30 Anesthesia Considerations
Patients with pituitary disease can pose many unique challenges to the anesthesiologist. The endocrine diseases that often accompany pituitary masses may cause changes in the patient’s airway, cardiovascular system, and various metabolic pathways. Such changes require specific preoperative evaluation and consideration throughout the perioperative period.
Many patients presenting with pituitary tumors suffer from functional adenomas. Although there are many subtypes of functional adenoma, the two that have the most impact on anesthetic management are those that secrete growth hormone, leading to acromegaly, and adrenocorticotropic hormone (ACTH), leading to Cushing’s disease.
Airway Management
Airway management is a primary concern of the anesthesiologist, and both acromegaly and Cushing’s disease may affect the ability to secure the airway.1–3 In two large reviews, the incidence of difficult intubation for acromegalics was 10%4 and 9.1%.5 In contrast, the incidence of difficult intubation in patients with Cushing’s disease, prolactinoma, or nonsecretory pituitary tumors was no different from that in the general population (1 to 4%).5
Acromegaly manifests with enlargement of the facial bones, especially the mandible,2 as well as hypertrophy of the laryngeal and pharyngeal soft tissue.6,7 Hypertrophy of the periepiglottic folds and calcinosis of the larynx may be seen, as may recurrent laryngeal nerve paresis.8 These anatomical changes may serve to make intubation technically difficult.
Four grades of airway involvement in acromegaly have been described: grade 1, no involvement; grade 2, soft tissue hypertrophy of the nasopharynx without glottic involvement; grade 3, glottic stenosis or vocal cord paresis; and grade 4, both soft tissue hypertrophy and glottic stenosis.9 The difficulties with intubation and ventilation were so commonly encountered in patients with grades 3 and 4 that in the past routine tracheostomy was recommended.10 The advent of awake fiberoptic bronchoscopic intubation as well as the increased use of alternative intubating devices has rendered the preoperative tracheostomy a rare occurrence.
Even in those patients whose anatomy does not appear to be difficult, such as patients with Mallampati class I or II airways, there may be a 20% incidence of difficult intubation.11 In Nemergut and Zuo’s5 review, fully 50% of the Mallampati class I and II patients went on to be difficult intubations.5
Additionally, acromegalic patients also commonly suffer from obstructive sleep apnea. This occurs in 25% of female and 70% of male acromegalic patients and may manifest as snoring or daytime somnolence.12 This incidence of sleep apnea must be considered in planning the induction of anesthesia, as it may compromise the ease of mask ventilation. It is also important in the postoperative period, as those patients with obstructive sleep apnea are known to have an increased incidence of postoperative ventilatory compromise.13
Of patients with Cushing’s disease, 33% also suffer from obstructive sleep apnea, with 18% of patients having severe sleep apnea.14 Many patients with Cushing’s disease become morbidly obese and may suffer from gastroesophageal reflux and delayed gastric emptying. This leads many anesthe-siologists to consider rapid sequence or awake intubation in this population as well.
Airway concerns actually may be increased postoperatively due to the presence of nasal packing, rendering postoperative mask ventilation less effective if necessary. Blind placement of any type of nasal airway, nasogastric tube, or nasal endotracheal tube is absolutely contraindicated in the immediate postoperative period.15 Thus, judicious titration of postoperative pain medication is essential to avoid the need for mask ventilation or any manipulation of the airway.
Over time, there may be regression of hypertrophied tissues in the acromegalic patient, and impaired vocal cord function may improve within 10 days of surgery.16,17 In the patient with Cushing’s disease, weight loss after surgery may lead to improvement in airway and ventilatory function.
Other pituitary tumors, for example prolactinoma or nonsecretory tumors, pose no additional risk of difficult intubation or ventilation.
Cardiovascular Concerns
The leading cause of death in untreated acromegaly is cardiac dysfunction.18 In acromegaly several cardiac manifestations of disease may occur, including endothelial dysfunction, left ventricular (LV) dysfunction, and dysrhythmia.19 Small-vessel coronary artery disease has been described in the acromegalic population,20 and endothelial-dependent vasodilation is impaired.21 Thus, any anginal symptoms should be considered as evidence for ischemia even in a patient with no independent risk factors.
Acromegalic cardiomyopathy is defined as cardiomyopathy secondary to chronic growth hormone excess in the absence of other causes. Incidence of acromegalic cardiomyopathy is 3 to 4 cases/million/year. Cardiomegaly with concentric hypertrophy and an increase in LV mass with normal LV dimensions are consistent findings. The heart may weigh up to 1300 g, whereas normal is less than 250 g.20 The severity of the hypertrophy is related to the duration of disease, and if LV dilatation occurs, the prognosis worsens. Left untreated, acromegalic cardiomyopathy progresses through three stages. In the early stage there is increased contractility and decreased systemic vascular resistance, leading to an increased cardiac output.22,23 There may be significant LV diastolic dysfunction in spite of the normal LV mass.22 In the intermediate stage, biventricular hypertrophy develops and diastolic dysfunction becomes evident.24 Although there is preserved systolic function at rest, the patient will have impaired exercise tolerance. The late stage of acromegalic cardiomyopathy is marked by dilatation of the ventricles, depressed systolic function, and congestive heart failure.3,22,23
If treatment occurs in the early or intermediate stage, ventricular hypertrophy may resolve, although diastolic dysfunction may persist, which is consistent with the histologic finding of interstitial fibrosis. At the time of diagnosis, 10% of patients have signs of high-output heart failure with diminished ejection fraction, and 3% have significant systolic dysfunction.25 As far as cardiac rhythm is concerned, the frequency and severity of ventricular dysrhythmia are significantly greater in acromegalics than in controls and appear to be correlated with LV mass.26 In addition, it has been variously reported that 18 to 60% of acromegalic patients suffer from hypertension.18,27–30 In addition to a direct effect from growth hormone, contributing factors are an increase in sympathetic tone, cardiac hyperkinesis, an increase in plasma volume, a reduction in atrial natriuretic peptide secretion, and hyperinsulinemia.31–36 Even in those patients with normal blood pressure, half have LV hypertrophy.37 Not surprisingly, many have diastolic dysfunction, with preserved systolic function.
In contrast to the acromegalic patient, the cardiovascular manifestations of Cushing’s disease are predominantly the consequence of the Cushing patient’s predisposition to significant hypertension. Up to 80% of Cushing’s patients have hypertension, with 50% having diastolic pressures >100 mm Hg if untreated.38 This propensity for hypertension is the direct result of excessive levels of corticosteroids.39,40 Hydrocortisone increases hepatic production of angiotensinogen, activating the renin-angiotensin system and increasing plasma volume.40 Furthermore, glucocorticoids lead to an increase in angiotensin II receptors on vascular smooth muscle cells.41 This in turn leads to an augmented response to both endogenous and perhaps exogenous catecholamines. Finally, glucocorticoid inhibition of vascular smooth muscle phospholipase A2 reduces the production of vasodilatory prostaglandins.42
Left ventricular hypertrophy, the expected consequence of hypertension, is far more severe in patients with Cushing’s disease than in those with essential hypertension, suggesting a direct effect of elevated cortisol levels. In addition, the incidence of asymmetric LV hypertrophy, with greater hypertrophy of the intraventricular septum, is also higher.43 Diastolic dysfunction occurs in at least 40% of Cushing’s disease patients.44 Electrocardiogram (ECG) changes include LV strain pattern. Most ECG and echocardiographic abnormalities return to normal within 1 year after resection of ACTH-secreting adenoma.45
In view of these potentially severe cardiac abnormalities, it may be prudent to obtain a resting ECG and echocardiogram in all patients with acromegaly and Cushing’s disease regardless of the patient’s age.
Other Preoperative Concerns
Other functional pituitary adenomas include thyrotropic adenoma, prolactinoma, and gonadotroph adenoma. Thyrotropic adenomas represent only 2.8% of all pituitary tumors and may cause hyperthyroidism.46 The signs and symptoms of hyperthyroidism are usually present and a goiter may even be observed. As patients are often treated for another cause of hyperthyroidism, the pituitary tumor can be large at the time of presentation, with 60% being locally invasive. Signs and symptoms of hyperthyroidism should be controlled medically prior to presentation for surgery.
There are no specific airway or cardiovascular concerns for patients with prolactinoma or gonadotroph adenoma. These patients often present with nonspecific symptoms. Women with prolactinoma usually present with amenorrhea, galactorrhea, and infertility.3 Many tumors (90%) respond to bromocriptine (dopamine agonist) therapy and thus do not require surgery. In men, however, prolactinomas present with erectile dysfunction, premature ejaculation, and loss of libido. These nonspecific symptoms may lead to a delayed diagnosis, and the patient may develop symptoms of macroadenoma.47
Once a tumor becomes a macroadenoma, the patient may present with symptoms of a sellar mass. These symptoms include headache, visual loss (bitemporal hemianopsia) from compression of the optic chiasm, and hypopituitarism from compression of the anterior pituitary.47 In extreme cases, especially if the tumor obstructs the third ventricle, the patient may present with symptoms of increased intracranial pressure (ICP). If symptoms of intracranial hypertension are present, care must be taken to avoid further increases in the ICP secondary to anesthesia management.
Hematologic and Metabolic Concerns
Although most patients presenting with pituitary tumors have an extensive hematologic, metabolic, and endocrinologic evaluation as part of their tumor workup, several studies are of particular importance to the anesthesiologist and should be obtained as close to the time of surgery as practical. These include baseline hemoglobin, as these cases can occasionally entail significant hemorrhage. Coagulation studies are not indicated unless the patient has a history consistent with an increased risk of bleeding. Serum electrolytes should be obtained to rule out hyponatremia, which may result from diabetes insipidus (DI) caused by posterior pituitary dysfunction. Serum glucose and perhaps hemoglobin A1c are useful in patients with Cushing’s disease. Fully 60% of patients with Cushing’s disease have glucose intolerance and 33% have diabetes mellitus.48 Furthermore, blood glucose may be increased in acromegaly secondary to insulin resistance.49 The “tightness” of perioperative glucose control is controversial; however, there is clear evidence that hyperglycemia is undesirable during periods of neuronal ischemia.50–52 A thyroid panel, to ensure euthyroid state, and a pregnancy test, especially in amenorrheic women, should also be obtained. Finally, an active type and screen are recommended.3,53
If panhypopituitarism is present, the patient should be given thyroid replacement and hydrocortisone. These medications should be continued on the morning of surgery.3,53 All patients should be given corticosteroid replacement with the exception of those with Cushing’s disease. In Cushing’s patients hydrocortisone is withheld and serum cortisol levels are obtained every 6 hours after resection. A decrease in serum cortisol serves as biochemical confirmation of successful surgical resection.54
Intraoperative Management
The anesthesia management of the patient is impacted by the surgical approach. For tumors with significant extrasellar extension, a craniotomy may be required, and anesthesia management for craniotomy is extensively discussed elsewhere. This section focuses on the anesthesia management of the pituitary tumor via the transnasal approach. Although traditionally performed with the assistance of an operating microscope, commonly this procedure is now performed with endoscope-guided surgical exposure and localization using a frameless stereotactic system.
Monitoring
Traditionally, placement of an arterial line was not considered necessary for transsphenoidal resection of pituitary tumor. An arterial line was reserved for patients who had significant cardiovascular disease or cardiovascular sequelae of acromegaly. Although usually not necessary prior to induction of anesthesia, an arterial line may be useful in quickly noting and responding to hemodynamic changes associated with intranasal injection or application of vasoactive substances, as well as with the rare, but potentially catastrophic, occurrence of massive hemorrhage if the carotid or another artery is perforated during the operation. Finally, an arterial line provides access for blood samples, which may be useful in the management of diabetes mellitus and DI. Of note, radial artery catheterization may have increased risk in acromegalic patients, especially those with symptoms of carpal tunnel syndrome. Fifty percent of patients have been found to have diminished ulnar blood flow.55 Thus an Allen’s test is recommended in acromegalic patients.
A monitor of central venous pressure is rarely indicated and is reserved for those with significant compromise in cardiac function.
Adequate intravenous access is important because of the rare occurrence of abrupt hemorrhage. Similarly, all patients should have crossmatched blood available.
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