- Email: [email protected]
Central Pontine Myelinolysis Following Rapid Correction of Hyponatremia in an Alcoholic
CASE REPORTS
Central Pontine Myelinolysis Following Rapid Correction of Hyponatremia in an Alcoholic James V. Walker, MO, and Raymond N. Englander, MO • An alcoholic patient presented with profound hyponatremia of uncertain etiology. Despite partial correction of hyponatremia within 24 hours, central pontine myelinolysis (CPM) ensued and the patient subsequently died. The optimal rate of correction of severe, symptomatic hyponatremia has not yet been elucidated. © 1988 by the National Kidney Foundation, Inc. INDEX WORDS: Hyponatremia; central pontine myelinolysis; alcoholism.
T
HERE IS STILL a great deal of controversy surrounding the optimal approach to treatment of severe, symptomatic hyponatremia. 1·6 We report a patient with alcoholism and profound hyponatremia whose serum sodium was brought to "acceptable" levels within 24 hours. This therapy resulted in initial neurological improvement but subsequent death secondary to central pontine myelinolysis (CPM). CASE REPORT A 41-year-old man was hospitalized in January 1984 after neighbors found him unresponsive. His history included chronic alcoholism and frostbite injury to several toes requiring amputation. He was not known to be taking medications and had no known history of other medical illness. On admission, the patient had a temperature of 36.6°C, BP of 1461100 mm Hg, pulse of 100 beats per minute, and respiratory rate of 16. His feet revealed prior toe amputations and some breakdown of the skin. Neurological examination revealed a semicomatose man with equal strength in all extremities. Stool guaiac was negative. Initial electrolytes and osmolality were noted (Table I). Calculated serum osmolality was 190 mosml kg H 20, serum chloride was 57 mEq/L (57 mmoIlL), and CO 2 was 27 mEq/L (27 mmolll). BUN was 9 mg/dL (3.2 mmollL) and creatinine was 0.8 mg/dL (70.72 I'moIlL). Arterial blood gas on room air revealed a P0 2 of 83 mm Hg. Thyroid function was normal. Initial bilirubin was 2.6 mg/dL (44.46 I'moIlL); SGPT, 368 lUlL; SGOT, 1,260 lUlL; LDH, 820 lUlL; creatinine phosphokinase (CPK), 28,000 lUlL; phosphorous, 1.9 mg/dL (0.61 mmoIlL); magnesium, 1.4 mg/dL (0.57 mmoIlL); and myoglobin, 2,178 ng/mL. Uric acid was 4.2 mgl dL (249.8 I'moI/L). Blood alcohol was < 0.02 g/dL and toxicology screen was negative. Subsequent phosphorous and magnesium levels were normal. A noncontrast computerized tomographic (CT) scan of the head was normal on admission. The patient was treated with furosemide, 40 mg, thiamine, cimetidine, and pyridoxine administered with 3 % saline solution with supplemental potassium, phosphorous, and magnesium. By nine hours after admission he was arousable and able to answer some questions appropriately. At 9.5 hours hypertonic saline was discontinued. By 24 hours after admission he was oriented to person, place, and time and had no focal neurological deficits. Total sodium chloride administered over the
first 24 hours was 920 mEq. At 48 hours he was feeding himself and smoking. However, by 60 hours he was more lethargic and developed dysarthria. At 72 hours he was stuporous and aphasic, and thereafter his neurological course deteriorated and was characterized by progressive development of flaccid quadriplegia, periods of Cheyne-Stokes respirations, unintelligible or no speech, and variable degrees of alertness. A repeat noncontrast CT scan of the head was normal. During this time no additional metabolic abnormalities were noted and hepatocellular dysfunction improved. He subsequently developed pneumonia and died 4 weeks after admission. Autopsy findings of the brain revealed changes characteristic of CPM (Fig 1).
DISCUSSION
The rapidity of treatment for severe, symptomatic hyponatremia and the possible association of CPM with overly vigorous correction are still controversial. 16 Aware of these controversies, we chose to correct the hyponatremia rapidly, based both on the severity of the patient's illness and on the fact that his presenting serum sodium of 93 mEq/L (93 mrnollL) was one of the lowest levels reported in the literature. Correction of serum sodium was achieved at a rate of 1.9 mEq/L (1.9 mmollL) per hour for the first eight hours and 1.25 mEq/L (1.25 mmollL) per hour over the first 24 hours to a level of 123 mEq/L (123 mmollL), which generally has been regarded as an acceptable level of correction (Table 1). This level was maintained at 48 hours and 72 hours; at that time the patient deteriorated. The highest serum sodium of 130 mEq/L (130 mmollL)was not reached until 96 hours after admission. An increase in serum sodium of IS to 19 From the Department of Internal Medicine and Nephrology, Sacred Heart General Hospital, Eugene, OR. Address reprint requests to James V. Walker, MD, 677 East 12th, Suite 410, Eugene, OR 97401. © 1988 by the National Kidney Foundation, Inc. 0272-6386/88/1206-0010$3.00/0
American Journal of Kidney Diseases, Vol XII, No 6 (December), 1988: pp 531-533
531
532
WALKER AND ENGLANDER Table 1. Time Admission
3h 8h 14 h 24 h 48 h 72 h 96 h
Laboratory Parameters After Admission
[Nal.: mEq/L (mmoI/L)
[Kl.; mEq/L (mmoI/L)
Osm.; mosm/kg H2O
Osmu: mosm/kg H2O
[Nal u; mEq/L (mmoI/L)
[Klu; mEq/L (mmoI/L)
93 105 108 112 123 124 123 130
3.1 2.8 2.5 4.0 3.7 4.4 3.8 4.1
193
608
14
47
259
743
149
Abbreviations: [Nal •. serum sodium concentration; [Kl •• serum potassium concentration; Osm •• serum osmolality; Osm u• urine osmolality; [Nal u• urine sodium concentration; [Klu' urine potassium concentration.
mEq/L (15 to 19 mmol/L) occurred during the time of administration of hypertonic saline (first 9.5 hours) and an increase of 30 to 31 mEq/L (30 to 31 mmol/L) during the first 24 and 48 hours of therapy. It is unclear whether CPM in our patient was a result of hyponatremia, due to the correction of it, or related principally to his history of chronic alcoholism. 3 Therefore, this case report cannot conclude that either a rapid or slow rate of correction of severe hyponatremia is more appropriate. However, recent studies have suggested that the amount of increase in serum sodium during initial treatment may play a critical role in the development of cerebral demyelination. \.4.6 Ayus et al suggest that the change in serum sodium should be < 25 mmollL in the "initial period of therapy" (an amount exceeded in our case), 6 but other recent case reports have described CPM occurring in patients whose serum sodium levels rose by only 15 mmollL in 24 hours. 7 Indeed, Sterns et al suggest that the sodium levels should be raised no more than 12 mmollL/d. 1
Additionally, whereas much of the literature suggests a therapeutic serum sodium goal of 120 mmol/L, recent clinical data from Sterns' group suggest that patients with chronic hyponatremia in the range of serum sodium < 105 mmollL may survive without neurological sequellae. 5 Thus, our patient began to demonstrate neurological improvement with a serum sodium level of 108 to 112 mmollL, an increase of 15 to 19 mmollL from admission. Based on recent clinical observations cited here, it would have been reasonable to maintain the serum sodium at this level for at least the first 48 hours of treatment rather than attempting to reach an arbitrary level of 120 mmol/L quickly. However, it is not clear if even this altered approach to management would have prevented the biphasic neurological response of apparent improvement followed by progressive deterioration described in patients treated for severe hyponatremia. 12 More information and guidelines on optimal therapeutic strategies for patients with profound hyponatremia are still needed . ACKNOWLEDGMENT We wish to thank Brent Kehn , MD. for preparation of the microscopic material. Dorothy Woosley kindly typed the manuscript.
REFERENCES
Fig 1. Photomicrograph of mid pons section (1 x). Luxol-fast blue stain showing demyelination pattern characteristic of central pontine myelinolysis.
1. Sterns RH, Riggs JE, Schochet SS Jr: Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med 314:1535-1542,1986 2. Arieff AL: Hyponatremia. convulsions. respiratory arrest and permanent brain damage after elective surgery in healthy women. N Engl J Med 314:1529-1534.1986 3. Arieff AL: Effects of water. acid-base and electrolyte disorders on the central nervous system, in Arieff AL, De Fronzo RA (eds): Fluid, Electrolyte and Acid-Base Disorders. New York, Churchill Livingston, 1985, pp 992-1007 4. Ayus JC, Krothapalli RK, Arieff AL: Changing concepts
CENTRAL PONTINE MYELINOLYSIS
in treatment of severe symptomatic hyponatremia. Rapid correction and possible relation to central pontine myelinolysis. Am 1 Med 78:897-902, 1985 5. Sterns RH: Severe symptomatic hyponatremia: Treatment and outcome. Ann Intern Med 107:656-664, 1987
533 6. Ayus IC, Krothapalli RK , Arieff AL: Treatment of symptomatic hyponatremia and its relation to brain damage. N Engl 1 Med 317: 1190-1195, 1987 7. Nielsen 1M: Central pontine myelinolysis complicating hyponatremia. Med 1 Australia 146:492-496, 1987
Central Pontine Myelinolysis Following Rapid Correction of Hyponatremia in an Alcoholic James V. Walker, MO, and Raymond N. Englander, MO • An alcoholic patient presented with profound hyponatremia of uncertain etiology. Despite partial correction of hyponatremia within 24 hours, central pontine myelinolysis (CPM) ensued and the patient subsequently died. The optimal rate of correction of severe, symptomatic hyponatremia has not yet been elucidated. © 1988 by the National Kidney Foundation, Inc. INDEX WORDS: Hyponatremia; central pontine myelinolysis; alcoholism.
T
HERE IS STILL a great deal of controversy surrounding the optimal approach to treatment of severe, symptomatic hyponatremia. 1·6 We report a patient with alcoholism and profound hyponatremia whose serum sodium was brought to "acceptable" levels within 24 hours. This therapy resulted in initial neurological improvement but subsequent death secondary to central pontine myelinolysis (CPM). CASE REPORT A 41-year-old man was hospitalized in January 1984 after neighbors found him unresponsive. His history included chronic alcoholism and frostbite injury to several toes requiring amputation. He was not known to be taking medications and had no known history of other medical illness. On admission, the patient had a temperature of 36.6°C, BP of 1461100 mm Hg, pulse of 100 beats per minute, and respiratory rate of 16. His feet revealed prior toe amputations and some breakdown of the skin. Neurological examination revealed a semicomatose man with equal strength in all extremities. Stool guaiac was negative. Initial electrolytes and osmolality were noted (Table I). Calculated serum osmolality was 190 mosml kg H 20, serum chloride was 57 mEq/L (57 mmoIlL), and CO 2 was 27 mEq/L (27 mmolll). BUN was 9 mg/dL (3.2 mmollL) and creatinine was 0.8 mg/dL (70.72 I'moIlL). Arterial blood gas on room air revealed a P0 2 of 83 mm Hg. Thyroid function was normal. Initial bilirubin was 2.6 mg/dL (44.46 I'moIlL); SGPT, 368 lUlL; SGOT, 1,260 lUlL; LDH, 820 lUlL; creatinine phosphokinase (CPK), 28,000 lUlL; phosphorous, 1.9 mg/dL (0.61 mmoIlL); magnesium, 1.4 mg/dL (0.57 mmoIlL); and myoglobin, 2,178 ng/mL. Uric acid was 4.2 mgl dL (249.8 I'moI/L). Blood alcohol was < 0.02 g/dL and toxicology screen was negative. Subsequent phosphorous and magnesium levels were normal. A noncontrast computerized tomographic (CT) scan of the head was normal on admission. The patient was treated with furosemide, 40 mg, thiamine, cimetidine, and pyridoxine administered with 3 % saline solution with supplemental potassium, phosphorous, and magnesium. By nine hours after admission he was arousable and able to answer some questions appropriately. At 9.5 hours hypertonic saline was discontinued. By 24 hours after admission he was oriented to person, place, and time and had no focal neurological deficits. Total sodium chloride administered over the
first 24 hours was 920 mEq. At 48 hours he was feeding himself and smoking. However, by 60 hours he was more lethargic and developed dysarthria. At 72 hours he was stuporous and aphasic, and thereafter his neurological course deteriorated and was characterized by progressive development of flaccid quadriplegia, periods of Cheyne-Stokes respirations, unintelligible or no speech, and variable degrees of alertness. A repeat noncontrast CT scan of the head was normal. During this time no additional metabolic abnormalities were noted and hepatocellular dysfunction improved. He subsequently developed pneumonia and died 4 weeks after admission. Autopsy findings of the brain revealed changes characteristic of CPM (Fig 1).
DISCUSSION
The rapidity of treatment for severe, symptomatic hyponatremia and the possible association of CPM with overly vigorous correction are still controversial. 16 Aware of these controversies, we chose to correct the hyponatremia rapidly, based both on the severity of the patient's illness and on the fact that his presenting serum sodium of 93 mEq/L (93 mrnollL) was one of the lowest levels reported in the literature. Correction of serum sodium was achieved at a rate of 1.9 mEq/L (1.9 mmollL) per hour for the first eight hours and 1.25 mEq/L (1.25 mmollL) per hour over the first 24 hours to a level of 123 mEq/L (123 mmollL), which generally has been regarded as an acceptable level of correction (Table 1). This level was maintained at 48 hours and 72 hours; at that time the patient deteriorated. The highest serum sodium of 130 mEq/L (130 mmollL)was not reached until 96 hours after admission. An increase in serum sodium of IS to 19 From the Department of Internal Medicine and Nephrology, Sacred Heart General Hospital, Eugene, OR. Address reprint requests to James V. Walker, MD, 677 East 12th, Suite 410, Eugene, OR 97401. © 1988 by the National Kidney Foundation, Inc. 0272-6386/88/1206-0010$3.00/0
American Journal of Kidney Diseases, Vol XII, No 6 (December), 1988: pp 531-533
531
532
WALKER AND ENGLANDER Table 1. Time Admission
3h 8h 14 h 24 h 48 h 72 h 96 h
Laboratory Parameters After Admission
[Nal.: mEq/L (mmoI/L)
[Kl.; mEq/L (mmoI/L)
Osm.; mosm/kg H2O
Osmu: mosm/kg H2O
[Nal u; mEq/L (mmoI/L)
[Klu; mEq/L (mmoI/L)
93 105 108 112 123 124 123 130
3.1 2.8 2.5 4.0 3.7 4.4 3.8 4.1
193
608
14
47
259
743
149
Abbreviations: [Nal •. serum sodium concentration; [Kl •• serum potassium concentration; Osm •• serum osmolality; Osm u• urine osmolality; [Nal u• urine sodium concentration; [Klu' urine potassium concentration.
mEq/L (15 to 19 mmol/L) occurred during the time of administration of hypertonic saline (first 9.5 hours) and an increase of 30 to 31 mEq/L (30 to 31 mmol/L) during the first 24 and 48 hours of therapy. It is unclear whether CPM in our patient was a result of hyponatremia, due to the correction of it, or related principally to his history of chronic alcoholism. 3 Therefore, this case report cannot conclude that either a rapid or slow rate of correction of severe hyponatremia is more appropriate. However, recent studies have suggested that the amount of increase in serum sodium during initial treatment may play a critical role in the development of cerebral demyelination. \.4.6 Ayus et al suggest that the change in serum sodium should be < 25 mmollL in the "initial period of therapy" (an amount exceeded in our case), 6 but other recent case reports have described CPM occurring in patients whose serum sodium levels rose by only 15 mmollL in 24 hours. 7 Indeed, Sterns et al suggest that the sodium levels should be raised no more than 12 mmollL/d. 1
Additionally, whereas much of the literature suggests a therapeutic serum sodium goal of 120 mmol/L, recent clinical data from Sterns' group suggest that patients with chronic hyponatremia in the range of serum sodium < 105 mmollL may survive without neurological sequellae. 5 Thus, our patient began to demonstrate neurological improvement with a serum sodium level of 108 to 112 mmollL, an increase of 15 to 19 mmollL from admission. Based on recent clinical observations cited here, it would have been reasonable to maintain the serum sodium at this level for at least the first 48 hours of treatment rather than attempting to reach an arbitrary level of 120 mmol/L quickly. However, it is not clear if even this altered approach to management would have prevented the biphasic neurological response of apparent improvement followed by progressive deterioration described in patients treated for severe hyponatremia. 12 More information and guidelines on optimal therapeutic strategies for patients with profound hyponatremia are still needed . ACKNOWLEDGMENT We wish to thank Brent Kehn , MD. for preparation of the microscopic material. Dorothy Woosley kindly typed the manuscript.
REFERENCES
Fig 1. Photomicrograph of mid pons section (1 x). Luxol-fast blue stain showing demyelination pattern characteristic of central pontine myelinolysis.
1. Sterns RH, Riggs JE, Schochet SS Jr: Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med 314:1535-1542,1986 2. Arieff AL: Hyponatremia. convulsions. respiratory arrest and permanent brain damage after elective surgery in healthy women. N Engl J Med 314:1529-1534.1986 3. Arieff AL: Effects of water. acid-base and electrolyte disorders on the central nervous system, in Arieff AL, De Fronzo RA (eds): Fluid, Electrolyte and Acid-Base Disorders. New York, Churchill Livingston, 1985, pp 992-1007 4. Ayus JC, Krothapalli RK, Arieff AL: Changing concepts
CENTRAL PONTINE MYELINOLYSIS
in treatment of severe symptomatic hyponatremia. Rapid correction and possible relation to central pontine myelinolysis. Am 1 Med 78:897-902, 1985 5. Sterns RH: Severe symptomatic hyponatremia: Treatment and outcome. Ann Intern Med 107:656-664, 1987
533 6. Ayus IC, Krothapalli RK , Arieff AL: Treatment of symptomatic hyponatremia and its relation to brain damage. N Engl 1 Med 317: 1190-1195, 1987 7. Nielsen 1M: Central pontine myelinolysis complicating hyponatremia. Med 1 Australia 146:492-496, 1987