Neurocritical Care

26. Diabetes Insipidus After Brain Tumor Surgery

A 40-year-old woman was evaluated for recurrent suprasellar pilocytic astrocytoma causing worsening headaches, visual loss, and hydrocephalus (Figure 26.1A). In the distant past her tumor had been treated with debulking and radiation. She was taking cabergoline to control her excessive prolactin production, levothyroxine for her hypothyroidism, and dexamethasone for treatment of tumor swelling. Until a couple of months ago she had been using low-dose DDAVP (desmopressin acetate) for diagnosis of central diabetes insipidus, but this medication had been discontinued after she developed hyponatremia. As a first step she underwent ventriculoperitoneal shunt placement with improvement of her symptoms. Six weeks later she was readmitted for tumor resection. The surgical approach was interhemispheric, transcallosal, and transventricular. Despite extensive adhesions to adjacent structures the tumor was successfully removed (Figure 26.1B). The pituitary infundibulum was noted to be infiltrated by the tumor. Within hours of the surgery, the patient developed marked polyuria (1.4 liters over the previous 90 minutes). Her serum sodium level has increased to 146 mmol/L from 138 mmol/L, serum osmolality is 297 mOsm/kg, urine osmolality is 113 mOsm/kg, and urine specific gravity is 1.003.

What do you do now?

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FIGURE 26.1 A) Preoperative MRI scan showing a large suprasellar enhancing mass with associated obstructive hydrocephalus. B) Postoperative MRI scan showing complete resection of the previously observed suprasellar mass. (Both MR images are gadolinium-enhanced sagittal T1 sequences.

Polyuria and hypernatremia after craniotomy point to a defect in vasopressin secretion. Neurosurgery in the region, particularly if transsphenoidal causes deficiency of arginine-vasopressin (AVP) secretion and central diabetes insipidus (DI) (Table 26.1). AVP increases the permeability to water of the renal cells lining the distal tubules and medullary collecting ducts. With AVP deficiency, water is not reabsorbed and large quantities of diluted urine are excreted. Patients can become rapidly dehydrated and develop severe hypertonic hypernatremia if their water intake is insufficient to compensate the loss. Ambulatory patients get thirsty and may maintain a balance through drinking large amounts of fluids (polydipsia). Critically ill and postneurosurgical patients depend entirely on the health care team to administer them enough fluids. With a severe disturbance, AVP needs to be fully replaced.

TABLE 26.1 Causes of Central Diabetes Insipidus in the NICU

Brain tumors*

   Pituitary adenoma

   Craniopharyngioma

   Pilocytic astrocytoma

   Meningioma

   Hypothalamic hamartoma

   Metastasis

   Lymphoma

Transsphenoidal neurosurgery*

Brain death*

Traumatic brain injury*

Langerhans cell histiocytosis

Erdheim Chester disease (non-Langerhans cell histiocytosis)

Sarcoidosis

Wegener’s granulomatosis

Subarachnoid hemorrhage

Sheehan’s syndrome (postpartum ischemic pituitary necrosis)

Asterisk indicates common causes in the NICU

When evaluating a neurological patient with polyuria—usually defined as 24-hour urinary excretion > 50 ml/kg of body weight—the first necessary piece of information is the serum sodium concentration. If the patient is markedly hypernatremic and the hypernatremia is not iatrogenic (e.g., after large doses of hypertonic saline or mannitol), the diagnosis of DI is very likely. The diagnosis is supported if the urine is hypotonic (urine osmolality < 300 mOsm/kg, urine specific gravity < 1.010) despite hypertonic serum. Moreover, the major improvement in urine concentration that follows the administration of DDAVP confirms the diagnosis.

The management of DI is more complicated than appreciated. Physicians need to follow the changes in serum sodium concentration and fluid balance very closely. The management of hypertonic hypernatremia from DI starts by maximizing adequate water replacement. One has to administer enough fluids to prevent or correct hypovolemia. Sodium chloride 0.9% (normal saline solution) is often quite hypotonic in relation to serum sodium concentration in these patients and it is the intravenous solution we generally use first, unless the degree of hypernatremia is becoming dangerously high (> 160 mmol/L). It is important to be cautious about the administration of hypotonic intravenous solutions to patients at risk of postoperative brain swelling, and we favor a less aggressive replacement of the free water deficit in these patients than usually recommended.

Calculating the free water deficit is useful to adequately treat patients with central DI. The formula for this calculation is:

Free water deficit = Normal TBW – Current TBW

where normal TBW (total body water) is 60% of lean body weight in kilograms in men and 50% in women, and current TBW is calculated as follows:

Current TBW = Normal TBW × (140/current serum sodium level)

Once the free water deficit is known, one can calculate the amount of fluids to give depending on the fluid tonicity:

Replacement fluid volume (in liters) = Free water deficit × (1/1 – X)

where X = replacement fluid sodium concentration – isotonic fluid sodium concentration (refer to Table 25.1 for information on sodium concentration in commonly used intravenous fluids).

As these formulas fail to tell us how the serum sodium concentration will change as we replace the fluid, we have found the following alternative formula to be useful in practice:

Change in serum Na = replacement fluid Na – serum Na/normal TBW + 1

This formula tells us how much the serum sodium concentration will change after the retention of 1 liter of the replacement fluid.

It is prudent to avoid rapid swings in serum sodium concentration. The risk of myelinolysis is unknown when correcting hypernatremia compared to hyponatremia, but we still prefer to reduce hypernatremia by not more than 10 mmol/L per day. In addition, and most important, patients with postoperative brain swelling could potentially worsen if a high serum sodium level is corrected too quickly. In such patients, lowering the sodium but maintaining a more moderate degree of hypernatremia may be a better therapeutic target.

Oral intake and enteral administration (via gastric tube) of free water are safe. We have seen patients in whom small volumes of intravenous hypotonic fluids were detrimental while large volumes of free water given by nasogastric tube were not. As a consequence, we prefer gastric free water flushes for the gradual correction of hypernatremia in neurocritical patients.

We start DDAVP when the polyuria is severe (more than 500 mL per hour for two consecutive hours or an average of more than 300 mL per hour over 4 hours) and when the serum sodium concentration is rising fast. We may start with a low dose, such as 1 microgram intravenously. Typically the urinary output begins to slow down within 15–20 minutes. If the response is insufficient after 60 minutes, we repeat a higher dose (1–2 micrograms). Monitoring of urinary output and serial serum sodium measurements should guide the timing of the next dose. Because gastric absorption may be poor in these patients, we prefer intravenous administration until we can be confident that we have defined a daily requirement and the situation is stable. At that point we may switch to nasal (or oral) formulations. Chlorpropamide (sometimes combined with a thiazide) has also been used to treat central DI. Although it is indeed a potent antidiuretic, we rarely administer this medication because it can provoke severe hypoglycemia.

Patients with aneurysmal subarachnoid hemorrhage who develop central DI represent another challenge. DI is relatively uncommon, but it may present early after rupture of a midline aneurysm and mostly in patients who present with poor clinical grade. The onset is sudden, and the hypernatremia can be quite severe, but the duration is short and it is generally followed by cerebral salt wasting. DDAVP and hypotonic intravenous fluids need to be used very cautiously in these patients as they may contribute to the abrupt occurrence of severe hyponatremia. This shift from hypernatremia to hyponatremia can also occur in patients with traumatic brain injury, but the change is slower. Finally, diabetes insipidus may be one of the first signs that a patient is meeting criteria for brain death. Usually hypotension accompanies the development of polyuria and hypernatremia (chapter 31).

Our patient was treated with a combination of crystalloids (a combination of 0.9% and 0.45% sodium chloride), enteral free water, and DDAVP (first intravenously and then orally after several days). Her stay in the ICU was extended by a week as a result of the need to closely monitor her labile DI. Eventually she recovered well except for short-term memory deficits likely due to fornix injury. Six months later, her urinary production and serum sodium levels were stable on oral DDAVP (0.4 mg twice daily). As it was the case in our patient, it is not uncommon that patients with brain tumors, brain trauma, or after neurosurgery need long-term treatment with DDAVP. These patients need a comprehensive endocrine evaluation for possible panhypopituitarism. In fact, even in the absence of signs of pituitary apoplexy, investigation of adrenal and thyroid function should be considered in any patient with central DI in the ICU.

TABLE 26.2 Protocol to Treat Diabetes Insipidus

STABLE HYPERNATREMIA (<150 mmol/L)

Monitor polyuria and match with fluid intake

Consider free water (250 ml) flushes through NG tube

Monitor body weight, urine specific gravity

RISING OR SEVERE HYPERNATREMIA

Start desmopressin 1 mcg IV and repeat if inadequate response (max 4 mcg/d in divided doses)

Start 0.45% sodium chloride or 5% dextrose and calculate infusion rate (see text)

Monitor serum sodium every 2-4 hours.

Monitor urine specific gravity

A protocol to treat diabetes insipidus is shown in Table 26.2.

KEY POINTS TO REMEMBER REGARDING DIABETES INSIPIDUS AFTER BRAIN TUMOR SURGERY

· Postoperative polyuria after surgery for a suprasellar tumor should promptly raise suspicion of diabetes insipidus.

· Diabetes insipidus can be a component of panhypopituitarism in patients with brain tumor, brain trauma, and infiltrating granulomatous diseases.

· Diabetes insipidus in a catastrophically injured patient may be one of the first signs of brain death.

· Diagnosis of diabetes insipidus is based on the presence of polyuria associated with hypernatremia, serum hyperosmolality, and urine hypoosmolality.

· Management of central diabetes insipidus consists of aggressive rehydration and intravenous administration of DDAVP.

· Be wary of giving hypotonic intravenous fluids to patients with brain swelling. Lowering serum sodium to a more moderate degree of hypernatremia primarily by administering free water through the gastric tube is a safer strategy in these patients.

Further Reading

Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000; 342:1493-1499.

Jane JA, Vance ML, Laws ER Neurogenic diabetes insipidus Pituitary. 2006; 9:327-329.

Krahulik D, Zapletalova J, Frysak Z, Vaverka M. Dysfunction of hypothalamic-hypophysial axis after traumatic brain injury in adults. J Neurosurg 2010; 113:581-584.

Kristof RA, Rother M, Neuloh G, Klingm ller D. Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study. J Neurosurg 2009; 111:555-562.

Nemergut EC, Dumont AS, Barry UT, Laws ER. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg 2005; 101:1170-1781.

Rabinstein AA Wijdicks EFM. Body water and electrolytes. In: Textbook of Neurointensive Care.(Layton AJ, Gabrielli A, Friedman WA 2004 , pp 555-577, Saunders, Philadelphia.

Verbalis JG. Management of disorders of water metabolism in patients with pituitary tumors. Pituitary 2002:5:119-132.