Excision of pheochromocytoma

Pheochromocytoma is a rare neuroendocrine disease of the adrenal gland where catecholamine-secreting tumors cause hypertension. Pheochromocytoma is present in 0.05% - 0.2% of hypertensive individuals, the incidence of the disease presents equally between men and women with a distribution across age groups but peaks in between 40 and 50 years of age. The classic presentation of the disease is a triad of symptoms including headache, palpitations, diaphoresis with a documented clinical sign of hypertension (present in 90% of patients with pheochromocytoma). However, patients can often present with less definitive symptoms such as tremor, anxiety, flushing, weight loss, and hyperglycemia. While the majority of pheochromocytoma emerges from adrenal tumors, roughly 15-20% can be extra-adrenal in etiology.

During the early part of the 20th century, the perioperative mortality of this disease ranged between 26-50%. As surgery is curative in about 90% of presenting cases, the mortality has decreased to roughly 1% in specialized centers. Surgical resection can be approached in a variety of ways: (1) open laparotomy; (2) laparoscopic transabdominal; (3) laparoscopic retroperitoneal; and (4) single incision laparoscopic retroperitoneal. Each approach has different indications, advantages and disadvantages, as well as unique line and monitoring choices. The largest North American series published about pheochromocytoma excision described 108 cases, where 90% were conducted laparoscopically, and the perioperative morbidity rate was 13% without a single mortality.

Excision of pheochromocytoma

Anesthesia type	General
Airway	ETT
Lines and access	Arterial line Additional large-bore PIVs ± Central venous catheter ± Pulmonary Artery Catheter ± Epidural catheter (dependant upon approach)
Monitors	Standard Monitors Invasive blood pressure monitor ± Central venous catheter ± Pulmonary Artery Catheter
Primary anesthetic considerations
Preoperative	Preoperative alpha-blockade
Intraoperative	Rapid episodes of extreme hypertension Severe hypotension after adrenal vein ligation Cardiovascular collapse Hyperglycemia Hypovolemia
Postoperative	Residual hypertension Prolonged hypotension (requiring vasopressors) Hyperglycemia/Hypoglycemia
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Preoperative management

Patient evaluation

System	Considerations
Neurologic	Investigate headaches and fatigue
Cardiovascular	Evaluate history of chest pain, palpitations, arrythmia and signs of heart failure Patients may require EKG or echocardiography Patients may present with catecholamine-induced, Takotsubo, or dilated cardiomyopathy
Respiratory	Classify obstructive or restrictive lung disease
Gastrointestinal
Hematologic
Renal	Evaluate electrolyte disturbances Evaluate fluid status as patients are often hypovolemic from catecholamine excess
Endocrine	Patients may be functionally hyperglycemic due to excessive catacholamine release
Other

Labs and studies

• ± electrocardiogram to investigate palpitations, arrhythmia, cardiac ischemia, bundle branch block, or left ventricular hypertrophy
• ± echocardiogram to assess signs of heart failure, Takotsubo cardiomyopathy, or to diagnose cardiac paragangliomas
• Capillary glucose to test temporary insulin resistance

Operating room setup

• Infusion manifold with high rate carrier
• Vasopressor infusion (typically non-direct sympathomimetics such as vasopressin)
• Direct vasodilator infusion
• ± insulin infusion to treat hyperglycemia
• Diluted push syringes of vasodilators and vasopressors to adjust blood pressure with sudden changes to blood pressure during catecholamine surges during induction and tumor manipulation.

Patient preparation and premedication

Perioperative α-blockade: α-blockade continues to be a staple medication therapy for 10-14 days prior to pheochromocytoma excision

• Choice between Irreversible non-selective α-blockade (Phenoxybenzamine) or non-selective α-blockade (Doxazosin, Prazosin, and Terazosin)
• α-blockade blockade adequacy was originally described by the Roizen Criteria:
  1. Blood pressures < 160/90 for 24 hours prior to surgery
  2. Absence of orthostatic hypotension
  3. Absence of ST or T-wave changes prior to surgery
  4. No more than 5 premature ventricular contractions in a minute.
• However, several centers have recently abandoned these strict criteria, given it's largely inpatient applications, and use a combination of symptoms of orthostatic hypotension, blood pressures, and duration of α-blockade to guide block adequacy.
• As titration of α-blockade increases prior to surgery, patients will typically exhibit tachycardia. At this time β-blockade or calcium-channel blockade may be introduced. It is still recommended to introduce β-blockade only after several days of α-blockade titration to avoid unopposed α-agonism from the circulating catecholamines, which may cause extreme hypertensive episodes for the patient.

Pre-Operative anxiolysis and analgesia:

• Catecholamine surges can occur with any noxious stimuli such as laryngoscopy, positive pressure ventilation, or abdominal insufflation. Preoperative anxiolysis and analgesia is useful to prevent catecholamine surges during these episodes.

Early Fluid Resuscitation:

• Patients are often intravascularly dry due to excessive catecholamines. Early infusion of fluid to establish euvolemia prior to the clamp of the adrenal vein is advisable.
• Without proper resuscitation during the day-of-surgery or early intraoperative period, patients may exhibit drastic hypotension once the pheochromocytoma is removed.

Regional and neuraxial techniques

• Epidural analgesia may be useful for patients undergoing open laparotomy approach for pheochromocytoma excision

Intraoperative management

Monitoring and access

• Standard monitors
• Arterial line for immediate blood pressure management and electrolyte sampling
• +/- Central Venous Catheter (CVC) for vasoactive drug infusions (some specialized centers are moving away from CVC insertion)
• +/- Pulmonary artery catheter for severe heart failure or pulmonary hypertension
• Foley catheter to monitor fluid status

Induction and airway management

• Endotracheal tube (consider armored ETT for prone position)

Positioning

• Supine for open laparotomy or combined procedures for multiple endocrine neoplasia presentations
• Lateral for transabdominal laparoscopic approach
• Prone for retroperitoneal laparoscopic approach

Maintenance and surgical considerations

• Consider pre-induction arterial line as catecholamine surge can occur during mask ventilation and intubation.
  • Some centers describe a conducting a phenylephrine titration prior to induction to test the adequacy of α-blockade
• Catecholamine surges can occur during the following intraoperative periods: intubation < Positioning < Insufflation < tumor manipulation
• Treat and control hypertension prior to adrenal vein ligation.
  • Start with vasodilators (nitroprusside, nitroglycerine, nicardipine, clevidipine) and then supplement with short-acting beta-blockade (esmolol)
• Surgery team should communicate with anesthesia team when the adrenal vein has been identified and prior to clamping
  • Anesthesia team should load patients with fluid prior to adrenal vein identification
  • Increase vasopressor support (i.e. vasopressin) to prevent sudden loss of blood pressure after ligation of adrenal vein. Titrate down vasodilators at this time.
• Anticipate sudden drops of blood pressure after adrenal vein clamping. Such changes can induce cardiac collapse.
  • Support blood pressure with vasopressors (i.e. vasopressin)

Emergence

• Extubation after case completion is customary

Postoperative management

Disposition

• Many centers still admit all pheochromocytoma patients to the intensive care units.
  • A percentage of patients will require vasopressor support after surgical completion until fluid shifts and physiology equilibrates
  • A small population of patients will continue to have circulating catecholamines for several hours and may require a few hours of vasodilation
• Specialty centers are able to titrate all vasopressors off by the end of the case and patients can be admitted into the PACU
• With diabetics, the sudden withdrawal of catecholamines can precipitate sudden hypoglycemia - particularly in patients on insulin drips intraoperatively

Pain management

• Open laparotomy may require epidural pain control
• Laparoscopic and particularly single-incision retroperitoneal support rarely require epidural pain management. Pain can be controlled using IV and PO pain medications.

Potential complications

• Sudden, wide, blood pressure changes can cause cardiac ischemia, cardiovascular collapse and ischemic or hemorrhagic stroke
• With diabetics, the sudden withdrawal of catecholamines can precipitate sudden hypoglycemia - particularly in patients on intraoperative insulin drips. Monitor post-operative glucose carefully.

Procedure variants

	Open Laparotomy	Transabdominal Laparoscopic	Retroperitoneal Laparoscopic	Single-Incision Retroperitoneal Laparoscopic
Unique considerations				High Insufflation pressures (20-30mmHg)
Position	Supine	Lateral	Prone	Prone and half jacknife position (praying position)
Surgical time	4-6 hrs	3-5 hrs	1.5 hrs	1.6 hrs
EBL			5 mL	5 mL
Postoperative disposition	PACU or ICU	PACU or ICU	PACU	PACU
Pain management	Epidural	Oral and IV pain medications	Oral pain medications	Oral pain medications (76%)
Potential complications			Subcutaneous emphysema	Subcutaneous emphysema
Length of Stay			1.4 days	1.1 days