Pediatric anesthesiology 2016 reviews

Saturday Session IV: In A Hormonal Fog: Anesthesia and Endocrine Disorders

Reviewed by Nicole Dobija, MD
University of Michigan, Mott Children’s Hospital

The afternoon started off a bit “foggy” with our last lecture first and our first lecture last, so to begin with the end…

Daniel Roke, MD (University of Arkansas), presented his lecture on “Steroid Therapy and Stress Dose of Steroids.” Dr. Roke’s lively lecture began with 100mg Hydrocortisone IV, any questions? He then delved into the topic with an overview on steroids, a discussion on perioperative adrenal insufficiency, cortisol and stress response, along with steroid side effects and recommendations.

A refresher on steroid synthesis begins with the adrenal cortex producing two classes of steroids, both the corticosteroids and androgens. The corticosteroids are further divided into the mineralocorticoids and the glucocorticoids. This division is based on carbohydrate metabolism, sodium retention, and effect on inflammation. Glucocorticoids increase carbohydrate metabolism and decrease inflammation. Mineralocorticoids increase sodium retention. The hypothalamic-pituitary-adrenal axis – HPA axis is critical to the stress response. Signaling from cytokine release at the surgical site, baroreceptor signaling as a result of hypovolemia, psychological stress and direct afferent signaling all stimulate the HPA axis and result in a perioperative stress response. Cortisol is released from the adrenal gland as a response to stress. Cortisol increases blood glucose and amino acid levels and blood pressure. In 1949, the development of cortisone allowed for a number of inflammatory conditions to be treated, thus leading to perioperative adrenal insufficiency. There were a number of case reports showing patients being treated with cortisone for arthritis or other inflammatory conditions, developing perioperative hemodynamic collapse and on autopsy show bilateral adrenal atrophy. Signs and symptoms such as hypotension, tachycardia, fever, lethargy, arthralgia, myalgia, nausea, emesis, and mental status changes help to diagnose adrenal insufficiency. There are few studies to identify it and the true incidence is unknown.  The treatment of adrenal insufficiency is supraphysiologic steroid administration of 4 times the baseline dose (25 mg) thus hydrocortisone 100 mg, for the adult patient.

As noted early, cortisol is a glucocorticoid. It has actions including gluconeogenesis, protein breakdown, release of fatty acids and anti-inflammatory action. Cortisol does have some mineralocorticoid effect. Hydrocortisone is a synthetic cortisol. Dexamethasone is also a glucocorticoid but has a much longer duration of action that doesn’t mimic the surge seen in the stress response. Dexamethasone has no mineralocorticoid effect.

Studies have cited cortisol secretory rates in children ranging between 6-12 mg/m2/day.  Assuming an average cortisol secretion of 9 mg/m2/day for the average unstressed male:

  • Birth: 3.6 kg, 50 cm, 0.22 m2 = 2 mg
  • 6 month old: 7.8 kg, 67 cm, 0.38 m2 = 3.5 mg
  • 1 year old: 10.4 kg, 76 cm, 0.46 m2 = 4 mg
  • 2 year old: 13 kg, 87 cm, 0.56 m2 = 5 mg
  • 5 year old: 18 kg, 109 cm, 0.74 m2 = 7 mg
  • 10 year old: 32 kg, 139 cm, 1.1 m2 = 10 mg

Recommendations for stress dose steroid dosing by Smith, 8th edition (2011), for minimally invasive procedures is hydrocortisone 50 mg/m2 (5.5 times normal daily production). For prolonged or significantly invasive procedures, the dosage of hydrocortisone is 100 mg/m2 (11 times normal daily production). Cote’s 5th edition (2013) recommends for fever, illness, or minor procedures, use a replacement dosing of 3-5 times oral maintenance dose and for critical illness or major procedures dosing of 5-10 times oral maintenance dose.
What is a normal stress response in children? Two recent studies, Hsu et al. 2012 and Taylor et al. 2013, show for urologic and sedated procedures that not all patients had a rise in their cortisol levels, but the highest of all the levels recorded is in the recovery period. Maybe our dosing regimen should be changed to allow for the peak concentration of hydrocortisone to occur at the end of surgery. Combining these recommendations we arrive at stress dosing of hydrocortisone for minor procedures of four times maintenance dose and for major procedures of six times maintenance dose with 1-2 day taper.

Dr. Roke finished this lecture discussing the side effects of steroids. Supraphysiologic dosing of steroids can lead to hyperglycemia, hypertension, fluid retention, and an increased risk of infection. Chronic dosing of steroids may lead to hypothalamic-pituitary-adrenal axis suppression. Multiple studies show that it can happen, but that it does not always happen with patients receiving supplemental steroids. Likelihood of adrenal suppression increases with increased dose and duration, decreasing the time between cessation and surgery. Laboratory testing can be expensive, slow, and unreliable for determining adrenal insufficiency from exogenous steroids.

Julie Williamson, DO (Emory University) presented the second lecture on the “Anesthetic Management of Thyroid Disease.” Dr. Williamson began with an overview of her lecture including how to optimize pre-op management to attain a euthyroid state, planning the anesthetic course for thyroidectomy, anticipating and managing perioperative problems, and in the future could we do outpatient thyroidectomies?

A quick review of physiology begins with the hypothalamus secreting thyroid releasing hormone (TRH), which causes a release of thyroid stimulating hormone (TSH) from the anterior pituitary. TSH causes the thyroid gland to release T4 and T3. Remember that T3 is the more active hormone and T4 is the prohormone that gets converted to T3 in the periphery. Medical diseases of the thyroid are classified as congenital, acquired or iatrogenic. Congenital thyroid disorders include trisomy 21, Turner’s and Klinefelter’s syndromes and Type 1 Diabetes mellitus. Surgical diseases of the thyroid can be benign such as Graves’ disease, goiters, toxic adenomas, and congenital hypothyroidism. They can also be malignant such as differentiated thyroid carcinoma and medullary thyroid carcinoma including the MEN 2A and 2B.

In the pediatric population, is Graves’ disease medical or surgical? Due to poor efficacy of keeping children in a euthyroid state, most thyroid adenomas are surgically removed in children. The side effect profile of PTU and methimazole can cause hepatotoxicity and fever, arthralgia and agranulocytosis respectively. Radioactive iodine has a risk of malignancy and could cause hyperparathyroidism.

Thyroid malignancy in childhood includes differentiated thyroid cancer, which generally has an advanced stage at presentation and medullary thyroid carcinoma. There is favorable prognosis and surgery usually requires a neck dissection for nodal involvement. The decision for which surgeon should operate on these children should be based on the best possible outcomes and lowest complications and this is found with surgeons who perform at least 30 or more cervical endocrine procedures annually.  Perioperative optimization includes methimizole for 1-2 months prior to resection. This is followed by SSKI (saturated solution of potassium iodine) TID for 10 days prior to surgery and a beta blocker as required. Prior to surgery the patient should have a normal heart rate, temperature and energy level.

The anesthetic management for thyroid surgery requires special consideration to avoid sympathetic stimulation. Many will use a deep anesthetic and a very smooth emergence, taking care to avoid ephedrine and epinephrine and use anticholinergics sparingly. Careful consideration includes avoiding muscle relaxation due to nerve monitoring for the surgical procedure and to avoid the need for reversal agents. Many surgeons utilize an endotracheal tube that has the capability for recurrent laryngeal nerve (RLN) monitoring. There has not been strong evidence that this prevents RLN injury. If the patient has exophthalmos, extra lubrication for the eyes and padding around the eyes should be performed to avoid corneal abrasions. The surgical positioning requires a shoulder roll for neck extension and reverse Trendelenberg to 30 degrees to facilitate gravitational drainage of the surgical site. Careful temperature monitoring and avoidance of postoperative nausea and vomiting is critical. At the end of the surgery, visualization of the vocal cords to ensure there was no injury to the recurrent laryngeal nerve.

One of the main complications of a thyroidectomy is bleeding. The area is very vascular and bleeding can occur until 72 hours postoperatively. There should be a low threshold to return to the operating room for exploration and the incision may have to be opened in the PACU to prevent airway compromise. Injuries to the recurrent laryngeal nerve can occur from traction, transection, entrapment or ischemia. The injury may be temporary or permanent. Unilateral injury results in a throaty, hoarse voice that cannot sustain the “eeee” sound. Bilateral injury is an airway emergency and results in severe stridor with the vocal cords fixed midline. Injury to the superior laryngeal nerve is more related to voice quality and usually requires only speech therapy.

Hypocalcemia can occur from a stunning of the parathyroid gland. iCa should be monitored postoperatively. Symptoms of hypocalcemia include perioral paresthesias, abdominal pain, tetany, laryngospasm, and QT prolongation, which can lead to cardiac arrest. Thyroid storm can occur intraoperatively and has been described up to 18 hours post surgery. It is a severe hypermetabolism from an overproduction of thyroid hormone. Symptoms include fever, tachycardia, ectopy, delirium, and heart failure. The differential should include malignant hyperthermia, although thyroid storm would have a normal ETCO2, pheochromocytoma, neuroleptic malignant syndrome, sepsis, anaphylaxis and light anesthesia. To treat a thyroid storm, one should cool the patient, ensure adequate oxygenation, correct acid base derangements and replace electrolytes. Propranolol may be used to block the conversion of T4 to T3. The use of anti-thyroid drugs such as SSKI and glucocorticoids may be needed.

Iatrogenic thyroid conditions may be a result of multiple iodine preps being used on a patient who may require frequent procedures and from iodine contrast being used in the catheterization labs on patient’s with congenital heart disease.

Is outpatient thyroidectomy in our future? In the adult population, on select “low risk” patient’s, outpatient thyroidectomies are being performed. Whether this will extend to pediatric patient’s, we will have to wait and see…

Our last lecture was from Edward C. Nemergut, MD (University of Virginia) entitled “Perioperative Management of Pituitary Surgery.” Pituitary tumors have been described and operated upon since ancient times. This review will cover the basic information about pituitary and sellar tumors, epidemiology, presentation and characteristics and will conclude with a case presentation.

Pituitary tumors account for 10% of diagnosed brain neoplasms. They are mainly asymptomatic and have a peak incidence during the 4th and 6th decade of life. Sellar tumors also occur in pediatrics and are mostly craniopharyngioma’s and Rathke’s cleft cysts with a mean age at presentation of 12 years of age. By definition, pituitary tumors are defined as macroadenomas (>10mm in any dimension) and microadenomas (<10mm in every dimension). They are also described according to their neuroendocrine status as functioning adenomas (producing a single predominant hormone, 70% of tumors), nonfunctioning (30% tumors) and silent (producing a hormone but the patient’s are asymptomatic).

Pituitary tumors present in one of three ways: from hormone excess, mass effect or as an incidental finding on intracranial imaging. Excessive hormone production is most commonly a prolactinoma (20-30%) resulting in hyperprolactinemia. Other less common hormone overproduction is increased ACTH causing Cushing’s syndrome, excessive growth hormone causing acromegaly or gigantism and less commonly increased TSH, LH/FSH and a mixed presentation. Mass effect from a pituitary tumor can cause headache, visual changes, or compression of normal gland causing anterior pituitary dysfunction. A rare presentation would be increased intracranial pressure or diabetes insipidus.

Craniopharyngioma’s are benign neoplasms that arise from the sella/suprasella region. They are rare and represent 1-3% of all brain tumors and occur 5-10% in children. There are approximately 350 new cases a year in the U.S. The most common type in pediatrics is the adamantinomatous type and it is locally aggressive. The presentation in children is of headaches with potentially raised ICP. Twenty percent of children may have visual disturbances. A Rathke’s cleft cyst is an embryological remnant that persists within the pituitary gland from Rathke’s pouch. Most are asymptomatic and have a similar presentation as a craniopharyngioma. The most common symptom is of a headache.

Incidental findings of a pituitary tumor occur with the work up from a head injury or evaluation of a chronic headache. Mass effect from these tumors can cause headache, nausea, DI-induced thirst, optic tract defects, papilledema, ischemic stroke and arterial compromise.

Medical treatment of pituitary tumors includes dopamine agonists. It is the treatment of choice for prolactinoma and may reduce symptoms in all patients. Patients with acromegaly are treated with somatostatin analogues although this is palliative and does not reduce tumor size. The surgical approach to pituitary tumor resection is either a bifrontal craniotomy or the transsphenoidal approach. The bifrontal craniotomy gives the surgeon better exposure of the optic nerves but has increased morbidity and mortality and is uncommon today. The transsphenoidal approach was first described in 1906 and refined by Cushing from 1910 – 1925. It has decreased the morbidity and mortality of pituitary tumor removal. Transsphenoidal techniques include the endonasal, endonasal endoscopic (most common today) and the sublabial (more common in pediatrics).

Surgery is the only treatment option that offers a potential cure. Success is highly dependent on the experience of the surgeon. This is both for pituitary tumors and craniopharyngioma’s. For a craniopharyngioma, the recurrence rate with surgery alone is 30-50%, combined with RT the recurrence is 10-25%.
The case presentation involves a 21-year-old male for transsphenoidal resection of a hormone secreting macroadenoma. His medical history in significant for hypertension for which he takes enalapril, recent bilateral carpal tunnel releases, and a recent decrease in functional capacity (previous high school athlete). His underlying diagnosis is acromegaly.

Carpal tunnel syndrome (CTS) can result from soft tissue hypertrophy and cause ulnar artery compression. Fifty percent of patients may be radial dominant and 90% of patients with CTS may be radial dominant with compromised ulnar blood flow, thus if a patient with acromegaly has CTS, radial arterial cannulation may have increased risks. The most common cause of death in untreated acromegaly is cardiovascular. Fifty percent of untreated patients die before age fifty. Hypertension with left ventricular hypertrophy (LVH) is present in 40% of patients and LVH is present in 50% of non-hypertensive patients. LVH occurs independently from hypertension. Stroke volume and cardiac output are preserved at rest but diastolic dysfunction severely limits activity. The result is a poorly compliant left ventricle with a need for high filling pressures and long diastolic filling time. LVH and diastolic function may improve following tumor resection in younger patients. In patients with long standing disease, function does not improve and is related to interstitial fibrosis. Eighty-six percent of patients with active untreated acromegaly have aortic and mitral valve abnormality. Diffuse coronary artery disease of the smaller vessels is also common. These patients may also have rhythm abnormalities especially during exercise.

Patients with acromegaly also have hypertrophy of the upper airway including the facial bones, mandible, and soft tissues of the nose, mouth, tongue and lips. There is also hypertrophy of the laryngeal and pharyngeal tissues causing a reduction in the size of the glottis and one may need a smaller endotracheal tube. There may be changes in vocal strength and hoarseness from hypertrophy of tissue causing recurrent laryngeal nerve injury. There is also reduction in cervical spine mobility. Obstructive sleep apnea is common in patients with acromegaly. Intubation can be potentially difficult, may be as high as 10% of patients. Have alternative intubating techniques available.

The case continues… the patient is safely induced and intubated. The surgeons place a lumbar intrathecal catheter and the nasal mucosa is infiltrated with a lidocaine and epinephrine solution. The patient is positioned and the surgery begins…

There are many ways to provide anesthesia for pituitary surgery. Rapidly cleared anesthetic agents are popular for a quick emergence and timely neurological examination. The mucosa is infiltrated with vasoconstricting agents to reduce bleeding and facilitate dissection. Injection of too much epinephrine can cause hypertension and dysrhythmias. The incidence of venous air embolism (VAE) is the semi-seated position for transsphenoidal surgery is reported at 10%. Incidence increases with increased head-up angle. A lumbar intrathecal catheter is used to assist in the visualization of the tumor. SCF can be injected or removed to move the tumor up or down in the operating field. There is a potential for significant blood loss given the proximity of the tumor to large intracranial arteries. Injury to the arteries is infrequent but would be fatal. There may be mild to moderate venous “oozing” from the cavernous sinus. At the end of surgery a fat graft may be placed to help prevent a CSF leak. Diabetes insipidus (DI) is one of the most common complications of pituitary surgeries. It results from a relative or absolute deficiency of antidiuretic hormone (ADH). DI can result from damage anywhere along the hypothalamus-pituitary axis and it is difficult to predict who will develop DI. The treatment must be individualized to each patient. The ultimate goal is restoration of euvolemia.

Some final thoughts about pituitary surgery are to remember not to place a naso-gastric tube or naso-pharyngeal airway in these patients as they have a persistent bony defect. It is unclear how long this defect can persist. Inadvertent intracranial instrumentation has occurred from these devices.

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