Efficacy of α-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial

Edward Buitenwerf, Thamara E Osinga, Henri J L M Timmers, Jacques W M Lenders, Richard A Feelders, Elisabeth M W Eekhoff, Harm R Haak, Eleonora P M Corssmit, Peter H L T Bisschop, Gerlof D Valk, Ronald Groote Veldman, Robin P F Dullaart, Thera P Links, Magiel F Voogd, Götz J K G Wietasch, Michiel N Kerstens, Edward Buitenwerf, Thamara E Osinga, Henri J L M Timmers, Jacques W M Lenders, Richard A Feelders, Elisabeth M W Eekhoff, Harm R Haak, Eleonora P M Corssmit, Peter H L T Bisschop, Gerlof D Valk, Ronald Groote Veldman, Robin P F Dullaart, Thera P Links, Magiel F Voogd, Götz J K G Wietasch, Michiel N Kerstens

Abstract

Context: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).

Objective: To determine which type of α-adrenergic receptor blocker provides the best efficacy.

Design: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898).

Setting: Multicenter study including 9 centers in The Netherlands.

Patients: 134 patients with nonmetastatic PPGL.

Intervention: Phenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized.

Main outcome measures: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.

Results: Median cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% (5.3-20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8-58.0) and 50.0 (35.3-63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.

Conclusions: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.

Keywords: -adrenergic receptor blocker; hemodynamic instability; pheochromocytoma; sympathetic paraganglioma.

© Endocrine Society 2019.

Figures

Figure 1.
Figure 1.
Flow-chart of the trial procedure. Abbreviations: BP, blood pressure; HR, heart rate; ER, extended-release; i.v., intravenous.
Figure 2.
Figure 2.
Cumulative distribution of the percentage of total intraoperative time with blood pressure outside the target values (ie, systolic blood pressure >160 mmHg and MAP x axis represents the cumulative time outside of the respective blood pressure targets. The y axis represents the cumulative proportion of patients.

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