Pheochromocytoma is a rare disease with an incidence in the general population of 0,005-0,1%. The prevalence in the hypertensive population is 0,1-0,6%. Headache, tachycardia, and sweating is the classical triad of symptoms. Hypertension is common and is sustained in half of the patients, paroxysmal in one-third, and absent in one-fifth. Fractionated metanephrines (plasma and urine) make the diagnosis. In the case of a cystic pheochromocytoma blood tests can be within the normal range, which makes preoperative diagnosis difficult. The rarity of this entity means there are no prospective studies with a significant number of patients to support the best management of these patients.
Since 2015, and following my learning from Prof Martin Walz, I am using the posterior retroperitoneoscopic approach to treat adrenal tumors, pheochromocytomas included. This approach allows for faster and more effective adrenalectomy, with a mean operative time of 38 min. Classically, pheochromocytoma patients are preoperatively treated with α blockade. While working in Essen, I was told that many patients were not being given α blockade and were doing well or even better than α blocked patients. This was totally out of the box. In Portugal, everybody told me that it was not possible to do. Even in the Surgery National Congress in Portugal, I was mocked by my fellow surgeons. Those who do not open their minds to something different will forever be small-minded and followers of the progress made by open-minded people.
In 2020, an "International multicenter review of preoperative management and outcome for catecholamine-producing tumors" was published in the British Journal of Surgery. It is a paper all surgeons and anesthesiologists must read. The reason for using α blockade is that it eventually reduces hemodynamic instability during surgery and reduces mortality. The α blockade is responsible for the low mortality of 1-3% in todays' pheochromocytoma surgery. Is this conclusion supported by high-quality science studies? No, it is not. Guidelines advise for the preoperative administration of α blockade. However, this recommendation is based on small studies from a single center and on personal clinical experience. Pheochromocytoma and Paraganglioma Initiative (PPI) collected data from 21 centers. This international group analyzed the outcomes of patients with and without α blockade:
Intraoperative hypertensive crises (> 250mmHg)
Perioperative morbidity related to hemodynamic instability
Mortality
They included 1870 patients treated for pheochromocytoma or paraganglioma between 2000 and 2017. Most patients underwent minimally invasive surgery. Of those, 343 patients did not receive α blockade. The Essen Center (from Prof. Martin Walz) included 504 patients (1/3 of the total). Of those, 247 underwent surgery with α blockade and 257 without it. Both groups were equal according to gender, weight, size of the tumor, typical symptoms, and biochemical profile (adrenaline and noradrenaline). Comparing patients with (1527) and without (343) α blockade, the authors found interesting results that should be considered:
1. Hypertensive crises were identical in both groups (p=0,086)
2. Postoperative complications related to catecholamines producing tumor:
Total = 5%
With α blockade = 5,9%
Without α blockade = 0,9%
p<0,001
3. Most common hemodynamic complications were:
Orthostatic dysregulation
Sustained arrhythmia
Cardiac decompensation
4. Mortality rate is identical
These results show that the preoperative α blockade was related to more hemodynamic-related complications. The preoperative α blockade was introduced several decades ago aiming at reducing complications. Although good-quality science was lacking, guidelines included α blockade as a rule to treat pheochromocytoma. The lack of support in good-quality science is a common problem in some guidelines (ERAS guideline for instance).
They are based on low-quality science, based on the personal clinical experience of a few, and based on small studies from a single center. There are no evidence-based data to support the management approach to pheochromocytomas and paragangliomas.
The efficacy and safety of α blockade use have never been proved. Now is the time to do it. The authors concluded that preoperative α blockade increases preoperative orthostatic hypotension. Additionally, α blockade does not decrease intraoperative hypertensive crises and does not reduce postoperative complications. However, it promotes sustained postoperative hypotension. Its use may lead to an unnecessary surgery delay. Therefore, we should question the use of preoperative α blockade.
A drawback of the present study is the absence of criteria for doing or not doing α blockade. Are there any patients who benefit from α blockade? Are there any patients who should not take α blockers? How can we decide? Should we stop using α blockade in all patients? These answers are lacking. However, from the PPI study group (21 centers), α blockade may not be necessary or even beneficial to use.
I leave you two final sentences from this work. "Management of patients with catecholamine-producing tumors, including the use of preoperative α-receptor blockers, has become largely dogmatic; additional studies will help clarify which patients if any, will benefit from each intervention." The authors keep going saying something I believe is crucial for evolution. These data "highlight the need for ongoing reassessment and discussion of the contemporary perioperative management of these patients". Questioning dogmas and certainties is paramount.
Surgeons and remaining doctors must always seek the reason and explanation for clinical practice. The "because we have always done this way" is not a valid answer. Additionally, "because the guideline says it" or "because it is the department's protocol" are not valid justifications for anything a surgeon decides to do. Study and learn.
Do not blindly accept an idea as a dogma. Always ask why. Think differently, do differently. Think out of the box and make the world goes round.
Link to PubMed:
Dr. Carlos Eduardo Costa Almeida
General Surgeon
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