doxazosine for Preoperative Treatment of Patients with a Pheochromocytoma (PRESCRIPT). Abstract OC7.5]

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