Slow Hyponatremia Case Study
Central Pontine Myelinolysis in the setting of Slow Hyponatremia Correction
Wu, Alex M.D.1, Chen, Hsiong M.D.2, Harvin, Lisa D.O., M.S.3
1. Resident – Department of Medicine, Franklin Square Medical Center, MD
2. Neurology Hospitalist – Department of Neurology, Franklin Square Medical Center, MD
3. Resident – Department of Medicine, Franklin Square Medical Center, MD
Introduction
Central Pontine Myelinolysis is often a feared complication of overly aggressive correction of hyponatremia. As a result, close monitoring and slow correction are desired in order to prevent such neurological outcome. We describe a case in which an elderly gentleman, with a past medical history of CML and Polio, who was admitted to our hospital for generalized weakness, …show more content…
likely secondary to hyponatremia (120 mmol/L) caused by SIADH, was found to have Central Pontine Myelinolysis. Despite close monitoring by the Medicine as well as the Nephrology team, even with gentle correction of serum sodium, with daily sodium correction not exceeding 7 mmol/L, via free water restriction, normal saline drip, fludrocortisone and salt tablet, he inadvertently developed Central Pontine Myelinolysis as revealed by MRI and neurological exam.
Case Report
A 73 year old Caucasian American gentleman was brought to our hospital with an acute presentation of generalized weakness and altered mental status. Nine days prior to his admission to the hospital, he developed sudden onset of generalized weakness, hindering his ability to ambulate and perform ADLs. He reported quickly recovering and felt well 2 days later. However, at a follow-up outpatient appointment with his primary care physician, his laboratory blood work demonstrated a serum sodium of 122 mmol/L. He was advised to go to the emergency room at the time, however he declined. Therefore, he was given a liter of normal saline at the office and was asked to return to his primary care physician for blood work. The repeat blood work revealed a sodium of 120 mmol/L, and he was immediately sent to our emergency room for work-up of his hyponatremia. He was consequently admitted to the hospital and was found to have profound hyponatremia (120 mmol/L with a baseline of 130-135 mmol/L according to the medical records from his primary care physician office). His past medical history included Chronic Myeloid Leukemia (CML), Polio, Rheumatoid Arthritis, Diabetes Type II and Coronary Artery Disease. In regards to his CML, he was in remission and was no longer being treated with Gleevac.
On admission, neurological exam revealed right sided weakness of his body which was unchanged from his baseline. He had a residual weakness related to his past Polio. Although he had poor oral intake prior to this admission, he remained clinically euvolemic. In consideration of his euvolemic status, SIADH was determined to be the most likely cause for his hyponatremia. Serum osmolality and urine osmolality were 270 mOsm/kg (lower than the normal limit) and 455 mOsm/kg (within the normal limit) on admission, respectively. The fractional excretion of sodium was 0.7%. Hypothyroidism and adrenal insufficiency were less likely based on the lab values of his thyroid function test and cortisol values. The serum TSH and free T4 were 2.610 uIU/mL and 1.18 ng/dL, respectively. Serum cortisol was within the normal limit with a value of 10.5 mcg/dL. His serum prealbumin was lower than the normal limit at 16.4 mg/dL. Cerebral salt wasting syndrome was also less likely after the urine osmolality was found to be high. He was initially placed on free water restriction, gentle normal saline drip and a high protein diet while his BMP was monitored closely. The serum sodium improved from 120 mmol/L to 127 mmol/L after his first day of admission (see Table 1). Initially, his altered mental status and hyponatremia slowly improved. Our Nephrology team later started him on 0.1 mg fludrocortisone and salt tablet. His serum sodium was monitored every 6 hours during the first 48 hours of admission. On day 3, a CT of the head was ordered which showed no acute abnormality, but cerebral atrophy with periventricular white matter changes (Fig 1). However, an MRI of the brain performed on day 5 showed prominent T2 hyperintensity in the pons (Figs 2, 3 & 4). His neurological examination was significant for lethargy and disorientation. Careful examination of eye movements demonstrated a deficit in bilateral eye adduction. Given the clinical and radiologic features, central pontine myelinolysis was suspected.
During his stay in the hospital, he later developed respiratory failure that required intubation. He was transferred to the ICU with a diagnosis of pneumonia. His chest x-ray revealed the finding of bilateral lower lung infiltrates, while a computed tomography angiography (CTA) showed no evidence of pulmonary embolism. The etiology of his pneumonia was mostly likely due to mucous plug that could not be cleared by the patient on his own. During his stay in the ICU, the patient continued to be on mechanical ventilation as well as DuoNeb and antibiotics (including doxycycline, vancomycin and ceftriaxone). Under the guidance of our Nephrology team, his fludrocortisone and salt tablet were slowly tapered off when the serum sodium reached around 140 mmol/L. He was maintained on normal saline, and his mean-arterial-blood pressure (MAP) was kept above 75 mmHg on average. During his stay in ICU, the patient was found to develop right-sided heart failure and oliguric AKI likely secondary to pre-renal hypo-perfusion with episodes of hypotension at night. A transtracheal echocardiogram was done on day 7 and day 13, which showed a ventricular ejection fraction of 60% and severe ventricular pressure and volume overload. In addition, the Creatinine reached 1.77 mg/dL on day 10 with an admission baseline of 0.70 mg/dL. D5W was started on day 8 along with furosemide diuresis to manage his CHF. His hyponatremia was corrected to a normal value of 140 mmol/L on day 9 and his daily serum sodium continued to climb to a final value of 154 mmol/L (see Fig 5 for the trend of serum sodium, see Table 1 for fluid administered and respective daily maximum serum sodium). At this point, due to the poor prognosis of his health with the failure of multiple organs, the philosophy of care was discussed with his family. On the 13th day of his stay in the ICU, his family made the decision to manage the patient with comfort care only. He was subsequently extubated on the same day. On the 14th day of his stay in the ICU, the patient expired with a serum sodium of 154 mmol/L and a Creatinine of 1.98 mg/dL. No other MRI was obtained.
Discussion
Hyponatremia is one of the most common electrolyte abnormalities encountered in the hospital setting. Current guidelines dictate a slow correction of sodium, not exceeding 10 mmol/24 hrs to prevent central pontine myelinolysis (CPM) (Greenberg et al, 2015, Spasovski et al, 2014, Verbalis et al, 2013, Verbalis et al, 2007). CPM is a non-inflammatory demyelinating disease characterized by the loss of myelin in the base of the pons and carries a poor prognosis, often times resulting in death. It was first described by Adams et al in 1958, in patients with hyponatremia in the setting of alcoholism and malnutrition (Adams, et al, 1958, Martin, 2004, Staikov, et al, 2015). The exact mechanism of demyelination remains unknown, however one proposed theory is that when osmotically active substances such as sodium are very low in the serum, free water shifts into the brain and the brain adapts by allocating water into the cerebrospinal fluid and redirecting intracellular solutes out of the cells. If serum osmolarity rises back to normal too quickly, an osmotic gradient develops and causes destruction of myelin. The pons is vulnerable as it is less capable of transporting solutes across membranes than other areas of the brain leading to localized pontine demyelination. Catastrophic outcomes such as pseudobulbar palsy, spastic tetraparesis, locked-in syndrome and death can occur (Martin, 2004). In the patient described above, he developed central pontine myelinolysis although daily sodium correction never exceeded current guidelines. Our patient was admitted with profound hyponatremia at a serum sodium of 120mmol/L. His serum sodium was corrected and climbed by only 7 mmol/L over a 24-hour period. His highest correction rate reached around 7 mmol/L on days 1, 6 and 7 (Fig 5). An MRI done on day 5, showed prominent T2 hyperintensity in the pons suggestive of central pontine myelinolysis. Although microvascular disease may have a similar appearance on MRI, it would not produce bilateral eye adduction palsies, which were otherwise unexplained, so osmotic demyelination was favored (Graff-Radford, et al, 2011). An old MRI of the brain was not available for comparison, it was unknown whether the changes detected on the image were present before admission or solely a consequence of the serum sodium correction since admission. However, an examination of his eyes did not reveal any neurological deficit on admission. With a past medical history of CML and Polio, and his suboptimal health status that may contribute to malnutrition status, our patient may have a lower-than-normal threshold for the correction of serum hyponatremia. In that sense, correction of serum hyponatremia is governed by conditions that are multifactorial. Additional researches may be beneficial to investigate whether correction of serum hyponatremia should be accompanied by concurrent treatment of malnutrition and alcoholism. Fig 1. CT of the Head Fig 2. MRI of the Brain, T2-Weighted FLAIR Fig 3. MRI of the Brain, T2-Weighted FLAIR Fig 4. MRI of the Brain, T2-Weighted FLAIR Fig 5. Trend of Serum Sodium Fluids Given by Day Daily Max Serum Sodium (mmol/L)
Day 1 Started at 1428
Normal saline 2 L 75 mL/h Started at 2225
Normal saline 2 L 75 mL/h 120
Day 2 127
Day 3 Started at 1407
Normal saline 0.5 L bolus 123
Day 4 124
Day 5 124
Day 6 Started at 1119
Normal saline 1 L 100 mL/h 129
Day 7 Started at 0007
Normal saline 1 L 100 mL/h Started 1300
Normal saline 1 L 50 mL/h 136
Day 8 Started at 0621
D5W + NaHCO3 1 L 200 mL/h 138
Day 9 140
Day 10 Started at 1012
Normal saline 1 L 100 mL/h Started at 1907
Lactated ringers 1 L 100 mL/h 140
Day 11 Started at 0410
Lactated ringers 1 L 100 mL/h 143
Day 12 148
Day 13 152
Day 14 154
Table 1. IV Fluids Administered References
1.
Adams RA, Victor M, Mancall EL. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholics and malnourished patients. Arch Neurol Psychiatry. 1959; 81(1): 154-172.
2. Graff-Radford, J, Fugate, JE, Kaufmann, TJ, Mandrekar, JN, and Rabinstein, AA. Mayo Clin Proc. 2011; 86(11): 1063-1067.
3. Greenberg A, Verbalis JG, Amin AN, Burst VR, Chiodo JA 3rd, Chiong JR, Dasta JF, Friend KE, Hauptman PJ, Peri A and Sigal SH. Kidney Int. 2015 Jul; 88(1): 167-77.
4. Martin, RJ. J Neurol Neurosurg Psychiatry 2004; 75(Suppl III): iii22–iii28.
5. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn E, Ichai C et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology 2014; 170: G1–G47.
6. Staikov I, Simeonova A, Mihnev N, Simeonov G, Davidov K and Kirova G. Central Pontine Myelinolysis in Patient with Normal Serum Sodium Levels, System Alcohol Use and Malnutrition- A Case Report. Austin J Clin Neurol 2015; 2(9): 1074.
7. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW and Sterns RH. Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations. Am J Med. 2007; 120: S1–S21.
8. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH and Thompson CJ. Am J Med. 2013 Oct; 126(10 Suppl 1):
S1-42.
Wu, Alex M.D.1, Chen, Hsiong M.D.2, Harvin, Lisa D.O., M.S.3
1. Resident – Department of Medicine, Franklin Square Medical Center, MD
2. Neurology Hospitalist – Department of Neurology, Franklin Square Medical Center, MD
3. Resident – Department of Medicine, Franklin Square Medical Center, MD
Introduction
Central Pontine Myelinolysis is often a feared complication of overly aggressive correction of hyponatremia. As a result, close monitoring and slow correction are desired in order to prevent such neurological outcome. We describe a case in which an elderly gentleman, with a past medical history of CML and Polio, who was admitted to our hospital for generalized weakness, …show more content…
likely secondary to hyponatremia (120 mmol/L) caused by SIADH, was found to have Central Pontine Myelinolysis. Despite close monitoring by the Medicine as well as the Nephrology team, even with gentle correction of serum sodium, with daily sodium correction not exceeding 7 mmol/L, via free water restriction, normal saline drip, fludrocortisone and salt tablet, he inadvertently developed Central Pontine Myelinolysis as revealed by MRI and neurological exam.
Case Report
A 73 year old Caucasian American gentleman was brought to our hospital with an acute presentation of generalized weakness and altered mental status. Nine days prior to his admission to the hospital, he developed sudden onset of generalized weakness, hindering his ability to ambulate and perform ADLs. He reported quickly recovering and felt well 2 days later. However, at a follow-up outpatient appointment with his primary care physician, his laboratory blood work demonstrated a serum sodium of 122 mmol/L. He was advised to go to the emergency room at the time, however he declined. Therefore, he was given a liter of normal saline at the office and was asked to return to his primary care physician for blood work. The repeat blood work revealed a sodium of 120 mmol/L, and he was immediately sent to our emergency room for work-up of his hyponatremia. He was consequently admitted to the hospital and was found to have profound hyponatremia (120 mmol/L with a baseline of 130-135 mmol/L according to the medical records from his primary care physician office). His past medical history included Chronic Myeloid Leukemia (CML), Polio, Rheumatoid Arthritis, Diabetes Type II and Coronary Artery Disease. In regards to his CML, he was in remission and was no longer being treated with Gleevac.
On admission, neurological exam revealed right sided weakness of his body which was unchanged from his baseline. He had a residual weakness related to his past Polio. Although he had poor oral intake prior to this admission, he remained clinically euvolemic. In consideration of his euvolemic status, SIADH was determined to be the most likely cause for his hyponatremia. Serum osmolality and urine osmolality were 270 mOsm/kg (lower than the normal limit) and 455 mOsm/kg (within the normal limit) on admission, respectively. The fractional excretion of sodium was 0.7%. Hypothyroidism and adrenal insufficiency were less likely based on the lab values of his thyroid function test and cortisol values. The serum TSH and free T4 were 2.610 uIU/mL and 1.18 ng/dL, respectively. Serum cortisol was within the normal limit with a value of 10.5 mcg/dL. His serum prealbumin was lower than the normal limit at 16.4 mg/dL. Cerebral salt wasting syndrome was also less likely after the urine osmolality was found to be high. He was initially placed on free water restriction, gentle normal saline drip and a high protein diet while his BMP was monitored closely. The serum sodium improved from 120 mmol/L to 127 mmol/L after his first day of admission (see Table 1). Initially, his altered mental status and hyponatremia slowly improved. Our Nephrology team later started him on 0.1 mg fludrocortisone and salt tablet. His serum sodium was monitored every 6 hours during the first 48 hours of admission. On day 3, a CT of the head was ordered which showed no acute abnormality, but cerebral atrophy with periventricular white matter changes (Fig 1). However, an MRI of the brain performed on day 5 showed prominent T2 hyperintensity in the pons (Figs 2, 3 & 4). His neurological examination was significant for lethargy and disorientation. Careful examination of eye movements demonstrated a deficit in bilateral eye adduction. Given the clinical and radiologic features, central pontine myelinolysis was suspected.
During his stay in the hospital, he later developed respiratory failure that required intubation. He was transferred to the ICU with a diagnosis of pneumonia. His chest x-ray revealed the finding of bilateral lower lung infiltrates, while a computed tomography angiography (CTA) showed no evidence of pulmonary embolism. The etiology of his pneumonia was mostly likely due to mucous plug that could not be cleared by the patient on his own. During his stay in the ICU, the patient continued to be on mechanical ventilation as well as DuoNeb and antibiotics (including doxycycline, vancomycin and ceftriaxone). Under the guidance of our Nephrology team, his fludrocortisone and salt tablet were slowly tapered off when the serum sodium reached around 140 mmol/L. He was maintained on normal saline, and his mean-arterial-blood pressure (MAP) was kept above 75 mmHg on average. During his stay in ICU, the patient was found to develop right-sided heart failure and oliguric AKI likely secondary to pre-renal hypo-perfusion with episodes of hypotension at night. A transtracheal echocardiogram was done on day 7 and day 13, which showed a ventricular ejection fraction of 60% and severe ventricular pressure and volume overload. In addition, the Creatinine reached 1.77 mg/dL on day 10 with an admission baseline of 0.70 mg/dL. D5W was started on day 8 along with furosemide diuresis to manage his CHF. His hyponatremia was corrected to a normal value of 140 mmol/L on day 9 and his daily serum sodium continued to climb to a final value of 154 mmol/L (see Fig 5 for the trend of serum sodium, see Table 1 for fluid administered and respective daily maximum serum sodium). At this point, due to the poor prognosis of his health with the failure of multiple organs, the philosophy of care was discussed with his family. On the 13th day of his stay in the ICU, his family made the decision to manage the patient with comfort care only. He was subsequently extubated on the same day. On the 14th day of his stay in the ICU, the patient expired with a serum sodium of 154 mmol/L and a Creatinine of 1.98 mg/dL. No other MRI was obtained.
Discussion
Hyponatremia is one of the most common electrolyte abnormalities encountered in the hospital setting. Current guidelines dictate a slow correction of sodium, not exceeding 10 mmol/24 hrs to prevent central pontine myelinolysis (CPM) (Greenberg et al, 2015, Spasovski et al, 2014, Verbalis et al, 2013, Verbalis et al, 2007). CPM is a non-inflammatory demyelinating disease characterized by the loss of myelin in the base of the pons and carries a poor prognosis, often times resulting in death. It was first described by Adams et al in 1958, in patients with hyponatremia in the setting of alcoholism and malnutrition (Adams, et al, 1958, Martin, 2004, Staikov, et al, 2015). The exact mechanism of demyelination remains unknown, however one proposed theory is that when osmotically active substances such as sodium are very low in the serum, free water shifts into the brain and the brain adapts by allocating water into the cerebrospinal fluid and redirecting intracellular solutes out of the cells. If serum osmolarity rises back to normal too quickly, an osmotic gradient develops and causes destruction of myelin. The pons is vulnerable as it is less capable of transporting solutes across membranes than other areas of the brain leading to localized pontine demyelination. Catastrophic outcomes such as pseudobulbar palsy, spastic tetraparesis, locked-in syndrome and death can occur (Martin, 2004). In the patient described above, he developed central pontine myelinolysis although daily sodium correction never exceeded current guidelines. Our patient was admitted with profound hyponatremia at a serum sodium of 120mmol/L. His serum sodium was corrected and climbed by only 7 mmol/L over a 24-hour period. His highest correction rate reached around 7 mmol/L on days 1, 6 and 7 (Fig 5). An MRI done on day 5, showed prominent T2 hyperintensity in the pons suggestive of central pontine myelinolysis. Although microvascular disease may have a similar appearance on MRI, it would not produce bilateral eye adduction palsies, which were otherwise unexplained, so osmotic demyelination was favored (Graff-Radford, et al, 2011). An old MRI of the brain was not available for comparison, it was unknown whether the changes detected on the image were present before admission or solely a consequence of the serum sodium correction since admission. However, an examination of his eyes did not reveal any neurological deficit on admission. With a past medical history of CML and Polio, and his suboptimal health status that may contribute to malnutrition status, our patient may have a lower-than-normal threshold for the correction of serum hyponatremia. In that sense, correction of serum hyponatremia is governed by conditions that are multifactorial. Additional researches may be beneficial to investigate whether correction of serum hyponatremia should be accompanied by concurrent treatment of malnutrition and alcoholism. Fig 1. CT of the Head Fig 2. MRI of the Brain, T2-Weighted FLAIR Fig 3. MRI of the Brain, T2-Weighted FLAIR Fig 4. MRI of the Brain, T2-Weighted FLAIR Fig 5. Trend of Serum Sodium Fluids Given by Day Daily Max Serum Sodium (mmol/L)
Day 1 Started at 1428
Normal saline 2 L 75 mL/h Started at 2225
Normal saline 2 L 75 mL/h 120
Day 2 127
Day 3 Started at 1407
Normal saline 0.5 L bolus 123
Day 4 124
Day 5 124
Day 6 Started at 1119
Normal saline 1 L 100 mL/h 129
Day 7 Started at 0007
Normal saline 1 L 100 mL/h Started 1300
Normal saline 1 L 50 mL/h 136
Day 8 Started at 0621
D5W + NaHCO3 1 L 200 mL/h 138
Day 9 140
Day 10 Started at 1012
Normal saline 1 L 100 mL/h Started at 1907
Lactated ringers 1 L 100 mL/h 140
Day 11 Started at 0410
Lactated ringers 1 L 100 mL/h 143
Day 12 148
Day 13 152
Day 14 154
Table 1. IV Fluids Administered References
1.
Adams RA, Victor M, Mancall EL. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholics and malnourished patients. Arch Neurol Psychiatry. 1959; 81(1): 154-172.
2. Graff-Radford, J, Fugate, JE, Kaufmann, TJ, Mandrekar, JN, and Rabinstein, AA. Mayo Clin Proc. 2011; 86(11): 1063-1067.
3. Greenberg A, Verbalis JG, Amin AN, Burst VR, Chiodo JA 3rd, Chiong JR, Dasta JF, Friend KE, Hauptman PJ, Peri A and Sigal SH. Kidney Int. 2015 Jul; 88(1): 167-77.
4. Martin, RJ. J Neurol Neurosurg Psychiatry 2004; 75(Suppl III): iii22–iii28.
5. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn E, Ichai C et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology 2014; 170: G1–G47.
6. Staikov I, Simeonova A, Mihnev N, Simeonov G, Davidov K and Kirova G. Central Pontine Myelinolysis in Patient with Normal Serum Sodium Levels, System Alcohol Use and Malnutrition- A Case Report. Austin J Clin Neurol 2015; 2(9): 1074.
7. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW and Sterns RH. Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations. Am J Med. 2007; 120: S1–S21.
8. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH and Thompson CJ. Am J Med. 2013 Oct; 126(10 Suppl 1):
S1-42.