33.1 Introduction

Endonasal surgery in pediatric patients is associated with a unique set of complications, the individual likelihood of which varies based upon the underlying abnormality/tumor as well as the specifications of the treatment chosen. Despite the considerable heterogeneity that exists among all lesions treated via the endonasal approach in children, a handful of postoperative complications are commonly encountered. In one study of 133 pediatric patients who underwent endonasal approaches, postoperative cerebrospinal fluid (CSF) leaks were detected in 14 patients (10.5%), new anterior pituitary endocrinopathy in 14 (10.5%), panhypopituitarism in 2 (1.8%), permanent diabetes insipidus (DI) in 12 (9.0%), transient DI in 8 (6.0%), syndrome of inappropriate antidiuretic hormone (SIADH) in 3 (2.3%), and development of hydrocephalus in 6 (4.5%). ¹ Additionally, postoperative hematoma and epistaxis were noted in 3 (2.3%) and 8 patients (6.0%), respectively. This is a significant complication burden for a delicate patient population.

Postoperative DI and SIADH can be categorized as disorders of fluid and electrolyte balance associated with dysfunction of the posterior pituitary. Anterior pituitary endocrinopathy and hypopituitarism are postoperative disorders of anterior pituitary function. CSF leaks and hydrocephalus involve postoperative disturbances of CSF homeostasis. Postoperative hematoma and epistaxis fall under emergent postoperative complications. Appropriate postoperative care requires vigilance in timely detection and treatment of these complications, which are discussed in the ensuing sections.

33.2 Detection and Management of Postoperative Posterior Pituitary Dysfunction

A proper understanding of normal physiology is beneficial in the diagnosis and management of postoperative disorders of fluid and electrolyte balance. Thorough knowledge of osmolality homeostasis, in particular, is essential. Elevations in plasma osmolality stimulate osmostat receptors in the anterolateral hypothalamus, which respond by signaling for the release of antidiuretic hormone (ADH). ADH, also known as L-arginine vasopressin, is produced in the bodies of magnocellular neurons in the paired supraoptic and paraventricular nuclei of the hypothalamus and transported down the pituitary stalk for storage in the posterior pituitary. Following release into the bloodstream, circulating ADH binds to V₂ receptors in the kidneys, which leads to synthesis of aquaporin-2 water channels and subsequent increased reabsorption of free water. This feedback loop tightly maintains plasma osmolality at 280 to 290 mOsm/kg. ²

Increases in serum osmolality result in high levels of circulating ADH, which serves to promote the retention of free water in the kidneys and normalize serum tonicity. On occasion, disruption of this feedback loop is encountered in pediatric patients following endonasal surgery. This is especially common in patients whose pituitary stalk has been manipulated or transected. Trauma to the stalk can result in a temporary or permanent inability to synthesize and/or release stores of ADH termed central DI. In assessing the risk that central DI poses to the patient, perhaps the most important variable is the integrity of the patient’s thirst mechanism. In the context of a compromised thirst mechanism (e.g., a patient who is obtunded or comatose or a very young patient unable to communicate thirst or gain access to water), the inability to concentrate urine can rapidly lead to life-threatening levels of hypernatremia. In these patients, vigilance in ensuring timely diagnosis and treatment of central DI is imperative.

In pediatric patients who undergo endonasal approaches in which the hypothalamus, pituitary stalk, pituitary gland, or superior hypophyseal arterial supply is subjected to operative manipulation, appropriate steps are taken postoperatively to optimize early diagnosis and/or treatment of DI. In this population, the foley catheter is continued following surgery for hourly measurement of urinary output. Urine samples are sent for specific gravities no less than every 6 hours. The arterial line is kept following surgery as well to allow for every 6 hour measurements of sodium (in setting of florid DI, this frequency can be increased as needed). In the immediate postoperative period, a low urine-specific gravity (≤1.005) combined with a high urine volume (>4 mL/kg/h for 2–3 consecutive hours) raises suspicion for early development of DI. If the thirst mechanism is intact and the patient is permitted to have unrestricted access to water, any small associated increase in osmolality results in increased thirst, and normal osmolality is restored with the generous oral intake of free water. ³ Florid DI can sometimes result in a large free water deficit that can be uncomfortable to recover using oral intake alone; additionally, copious urinary output—especially during nighttime hours—can adversely affect patient rest and comfort. In this instance, treatment with an ADH analog such as dDAVP (desmopressin) is often advised to help improve patient comfort. When actively receiving dDAVP, the serum sodium and osmolality are periodically measured to help assess the efficacy of the treatment. In cases of postoperative DI in which the thirst mechanism is not intact, treatment with dDAVP and calculated free water supplementation with input from an endocrinology or pediatric intensive care service is imperative.

Many options exist for replacing ADH in the postoperative patient with central DI. Pitressin is a synthetic form of L-arginine vasopressin that has potent antidiuretic effects. However, because of its short half-life and effect on blood pressure, it is uncommonly utilized for management. dDAVP is an alternative medication that lacks the hypertensive effects of Pitressin and is associated with a longer half-life. ⁴ This medication is well suited for the management of DI and can be obtained in intranasal, oral, and parental forms. In patients who have undergone endonasal surgery, the intranasal preparation is sometimes avoided. In small children, however, use of the endonasal preparation in conjunction with the rhinal tube sometimes allows administration of lower doses of dDAVP (≤5 mcg) that can be titrated more readily. When this strategy is employed (often in small children or patients with high receptor sensitivity), the medication should be administered in the nostril where the nasal mucosa was not disrupted to ensure maximal absorption. Use of bilateral nasoseptal flaps is a contraindication to use of intranasal dDAVP. Initial oral dDAVP doses in pediatric patients older than 4 years often begin at 0.05 mg (half of a 0.1-mg tablet). Initial IV or subcutaneous doses in pediatric patients range from 0.1 to 0.5 mcg based on age and weight. The duration of ADH-related effects is usually 6 to 12 hours. Subsequent doses, often delivered twice a day, are titrated according to the effect of the initial dose. Following initiation of desmopressin, a graduated regimen for monitoring sodium has been recommended, with measurement of serum sodium every 6 hours for the first 24 to 48 hours, every 8 hours for the next 24 hours, and every 12 hours thereafter until stabilization. As overtreatment of transient DI remains a common and preventable source of unnecessary increased length of hospital stay, it is preferable in many cases to aim for return of increase in urinary output prior to redosing.

Treatment with dDAVP results in a state of nonsuppressible ADH activity. For this reason, perhaps the greatest risk associated with treatment is progressive hyponatremia and related sequelae (e.g., hyponatremia-related seizures). While peak onset of DI is on the second postoperative day, previous studies have noted new onset as late as 11 days following surgery. ⁵ Infrequently, the neurosurgeon will be faced with a scenario where DI has gone undetected until presentation at an advanced stage. In this instance, formal calculation of water deficit is useful to guide strategies for correction. The following formula is used to calculate overall water deficit: water deficit = 0.6 × preoperative weight × (1 – 140/[Na⁺]). The hyperosmolarity should be corrected over a protracted period to avoid issues relating to cerebral edema. ⁶ Oral replacement with water or IV supplementation with D5W (dextrose in 5% water) is utilized. In the vast majority of cases unrelated to treatment of craniopharyngioma and/or stalk resection, DI is transient and resolves within a few days of the procedure. Permanent DI is incurred if ≥90% of the vasopressin-secreting neurons are destroyed and involves long-term follow-up with the endocrinology service. ⁷

In addition to DI, providers should remain aware of the SIADH—which complicated the postoperative course of 2.3% of patients in the pediatric endonasal series by Chivukula et al. ¹ SIADH, in contrast to DI, peaks in incidence on the seventh postoperative day. ⁸ Comparatively speaking, SIADH is much less common following endonasal procedures than DI. However, as it is relatively common for patients to have been discharged home prior to onset of SIADH, education regarding the possibility of this occurrence is of paramount importance. In patients who have noted any form of subacute decline after discharge home following endonasal surgery, it is important to obtain a serum sodium level. The authors routinely obtain an outpatient serum sodium in all patients with sellar pathology who have been discharged from the hospital on postoperative day 6. An early diagnosis of hyponatremia in this setting helps avoid severe clinical sequelae.

Symptomatic hyponatremia requires readmission for evaluation and correction. Fluid restriction with occasional IV or oral sodium supplementation is recommended if SIADH is present. Vasopressin receptor antagonists can also be considered on an individual basis in severe cases. Hypothyroidism and adrenal insufficiency should be ruled out, as both can cause hyponatremia that is falsely attributed to SIADH. Dual etiologies sometimes exist, which can make correction and management of hyponatremia cumbersome. The occurrence of cerebral salt wasting (CSW), while sometimes encountered following craniotomies, tends to be rare following endonasal procedures. While SIADH is statistically more common in this setting, differentiation of SIADH from CSW is occasionally challenging. CSW involves renal loss of sodium following intracranial surgery and results in characteristic hypovolemic hyponatremia. This phenomenon may relate to increased release of brain natriuretic peptide (BNP) from the hypothalamus secondary to physiologic or traumatic disturbance. ² In contrast to CSW, patients with SIADH exhibit euvolemic hyponatremia. Volume status is the most important characteristic used to differentiate the two pathologies; trends of weight gain and water balance, central venous pressure (CVP), and urine sodium help with confirmation. CSW is managed by treatment of the underlying problem if reversible (e.g., meningitis, hydrocephalus, adrenal insufficiency) followed by volume replacement. Oral or IV sodium supplementation and/or fludrocortisone can be added in an iterative manner if necessary. In treatment of all causes of hyponatremia, care is taken to avoid overexuberant correction of hyponatremia that may predispose to central pontine myelinolysis.

33.3 Detection and Management of Postoperative Anterior Pituitary Dysfunction

All pediatric patients scheduled to undergo endonasal surgery undergo routine assessment of hypothalamic and pituitary function prior to surgery. In the event this assessment demonstrates some element of insufficiency, supplementation is provided prior to surgical intervention. In patients with normal preoperative pituitary function, endonasal surgery is often associated with some degree of risk for subsequent development of anterior pituitary insufficiency. This risk is heavily dependent on the pathology at hand (craniopharyngioma, in particular, is associated with a high risk of postoperative anterior pituitary insufficiency) in addition to specific details of the procedure. In the cases in which the pathology and operative findings support a high postoperative risk to anterior pituitary dysfunction, patients are often maintained on glucocorticoids prior to clinical reevaluation in an outpatient setting 4 to 12 weeks following surgery. Patients with preexistent anterior pituitary deficiency sometimes recovery pituitary function following surgery. In these patients, the hormonal supplementation should continue until evidence of recovery at the first outpatient endocrine visit.

In pediatric patients who undergo endonasal surgery for sellar pathology, our practice has been to pretreat with a single dose of hydrocortisone prior to surgery. If the operative findings are consistent with low risk to the stalk and gland, an attempt is made to wean hormonal supplementation in the early postoperative period. Determination of the postoperative integrity of the hypothalamic–pituitary–adrenal (HPA) axis integrity is of vital importance. ⁹ Multiple studies conducted in the adult population have attempted to designate a cortisol-level threshold predictive of HPA axis sufficiency; levels between 10 and 17 μg/dL have been entertained. ^{10 ,​ 11} However, others continue to favor the insulin hypoglycemia test as perhaps a more accurate assessment. ¹² In patients known to have intact HPA axis integrity prior to surgery, the authors prefer to give a single dose of stress-dose hydrocortisone immediately prior to surgery. A cortisol level is subsequently obtained a minimum of 24 hours following the initial dose of hydrocortisone (in procedures that begin at 7:30 am, this level is obtained the morning of postoperative day 1; in all other cases, this level is obtained the morning of postoperative day 2). If the cortisol level is less than 15 μg/dL, the patient is placed on daily glucocorticoid supplementation with plans to electively reevaluate the HPA axis approximately 6 weeks following surgery with an adrenocorticotropic hormone (ACTH) stimulation test.

The ability to detect anterior pituitary dysfunction following endonasal surgery is of paramount importance. In pediatric patients who have undergone endonasal surgery and remain off glucocorticoid supplementation, it is good practice to routinely consider signs and symptoms of cortisol deficiency—including hypotension, nausea, malaise, hyponatremia, and difficulties with thermoregulation. Although multiple corticosteroid preparations are available, hydrocortisone prescribed at 7 to 20 mg/m²/d (5–15 mg/d) given orally in two or three divided doses is considered the most physiologic replacement. Hypothyroidism is usually detected 3 to 7 days after surgery and can be picked up with a free T4 serum measurement. Thyroid supplementation is usually initiated immediately after insufficiency is detected. Total replacement levothyroxine dose is 100 mcg/m²/d. However, the authors’ practice has been to initiate thyroid replacement at much lower doses and titrate higher if necessary, as pituitary–thyroid axis deficiency is often incomplete and/or transient. Growth hormone deficiency and hypogonadism are evaluated and addressed at the first endocrine evaluation after surgery 4 to 12 weeks, as diagnosis is not accurate in the immediate postoperative period, and there is no urgency in replacement either.