Authors: M. Aaron Chyfetz, MD, MSc and Julia Metzner, MD
Patient with Pituitary Adenoma for Transsphenoidal Resection
Case: A 45-year-old male was referred to the neurosurgical clinic with the diagnosis of acromegaly caused by a growth hormone (GH) secreting pituitary adenoma. He was scheduled for an endoscopic transsphenoidal resection (TSS) of the tumor.
PMH: Hypertension, Hypothyroidism, Osteoarthritis and OSA on CPAP during sleep.
Medications: Amlodipine, Levothyroxine, Lisinopril, and Ibuprofen.
Social History: Former smoker, quit 15 years ago.
Past Surgical/Anesthetic History: Tonsillectomy as a child and Right Carpal Tunnel Release 2 years ago with no anesthetic difficulties.
Physical Examination: a 188 cm, 110 kg (BMI 31) well-developed male. Heavy mandible, frontal bossing, and macroglossia. Significantly enlarged hands and feet.
Neurological Examination: He is oriented to person, place and time. No focal deficits.
Imaging (MRI): 1.8×1.3×1.3 cm pituitary mass in inferior sella with possible involvement of right cavernous sinus. Optic chiasm normal.
Vitals: BP 155/85, HR 72/min, RR 14/min, SpO2 98%
Labs: Na 144, K 4.2, Chloride 108, CO2: 22, Glucose 154, BUN/Creatinine 24/1.22, Calcium 9.3. WBC 5.5, H/H 11.8/36.2, Plt 257. IGF-1 962 (insulin-like growth factor-1).
- What are the epidemiologic features of pituitary tumors?
- What preoperative evaluation is important in this patient? Do you require any additional information if acromegaly is diagnosed?
Case Continued: Prior to the surgery, the patient presents with sudden onset of headache, dizziness, and decreased visual acuity.
- What are you concerned about? How will this affect you peri-operative management?
- How is this surgery performed? Describe the anatomical boundaries encountered during TSS. What nerves and vasculature are contained in the cavernous sinus?
- What are the goals for induction and maintenance of anesthesia in this patient? Do you anticipate difficulties with airway management? If this patient’s voice was noticeably hoarse, would this alter your approach?
- What intraoperative monitoring and vascular access would you like to have for this case?
- The surgeon plans to place a lumbar drain following induction of anesthesia. What is the advantage and benefit of lumbar drain placement? What are the anesthetic implications?
- Does this type of surgery call for perioperative steroid supplementation?
Case Continued: The surgical team secured the head with Mayfield skull clamps and preps the nasal cavity. Prior to incision, the surgeon places an epinephrine pledge in the nasal cavity. The blood pressure spikes to 230/110.
- What is the appropriate anesthetic management to maintain stable intraoperative hemodynamics?
- The surgery starts and goes smoothly. Despite attempts to maintain euvolemia, you find that during the last hours of surgery the urine output has been around 800 ml/hour. What is the likely explanation for this? How would you manage?
Case Continued: During resection, the surgeon encounters ongoing bleeding from the surgical field.
- What is the likely cause of surgical bleeding? What is the appropriate treatment?
- What are the considerations for extubation and postoperative care?
Pituitary adenomas, the third most common intracranial tumor, are estimated to be present (but not always detected) in 15 to 20% of the population. . They can be classified by size at the time of brain imaging (MRI) as either microadenomas (<10 mm) or macroadenomas (>10 mm) and as either functioning or non-functioning, depending on whether they are hormone-secreting. Patients with functioning adenomas often present with symptoms of hormone excess, while those with non-functioning adenomas show clinical signs of mass effect on the third ventricle, such as headaches, visual impairment, and cranial nerve dysfunction. The hormones secreted by pituitary adenomas include prolactin, growth hormone (GH) causing acromegaly, cortisol (ACTH) resulting in Cushing disease, and rarely thyroid-stimulating hormone (TSH) manifested by thyroid dysfunction .
In more than 95% of cases, acromegaly results from the overproduction of GH and insulin-like growth factor-1 (IGF-1) by a pituitary adenoma. It has an annual incidence of 3 to 4 cases per 1 million people. It generally affects both males and females equally and the average age at diagnosis ranges from 40 to 50 years. High circulating levels of GH and IGF-1 are the basis for symptomology and its associated complications .
Preoperative evaluation should focus on the symptoms associated with the tumor, coexisting medical conditions, laboratory analysis, and brain imaging (MRI).
- Symptoms and signs
Acromegalic changes tend to progress insidiously, and early signs may not be readily apparent for decades. Typically, these patients will exhibit a general overgrowth of skeletal, connective, and soft tissues. Hands and feet become significantly enlarged while facial features become coarse with pronounced frontal bossing, enlargement of the nose, ears, lips, and mandibular prognatism. GH excess produces hypertrophy of the soft tissues of the tongue, paranasal sinuses, soft palate, epiglottis, and laryngeal structures. Hoarseness and changes in voice tone should alert the anesthesiologist to the possibility of laryngeal stenosis or damage of the recurrent laryngeal nerve with vocal cord compromise.
- Coexisting medical conditions
- Obstructive sleep apnea (OSA): secondary to macroglossia and upper airway enlargement, OSA can be detected in over 70% of acromegalic patients. A history of loud snoring associated with day-time somnolence should be sought and sleep studies ordered if clinically indicated.
- Cardiovascular disorders: Hypertension is noted in about 40% of the patients and is often associated with left ventricular hypertrophy (LVH), diastolic dysfunction, or dilated cardiomyopathy . Acromegalic patients may also have conduction defects, arrhythmias, and accelerated coronary artery disease. Therefore, preoperative screening should include a 12-lead ECG, and if clinical symptoms suggest cardiac compromise, e.g., dyspnea, fatigue, exercise intolerance, a transthoracic echocardiogram may be a reasonable option.
- Metabolic complications: GH oversecretion may lead to glucose intolerance and diabetes mellitus; tight glucose control should be considered during the perioperative period.
- Laboratory analysis should include a complete blood count (CBC), basic metabolic panel (BMP) to evaluate for electrolyte abnormalities, and hormone panel with serum levels of GH and IGF-1.
- Brain imaging: Magnetic resonance imaging (MRI) is the most sensitive imaging technique; it can detect tumors as small as 2 mm in diameter, and help pinpoint proximity to the optic chiasm, compression of the surrounding tissues, or invasion to the cavernous sinus, and encasement of the carotid artery .
- Visual Field Testing: Visual field symptoms secondary to pituitary masses commonly include visual field defects, loss of central vision and diplopia secondary to compression of the optic nerve and chiasm . Preoperative ophthalmologic evaluation is recommended as it can quantitatively document preoperative impairment and serve as a prognostic marker for postoperative recovery.
Pituitary apoplexy is sudden hemorrhage or infarction of the pituitary gland commonly occurring alongside pituitary adenomas. While subclinical apoplexy occurs in up to 25% of pituitary tumors, acute apoplexy presents with headache, visual disturbances and endocrine dysregulation and if untreated may result in vision loss, coma and hemodynamic instability . A thunderclap headache is the most common symptom and visual symptoms occur secondary to increased pressure and compression of the optic chiasm and cavernous sinuses. Corticotropic deficiency with hypotension and hyponatremia may also occur.
MRI is the imaging modality of choice as it permits the detection of acute bleeding and hemorrhage. Once confirmed, management is typically surgical as it allows resection of the apoplectic mass and global resolution of neurologic and visual symptoms. Complications of emergent surgery include CSF leak and Diabetic Insipidus (DI).
Surgical conduit and key anatomical landmarks
Traditionally pituitary tumors were removed through an open craniotomy; however, the advent of endoscopy has revolutionized the procedure over the past 2 decades . Transphenoidal surgery (TSS) is a minimally invasive procedure in which the surgeon uses a flexible endoscope through the nostril and neuro-navigation to gain access to the pituitary gland and remove the tumor.
The pituitary gland is situated between the two paired cavernous sinuses. The surgical approach involves displacement of the turbinate in the nare, enlargement of the sphenoid ostium and incision of the dura with curettage of the lesion in the sella .
An enlarging pituitary adenoma will expand in the area of least resistance and may compress the cavernous sinus. Cavernous sinus syndrome is related to mass effect causing vision and sensory deficits. The olfactory tracts, second through sixth cranial nerves, and carotid arteries lie in close proximity to the sphenoid bone. Cavernous sinus syndrome disrupts cranial nerves III, IV, and VI presenting with a fixed, dilated pupil. Injury to the internal carotid artery is a feared complication of this approach occurring in 0.4 to 1.1% of cases and carrying an associated mortality and morbidity of 14% and 24%, respectively . In fear of this complication we recommend a valid type and crossmatch with 2 units of pRBC available.
As noted previously, acromegaly causes significant changes in airway anatomy which can make airway management challenging. Facial bone hypertrophy, specifically of the nose and mandible may render adequate preoxygenation and effective mask ventilation difficult . The incidence of difficult intubation in acromegalics is 4 to 5 times higher than in normal patients . Soft tissue overgrowth with distortion of pharyngeal and laryngeal structures, large epiglottis, and impaired mobility of the cervical spine explain this finding. Thickened vocal cords and subglottic stenosis may require smaller tracheal tubes than anticipated. Patients with evidence of stridor, dyspnea, or hoarseness should be referred to undergo flexible indirect laryngoscopy in order to detect laryngeal narrowing or recurrent laryngeal nerve palsy [2,7]. Although thorough airway evaluation is mandatory, many studies show that acromegaly is associated with a high incidence of unanticipated difficult intubation, despite reassuring Mallampati grades (1,2) or upper lip bite test .
Since there are no concrete data available to specifically recommend one intubation technique, (i.e. video laryngoscopy, gum elastic boogie, or Airtraq laryngoscope) over another, the availability of equipment and resources and formulation of a back-up plan is paramount in patients with anticipated difficult airway. Nevertheless, if laryngeal involvement is suspected, awake fiberoptic intubation is often considered the safest approach in patients with advanced acromegaly.
Monitoring of the patient involves standard American Society of Anesthesiology (ASA) monitors, an arterial line for hemodynamic control and a foley catheter to monitor urine output. A patient with acromegaly may present difficult arterial cannulation due to carpel tunnel syndrome and have poor collateral circulation in the distal extremity .
Maintenance of anesthesia
The primary anesthetic goals are similar to any procedure in Neuro Anesthesia. One must provide steady state anesthesia and maintain homeostasis with stable hemodynamics. It is imperative to avoid significant fluctuations in vital signs which may increase bleeding and disrupt the surgical operating conditions.
Short acting anesthetic agents and opioids are ideal as they prevent hypertension and tachycardia in addition to facilitating rapid emergence and extubation. We commonly use remifentanil, propofol, dexmedetomidine (precedex) and/or a volatile agent. Precedex, an alpha-2 adrenergic receptor agonist, has been shown to have optimal characteristics secondary to its sympatholytic and antinociceptive properties . Precedex infusion during surgery has been shown to reduce intraoperative bleeding and increase surgeon satisfaction . Surgeon’s may request hypotension to minimize bleeding in the surgical field which can be achieved with titration of dexmedetomidine, beta blockers, or nicardipine 
Following intubation, the patient is positioned supine with the head slightly elevated and neck flexed. The surgeon will employ a stereotactic navigation system with or without Mayfield pins to locate the pituitary mass. The face is carefully prepped and the surgeon prepares the nares with local anesthetic and a vasoconstrictor (Cocaine, Afrin and/or Lidocaine with Epinephrine). To facilitate access to the tumors, the surgeon will dissect and drill allowing access to the dura. The tumor is carefully curated and sent to pathology. At this point, a CSF leak may become evident. The nares are closed with packing and/or a fat harvest graft and a dressing applied.
Lumbar drain placement
Resection of large pituitary adenomas are associated with complications including CSF leak which result in increased length of stay and the risk of meningitis . Many neurosurgeons place a lumbar intrathecal catheter to also assist in visualization of the tumor.
Preoperative lumbar drain placement has been advocated by many neurosurgeons as a prophylactic measure to decrease the incidence of postoperative CSF leak by decreasing intracranial pressure. In addition, the catheter can be used to manipulate cerebrospinal fluid (CSF) pressure by the injection of saline or removal of CSF . Lumbar drain placement is not without complications which include dural puncture, subdural or subarachnoid hemorrhage, retained catheter, nerve root irritation and abducens nerve palsy .
Intraoperative steroid supplementation during transsphenoidal surgery
Patients with pituitary adenomas have deregulation of the hypothalamic-pituitary-adrenal (HPA) axis requiring perioperative glucocorticoid therapy. Dexamethasone has minimal mineralocorticoid activity in comparison to hydrocortisone. However, current literature contradicts the routine use of steroids in the perioperative period and Dexamethasone has been shown to cause HPA suppression in pituitary surgery [15, 16]. Protocols in many centers, (including ours) use steroid sparing to avoid unnecessary exposure to glucocorticoids if possible.
Prior to incision, the surgeon places an epinephrine pledge in the nasal cavity. The blood pressure spikes to 230/110. What is the appropriate management?
Surgical dissection of the nasal mucosa causes significant bleeding whereas epinephrine pledges are commonly used intraoperatively to promote vasoconstriction and improve operative conditions . The dose of epinephrine is limited by its co-administration of a local anesthetic. The systemic absorption of epinephrine increases the risk of arrhythmias and hemodynamic instability. These rapid changes in blood pressure present unique consideration in Neurosurgery and can cause intraoperative and postoperative complications.
The management of epinephrine induced hypertension requires prompt diagnosis and treatment. Treatment of tachycardia is done with beta-blockers such as labetalol and esmolol. Severe hypertension should be rapidly corrected with direct acting vasodilators such as nitroglycerine, sodium nitroprusside, or most often nicardipine.
High urine output during transsphenoidal surgery
Fluid and water balance must be carefully measured intraoperative. Pituitary adenomas do not commonly cause diabetes insipidus preoperative . Preoperative laboratory analysis should include evaluation of renal function and baseline values in serum electrolytes specifically sodium and potassium and blood glucose levels.
Central diabetes insipidus is a complication of pituitary surgery resulting in decreased secretion of antidiuretic hormones causing polyuria and polydipsia. The diagnosis of intraoperative DI requires no cofounding medication administration including diuretics and mannitol. Overhydration with intravenous fluids and osmotic diuresis due to hyperglycemia must also be excluded . Serial sodium values will continue to increase despite attempts to maintain euvolemia with crystalloid administration.
Diabetes insipidus usually develops postoperative within 24 hours. The diagnosis is made based on increased plasma osmolality (>295 mosmol/kg, hypotonic urine (<300 mosmol/kg) and high urine output (>2 ml/kg/hr) . Early treatment of DI is critical to prevent hypernatremia and dehydration. The treatment of choice for central DI is replacement of fluid losses with isotonic crystalloids and medical management with desmopressin (DDAVP).
Massive hemorrhage during transsphenoidal surgery is a rare complication which may result in permanent disability or death. Sudden bleeding should be controlled by immediately packing the nasal cavity and ipsilateral carotid occlusion if internal carotid injury is suspected . Maintenance of cerebral perfusion pressure through volume resuscitation, inotropes and pressors is important to minimize the risk of cerebral ischemia. Lesions of the sphenopalatine artery and postoperative venous bleeding should be treated via angiography and embolization [20, 21].
Considerations for Extubation
At the conclusion of the surgical procedure, the nasal cavity is closed and packing applied by the surgical team. The ideal anesthetic plan in a Neurosurgical procedure facilitates a rapid emergences and speedy assessment of neurological form and function. The wake up must be smooth and free of movement, bucking and coughing as this may raise intracranial pressure and result in a CSF leak.
Prior to extubation, the patient must be hemodynamically stable and demonstrate adequate respiratory drive and effort. It is imperative to thoroughly suctioning secretions and blood and ensure the patient is fully awake and reversed of neuromuscular blockade.
Upper airway obstruction is a key concern post-extubation in an acromegalic patient. Acromegalic patients are predisposed to upper obstruction and obstructive sleep apnea secondary to craniofacial abnormalities including a small, collapsible pharyngeal diameter, larger tongue volume and accumulation of upper airway adipose tissue ([7, 22]). CPAP and nasopharyngeal airways are an absolute contraindication. A multidisciplinary approach may be required to monitor and support the airway in the immediate postoperative period.
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