American Journal of Therapeutics 23, e579–e582 (2016)
Diagnosis and Treatment of Cerebral Salt Wasting Syndrome With Cryptococcal Meningitis in HIV Patient Sunggeun Lee, MD,* Anitsira Collado, MD, Montish Singla, MD, Roger Carbajal, MD, Ashok Chaudhari, MD, and Donald Baumstein, MD
Hyponatremia is one of the most common electrolyte imbalances in HIV patients. The differential diagnosis may include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency. Here, we describe a case of hyponatremia secondary to cerebral salt wasting syndrome (CSWS) in an HIV patient with cryptococcal meningitis. A 52-yearold man with a history of diabetes and HIV was admitted for headache and found to have cryptococcal meningitis. He was also found to have asymptomatic hyponatremia. He had signs of hypovolemia, such as orthostatic hypotension, dry mucosa, decreased skin turgor, hemoconcentration, contraction alkalosis, and high BUN/Cr ratio. The laboratory findings revealed sodium of 125 mmol/L, potassium of 5.5 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and urine chloride of 162 mmol/L. We started normal saline for hypovolemia, each 1 L prior and after amphotericin therapy. However, hypovolemia did not improve significantly despite IV fluid. Cosyntropin stimulation test was negative, and renin level was 0.25 ng$mL21$h, with the aldosterone level of ,1 ng/dL, the serum brain natriuretic peptide of 15 pg/mL, and serum uric acid of 2.8 mg/dL. The diagnosis of CSWS was suspected, fludrocortisone was tried, and hypovolemia and hyponatremia improved. Cryptococcal meningitis in HIV patients can present with CSWS, and the distinction between CSWS and SIADH is important because the treatment for CSWS is different than that of SIADH. Both share a similar clinical picture except that CSWS presents with constant hypovolemia despite volume replacement. Salt tablets, normal saline, or fludrocortisone can be used for treatment. Keywords: hyponatremia, HIV, syndrome of inappropriate antidiuretic hormone secretion, cerebral salt wasting syndrome, ADH, BNP, ANP, cryptococcal meningitis, amphotericin
BACKGROUND Hyponatremia is one of the most common electrolyte imbalances in HIV patients. The differential diagnosis may include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency. The diagnosis can often be challenging because some aspects of the clinical
Division of Nephrology, Department of Medicine, Metropolitan Hospital Center, New York Medical College, New York, NY. *Address for correspondence: Division of Nephrology, Department of Medicine, 1901 1st, Avenue, New York, NY. E-mail: maximum2013@ gmail.com
presentations overlap. Here, we describe a case of hyponatremia secondary to cerebral salt wasting syndrome (CSWS) in an HIV patient with cryptococcal meningitis (CM). We will discuss the challenges of diagnosis, the potential pathogenic mechanism, and treatment options.
CASE PRESENTATION A 52-year-old man with a medical history of diabetes and HIV was admitted for headache and found to have CM. He was also found to have asymptomatic hyponatremia with sodium of 125 mmol/L. He denied feeling any symptoms of thirst, dizziness, diarrhea, vomiting, shortness of breath, or leg swelling. He did not take any medications such as diuretics or antidepressants before
1075–2765 Copyright Ó 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e580
hospitalization. On physical examination, blood pressure was 110/70 and heart rate was 90 per minutes. He showed signs of hypovolemia, such as orthostatic hypotension, dry mucosa, and decreased skin turgor. The laboratory findings revealed sodium of 125 mmol/L, potassium of 5.5 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and urine chloride of 162 mmol/L. Hypovolemia was also supported by laboratory values: hematocrit of 43%, serum bicarbonate of 28 mmol/L, and high BUN/Cr ratio of 16/0.6 mg/dL. The initial impression was hypovolemic hypotonic hyponatremia. Although the patient was hypovolemic clinically, the high sodium and chloride levels in his urine did not correlate with the diagnosis of hypovolemia, which made this case challenging to diagnose. Unlike the usual scenario of hypovolemic hyponatremia improving relatively fast after the volume repletion, his hyponatremia did not improve after the 2 days of the normal saline treatment. Amphotericin, which is the preferred treatment of CM, is nephrotoxic and should be given with a normal saline to prevent acute kidney injury. The normal saline had to be continued for that reason, administrating 1 L prior and after the amphotericin therapy. Salt tablets were also started for hyponatremia, increased up to 9 g daily. The patient still remained hypovolemic and hyponatremic despite fluid therapy and 9 g of salt tablets daily for 3 days. Further workup revealed that the serum renin level was 0.25 ng$mL21$h21, with the aldosterone level of ,1 ng/dL, the serum brain natriuretic peptide (BNP) of 15 pg/mL, serum uric acid of 2.8 mg/dL. The cosyntropin stimulation test was negative, ruling out adrenal insufficiency. All the clinical evidence fit toward to diagnosis of CSWS. Therefore, fludrocortisone 0.2 mg was tried and hypovolemia and hyponatremia improved. Urine sodium decreased to 83 mmol/L and serum sodium improved to 137 mmol/L the next day. However, this improvement could be attributed to his CM being clinically improved as well.
DISCUSSION CSWS is one of the rare causes of hyponatremia. It is characterized with an inappropriate sodium wasting in urine in the setting of any cerebral pathology. CSWS is most commonly associated with subarachnoid hemorrhage (SAH) and also has been reported associated with other variety of diseases, such as head trauma, brain tumors, neuroleptic malignant syndrome, or bacterial meningitis.1–4 The prevalence of CSWS associated with SAH ranges from 6.5% to 75% depending on previous studies.5–7 This is because that diagnosing American Journal of Therapeutics (2016) 23(2)
Lee et al
CSWS requires adequate clinical skills to assess the patient’s volume status, which is sometimes difficult to do, and there is no standard measure to quantify the effective arterial volume. The pathogenesis of CSWS is not completely understood; there are several hypotheses so far. The first hypothesis is that an impaired sympathetic neural input caused by the cerebral pathology may induce CSWS.8 The sympathetic nervous system plays an important role in sodium reabsorption in response to decreased circulatory volume. In normal physiology, the carotid bodies sense decreased circulatory volume and directly increase sodium reabsorption in proximal tubule. Indirectly, sympathetic b-adrenergic stimulation results in the activation of the renin–angiotensin system, which increases reabsorption of sodium in response to hypovolemia. When a patient’s sympathetic neural input is impaired, the patient will not be able to reabsorb the sodium from tubules, and natriuresis will occur even in hypovolemic status. Evidence conflicting with this theory is that most patients who had a cerebrovascular event have sympathetic overactivity, which is one of the reasons why cerebrovascular events often precede pulmonary or cardiovascular complications.9 The second hypothesis is that an increased level of natriuretic factors may play a role in pathogenesis of CSWS, such as atrial natriuretic peptide (ANP), BNP, C-type natriuretic peptide, and dendroaspis natriuretic peptide. In multiple studies, it was shown that an increased level of BNP and ANP after the SAH was associated with hypovolemia and hyponatremia.10–12 ANP is an amino acid peptide, which is mainly released by atrial myocytes in response to atrial distension and sympathetic stimulation. The main function of ANP is direct vasodilation, and diuresis and natriuresis by diminishing sodium reabsorption in the proximal tubule and the medullary collecting tubule. Therefore, the ANP level is mainly increased in patients with hypervolemia, heart failure, or hypertension.13 BNP is synthesized mainly by the ventricles, and it has similar physiological actions with ANP. BNP is now well known as one of the diagnostic markers for heart failure. In normal physiology, ANP/BNP is released in response to increased plasma volume and inhibits renin release, thereby increasing natriuresis. In CSWS, ANP/BNP is released in response to increased intracranial pressure associated with the attributing cerebral pathology. This is supported by a study that showed direct correlation with ANP/BNP level and intracranial pressure.14 Some speculated that this may be one of the protective mechanisms of the brain to protect itself from the pressure injury by increasing natriuresis. www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e581
Cerebral Salt Wasting Syndrome With Cryptococcal Meningitis
The diagnosis of CSWS can be challenging. It is often misdiagnosed with SIADH initially. This is because both diseases share very similar clinical presentations such as high urine osmolality (.100 mOsm/kg), high urine sodium concentration (.40 mmol/L), decreased serum uric acid, and decreased serum osmolality. Distinguishing between CSWS and SIADH is important because the treatment for CSWS is different than that of SIADH, and an inappropriate treatment can lead to critical consequences. The main pathogenesis of SIADH is impaired water excretion caused by excessive antidiuretic hormone (ADH). In other words, SIADH is a disorder of water regulation and should not affect patient’s volume status, which is why SIADH patients are usually euvolemic. However, the main pathogenesis of CSWS is salt wasting through the kidney, which makes a patient hypovolemic. Persistent hypovolemia, despite volume resuscitation, is the key feature of CSWS. Therefore, assessment of volume status is the key for differentiating between these 2 diseases. The signs and symptoms of hypovolemia include postural dizziness or postural hypotension, decreased skin turgor, low arterial blood pressure, tachycardia, reduced jugular venous pressure, or elevated serum creatinine– blood urea nitrogen ratio. Following daily fluid balance also can give you a good sense of the volume status of the patient. The measurement of CVP can guide the diagnosis and treatment of CSWS by estimating more accurate intravascular volume status. One study suggested a successful treatment model of CSWS with monitoring fluid status guided by central venous pressure measuring.15 This patient has met the criteria of CSWS: hypovolemia, hyponatremia with low plasma osmolality, an inappropriately elevated urine osmolality, a urine sodium level above 40 mEq/L, and a low serum uric acid concentration. The laboratory findings only can suggest SIADH: sodium of 125 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and serum uric acid 2.8 mg/dL. However, the patient also showed clinical evidence of hypovolemia: episodes of hypotension, dry mucosa and decreased skin turgor, hemoconcentration, contraction alkalosis, and high BUN/Cr ratio. The patient was also making approximately 3 L of urine everyday despite normal saline fluid therapy. This comprehensive analysis of the data and thorough physical examination helped us to reach the diagnosis of CSWS. Other features of CSWS can include low renin and aldosterone levels, a normal or high ADH level, and high natriuretic peptide levels (ANP, BNP, C-type natriuretic peptide, dendroaspis natriuretic peptide). This patient had low renin and aldosterone level. However, the BNP and ADH value was normal. www.americantherapeutics.com
Normal saline is the first-line therapy for the treatment of CSWS. It is different from that of SIADH, which is fluid restriction. If the patient does not respond to normal saline, salt tablets can be administered or the mineralocorticoid, such as fludrocortisone, can also be used. In this case, the patient had an excellent response to fludrocortisone 2 mg but not to normal saline therapy or sodium tablets. Considering the main pathology of CSWS is salt wasting through proximal renal tubules, increasing reabsorption of sodium in distal collecting tubules by fludrocortisone seems to be working adequately for CSWS. One should be cautious about overcorrection leading to osmotic myelinolysis when using fludrocortisone or hypertonic saline. The serum sodium should not be increased more than 6–8 mmol/L in the first 24 hours, no more than 9 mEq/L over any given 24-hour period.16 Serum sodium concentration should be frequently monitored throughout the treatment.
CONCLUSIONS CSWS is one of the causes of hyponatremia characterized with inappropriate sodium wasting in urine in the setting of any cerebral pathology. It is crucial to distinguish between CSWS and SIADH because the treatments are different and an inappropriate treatment can lead to critical consequences. Hypovolemia is a key finding of CSWS, which differentiates it with SIADH. Treatment of CSWS includes normal saline, salt tablets, or fludrocortisone.
REFERENCES 1. Oster JR, Perez GO, Larios O, et al. Cerebral salt wasting in a man with carcinomatous meningitis. Arch Intern Med. 1983;143:2187. 2. Erduran E, Mocan H, Aslan Y. Another cause of hyponatraemia in patients with bacterial meningitis: cerebral salt wasting. Acta Paediatr. 1997;86:1150. 3. Filippella M, Cappabianca P, Cavallo LM, et al. Very delayed hyponatremia after surgery and radiotherapy for a pituitary macroadenoma. J Endocrinol Invest. 2002; 25:163. 4. Lenhard T. Cerebral salt-wasting syndrome in a patient with neuroleptic malignant syndrome. Arch Neurol. 2007; 64:122–125. 5. Sherlock M, O’Sullivan E, Agha A, et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2006;64:250–254. 6. Nelson PB, Seif SM, Maroon JC, et al. Hyponatremia in intracranial disease: perhaps not the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Neurosurg. 1981;55:938–941. American Journal of Therapeutics (2016) 23(2)
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e582 7. Wijdicks EF, Vermeulen M, ten Haaf JA, et al. Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm. Ann Neuro. 1985;18:211–216. 8. Palmer BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab. 2003;14:182. 9. Samuels MA. The brain-heart connection. Circulation. 2007; 116:77–84. 10. Dorhout Mees SM. Brain natriuretic peptide concentrations after aneurysmal subarachnoid hemorrhage: relationship with hypovolemia and hyponatremia. Neurocrit Care. 2011; 14:176–181. 11. Nakagawa I. Hyponatremia is predictable in patients with aneurysmal subarachnoid hemorrhage–clinical significance of serum atrial natriuretic peptide. Acta Neurochir (Wien). 2010;152:2147–2152.
American Journal of Therapeutics (2016) 23(2)
Lee et al 12. Singh S, Bohn D, Carlotti AP, et al. Cerebral salt wasting: truths, fallacies, theories, and challenges. Critcare Med. 2002;30:2575–2579. 13. Wilkins MR, Redondo J, Brown LA. The natriureticpeptide family. Lancet. 1997;349:1307. 14. Berendes E, Walter M, Cullen P, et al. Secretion of brain natriuretic peptide in patients with aneurismal subarachnoid haemorrhage. Lancet. 1997;349: 245–249. 15. Damaraju SC, Rajshekhar V, Chandy MJ. Validation study of a central venous pressure-based protocol for the management of neurosurgical patients with hyponatremia and natriuresis. Neurosurgery. 1997;40: 312–316. 16. Sterns RH. The treatment of hyponatremia. Semin Nephrol. 2009;29:282.
www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Diagnosis and Treatment of Cerebral Salt Wasting Syndrome With Cryptococcal Meningitis in HIV Patient Sunggeun Lee, MD,* Anitsira Collado, MD, Montish Singla, MD, Roger Carbajal, MD, Ashok Chaudhari, MD, and Donald Baumstein, MD
Hyponatremia is one of the most common electrolyte imbalances in HIV patients. The differential diagnosis may include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency. Here, we describe a case of hyponatremia secondary to cerebral salt wasting syndrome (CSWS) in an HIV patient with cryptococcal meningitis. A 52-yearold man with a history of diabetes and HIV was admitted for headache and found to have cryptococcal meningitis. He was also found to have asymptomatic hyponatremia. He had signs of hypovolemia, such as orthostatic hypotension, dry mucosa, decreased skin turgor, hemoconcentration, contraction alkalosis, and high BUN/Cr ratio. The laboratory findings revealed sodium of 125 mmol/L, potassium of 5.5 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and urine chloride of 162 mmol/L. We started normal saline for hypovolemia, each 1 L prior and after amphotericin therapy. However, hypovolemia did not improve significantly despite IV fluid. Cosyntropin stimulation test was negative, and renin level was 0.25 ng$mL21$h, with the aldosterone level of ,1 ng/dL, the serum brain natriuretic peptide of 15 pg/mL, and serum uric acid of 2.8 mg/dL. The diagnosis of CSWS was suspected, fludrocortisone was tried, and hypovolemia and hyponatremia improved. Cryptococcal meningitis in HIV patients can present with CSWS, and the distinction between CSWS and SIADH is important because the treatment for CSWS is different than that of SIADH. Both share a similar clinical picture except that CSWS presents with constant hypovolemia despite volume replacement. Salt tablets, normal saline, or fludrocortisone can be used for treatment. Keywords: hyponatremia, HIV, syndrome of inappropriate antidiuretic hormone secretion, cerebral salt wasting syndrome, ADH, BNP, ANP, cryptococcal meningitis, amphotericin
BACKGROUND Hyponatremia is one of the most common electrolyte imbalances in HIV patients. The differential diagnosis may include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency. The diagnosis can often be challenging because some aspects of the clinical
Division of Nephrology, Department of Medicine, Metropolitan Hospital Center, New York Medical College, New York, NY. *Address for correspondence: Division of Nephrology, Department of Medicine, 1901 1st, Avenue, New York, NY. E-mail: maximum2013@ gmail.com
presentations overlap. Here, we describe a case of hyponatremia secondary to cerebral salt wasting syndrome (CSWS) in an HIV patient with cryptococcal meningitis (CM). We will discuss the challenges of diagnosis, the potential pathogenic mechanism, and treatment options.
CASE PRESENTATION A 52-year-old man with a medical history of diabetes and HIV was admitted for headache and found to have CM. He was also found to have asymptomatic hyponatremia with sodium of 125 mmol/L. He denied feeling any symptoms of thirst, dizziness, diarrhea, vomiting, shortness of breath, or leg swelling. He did not take any medications such as diuretics or antidepressants before
1075–2765 Copyright Ó 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e580
hospitalization. On physical examination, blood pressure was 110/70 and heart rate was 90 per minutes. He showed signs of hypovolemia, such as orthostatic hypotension, dry mucosa, and decreased skin turgor. The laboratory findings revealed sodium of 125 mmol/L, potassium of 5.5 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and urine chloride of 162 mmol/L. Hypovolemia was also supported by laboratory values: hematocrit of 43%, serum bicarbonate of 28 mmol/L, and high BUN/Cr ratio of 16/0.6 mg/dL. The initial impression was hypovolemic hypotonic hyponatremia. Although the patient was hypovolemic clinically, the high sodium and chloride levels in his urine did not correlate with the diagnosis of hypovolemia, which made this case challenging to diagnose. Unlike the usual scenario of hypovolemic hyponatremia improving relatively fast after the volume repletion, his hyponatremia did not improve after the 2 days of the normal saline treatment. Amphotericin, which is the preferred treatment of CM, is nephrotoxic and should be given with a normal saline to prevent acute kidney injury. The normal saline had to be continued for that reason, administrating 1 L prior and after the amphotericin therapy. Salt tablets were also started for hyponatremia, increased up to 9 g daily. The patient still remained hypovolemic and hyponatremic despite fluid therapy and 9 g of salt tablets daily for 3 days. Further workup revealed that the serum renin level was 0.25 ng$mL21$h21, with the aldosterone level of ,1 ng/dL, the serum brain natriuretic peptide (BNP) of 15 pg/mL, serum uric acid of 2.8 mg/dL. The cosyntropin stimulation test was negative, ruling out adrenal insufficiency. All the clinical evidence fit toward to diagnosis of CSWS. Therefore, fludrocortisone 0.2 mg was tried and hypovolemia and hyponatremia improved. Urine sodium decreased to 83 mmol/L and serum sodium improved to 137 mmol/L the next day. However, this improvement could be attributed to his CM being clinically improved as well.
DISCUSSION CSWS is one of the rare causes of hyponatremia. It is characterized with an inappropriate sodium wasting in urine in the setting of any cerebral pathology. CSWS is most commonly associated with subarachnoid hemorrhage (SAH) and also has been reported associated with other variety of diseases, such as head trauma, brain tumors, neuroleptic malignant syndrome, or bacterial meningitis.1–4 The prevalence of CSWS associated with SAH ranges from 6.5% to 75% depending on previous studies.5–7 This is because that diagnosing American Journal of Therapeutics (2016) 23(2)
Lee et al
CSWS requires adequate clinical skills to assess the patient’s volume status, which is sometimes difficult to do, and there is no standard measure to quantify the effective arterial volume. The pathogenesis of CSWS is not completely understood; there are several hypotheses so far. The first hypothesis is that an impaired sympathetic neural input caused by the cerebral pathology may induce CSWS.8 The sympathetic nervous system plays an important role in sodium reabsorption in response to decreased circulatory volume. In normal physiology, the carotid bodies sense decreased circulatory volume and directly increase sodium reabsorption in proximal tubule. Indirectly, sympathetic b-adrenergic stimulation results in the activation of the renin–angiotensin system, which increases reabsorption of sodium in response to hypovolemia. When a patient’s sympathetic neural input is impaired, the patient will not be able to reabsorb the sodium from tubules, and natriuresis will occur even in hypovolemic status. Evidence conflicting with this theory is that most patients who had a cerebrovascular event have sympathetic overactivity, which is one of the reasons why cerebrovascular events often precede pulmonary or cardiovascular complications.9 The second hypothesis is that an increased level of natriuretic factors may play a role in pathogenesis of CSWS, such as atrial natriuretic peptide (ANP), BNP, C-type natriuretic peptide, and dendroaspis natriuretic peptide. In multiple studies, it was shown that an increased level of BNP and ANP after the SAH was associated with hypovolemia and hyponatremia.10–12 ANP is an amino acid peptide, which is mainly released by atrial myocytes in response to atrial distension and sympathetic stimulation. The main function of ANP is direct vasodilation, and diuresis and natriuresis by diminishing sodium reabsorption in the proximal tubule and the medullary collecting tubule. Therefore, the ANP level is mainly increased in patients with hypervolemia, heart failure, or hypertension.13 BNP is synthesized mainly by the ventricles, and it has similar physiological actions with ANP. BNP is now well known as one of the diagnostic markers for heart failure. In normal physiology, ANP/BNP is released in response to increased plasma volume and inhibits renin release, thereby increasing natriuresis. In CSWS, ANP/BNP is released in response to increased intracranial pressure associated with the attributing cerebral pathology. This is supported by a study that showed direct correlation with ANP/BNP level and intracranial pressure.14 Some speculated that this may be one of the protective mechanisms of the brain to protect itself from the pressure injury by increasing natriuresis. www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e581
Cerebral Salt Wasting Syndrome With Cryptococcal Meningitis
The diagnosis of CSWS can be challenging. It is often misdiagnosed with SIADH initially. This is because both diseases share very similar clinical presentations such as high urine osmolality (.100 mOsm/kg), high urine sodium concentration (.40 mmol/L), decreased serum uric acid, and decreased serum osmolality. Distinguishing between CSWS and SIADH is important because the treatment for CSWS is different than that of SIADH, and an inappropriate treatment can lead to critical consequences. The main pathogenesis of SIADH is impaired water excretion caused by excessive antidiuretic hormone (ADH). In other words, SIADH is a disorder of water regulation and should not affect patient’s volume status, which is why SIADH patients are usually euvolemic. However, the main pathogenesis of CSWS is salt wasting through the kidney, which makes a patient hypovolemic. Persistent hypovolemia, despite volume resuscitation, is the key feature of CSWS. Therefore, assessment of volume status is the key for differentiating between these 2 diseases. The signs and symptoms of hypovolemia include postural dizziness or postural hypotension, decreased skin turgor, low arterial blood pressure, tachycardia, reduced jugular venous pressure, or elevated serum creatinine– blood urea nitrogen ratio. Following daily fluid balance also can give you a good sense of the volume status of the patient. The measurement of CVP can guide the diagnosis and treatment of CSWS by estimating more accurate intravascular volume status. One study suggested a successful treatment model of CSWS with monitoring fluid status guided by central venous pressure measuring.15 This patient has met the criteria of CSWS: hypovolemia, hyponatremia with low plasma osmolality, an inappropriately elevated urine osmolality, a urine sodium level above 40 mEq/L, and a low serum uric acid concentration. The laboratory findings only can suggest SIADH: sodium of 125 mmol/L, urine osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and serum uric acid 2.8 mg/dL. However, the patient also showed clinical evidence of hypovolemia: episodes of hypotension, dry mucosa and decreased skin turgor, hemoconcentration, contraction alkalosis, and high BUN/Cr ratio. The patient was also making approximately 3 L of urine everyday despite normal saline fluid therapy. This comprehensive analysis of the data and thorough physical examination helped us to reach the diagnosis of CSWS. Other features of CSWS can include low renin and aldosterone levels, a normal or high ADH level, and high natriuretic peptide levels (ANP, BNP, C-type natriuretic peptide, dendroaspis natriuretic peptide). This patient had low renin and aldosterone level. However, the BNP and ADH value was normal. www.americantherapeutics.com
Normal saline is the first-line therapy for the treatment of CSWS. It is different from that of SIADH, which is fluid restriction. If the patient does not respond to normal saline, salt tablets can be administered or the mineralocorticoid, such as fludrocortisone, can also be used. In this case, the patient had an excellent response to fludrocortisone 2 mg but not to normal saline therapy or sodium tablets. Considering the main pathology of CSWS is salt wasting through proximal renal tubules, increasing reabsorption of sodium in distal collecting tubules by fludrocortisone seems to be working adequately for CSWS. One should be cautious about overcorrection leading to osmotic myelinolysis when using fludrocortisone or hypertonic saline. The serum sodium should not be increased more than 6–8 mmol/L in the first 24 hours, no more than 9 mEq/L over any given 24-hour period.16 Serum sodium concentration should be frequently monitored throughout the treatment.
CONCLUSIONS CSWS is one of the causes of hyponatremia characterized with inappropriate sodium wasting in urine in the setting of any cerebral pathology. It is crucial to distinguish between CSWS and SIADH because the treatments are different and an inappropriate treatment can lead to critical consequences. Hypovolemia is a key finding of CSWS, which differentiates it with SIADH. Treatment of CSWS includes normal saline, salt tablets, or fludrocortisone.
REFERENCES 1. Oster JR, Perez GO, Larios O, et al. Cerebral salt wasting in a man with carcinomatous meningitis. Arch Intern Med. 1983;143:2187. 2. Erduran E, Mocan H, Aslan Y. Another cause of hyponatraemia in patients with bacterial meningitis: cerebral salt wasting. Acta Paediatr. 1997;86:1150. 3. Filippella M, Cappabianca P, Cavallo LM, et al. Very delayed hyponatremia after surgery and radiotherapy for a pituitary macroadenoma. J Endocrinol Invest. 2002; 25:163. 4. Lenhard T. Cerebral salt-wasting syndrome in a patient with neuroleptic malignant syndrome. Arch Neurol. 2007; 64:122–125. 5. Sherlock M, O’Sullivan E, Agha A, et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2006;64:250–254. 6. Nelson PB, Seif SM, Maroon JC, et al. Hyponatremia in intracranial disease: perhaps not the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Neurosurg. 1981;55:938–941. American Journal of Therapeutics (2016) 23(2)
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e582 7. Wijdicks EF, Vermeulen M, ten Haaf JA, et al. Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm. Ann Neuro. 1985;18:211–216. 8. Palmer BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab. 2003;14:182. 9. Samuels MA. The brain-heart connection. Circulation. 2007; 116:77–84. 10. Dorhout Mees SM. Brain natriuretic peptide concentrations after aneurysmal subarachnoid hemorrhage: relationship with hypovolemia and hyponatremia. Neurocrit Care. 2011; 14:176–181. 11. Nakagawa I. Hyponatremia is predictable in patients with aneurysmal subarachnoid hemorrhage–clinical significance of serum atrial natriuretic peptide. Acta Neurochir (Wien). 2010;152:2147–2152.
American Journal of Therapeutics (2016) 23(2)
Lee et al 12. Singh S, Bohn D, Carlotti AP, et al. Cerebral salt wasting: truths, fallacies, theories, and challenges. Critcare Med. 2002;30:2575–2579. 13. Wilkins MR, Redondo J, Brown LA. The natriureticpeptide family. Lancet. 1997;349:1307. 14. Berendes E, Walter M, Cullen P, et al. Secretion of brain natriuretic peptide in patients with aneurismal subarachnoid haemorrhage. Lancet. 1997;349: 245–249. 15. Damaraju SC, Rajshekhar V, Chandy MJ. Validation study of a central venous pressure-based protocol for the management of neurosurgical patients with hyponatremia and natriuresis. Neurosurgery. 1997;40: 312–316. 16. Sterns RH. The treatment of hyponatremia. Semin Nephrol. 2009;29:282.
www.americantherapeutics.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
