Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
Department of Anesthesiology, UCLA David Geffen School of Medicine, Los Angeles, California.
Endocr Pract. 2022 Sep;28(9):889-896. doi: 10.1016/j.eprac.2022.06.013. Epub 2022 Jul 7.
Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine.
We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs.
Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin.
Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.
苯氧苄胺（非选择性、非竞争性α受体阻滞剂）是治疗嗜铬细胞瘤的首选药物，但多沙唑嗪（选择性、竞争性α受体阻滞剂）可能同样有效。我们比较了多沙唑嗪与苯氧苄胺的疗效。
我们在一家三级转诊中心进行了一项前瞻性研究，对接受嗜铬细胞瘤或副神经节瘤切除术的患者进行随机分组，分别接受苯氧苄胺或多沙唑嗪预处理。由于苯氧苄胺的成本较高，导致大量患者转为使用多沙唑嗪。随后我们停止了随机分组，并纳入了连续的苯氧苄胺患者进行病例对照研究设计。通过静脉输注递增剂量的苯肾上腺素来评估α受体阻断的效果。主要结局为死亡率、心血管并发症和入住重症监护病房。次要结局为血流动力学不稳定指数（手术偏离血流动力学目标的比例）、苯肾上腺素滴定试验评估的阻滞充分性以及药物成本。
前瞻性纳入了 24 例患者（多沙唑嗪组 n=20，苯氧苄胺组 n=4），并加入了 15 例接受苯氧苄胺治疗的历史患者（苯氧苄胺组 n=19）。两组均未发生重大心血管并发症。苯肾上腺素剂量反应曲线显示，苯氧苄胺组的血压升高幅度小于多沙唑嗪组（线性回归系数分别为 0.008 与 0.018，P=0.01），提示苯氧苄胺组的α受体阻滞作用更好。苯氧苄胺组和多沙唑嗪组的血流动力学不稳定指数中位数分别为 14%和 13%（P=0.56）。苯氧苄胺的日最高费用中位数为 442.20 美元，而多沙唑嗪为 5.06 美元。
苯氧苄胺可能比多沙唑嗪更好地抑制术中高血压，但这种差异并未转化为更少的心血管并发症，并且被显著增加的成本所抵消。
