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From profound hypokalemia to fatal rhabdomyolysis after severe head injury
Letters to the Editor
FROM PROFOUND HYPOKALEMIA TO FATAL RHABDOMYOLYSIS AFTER SEVERE HEAD INJURY
Figure 2. Photomicrographs of left lung biopsy findings: A. Low-power view of a typical granuloma (G) and well-differentiated neoplastic glands in perivascular lymphatic channels (arrows) (hematoxylin and eosin stain ⫻ 120). B. Higher-power view of A (hematoxylin and eosin ⫻ 250). C. Higher-power view of granuloma showing multinucleated giant cells (hematoxylin and eosin ⫻ 250). D. immunohistochemical staining for B lymphocytes (CD 20) showing dark brown staining in positive cells.
to establish the true nature of a granuloma-associated condition. Jenny T. Mao, MD Michael C. Fishbein, MD Divisions of Pulmonary and Critical Care Medicine and Anatomic Pathology University of California, Los Angeles School of Medicine Los Angeles, California
3.
4.
5.
6. 1. Brincker H, Pedersen NT. Immunohistologic separation of B-cell positive granulomas from B-cell negative granulomas in paraffin-embedded tissue with special reference to tumor-related sarcoid reactions. APMIS: Acta Pathologica Mmicrobiologica, et Immunologica, Scandinavia. 1991;99: 282–290. 2. Nadel EM, Ackerman LV. Lesions resembling Boeck’s sarcoid in lymph nodes
7.
8.
draining an area containing a malignant neoplasm. Am J Clin Pathol. 1950;20:952– 957. Brincker H. Sarcoid reactions in malignant tumours. Cancer Treat Rev. 1986;13:147– 156. Kamiyoshihara M, Kawashima O, Ishikawa S, Morishita Y. Sarcoid reactions in primary pulmonary carcinoma: report of seven cases. Oncol Rep. 1998;1:177–180. Hunsaker AR, Munden RF, Pugatch RD, Mentzer SJ. Sarcoidlike reaction in patients with malignancy. Radiology. 1996;200:255– 261. Tagen JM, Naess A, Aasen T, Morild I. Non-caseating granulomas in patients with hematologic malignancies: a report of three cases. Acta Med Scand. 1988;223: 83– 87. O’Connell MJ, Schimpff SC, Kirschner RH, et al. Epitheiloid granulomas in Hodgkin’s disease: a favorable prognostic sign? JAMA. 1975;233:886 – 889. Brincker H. Interpretation of granulomatous lesions in malignancy. Acta Oncol. 1992;6:85– 89. November 2000
To the Editor: A 28-year-old man was admitted to the intensive care unit because of a severe head injury after a traffic accident. A computed tomographic scan of the brain showed a fracture of the right frontal bone and the base of skull, with cerebral contusion and subdural hemorrhage. Emergency craniotomy and intracranial pressure monitoring were performed. Postoperatively, he was treated with amoxicillin/clavulanate (1.2 g every 6 hours) and 100 mL of a 20% mannitol solution intravenously to reduce cerebral edema. However, he developed marked diuresis with urine output up to 200 mL per hour. His serum sodium level increased to ⬎160 mmol/L, his serum potassium level decreased to 1.9 mmol/L, and his serum phosphate level decreased to ⬍0.2 mmol/L within 11 hours (Table 1). He was diagnosed with central diabetes insipidus and treated with subcutaneous desmopressin (4 g every 4 hours), intravenous potassium (up to 15 to 20 mmol per hour), and fluids (5% dextrose at 105 to 200 mL per hour). However, profound hypokalemia persisted. A spot urine potassium level was 21 mmol/L when his serum potassium level was 1.5 mmol/L, suggesting persistent renal loss of potassium. The polyuric and hyperosmolar status became unresponsive to desmopressin, indicating the development of nephrogenic diabetes insipidus due to profound hypokalemia. One day later, myoglobinuria and rhabdomyolysis developed with an elevated serum creatine kinase level (to a peak of 42,280 mmol/L). Rhabdomyolysis was complicated by acute renal failure with a rapid rise in his serum creatinine level (Table) that required dialysis. Although potassium replacement had been stopped when the serum potassium level was 2.3
THE AMERICAN JOURNAL OF MEDICINE威
Volume 109 599
Letters to the Editor
Table 1. Serial Changes in Serum Creatinine and Electrolytes Level after Admission Time after Admission (Hours) Serum creatinine (mol/L)* Serum potassium (mmol/L) Serum sodium (mmol/L) Serum phosphate (mmol/L)
0
9
20
30
41
55
62
90 4.2 142 1.6
126 3.4 147 0.6
146 1.9 ⬎160 ⬍0.2
216 1.6 ⬎160 —
366 1.5 ⬎160 ⬍0.2
556 2.3 ⬎160 1.2
765 8.9 155 5.3
* To convert to mg/dL, divide creatinine by 88.4.
mmol/L, he developed severe hyperkalemia 7 hours later. Despite dialysis and inotropic support, he died of circulatory failure and ventricular tachyarrhythmias due to refractory metabolic acidosis and hyperkalemia. Hypokalemia has been reported in patients after severe head injury (1– 4), perhaps as a result of the large catecholamine release that accompanies severe head trauma, which induces a shift of potassium from the extracellular to the intracellular space (2,4,5). Furthermore, the development of central diabetes insipidus and the use of mannitol can lead to excessive diuresis and may have contributed to the profound hypokalemia in this patient. This hypokalemia caused nephrogenic diabetes insipidus, which rendered the polyuric condition unresponsive to desmopressin. The subsequent hyperkalemia was likely due to the release of potassium from the necrotic muscle during rhabdomyolysis, aggravated by acute renal failure. In this patient, several factors contributed to the development of the fatal rhabdomyolysis, including hypokalemia, hypophosphatemia, and hyperosmolarity due to diabetes insipidus (3,6 – 8). Cautious use of osmotic diuretic agents for cerebral edema and careful diagnosis and treatment of hypokalemia and diabetes insipidus after head injury are required to prevent these complications. Hung-Fat Tse, MB, MD Chi-Keung Yeung, MB Department of Medicine Queen Mary Hospital The University of Hong Kong Hong Kong, China 600
November 2000
1. Trouwborst A, Kooijman J. The alterations of plasma potassium in patients with severe acute head injury. Injury. 1984;15:293–295. 2. Schaefer M, Link J, Hannemann L, Rudolph KH. Excessive hypokalemia and hyperkalemia following head injury. Intensive Care Med. 1995;21:235–237. 3. Chen CM, Chen JC, Kao MC. Severe rhabdomyolysis with good recovery in a patient with head injury: case report. Neurosurgery. 1997;41:293–296. 4. Lazar L, Erez I, Gutermacher M, Katz S. Brain concussion produces transient hypokalemia in children. J Pediatr Surg. 1997;32: 88 –90. 5. Kaltofen A, Lindner KH, Ensinger H, Ahnefeld FW. The modification of the potassium concentration in blood by catecholamines. A literature review. Anasth Intensivther Notfallmed. 1990;25:405– 410. 6. Knochel J, Schlein E. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest. 1972;51:1750 –1758. 7. Knochel JP, Barcenas C, Cotton JR, et al. Hypophosphatemia and rhabdomyolysis. J Clin Invest. 1978;62:1240 –1246. 8. Kung AW, Pun KK, Lam KS, Yeung RT. Rhabdomyolysis associated with cranial diabetes insipidus. Postgrad Med J. 1991;67: 912–913.
EFFECTS OF DIETARY PHYTOSTEROLS ON CHOLESTEROL METABOLISM AND ATHEROSCLEROSIS: CLINICAL AND EXPERIMENTAL EVIDENCE To the Editor: In their review of the effects of dietary phytosterols, Moghadasian and Frohlich (1) did not accurately cite our findings concerning the reproductive toxicity of plant stanol esters
THE AMERICAN JOURNAL OF MEDICINE威
Volume 109
(2). The authors cited four effects as evidence of reproductive toxicity; however, we did not find these effects to be toxicologically important. The first effect was that consumption of a diet supplemented with 4.4% of stanol esters was associated with a significant increase in the absolute and relative weights of the testes and relative weights of the epididymides in rats of the F1 generation. The changes in these mean organ weights were observed only in the mid-dose group and not in the high-dose (8.8%) group. Therefore, they were not considered to be treatment-related effects. Macroscopic or microscopic evaluation of these organs did not reveal any substantial effects in any treatment group. The second effect cited by Modhadasian and Frohlich was changes in spermatozoal counts in the F1 generation rats. This was not a statistically significant finding, as the number of rats with decreased spermatozoal counts in the high-dose group (6 of 28) was similar to that among the control group (5 of 28). The remaining two effects, reduced postimplantation loss (observed only in F1 generation rats) and increased male and female fertility indexes (observed only in F0 generation rats), were not statistically significant and were actually a function of unusually low control group rates for those endpoints. In addition, the data for all treated groups were well within historical controls for this rat species (Table). Thus, the data do not support the conclusion that these are toxicologically important effects, as cited by Moghadasian and Frohlich in their
FROM PROFOUND HYPOKALEMIA TO FATAL RHABDOMYOLYSIS AFTER SEVERE HEAD INJURY
Figure 2. Photomicrographs of left lung biopsy findings: A. Low-power view of a typical granuloma (G) and well-differentiated neoplastic glands in perivascular lymphatic channels (arrows) (hematoxylin and eosin stain ⫻ 120). B. Higher-power view of A (hematoxylin and eosin ⫻ 250). C. Higher-power view of granuloma showing multinucleated giant cells (hematoxylin and eosin ⫻ 250). D. immunohistochemical staining for B lymphocytes (CD 20) showing dark brown staining in positive cells.
to establish the true nature of a granuloma-associated condition. Jenny T. Mao, MD Michael C. Fishbein, MD Divisions of Pulmonary and Critical Care Medicine and Anatomic Pathology University of California, Los Angeles School of Medicine Los Angeles, California
3.
4.
5.
6. 1. Brincker H, Pedersen NT. Immunohistologic separation of B-cell positive granulomas from B-cell negative granulomas in paraffin-embedded tissue with special reference to tumor-related sarcoid reactions. APMIS: Acta Pathologica Mmicrobiologica, et Immunologica, Scandinavia. 1991;99: 282–290. 2. Nadel EM, Ackerman LV. Lesions resembling Boeck’s sarcoid in lymph nodes
7.
8.
draining an area containing a malignant neoplasm. Am J Clin Pathol. 1950;20:952– 957. Brincker H. Sarcoid reactions in malignant tumours. Cancer Treat Rev. 1986;13:147– 156. Kamiyoshihara M, Kawashima O, Ishikawa S, Morishita Y. Sarcoid reactions in primary pulmonary carcinoma: report of seven cases. Oncol Rep. 1998;1:177–180. Hunsaker AR, Munden RF, Pugatch RD, Mentzer SJ. Sarcoidlike reaction in patients with malignancy. Radiology. 1996;200:255– 261. Tagen JM, Naess A, Aasen T, Morild I. Non-caseating granulomas in patients with hematologic malignancies: a report of three cases. Acta Med Scand. 1988;223: 83– 87. O’Connell MJ, Schimpff SC, Kirschner RH, et al. Epitheiloid granulomas in Hodgkin’s disease: a favorable prognostic sign? JAMA. 1975;233:886 – 889. Brincker H. Interpretation of granulomatous lesions in malignancy. Acta Oncol. 1992;6:85– 89. November 2000
To the Editor: A 28-year-old man was admitted to the intensive care unit because of a severe head injury after a traffic accident. A computed tomographic scan of the brain showed a fracture of the right frontal bone and the base of skull, with cerebral contusion and subdural hemorrhage. Emergency craniotomy and intracranial pressure monitoring were performed. Postoperatively, he was treated with amoxicillin/clavulanate (1.2 g every 6 hours) and 100 mL of a 20% mannitol solution intravenously to reduce cerebral edema. However, he developed marked diuresis with urine output up to 200 mL per hour. His serum sodium level increased to ⬎160 mmol/L, his serum potassium level decreased to 1.9 mmol/L, and his serum phosphate level decreased to ⬍0.2 mmol/L within 11 hours (Table 1). He was diagnosed with central diabetes insipidus and treated with subcutaneous desmopressin (4 g every 4 hours), intravenous potassium (up to 15 to 20 mmol per hour), and fluids (5% dextrose at 105 to 200 mL per hour). However, profound hypokalemia persisted. A spot urine potassium level was 21 mmol/L when his serum potassium level was 1.5 mmol/L, suggesting persistent renal loss of potassium. The polyuric and hyperosmolar status became unresponsive to desmopressin, indicating the development of nephrogenic diabetes insipidus due to profound hypokalemia. One day later, myoglobinuria and rhabdomyolysis developed with an elevated serum creatine kinase level (to a peak of 42,280 mmol/L). Rhabdomyolysis was complicated by acute renal failure with a rapid rise in his serum creatinine level (Table) that required dialysis. Although potassium replacement had been stopped when the serum potassium level was 2.3
THE AMERICAN JOURNAL OF MEDICINE威
Volume 109 599
Letters to the Editor
Table 1. Serial Changes in Serum Creatinine and Electrolytes Level after Admission Time after Admission (Hours) Serum creatinine (mol/L)* Serum potassium (mmol/L) Serum sodium (mmol/L) Serum phosphate (mmol/L)
0
9
20
30
41
55
62
90 4.2 142 1.6
126 3.4 147 0.6
146 1.9 ⬎160 ⬍0.2
216 1.6 ⬎160 —
366 1.5 ⬎160 ⬍0.2
556 2.3 ⬎160 1.2
765 8.9 155 5.3
* To convert to mg/dL, divide creatinine by 88.4.
mmol/L, he developed severe hyperkalemia 7 hours later. Despite dialysis and inotropic support, he died of circulatory failure and ventricular tachyarrhythmias due to refractory metabolic acidosis and hyperkalemia. Hypokalemia has been reported in patients after severe head injury (1– 4), perhaps as a result of the large catecholamine release that accompanies severe head trauma, which induces a shift of potassium from the extracellular to the intracellular space (2,4,5). Furthermore, the development of central diabetes insipidus and the use of mannitol can lead to excessive diuresis and may have contributed to the profound hypokalemia in this patient. This hypokalemia caused nephrogenic diabetes insipidus, which rendered the polyuric condition unresponsive to desmopressin. The subsequent hyperkalemia was likely due to the release of potassium from the necrotic muscle during rhabdomyolysis, aggravated by acute renal failure. In this patient, several factors contributed to the development of the fatal rhabdomyolysis, including hypokalemia, hypophosphatemia, and hyperosmolarity due to diabetes insipidus (3,6 – 8). Cautious use of osmotic diuretic agents for cerebral edema and careful diagnosis and treatment of hypokalemia and diabetes insipidus after head injury are required to prevent these complications. Hung-Fat Tse, MB, MD Chi-Keung Yeung, MB Department of Medicine Queen Mary Hospital The University of Hong Kong Hong Kong, China 600
November 2000
1. Trouwborst A, Kooijman J. The alterations of plasma potassium in patients with severe acute head injury. Injury. 1984;15:293–295. 2. Schaefer M, Link J, Hannemann L, Rudolph KH. Excessive hypokalemia and hyperkalemia following head injury. Intensive Care Med. 1995;21:235–237. 3. Chen CM, Chen JC, Kao MC. Severe rhabdomyolysis with good recovery in a patient with head injury: case report. Neurosurgery. 1997;41:293–296. 4. Lazar L, Erez I, Gutermacher M, Katz S. Brain concussion produces transient hypokalemia in children. J Pediatr Surg. 1997;32: 88 –90. 5. Kaltofen A, Lindner KH, Ensinger H, Ahnefeld FW. The modification of the potassium concentration in blood by catecholamines. A literature review. Anasth Intensivther Notfallmed. 1990;25:405– 410. 6. Knochel J, Schlein E. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest. 1972;51:1750 –1758. 7. Knochel JP, Barcenas C, Cotton JR, et al. Hypophosphatemia and rhabdomyolysis. J Clin Invest. 1978;62:1240 –1246. 8. Kung AW, Pun KK, Lam KS, Yeung RT. Rhabdomyolysis associated with cranial diabetes insipidus. Postgrad Med J. 1991;67: 912–913.
EFFECTS OF DIETARY PHYTOSTEROLS ON CHOLESTEROL METABOLISM AND ATHEROSCLEROSIS: CLINICAL AND EXPERIMENTAL EVIDENCE To the Editor: In their review of the effects of dietary phytosterols, Moghadasian and Frohlich (1) did not accurately cite our findings concerning the reproductive toxicity of plant stanol esters
THE AMERICAN JOURNAL OF MEDICINE威
Volume 109
(2). The authors cited four effects as evidence of reproductive toxicity; however, we did not find these effects to be toxicologically important. The first effect was that consumption of a diet supplemented with 4.4% of stanol esters was associated with a significant increase in the absolute and relative weights of the testes and relative weights of the epididymides in rats of the F1 generation. The changes in these mean organ weights were observed only in the mid-dose group and not in the high-dose (8.8%) group. Therefore, they were not considered to be treatment-related effects. Macroscopic or microscopic evaluation of these organs did not reveal any substantial effects in any treatment group. The second effect cited by Modhadasian and Frohlich was changes in spermatozoal counts in the F1 generation rats. This was not a statistically significant finding, as the number of rats with decreased spermatozoal counts in the high-dose group (6 of 28) was similar to that among the control group (5 of 28). The remaining two effects, reduced postimplantation loss (observed only in F1 generation rats) and increased male and female fertility indexes (observed only in F0 generation rats), were not statistically significant and were actually a function of unusually low control group rates for those endpoints. In addition, the data for all treated groups were well within historical controls for this rat species (Table). Thus, the data do not support the conclusion that these are toxicologically important effects, as cited by Moghadasian and Frohlich in their