Distinguishing cerebral salt wasting syndrome and syndrome of inappropriate ADH in a patient with traumatic brain injury

Abstract

A previously healthy 48-year-old woman was referred to our intensive care unit (ICU) from a neurosurgical ward due to deterioration of her conscious level. She had a road traffic accident 6 days earlier. On admission to the hospital, a brain CT demonstrated subarachnoid haemorrhage which was considered not amenable to surgical intervention. A second CT brain performed shortly after admission to ICU showed no change in comparison to the initial CT. Serum sodium level on ICU admission was 108 mEq/L; serum and urine osmolalities were 223 mOsm/kg and 438 mOsm/kg, respectively. Her hyponatraemia was initially attributed to syndrome of inappropriate antidiuretic hormone. However, a clinical impression of low volume status raised the suspicion of cerebral salt wasting syndrome. She was managed by infusion of hypertonic saline and fluids for 5 days and discharged from ICU after improvement of her conscious level and normalisation of serum sodium.

Background

Hyponatraemia is the most prevalent electrolyte imbalance complicating serious traumatic brain injury.¹ However, it can also occur in association with central nervous system infections and tumours.² Hyponatraemia complicating traumatic brain injury could be attributed either to syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSWS). The disparate nature of management of these conditions makes discrimination between them crucial.¹

We present a case of CSWS following traumatic subarachnoid haemorrhage.

Case presentation

A previously healthy 48-year-old woman suffered a traumatic brain injury as a result of a road traffic accident (RTA). At initial presentation, she was fully conscious (Glasgow Coma Scale (GCS) 15/15) and had stable vital signs. Her brain CT scan demonstrated subarachnoid haemorrhage, which was considered not amenable to surgical intervention; no other major injuries were detected. She was referred to our centre from another hospital 6 days after the RTA for admission under observation to the neurosurgical ward. Our centre is the tertiary referral centre for neurosurgical related conditions in the southern region of Ireland. At initial presentation, her serum sodium concentration had been 139 mEq/L; no subsequent measurement of serum sodium was performed prior to transfer to our hospital. After arrival to our hospital, her conscious level deteriorated, GCS 11/15 (E2V4M5). She suffered from generalised tonic-colonic convulsions which lasted for 1 min and was transferred immediately to our intensive care unit (ICU). On admission, she was confused (postictal state) and her physical examination revealed tachycardia (heart rate 120/min), borderline systemic hypotension (90/45 mmHg) and diminished skin turgor. Cumulative urine output over the first day of ICU admission was 3 litres.

Investigations

Initial workup, prior to referral to our centre, revealed subarachnoid haemorrhage with no subdural or extradural bleed detectable on brain CT and her serum sodium concentration to be 139 mEq/L. On ICU admission (6 days after the RTA), a follow-up brain CT revealed no change in comparison to the initial scan, and serum sodium was 108 mEq/L. At this time, serum and urine osmolalities were 223 mOsm/kg and 438 mOsm/kg, respectively, and urinary sodium concentration was 142 mEq/L. Serial serum and urine osmolality were recorded thereafter (figure 1). Additionally, serial blood urea nitrogen (BUN) to creatinine ratios (BCR) demonstrated BCR >20 (figure 2). Her thyroid and adrenal biochemical profiles were normal. On the third day of her ICU admission, brain natriuretic peptide (BNP) was abnormally increased (43 pg/mL).

Figure 1.

Serum and urine osmolalities during intensive care unit stay.

Figure 2.

Serial BUN, creatinine and BCR during intensive care stay. BUN, blood urea nitrogen; BCR, BUN to creatinine ratio.

Differential diagnosis

No further seizures were detected and a normal follow-up brain CT excluded further bleeding or mass effects as causes of her deterioration of conscious level. An electroencephalogram was not performed because the patient’s conscious level improved as serum sodium concentration corrected. Her normal thyroid and adrenal biochemical profiles rendered hypothyroidism and adrenal insufficiency unlikely. Moreover, iatrogenic hyponatraemia was excluded based on the following: (1) absence of clinical signs of hypervolaemia (such as congested neck veins, or crackles on auscultation of the basal lung fields), (2) the presence of tachycardia, diminished skin turgor and BCR >20 all, of which are consistent with hypovolaemia and (3) normoglycaemia, which effectively excludes the inadvertent administration of dextrose 5%. She did not receive any diuretics or mannitol during her previous hospital admission which rendered these causes unlikely for her hypovolaemic hyponatraemia. SIADH was ruled out because of her hypovolaemic status. Low serum sodium (108 mEq/L), low plasma osmolality (223 mOsm/kg), high urinary sodium (142 mEq/L) in addition to low volume status (tachycardia, labile blood pressure, diminished skin turgor, BCR >20) and elevated BNP concentrations confirmed the suspicion of CSW syndrome.

Treatment

Hypertonic saline and volume replacement were commenced. The relationship between sodium intake and serum sodium concentration is detailed in figure 3. After 4 days of intravenous sodium replacement, her serum sodium had normalised, and her conscious level improved markedly.

Figure 3.

Relation between serum sodium and sodium intake during ICU stay. ICU, intensive care unit.

Outcome and follow-up

The patient was discharged back to the ward 5 days after ICU admission as her serum sodium concentration remained normal and stable. She remained in the ward for a further 7 days to monitor her continued recovery at which point she was discharged home.

Discussion

CSWS is a disorder of salt and water excretion which occurs secondary to cerebral pathology and in the absence of renal dysfunction.³ Although CSWS was first described by Peters and colleagues,⁴ its pathogenesis has not been well understood until recently. One theory postulates that it results from increased production of BNP due to direct cerebral damage or stress-induced dysregulated sympathetic activity.¹ Increased BNP levels could impair proximal tubular salt transport resulting in natriuresis.³ Previous case reports of CSWS have demonstrated elevated serum BNP concentrations in patients with traumatic brain injury.^{5 6} The BNP range deemed normal for our patient’s age range (40–50 years) is <10 pg/ mL.⁷ In the case, we describe, BNP was measured on the third day of ICU admission due to raised suspicion of CSWS given the fact of persistent natriuresis despite hypovolaemia and hypertonic saline administration. In an animal model of subarachnoid haemorrhage, BNP levels were not associated with CSWS in an experimental study.⁸ Hence, increased BNP concentration alone cannot be considered as confirmation of a diagnosis of CSWS.

Discrimination between CSWS and SIADH is difficult because both conditions may share similar laboratory findings.¹ Despite the greater incidence of CSWS after brain injury, there is no consensus regarding criteria for its diagnosis.⁹ Clinical presentation, which can range from mild confusion to coma and seizures (as in the case we present), depends on the degree of hyponatraemia. Hyponatraemia is a hallmark of both conditions. In the case we describe, laboratory findings were: severe hyponatraemia (108 mEq/L), low plasma osmolality (223 mOsm/kg) despite hypertonic saline treatment, and elevated urinary osmolality, sodium and chloride (438 mOsm/kg, 142 mmol/L, 166 mmol/L, respectively). Fluid volume status is the key to differentiate between the two condition: CSWS is associated with hypovolaemia, and SIADH is accompanied by a normal or slight increased extracellular fluid status.¹⁰ Our patient was suffering from orthostatic hypotension and her physical examination revealed tachycardia, diminished skin turgor.

BCR is a useful investigation to differentiate between prerenal failure (severe dehydration and hypovolaemia are the principal causes) and intrinsic renal failure with a threshold of 20 indicative of prerenal cause.¹¹ In the presented case, BCR was more than 20 (figure 2). Excluding other metabolic causes of hyponatraemia, such as hypothyroidism and adrenal insufficiency is mandatory.¹² In our case, biochemical markers of thyroid and adrenal function were normal.

As the management of CSWS and SIADH is different, distinguishing between both conditions early in the clinical course is paramount. Misdiagnosis could be associated with harmful management. Fluid restriction and diuretics is the mainstay of management of SIADH, and aggressive fluid volume and sodium replacement is central to the treatment of CSWS.¹⁰

Fludrocortisone, a potent mineralocorticoid, had been reported as effective in the management of CSWS. It is suggested that fludrocortisone can decrease the requirement for sodium replacement therapy through its direct effect on sodium reabsorption in the proximal renal tubules.3 5 13 14 However, the use of fludrocortisone is commonly associated with adverse effects such as hypokalaemia, hyperglycaemic and systemic hypertension. Therefore, it is not recommended to use it unless salt and fluid replacement have failed to control natriuresis.¹⁵

Learning points.

• Cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) are the most common causes of hyponatraemia in a patient who has suffered traumatic brain injury.

• Evaluation of the fluid volume status is the key to differentiate between CSWS and SIADH.

• Because of its adverse effects, fludrocortisone is reserved only for severe cases of CSWS which are resistant to salt and fluid replacement.