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Anesthesia for the adult with pheochromocytoma
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Anesthesia for the adult with pheochromocytoma
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Literature review current through: Sep 2017. | This topic last updated: Dec 06, 2016.

INTRODUCTION — Pheochromocytomas are neoplasms of chromaffin tissue that synthesize catecholamines. Pheochromocytoma is a rare disorder that presents challenges for the anesthesiologist. By some estimates, 25 to 50 percent of hospital deaths of patients with unmanaged or unknown pheochromocytoma occur during induction of anesthesia or during operative procedures for other conditions [1]. Since treatment of pheochromocytoma almost always includes surgical resection, most of these patients will require anesthesia.

Paragangliomas are neuroendocrine tumors that arise from the extra-adrenal autonomic ganglia and are indistinguishable from pheochromocytomas at the cellular level. They can secrete catecholamines and present clinically like pheochromocytomas, so the concerns for anesthesia for patients with paragangliomas are the same.

This topic will discuss the preoperative evaluation, intraoperative management, and postoperative care of patients who will undergo resection of pheochromocytoma. The diagnosis and presentation, epidemiology, and genetics of pheochromocytoma, as well as medical optimization prior to surgery, pheochromocytoma during pregnancy, and nonsurgical treatment of pheochromocytoma, are discussed separately. (See "Clinical presentation and diagnosis of pheochromocytoma" and "Treatment of pheochromocytoma in adults" and "Paraganglioma and pheochromocytoma: Management of malignant disease" and "Pheochromocytoma in genetic disorders" and "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery' and "Clinical presentation and diagnosis of pheochromocytoma", section on 'Pheochromocytoma in pregnancy'.)

PERIANESTHETIC RISKS AND OUTCOMES — Many patients who undergo pheochromocytoma resection exhibit labile blood pressure (BP), arrhythmias, and tachycardia during and after surgery, though most can be managed without lasting morbidity or mortality. Because of the rarity of pheochromocytoma, most data on the anesthetic management and perioperative outcomes have been reported in small case series that spanned many years. The following observational studies illustrate the complications seen in patients with known pheochromocytoma who present for resection:

An observational study of 108 resections performed at a single institution reported no intraoperative deaths, two intraoperative arrhythmias (which were not defined), and one postoperative stroke [2].

Another observational study of 143 cases reported no deaths or myocardial infarctions [3]. Twenty-five percent had sustained hypertension during surgery, and 14 percent experienced a systolic BP (SBP) >220 mmHg for a mean duration of nine minutes. Four percent required prolonged postoperative endotracheal intubation. Significant risk factors for adverse perioperative events included large tumor size, increased levels of preoperative catecholamines, and longer duration of surgery.

A third single-institution observational study of 81 laparoscopic resections reported no deaths or myocardial infarctions [4]. Intraoperative hypertension (SBP >170 mmHg) and hypotension (SBP <90) occurred in 53 and 28 percent of patients, respectively. Tumor size over 6 cm correlated with longer surgical time, but not with increased BP lability.

Risks are much higher for patients with unrecognized pheochromocytoma who undergo anesthesia for unrelated surgery. In this setting, the patient can present with unexplained severe hypertension, tachycardia, arrhythmias, and cardiovascular collapse after induction of anesthesia [5] or at any time during surgery (eg, after administration of metoclopramide [6]). Mortality for such patients approaches 80 percent [7].

PREOPERATIVE EVALUATION — Preoperative evaluation and medical management for pheochromocytoma resection should be multidisciplinary, including the surgeon, anesthesiologist, and endocrinologist. Once the diagnosis is confirmed, the patient must be evaluated for possible end organ damage caused by excess catecholamine secretion, and preoperative medical preparation should be started. (See "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery'.)

Timing and goals — We assess patients with pheochromocytoma at least 7 to 14 days prior to resection to allow time for modification of treatment, if necessary. Prior to this evaluation, the endocrinologist will have titrated therapy aimed at minimizing the physiologic impact of catecholamine release. This preoperative medical therapy usually takes 10 to 14 days.

The focus of our evaluation includes an assessment of the following:

End organ damage that may affect anesthetic management. (See 'End organ damage' below.)

The preoperative medical therapy used, which may impact intraoperative and postoperative events. (See 'Preoperative medical therapy' below.)

Whether the preoperative medical therapy has attained its goals (ie, control of hypertension and normalization of intravascular volume). (See 'Preoperative testing' below.)

Details regarding preoperative medical therapy are discussed in more detail separately. (See "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery'.)

Clinical assessment — The classic triad of symptoms of pheochromocytoma consists of hypertension, headache, and sweating, though most patients with pheochromocytoma do not present with all three. Other, less common signs and symptoms include orthostatic hypotension, blurred vision, papilledema, weight loss, polyuria, polydipsia, and constipation. (See "Clinical presentation and diagnosis of pheochromocytoma", section on 'Clinical presentation'.)

Some hereditary conditions are associated with pheochromocytoma (eg, von Hippel Lindau, multiple endocrine neoplasia type 2, neurofibromatosis type 1). When patients with these conditions present for other surgical procedures, signs and symptoms suggesting pheochromocytoma should be elicited. (See "Pheochromocytoma in genetic disorders", section on 'Familial pheochromocytoma'.)

End organ damage — In addition to the routine preoperative anesthesia history and physical examination, evaluation should focus on potential end organ damage resulting from excess catecholamine secretion. Excess catecholamines secreted by pheochromocytomas can cause pathophysiological changes in the cardiovascular and other systems, as shown in the table (table 1) [8,9].

Of these, damage to the cardiovascular system is the most likely to impact outcomes with anesthesia. Catecholamine excess can result in volume depletion, postural hypotension, organ or limb ischemia, aortic dissection, angina, myocardial infarction, acute or chronic cardiomyopathy, congestive heart failure, and arrhythmias [10,11]. The goal of preoperative medical therapy is to control hypertension and reverse volume depletion. (See 'Preoperative medical therapy' below.)

Preoperative cardiac evaluation should include an electrocardiogram (ECG) to evaluate for possible ischemic changes and rhythm disturbances. ST and T wave changes suggestive of ischemia should resolve with preoperative medical preparation; if necessary, surgery should be delayed until active ischemia has resolved and arrhythmias are adequately controlled prior to elective surgery.

For most patients, an echocardiogram should be performed to assess ventricular function, chamber size, and wall motion. A Holter monitor is rarely indicated as arrhythmias should resolve with preoperative medical preparation.

Preoperative medical therapy — Preoperative medical therapy aimed at minimizing the physiologic impact of catecholamine release is a key component of the care of a patient with a catecholamine-secreting neoplasm.

Goals of therapy — Preoperative pharmacologic preparation is indicated for all patients with catecholamine-secreting neoplasms. Preoperative alpha-adrenergic blockade may prevent or reduce hypertensive crises during surgery for pheochromocytoma, allow intravascular volume expansion, and improve cardiac function in patients with catecholamine-induced myocarditis and cardiomyopathy. While this process is usually managed by an endocrinologist, the anesthesiologist should understand the regimen used and the goals of therapy, which are twofold (see "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery'):

Control of hypertension, including prevention of hypertensive crisis during surgery

Normalization of intravascular volume

There is no universally accepted regimen, and clinical practice varies. Options include combined alpha-adrenergic and beta-adrenergic blockade, calcium channel blockers, and metyrosine. A high-sodium diet is usually incorporated to aid in the expansion of intravascular volume. Details of various regimens are discussed separately. (See "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery'.)

Preparation often takes between 10 and 14 days. Effectiveness of medical preparation is assessed by twice-daily orthostatic blood pressure (BP) measurements, typically aiming for a seated BP of 120/80 mmHg, a standing systolic blood pressure (SBP) ≥90 mmHg, and a heart rate between 60 and 70 beats/minute (bpm) seated and 70 to 80 bpm standing.

Impact on intraoperative management — The medications used for preoperative management of catecholamine excess have different properties that may impact the likelihood and management of perioperative hemodynamic changes. While the regimen is usually selected and managed by an endocrinologist, the anesthesiologist must understand the potential impact on intraoperative management. Details of various regimens are discussed separately. (See "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery'.)

Combined alpha- and beta-adrenergic blockade is the most commonly implemented strategy. Alpha blockade is initiated first, and for patients with tachycardia or arrhythmias, beta blockade is typically added cautiously several days before surgery. The beta-adrenergic blocker should never be started before the alpha blocker because blockade of vasodilatory peripheral beta-adrenergic receptors with unopposed alpha-adrenergic stimulation can lead to a further elevation in BP. Calcium channel blockers (eg, nicardipine) are sometimes used to supplement combined alpha and beta blockade or as an alternative for patients with intolerable side effects from other regimens.

Alpha-adrenergic blockade – Several different alpha-adrenergic blocking medications may be administered preoperatively for pheochromocytoma resection. These medications prevent or mitigate hypertension during surgery prior to clamp of the effluent venous drainage from the tumor, but they can cause hypotension after that point, when catecholamine secretion drops precipitously. (See 'Stages of surgery' below.)

PhenoxybenzaminePhenoxybenzamine is an irreversible, long-acting, nonspecific alpha-adrenergic blocking agent [12]. While phenoxybenzamine is effective for prevention of intraoperative hypertension, postoperative return of normal adrenergic function may be delayed because of its long duration of action. BP support may be required into the postoperative period after phenoxybenzamine pretreatment.

Selective alpha1-adrenergic blockers – In contrast to phenoxybenzamine, selective alpha1 blockers (eg, doxazosin, prazosin, and terazosin) are reversible and are shorter-acting. In an observational study of 35 patients with pheochromocytoma or paraganglioma undergoing resection, pretreatment with doxazosin appeared to be as effective as phenoxybenzamine for control of BP and heart rate before and during surgery [13]. Compared with those who were pretreated with phenoxybenzamine, patients treated with doxazosin had less preoperative postural hypotension, required less fluid administration after the effluent vein was clamped (phase II), and recovered to normal BP more rapidly at the end of surgery.

Urapidil is a selective alpha1-adrenergic blocker with a central sympatholytic effect mediated by stimulation of serotonin 5HT1A receptors, and is available in some countries outside the United States [14]. Small studies have described preoperative alpha blockade with three days of intravenous (IV) urapidil [15,16].

Beta blockade – Beta blockade is especially important for those patients with tumors that secrete large amounts of epinephrine, with resultant tachycardia and arrhythmias. Beta blockade is started at a low dose using short-acting oral medication (eg, propranolol). If tolerated, longer-acting and higher-dose medication is added. Complications may occur in patients with asthma or congestive heart failure. Patients with occult catecholamine-induced cardiomyopathy may develop congestive heart failure and pulmonary edema with beta blocker use.

Calcium channel blockade – As with preoperative alpha blockade, calcium channel blockers do not prevent all hemodynamic changes during these procedures. Calcium channel blockers, when combined with potent inhalation anesthetics, can cause hypotension. Treatment with calcium chloride may be indicated. (See "Treatment of pheochromocytoma in adults", section on 'Calcium channel blockers'.)

Metyrosine – Metyrosine is a competitive inhibitor of tyrosine hydroxylase, a rate-limiting enzyme, in the formation of catecholamines [12]. Some institutions use a five-day (short-term) preprocedure preparation protocol using metyrosine, while others use metyrosine to supplement preoperative alpha blockade [17]. With short-term therapy, the most common side effect is hypersomnolence, while side effects of longer-term treatment may be disabling [17]. The extrapyramidal effects of haloperidol, which may be administered during anesthesia, may be potentiated by metyrosine. (See "Treatment of pheochromocytoma in adults", section on 'Metyrosine'.)

Preoperative testing — Preoperative laboratory testing should be performed as it would be for any patient having major surgery, including blood glucose, electrolytes, blood urea nitrogen, creatinine, and complete blood count.

Blood type and screen should be performed. Transfusion thresholds used for other surgical patients are appropriate for patients with catecholamine-secreting tumors. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)

Biochemical testing for excess catecholamine secretion for the diagnosis of pheochromocytoma is discussed separately. (See "Clinical presentation and diagnosis of pheochromocytoma", section on 'Approach to initial evaluation'.)

Chest radiograph should be performed to assess for cardiomegaly and pulmonary edema.

SURGICAL APPROACH — Adrenalectomy for pheochromocytoma can be performed via laparotomy or laparoscopy. Laparoscopy with either a transabdominal or retroperitoneal approach is the procedure of choice for patients with solitary intraadrenal pheochromocytomas that are less than 8 cm in diameter and that have no malignant radiologic features. A retrospective review of 102 patients who underwent adrenalectomy for pheochromocytoma at one institution reported that more than 90 percent were performed laparoscopically, with four patients converted to either hand-assisted or open procedures [18]. (See "Treatment of pheochromocytoma in adults".)

Open procedures can be performed using a transperitoneal approach, a subcostal or midline incision, or a retroperitoneal flank approach.

STAGES OF SURGERY — Surgical resection of pheochromocytoma can be divided into two phases based on ligation of the blood supply to the tumor. Close communication between the surgeon and the anesthesiologist allows anticipation of hemodynamic changes during the course of surgery.

Phase I — Phase I includes the portion of surgery during which the tumor is dissected and the vascular supply is isolated, before clamping of the effluent vein. This phase is often characterized by periods of severe episodic hypertension and arrhythmias as adrenal manipulation releases catecholamines. Phase I also includes endotracheal intubation and insufflation of the abdomen with carbon dioxide (CO2) for laparoscopy, both of which can also result in marked hypertension and arrhythmias [19-22].

Endotracheal intubation – Catecholamine levels can rise during surgery in patients without pheochromocytoma (200 to 2000 pg/mL) but can rise much higher in patients with these tumors (2000 to 20,000 pg/mL), with potential for severe hypertension and arrhythmias [22,23]. The elevation in catecholamines associated with intubation can be prevented or minimized with deep anesthesia, even in patients with pheochromocytoma [24].

Peritoneal insufflation – Peritoneal insufflation during laparoscopic resection of pheochromocytoma can lead to hypertension and increased catecholamine levels [4,21,22]. Several mechanisms may be responsible for this response, including compression of the tumor, a change in tumor blood flow, and the sympathetic response to the hypercapnia related to CO2 absorption [22,25].

Tumor manipulation – Tumor manipulation during either laparoscopic or open adrenalectomy for pheochromocytoma causes the greatest release of catecholamines and the highest blood pressure (BP) recordings [4,21,22]. Catecholamines can remain high even after ligation of the adrenal vein, a phenomenon possibly related to the hypervascularity of some tumors (figure 1).

Phase II — Phase II is the portion of surgery after the effluent vein is clamped. Precipitous hypotension can occur because of the sudden drop in endogenous catecholamine levels, the chronic downregulation of alpha-adrenergic receptors, the presence of alpha-blocking medication, and intravascular volume depletion [4,21,22,26]. Vasopressor support is often necessary.

ANESTHESIA MANAGEMENT

Choice of anesthetic technique — General anesthesia, with or without epidural anesthesia, is used for pheochromocytoma resection. If epidural anesthesia is used during surgery, the resulting sympathectomy and vasodilation may exaggerate hypotension during stage II of the surgery, especially for patients who have received phenoxybenzamine for alpha-adrenergic blockade. (See 'Impact on intraoperative management' above.)

An epidural catheter may be placed before open or laparoscopic adrenalectomy for postoperative pain control. We place the epidural prior to induction of anesthesia and administer a test dose with or without epinephrine for patients with pheochromocytoma. We do not activate the epidural during surgery in order to avoid the sympathectomy that results. Dilute solutions of opioids combined with local anesthetic are infused while titrating vasopressors to blood pressure (BP) starting during closure of the abdomen. (See "Management of acute perioperative pain", section on 'Epidural analgesia with local anesthetics and opioids'.)

Monitoring and venous access — As for any general anesthetic, standard American Society of Anesthesiologists (ASA) monitors (eg, blood pressure, electrocardiography, oxygen saturation, capnography, and temperature) are applied. Large-bore venous access should be obtained. For pheochromocytoma, additional monitoring and venous access may be added as follows:

Arterial pressure monitoring – Continuous intraarterial BP monitoring is used for all patients with pheochromocytoma. For patients who remain hypertensive preoperatively, we place the arterial catheter prior to induction. For patients with well-controlled preoperative BP, when personnel are available to assist, we place the arterial line during induction but prior to endotracheal intubation.

Central venous catheterization – We place a central venous catheter for most patients with pheochromocytoma, primarily for secure and effective administration of vasoactive drugs.

Pulmonary artery (PA) catheterization and transesophageal echocardiography (TEE) – PA catheterization and TEE may be indicated for patients with known depressed cardiac function, though these modalities are rarely required. In one large series of patients undergoing pheochromocytoma, very few patients required a PA catheter [26].

Premedication — Patients should be premedicated (eg, midazolam 1 to 2 mg intravenously [IV], titrated to effect) as they would be for other surgeries in order to allay anxiety and to facilitate smooth and atraumatic placement of arterial, central, and additional peripheral venous catheters.

Induction and maintenance of anesthesia — A wide variety of medications can be used for the induction and maintenance of anesthesia for patients with pheochromocytoma. Ketamine should be avoided in most cases because of its sympathomimetic properties, and halothane should not be administered because of its potential to cause arrhythmias. (See "General anesthesia: Intravenous induction agents", section on 'Ketamine' and "General anesthesia: Induction".)

General principles for the induction and maintenance of anesthesia for these patients include the following:

Aim for a smooth induction, with adequate depth of anesthesia to prevent a hypertensive response to endotracheal intubation.

Communicate openly with the surgeon to anticipate events likely to cause hemodynamic instability (ie, insufflation of the abdomen, tumor manipulation, ligation of tumor blood supply).

Medications to avoid — A number of medications commonly used in anesthesia should be avoided or used cautiously in patients with pheochromocytoma. When patients having anesthesia for other procedures exhibit severe hypertension, arrhythmias, or other unexplained adverse reactions to these medications, occult pheochromocytoma should be suspected.

Dopamine-blocking drugsMetoclopramide is contraindicated for patients with pheochromocytoma. Metoclopramide has been reported to induce hypertensive crisis and, in some cases, adrenergic myocarditis with cardiogenic shock in patients with pheochromocytoma [6,27-29]. The mechanism is likely multifactorial; metoclopramide inhibits dopaminergic suppression of presynaptic norepinephrine release and has also been shown to directly stimulate release of catecholamines from pheochromocytoma cells [30].

There are case reports of hypertensive crisis when large doses of droperidol were administered to patients with pheochromocytoma without alpha blockade. Small doses (0.625 mg IV) of droperidol, as well as droperidol used as part of neuroleptic anesthesia, have been used safely in patients with preoperative alpha blockade [31]. Haloperidol, which is often used in small doses (eg, 1 mg IV) for prevention and treatment of postoperative nausea and vomiting, shares structural similarities with droperidol and should similarly be used with caution in patients with pheochromocytoma.

Glucagon – Glucagon is contraindicated in patients with pheochromocytoma. It has been shown to release catecholamines from these tumors and has been associated with hypertensive crisis [32]. In the past, glucagon stimulation was used as part of a diagnostic test for pheochromocytoma.

Sympathomimetic drugs – Ketamine and cocaine should be avoided for these patients because of their sympathomimetic properties and the potential to exacerbate hypertension and arrhythmias. Halothane sensitizes the myocardium to catecholamines, is associated with arrhythmias, and should be avoided for these patients. Ephedrine is an indirect-acting alpha and beta agonist used to treat hypotension. It should be avoided until the tumor is excised in order to prevent an exaggerated response via release of catecholamines from the tumor.

Histamine-releasing medications – Drugs that release histamine when given in large doses (eg, morphine, atracurium) should theoretically be avoided for patients with pheochromocytoma. However, when given slowly, histamine release can be minimized, and both morphine and atracurium have been used safely in these patients. [26]

TREATMENT OF INTRAOPERATIVE HEMODYNAMIC CHANGES — Vasopressors, vasodilators, and antiarrhythmic medications should be prepared in advance and ready for immediate administration. A number of intravenous (IV) medications have been used to treat hemodynamic perturbations during pheochromocytoma resection. In this setting, drugs are chosen for ease of titration, with rapid effect and quick offset, to respond to changing hemodynamic conditions.

Treatment of hypertension and arrhythmias — Most patients with pheochromocytoma become hypertensive at some point during surgery. When severe hypertension occurs, the surgeon should be alerted, and treatment should begin immediately. Surgery may need to be paused to allow for blood pressure (BP) control.

Antihypertensive medications — Drugs used to control hypertension during pheochromocytoma resection include the following:

Nitroprusside – Nitroprusside, an ultrashort-acting vasodilator, is our drug of choice for intraoperative hypertensive crisis. It is typically administered as an infusion at 0.5 to 5 mcg/kg/minute and adjusted every few minutes for target BP response. To prevent thiocyanate toxicity, prolonged nitroprusside infusion should not exceed 3 mcg/kg/minute. Reflex tachycardia is often treated with infusion of a short-acting beta blocker (esmolol).

Phentolamine – Phentolamine is a nonselective alpha blocker that can be administered intravenously. An initial test dose of 1 mg is administered, followed by a 5-mg bolus and/or continuous infusion (0.5 to 1 mg/minute IV) [12].

Nicardipine – Nicardipine, a calcium channel blocker, can be started at 5 mg/hour and increased by 2.5 mg every 15 minutes to desired effect, not exceeding 15 mg/hour [12].

Labetalol – Labetalol is a combined alpha and beta blocker that can be administered intravenously (5 to 20 mg IV).

Esmolol – Esmolol is an ultrashort-acting selective beta1-adrenergic blocker. It can be administered by bolus (10 to 50 mg IV) or by infusion (25 to 250 mcg/kg/minute).

Magnesium – Magnesium is a vasodilator that inhibits catecholamine release from the adrenal medulla, antagonizes alpha-adrenergic receptors, and is a calcium antagonist [33-35]. In addition, it is an antiarrhythmic with cardiac membrane-stabilizing effects. Theoretically, magnesium may be useful for patients with arrhythmias associated with pheochromocytoma who are intolerant of beta blockers.

We do not routinely administer magnesium for pheochromocytoma resection; we reserve magnesium for patients whose BP is particularly difficult to control.

Magnesium has been used in bolus form and as an infusion for BP stabilization during pheochromocytoma resection. The literature on the effects of magnesium in this setting is inconsistent. A number of case reports and small series have reported that magnesium has a beneficial hemodynamic effect during these procedures [36,37]. However, a retrospective review of 64 patients who underwent alpha blockade prior to surgery for pheochromocytoma found no improvement in hemodynamic stability with magnesium administration [38].

Magnesium sulphate is usually administered with a bolus of 2 to 4 g IV over 20 minutes after induction and endotracheal intubation, followed by infusion at 1 to 2 g/hour IV, with the infusion adjusted based on blood levels. The infusion is discontinued once the venous drainage from the tumor is ligated or the tumor is removed.

Because magnesium potentiates the effects of neuromuscular blocking agents (NMBAs), dosing and reversal of NMBAs should be guided by a peripheral nerve stimulator.

Antiarrhythmics — Supraventricular tachycardia is common during these procedures, though any arrhythmia is possible, including ventricular ectopy. IV lidocaine, beta blockade with esmolol as above, or treatment with amiodarone (especially for patients with impaired cardiac pump function) may be necessary. Treatment of arrhythmias is discussed more fully separately. (See "Overview of the acute management of tachyarrhythmias".)

Treatment of hypotension — Hypotension should be treated with aggressive administration of IV fluid, discontinuation of vasodilator infusions, and administration of rapidly acting vasopressors. Drugs commonly used to support BP in this setting include the following:

Phenylephrine – Phenylephrine is our drug of choice for the management of hypotension during these procedures. It is a pure alpha agonist with a short half-life that can be given by bolus (40 to 160 mcg IV) or infusion (wide range of dosing; 10 to 200 mcg/minute IV), titrated to effect.

EphedrineEphedrine is an indirect-acting alpha and beta agonist. It should be avoided before tumor removal. When hypotension occurs after tumor resection, ephedrine can be given by bolus (5 to 25 mg IV, repeated as needed). Ephedrine should not be administered during paraganglioma resection or during incomplete pheochromocytoma resection to avoid release of catecholamines and severe hypertension.

Norepinephrine – Norepinephrine is a combined alpha and beta agonist that is given by infusion (wide range of dosing; 2 to 20 mcg/minute IV), titrated to effect.

Vasopressin – Vasopressin infusion (initial dose 0.01 to 0.03 units/minute; maintenance dose 0.03 to 0.04 units/minute) has been used in cases of refractory hypotension after tumor removal, commonly after significant blood loss or in patients with extremely high preoperative levels of catecholamines, to supplement other vasopressors [11,39-41].

OUR ANESTHETIC STRATEGY — A variety of anesthetic techniques and medications can be used for resection of pheochromocytoma. Our usual strategy is as follows, unless medical comorbidities require modification:

Premedication – We administer midazolam up to 2 mg intravenously (IV) in divided doses, with small doses of fentanyl (25 mcg IV) titrated to enhance analgesia prior to arterial line and/or epidural placement. (See 'Premedication' above.)

Line placement – We insert an arterial catheter under local anesthesia or, if assistance is available, after induction of anesthesia but prior to intubation. We typically place a central venous catheter after induction and intubation but prior to positioning and incision. (See 'Monitoring and venous access' above.)

Epidural placement – For open procedures, we place a low thoracic epidural for postoperative pain control. For laparoscopic surgeries, we do not typically place epidural catheters for postoperative pain management. Epidural catheter placement is tested with local anesthetic (typically 3 mL of 1.5% lidocaine). (See 'Choice of anesthetic technique' above.)

Induction of anesthesia – We induce anesthesia as follows:

Fentanyl 1 to 3 mcg/kg IV

Lidocaine 1 mg/kg IV

Propofol 1 to 2 mg/kg IV

Nondepolarizing neuromuscular blocking agent (NMBA) (eg, rocuronium 0.5 mg/kg IV) (see 'Induction and maintenance of anesthesia' above)

Maintenance of anesthesia – We maintain inhalational anesthesia at 1 minimum alveolar concentration (MAC), adjusted for age. Opioids are administered as required.

Treatment of hemodynamic changes – We treat hemodynamic changes as follows (see 'Treatment of intraoperative hemodynamic changes' above):

During phase I of surgery, we typically aim to keep systolic blood pressure (SBP) between 100 and 160 mmHg. Blood pressure (BP) during phase I is often very labile; vasodilator infusion may require frequent adjustment or pause.

-We treat BP elevations with nitroprusside, administered by an infusion of 0.5 to 4 mcg/kg/minute or a bolus of 20 mcg, supplemented as needed by boluses of phentolamine 1 to 5 mg IV.

-We treat hypotension with phenylephrine, administered by a bolus of 40 to 160 mcg IV or an infusion of 20 to 200 mcg/minute IV.

During phase II of surgery, we treat hypotension with the following sequence of medication, as necessary:

-IV fluid bolus.

-Phenylephrine bolus of 40 to 160 mcg or infusion of 20 to 200 mcg/minute.

-Ephedrine 5 to 25 mg bolus IV; however, ephedrine should not be used in paraganglioma resection or if incomplete pheochromocytoma resection is suspected.

-Norepinephrine 2 to 20 mcg/minute IV, if necessary.

-Vasopressin 0.03 to 0.04 units/minute.

Postoperative disposition – Most patients can be extubated at the end of surgery and can be transferred to the post-anesthesia care unit (PACU) for further monitoring. Patients who require vasoactive medications (eg, phenylephrine, norepinephrine, or vasopressin infusion) to maintain adequate BP are subsequently transferred to the intensive care unit (ICU). In addition, we transfer patients to the ICU for closer monitoring if the intraoperative course was eventful (ie, significant blood loss and fluid administration).

POSTOPERATIVE CARE — The majority of patients who undergo laparoscopic pheochromocytoma resection can be observed in the post-anesthesia care unit (PACU) and then sent to a hospital floor, though some patients require intensive care postoperatively [4]. Postoperative concerns specific to pheochromocytoma resection include the following:

Hemodynamic instability – In most cases, extended recovery room or intensive care stays are for hemodynamic monitoring. Transient postoperative hypotension is common due to downregulation of alpha-adrenergic receptors, residual effects of long-acting antihypertensive medications, or hypovolemia. Fifty percent of patients remain hypertensive for one to three days after excision of pheochromocytoma; 75 percent of patients become normotensive after 10 days of surgery [42].

Hypoglycemia – Hypoglycemia can occur intraoperatively or postoperatively because of a rebound increase in insulin secretion, as the catecholamine inhibition of insulin secretion is eliminated with tumor removal [43]. Hypoglycemia should be suspected when patients are slow to emerge from anesthesia or are lethargic postoperatively. Blood glucose should be measured every six hours postoperatively, and more frequently if hypoglycemia develops.

Adrenal insufficiency – Patients who undergo bilateral adrenalectomy are at risk for acute postoperative adrenal insufficiency and therefore require glucocorticoid replacement. Regimens for replacement vary among institutions. Our typical regimen is as follows:

Hydrocortisone 100 mg IV with induction of anesthesia

Hydrocortisone 100 mg IV every eight hours for 24 hours

Hydrocortisone taper over three days to maintenance dose (eg, hydrocortisone 25 mg IV or by mouth [PO] twice daily, or prednisone 10 mg PO daily)

Patients who undergo bilateral adrenalectomy require lifelong steroid supplementation. (See "Treatment of adrenal insufficiency in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pheochromocytoma".)

SUMMARY AND RECOMMENDATIONS

Anesthetic management for resection of pheochromocytoma or paraganglioma can be challenging, with periods of perioperative hemodynamic instability, tachycardia, and arrhythmias.

Many patients who undergo pheochromocytoma resection exhibit labile blood pressure (BP), arrhythmias, and tachycardia during and after surgery, though most can be managed without lasting morbidity or mortality. Risks are much greater for patients who are found incidentally to have pheochromocytoma during unrelated surgery. (See 'Perianesthetic risks and outcomes' above.)

Preoperative evaluation should include assessment for end organ damage from elevated catecholamines and confirmation of effective medical preparation for surgery. Medical preparation should include alpha-adrenergic blockade, beta blockade if necessary, and normalization of intravascular volume. (See 'Preoperative evaluation' above and 'Preoperative medical therapy' above.)

Pheochromocytoma resection can be divided into two phases of surgery based on ligation of the tumor blood supply (see 'Stages of surgery' above):

Phase I (prior to ligation of the effluent vein) is often characterized by periods of hypertension, tachycardia, and arrhythmias, particularly during endotracheal intubation, insufflation of the abdomen during laparoscopic procedures, and tumor manipulation.

Phase II (after ligation of the effluent vein) is often complicated by hypotension.

General anesthesia is used for pheochromocytoma resection. A variety of techniques and medications can be used for induction and maintenance of anesthesia. Goals for anesthesia management should include:

Smooth induction with adequate depth of anesthesia to prevent a hypertensive response to endotracheal intubation.

Close communication with the surgeon to allow anticipation of events likely to cause hemodynamic instability. (See 'Induction and maintenance of anesthesia' above.)

We place an intraarterial catheter for continuous BP monitoring and a central venous catheter for drug administration. (See 'Monitoring and venous access' above.)

We place an epidural catheter for postoperative pain control for open adrenalectomy but usually not for laparoscopic procedures.

A variety of vasoactive medications with rapid onset of effect and short duration of action should be available and ready for administration to respond quickly to hemodynamic changes. (See 'Treatment of intraoperative hemodynamic changes' above.)

Our typical regimen for the treatment of hemodynamic changes is as follows (see 'Our anesthetic strategy' above):

During phase I of surgery, we typically aim to keep systolic BP (SBP) between 100 and 160 mmHg.

-We treat BP elevations with nitroprusside administered by an infusion of 0.5 to 4 mcg/kg/minute or a bolus of 20 mcg, supplemented as needed by boluses of phentolamine 1 to 5 mg intravenously (IV).

-We treat hypotension with phenylephrine, administered by a bolus of 40 to 160 mcg IV or an infusion of 20 to 200 mcg/minute IV.

During phase II of surgery, we treat hypotension with the following sequence of medication, as necessary:

-IV fluid bolus

-Phenylephrine bolus of 40 to 160 mcg or infusion of 20 to 200 mcg/minute

-Norepinephrine 2 to 20 mcg/minute IV, if necessary

-Vasopressin 0.03 to 0.04 units/minute

Postoperative concerns for patients after pheochromocytoma resection include recovery of normal adrenergic function with stable BP, potential for rebound hypoglycemia, and possible adrenal insufficiency. (See 'Postoperative care' above.)

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REFERENCES

  1. Fleisher L, Mythen M. Anesthetic implications of concurrent diseases.. In: Miller's Anesthesia, 8th ed, Miller RD, Cohen NH, Eriksson LI, et al (Eds), Elsevier, Philadelphia 2015. p.1170.
  2. Goldstein RE, O'Neill JA Jr, Holcomb GW 3rd, et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999; 229:755.
  3. Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000; 91:1118.
  4. Kercher KW, Novitsky YW, Park A, et al. Laparoscopic curative resection of pheochromocytomas. Ann Surg 2005; 241:919.
  5. Myklejord DJ. Undiagnosed pheochromocytoma: the anesthesiologist nightmare. Clin Med Res 2004; 2:59.
  6. Sheinberg R, Gao WD, Wand G, et al. Case 1--2012. A perfect storm: fatality resulting from metoclopramide unmasking a pheochromocytoma and its management. J Cardiothorac Vasc Anesth 2012; 26:161.
  7. O'Riordan JA. Pheochromocytomas and anesthesia. Int Anesthesiol Clin 1997; 35:99.
  8. Subramaniam R. Pheochromocytoma – Current concepts in diagnosis and management. Trends in Anaesth Crit Care 2011; 1:104.
  9. Zuber SM, Kantorovich V, Pacak K. Hypertension in pheochromocytoma: characteristics and treatment. Endocrinol Metab Clin North Am 2011; 40:295.
  10. Agarwal V, Kant G, Hans N, Messerli FH. Takotsubo-like cardiomyopathy in pheochromocytoma. Int J Cardiol 2011; 153:241.
  11. Lord MS, Augoustides JG. Perioperative management of pheochromocytoma: focus on magnesium, clevidipine, and vasopressin. J Cardiothorac Vasc Anesth 2012; 26:526.
  12. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th ed, Brunton LL, Chabner BA, Knollmann CB (Eds), McGraw Hill, New York 2011. p.309.
  13. Prys-Roberts C, Farndon JR. Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. World J Surg 2002; 26:1037.
  14. Buch J. Urapidil, a dual-acting antihypertensive agent: Current usage considerations. Adv Ther 2010; 27:426.
  15. Habbe N, Ruger F, Bojunga J, et al. Urapidil in the preoperative treatment of pheochromocytomas: a safe and cost-effective method. World J Surg 2013; 37:1141.
  16. Gosse P, Tauzin-Fin P, Sesay MB, et al. Preparation for surgery of phaeochromocytoma by blockade of alpha-adrenergic receptors with urapidil: what dose? J Hum Hypertens 2009; 23:605.
  17. Young WF, Jr. Endocrine Hypertension. In: William's Textbook of Endocrinology, 12th ed, Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (Eds), Elsevier, Philadelphia 2011. p.547.
  18. Shen WT, Grogan R, Vriens M, et al. One hundred two patients with pheochromocytoma treated at a single institution since the introduction of laparoscopic adrenalectomy. Arch Surg 2010; 145:893.
  19. Plouin PF, Amar L, Lepoutre C. Phaeochromocytomas and functional paragangliomas: clinical management. Best Pract Res Clin Endocrinol Metab 2010; 24:933.
  20. Brunaud L, Boutami M, Nguyen-Thi PL, et al. Both preoperative alpha and calcium channel blockade impact intraoperative hemodynamic stability similarly in the management of pheochromocytoma. Surgery 2014; 156:1410.
  21. Joris JL, Hamoir EE, Hartstein GM, et al. Hemodynamic changes and catecholamine release during laparoscopic adrenalectomy for pheochromocytoma. Anesth Analg 1999; 88:16.
  22. Flávio Rocha M, Faramarzi-Roques R, Tauzin-Fin P, et al. Laparoscopic surgery for pheochromocytoma. Eur Urol 2004; 45:226.
  23. Cryer PE. Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med 1980; 303:436.
  24. Marty J, Desmonts JM, Chalaux G, et al. Hypertensive responses during operation for phaeochromocytoma: a study of plasma catecholamine and haemodynamic changes. Eur J Anaesthesiol 1985; 2:257.
  25. de La Chapelle A, Deghmani M, Dureuil B. [Peritoneal insufflation can be a critical moment in the laparoscopic surgery of pheochromocytoma]. Ann Fr Anesth Reanim 1998; 17:1184.
  26. Prys-Roberts C. Phaeochromocytoma--recent progress in its management. Br J Anaesth 2000; 85:44.
  27. Eisenhofer G, Bornstein SR. Surgery: Risks of hemodynamic instability in pheochromocytoma. Nat Rev Endocrinol 2010; 6:301.
  28. Maxwell PH, Buckley C, Gleadle JM, Mason PD. Nasty shock after an anti-emetic. Nephrol Dial Transplant 2001; 16:1069.
  29. Leow MK, Loh KC. Accidental provocation of phaeochromocytoma: the forgotten hazard of metoclopramide? Singapore Med J 2005; 46:557.
  30. Guillemot J, Compagnon P, Cartier D, et al. Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. Endocr Relat Cancer 2009; 16:281.
  31. Desmonts JM, le Houelleur J, Remond P, Duvaldestin P. Anaesthetic management of patients with phaeochromocytoma. A review of 102 cases. Br J Anaesth 1977; 49:991.
  32. Hosseinnezhad A, Black RM, Aeddula NR, et al. Glucagon-induced pheochromocytoma crisis. Endocr Pract 2011; 17:e51.
  33. Bara M, Guiet-Bara A, Durlach J. Regulation of sodium and potassium pathways by magnesium in cell membranes. Magnes Res 1993; 6:167.
  34. Houston M. The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertens (Greenwich) 2011; 13:843.
  35. Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J 1984; 108:188.
  36. James MF, Cronjé L. Pheochromocytoma crisis: the use of magnesium sulfate. Anesth Analg 2004; 99:680.
  37. Herroeder S, Schönherr ME, De Hert SG, Hollmann MW. Magnesium--essentials for anesthesiologists. Anesthesiology 2011; 114:971.
  38. Siddiqi HK, Yang HY, Laird AM, et al. Utility of oral nicardipine and magnesium sulfate infusion during preparation and resection of pheochromocytomas. Surgery 2012; 152:1027.
  39. Tan SG, Koay CK, Chan ST. The use of vasopressin to treat catecholamine-resistant hypotension after phaeochromocytoma removal. Anaesth Intensive Care 2002; 30:477.
  40. Augoustides JG, Abrams M, Berkowitz D, Fraker D. Vasopressin for hemodynamic rescue in catecholamine-resistant vasoplegic shock after resection of massive pheochromocytoma. Anesthesiology 2004; 101:1022.
  41. Thillaivasan A, Arul GS, Thies KC. Vasopressin for the treatment of catecholamine-resistant hypotension during a phaeochromocytoma resection in a 6-year-old child. Eur J Anaesthesiol 2010; 27:991.
  42. Schwartz JJ, Akhtar S, Rosenbaum SH. Endocrine function. In: Clinical Anesthesia, Barash PG, Cullen BF, Stoelting RK, et al (Eds), Wolters Kluwer, Philadelphia 2013. p.1326.
  43. Bravo EL, Tagle R. Pheochromocytoma: state-of-the-art and future prospects. Endocr Rev 2003; 24:539.
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