Bad Medicine

Pheochromocytoma is one of the important secondary causes of hypertension. Catecholamines are normally secreted by Chromaffin cells in the adrenal gland medulla most of them. Catecholamines are usually stored in secretory vesicles inside these cells, and get secreted into circulation when a stimulus arrives from the sympathetic nervous system. Pheochromocytoma is a pathologic tumor that releases catecholamines in the bloodstream in higher amounts than normal. Noradrenaline is usually secreted continuously, while Adrenaline is released in paroxysmal episodes. . The continuous secretion of noradrenaline causes hypertension. Catecholamines have two types of receptors; 1. Alpha 2. Beta.

Catecholamines receptors are classified as following :

1. Alpha-1: Smooth muscle contraction
2. Alpha-2: Various effects on smooth muscle (most likely: vasoconstriction)
3. Beta-1: Increased heart rate and atrial contractility
4. Beta-2: Smooth muscle relaxation, Bronchodilation
5. Beta-2: Induces lipolysis

Each receptor has various degrees of affinity to adrenaline or noradrenline. For example: Alpha-1 has stronger affinity towards noradrenline than adrenaline. That's why symptoms of pheochromocytoma patient differ by the pattern of secretion of adrenaline and noradrenaline. Commons symptoms and signs are:

• Headache
• High blood pressure
• Tachycardia
• Anexiety
• Diaphoresis, especially at night

The patient typically experiences those symptoms in a paroxysmal manner, because of the paroxysmal manner of secretion of adrenaline. Some other reported signs and symptoms are:

• Pallor
• Weight loss
• Constipation
• Heat intolerance
• High blood glucose level

Now, after we have quickly reviewed catecholamines and pheochromocytoma, we can discuss how that mistake happens, which is a fatal mistake!

A mistake with a pheochromocytoma patient

Read this case with me:

Unprepared patient

a 62 year old male patient is presented to the operating room for the removal of a right adrenal mass. His blood pressure before the operation is 180/105. The patient is hypertensive pre-operatively, but he hasn't taken his daily dose yet. The patient was a little sweaty and had a slight tremor, but stated that this was normal for him. Hypertension medication is given to the patient, and he was monitored for 2 hours.

On entering the OR his blood pressure was 160/95, heart rate was 90. He was connected to monitors, and was put on 100% oxygen mask. Anesthesia was induced using fentanyl, lidocaine, propofol and rocuronium.

The doctors started an attempt to insert the endotracheal tube, but were interrupted by a significant event; the patient's blood pressure acutely rises to 200/110! The Anesthiologist decides to increase the depth of the anethesia by raising the minimum alveolar concentration of isoflurane along with additional propofol, fentanyl and esmolol. The blood pressure continued to rise reaching the 300/150!. The patient is still under oxygen mask.

Intravenous nitroprusside, nitroglycerine and labetalol beta-blocker were given by the anesthesiologist with no response.

What do you think? What happened? How can this patient be saved? What went wrong?

The patient had a pheochromocytoma, but unfortunately it was not diagnosed before the operation. The induction of anesthesia caused a catecholamine crisis, i.e. a sharp increase in the levels of catecholamines in his blood.

The reason why general anesthesia causes catecholamine crisis is still unclear, but some studies suggest that rocuronium muscle relaxant could be stimulating sympathetic nervous system. Some attribute the cause to the patient's anxiety, while others attribute it to mechanical stimulation of the adrenal gland by applying pressure to the patient's abdomen.

Whatever the mechanism of the cateholamine crisis is, it happened to the patient. We reviewed that beta-2 receptos induce smooth muscle relaxation, while alpha-1 receptors cause smooth muscle contraction..

Imagine giving this patient a beta blocker to treat his high blood pressure. What would happen? Normally, catecholamines stimulate alpha receptors, which cause smooth muscle contraction, and beta receptors, which cause smooth muscle relaxation, creating a kind of balance. But when we prescribe a beta blocker, the catecholamines in the patient's bloodstream will only act on the alpha receptors and will not reach the beta receptors, leading to only unopposed smooth muscle contraction. This will lead to vasoconstriction and a severe rise in blood pressure! Yes, the blood pressure medication will raise his blood pressure instead of treating it!

How to save the patient?

So... how do we save this patient? How do we reduce his blood pressure? The solution is simple, and maybe you have guessed it! The patient needs an alpha antagonist to block catecholamines from reaching alpha receptors, thus preventing the vasoconstriction of those blood vessels. Let's continue the story:

The anesthesiologist suspects that the patient has pheochromocytoma. He gives the patient an IV bolus of phentolamine alpha antagonist. The blood pressure of the patient drops to 180/95 within 2 minutes. Surgery was canceled, the patient was intubated and sent to the intensive care unit for close monitoring.

A common mistake

You might think that the mistake I told you about here is uncommon, and it's rare that doctors fall into it, but have you asked yourself why do they call it The Anesthesiologist Nightmare?

Pheochromocytoma resection is one of the biggest challenges facing an anesthesiologist. Patients are usually prepared for surgery by taking alpha-blockers two weeks before the procedure, or midazolam to reduce anxiety. However, the biggest challenge lies not in preparing the patient for surgery, but in diagnosing them before surgery! Some studies indicate that 80% of undiagnosed pheochromocytoma patients die in the operating room due to improper preparation and lack of preoperative diagnosis.

Pheochromocytoma is rare, representing 1 per 2000 poeple, and the cause of hypertension in 2 per 1000 hypertensive patient. The prevelance varies from one study to another, and many patients are diagnosed incidentally because this disease is often undiagnosed and treated as primary hypertension. We can avoid this mistake by taking a detailed medical history from the patient and ensuring that we do not suspect a secondary cause of high blood pressure.

The rarity of the disease is no excuse for making this mistake. If the error can be easily avoided, why not consider it?

Underdiagnosis of the disease and prescribing beta-blockers could be fatal, since it will cause an increase, instead of a decrease, in blood pressure as we've said. That's why: suspect that the high blood pressure is caused by pheochromocytoma if the patient has its symptoms like:

• Diaphoresis attakcs, especially at night. Ask the patient questions like Do you sweat untill your clothes become soaked in water? Does it wake you up from sleep? When does the attack come?
• Tachycardia associated with high blood pressure.
• Symptoms like headache, palpitations, and diaphoresis come in paroxysmal surprising pattern.

Read more details about pheochromocytoma

Regarding the answer to the question I promised you at the end of the article, anesthesiologists do not insert an endotracheal tube when blood pressure is high to avoid further elevation of blood pressure. The base of the tongue has baroreceptors that stimulate the sympathetic nervous system . When this area is stimulated by a laryngoscope or inserting an intubation, the body quickly responds and attempts to prepare for the fight-or-flight response, sensing that a foreign body is about to enter the airway. The body will attempt to prepare for this risk by stimulating the sympathetic nervous system, which will increase the concentration of catecholamines in the patient's blood, further increasing his blood pressure. This is why inserting an endotracheal tube is postponed until after the patient's blood pressure has stabilized. It is worth noting that the response to an endotracheal intubation includes several physiological reactions, which vary depending on age.

References

1. Gupta PK, Marwaha B. Pheochromocytoma. [Updated 2024 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK589700/
2. Farzam K, Kidron A, Lakhkar AD. Adrenergic Drugs. [Updated 2023 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534230/
3. Myklejord DJ. Undiagnosed pheochromocytoma: the anesthesiologist nightmare. Clin Med Res. 2004 Feb;2(1):59-62. doi: 10.3121/cmr.2.1.59. PMID: 15931336; PMCID: PMC1069072.
4. Sonntagbauer M, Koch A, Strouhal U, Zacharowski K, Weber CF. Catecholamine crisis during induction of general anesthesia : A case report. Anaesthesist. 2018 Mar;67(3):209-215. English. doi: 10.1007/s00101-018-0409-6. Epub 2018 Feb 5. PMID: 29404657.
5. Chraemmer-Jørgensen B, Hertel S, Strøm J, Høilund-Carlsen PF, Bjerre-Jepsen K. Catecholamine response to laryngoscopy and intubation. The influence of three different drug combinations commonly used for induction of anaesthesia. Anaesthesia. 1992 Sep;47(9):750-6. doi: 10.1111/j.1365-2044.1992.tb03252.x. PMID: 1415971.
6. Physiologic and Pathophysiologic Responses to Intubation, available from: https://clinicalgate.com/physiologic-and-pathophysiologic-responses-to-intubation/