Pheochromocytomas are rare neuroendocrine tumors derived from catecholamine secreting chromaffin cells located within the adrenal medulla. Currently, the mainstay of perioperative management in pheochromocytoma (PCT) has been nonselective and irreversible α-blockade with phenoxybenzamine.^1,2 This medication, in combination with preoperative fluid and sodium resuscitation to counter a chronically volume contracted state, has been a standardized perioperative pathway for reliable catecholamine management prior to PCT resection.^3,4 Notably, a complicating factor for PCT management has been its high outpatient costs and financial toxicity. This author, using his own health plan benefits, was quoted up to $3500 for an outpatient course of phenoxybenzamine alone depending on pharmacy location (Table). While ultimate out-of-pocket costs will depend on the available insurance and benefits, clearly this is an area of concern and an opportunity for improvement.

Table. Medication costs by location.^a

Do Alternatives Exist?

Other medications, such as terazosin and doxazosin, offer selective, reversible α-1 antagonism with the added benefit of pharmacologic familiarity with practicing urologists. Additionally, these medications are widely available in many pharmacies, as opposed to phenoxybenzamine which often must be picked up at specialty pharmacies. Reversable α-1 antagonists are also more affordable; a similar query into a course of treatment returned $10 to $30 US dollars (Table).

Notably, while terazosin and doxazosin should theoretically provide comparable clinical end points for perioperative PCT management compared to phenoxybenzamine, the literature exploring these agents for primary α-blockade in PCT remains limited. Randomized trials exploring the use of these medications in the setting of PCT currently do not exist. Few α-1–specific protocols exist within the literature. A review article from the Netherlands found 5 limited studies comparing selective α-1 blockers to phenoxybenzamine but noted that protocols differed significantly from each other and that studies were hampered by very small sample sizes.⁵ In addition, intraoperative observations regarding hemodynamic patterns are limited and postoperative outcome data are scant.

Contemporary Observations

To this end, we discuss a protocol currently in use at the University of Oklahoma Health Science center focused on α-blockade using α-1–specific, reversible agents. Patients undergo preoperative α-blockade for an average of 2 to 3 weeks with a selective α-blocker (terazosin, doxazosin, prazosin). The choice of agent is dependent upon the prescriber’s familiarity with that specific medication. Patients were sent home with a blood pressure monitor, instructed to check blood pressure 3 times a day and to record and submit the values to the prescribing physician on a regular basis. For reversible α-1 agents, patients were started on the lowest dose and then dose-escalated up to the point of symptomatic dizziness or orthostasis upon standing. Patients were then instructed to maintain their target dosing level until surgery. We also discussed the importance of volume resuscitation via high sodium and fluid supplementation to counteract a chronically volume contracted state. Additionally, preoperative evaluation and close collaboration with colleagues in primary care, endocrinology, and/or cardiology is essential to help with optimization of major comorbidities and to help finalize any adjustments of adjunct antihypertensive medications. Surgery should be performed once blood pressure is stable on an α-1 antihypertensive medication. We prefer a robotic-assisted laparoscopic approach for the vast majority of pheochromocytomas.

Based on initial results, we have not noticed major differences in perioperative outcomes between groups using phenoxybenzamine vs α-1–specific antagonists. Specifically, this includes intraoperative hemodynamics, estimated blood loss, blood transfusion requirements, or operative time. We also did not see a difference in ICU requirements or upgrades, hypotensive or tachycardic episodes, hospital length of stay, or in 30-/60-day readmissions (data not shown).

Other Considerations

While our initial experience suggests that selective α-1 blockade of pheochromocytoma patients may be an efficacious, cost-effective, and safe alternative, further studies are clearly needed. Additionally, multidisciplinary care of patients with pheochromocytoma is paramount. A referral to an endocrinologist should be strongly considered to help assist with medical comanagement. Patients with a history of cardiac complications, multiple blood pressure medications, or sequelae of hypertrophic cardiomyopathy secondary to long-term vasoconstriction should be referred to cardiology and/or primary care for consideration of electrocardiogram, echocardiogram, and blood pressure optimization with close postoperative follow-up. Additionally, our anesthesia colleagues should be notified in advance of the type of α-blockade used. While initial observations suggest no difference in global perioperative outcomes between agents, reversible vs nonreversible α-antagonism can influence the choice of vasoactive medications required intraoperatively. These variables can be carefully managed if anticipated ahead of time.

Conclusions

Use of selective, reversible α-blockade may be an alternative to phenoxybenzamine for perioperative PCT management. Use of reversible α-blockade may also have the advantage of easier prescription accessibility and lower cost (Figure).