Rhabdomyolysis caused by hypernatremia
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《美国医学杂志》
1 Cukurova University Medical Faculty, Department of Pediatric Neurology, Adana, Turkey
2 Cukurova University Medical Faculty, Department of PICU, Adana, Turkey
Rhabdomyolysis is a clinical picture which is rarely seen in children. In this case report here it is presented a patient who has biochemical and clinical signs of rhabdomyolysis and admitted to our clinic with hypernatremia. The authors think that it is necessary to be alert for rhabdomyolysis in severe hypernatremia cases.
Keywords: Hypernatremia; Rhabdomyolysis
Severe hypernatremia (serum sodium level> 190 mEq/L) may lead to neurological signs like agitation, convulsions, lethargy, and coma besides the common symptoms such as fever, vomiting, tachypnea, high-pitched crying, changes in skin turgor. Generalized muscle weakness is less frequently seen.[1],[2] Rhabdomyolysis is characterized by systemic signs and symptoms of the muscle cell injury which causes the intracellular components like myoglobin, enzymes, electrolytes to come out of muscle into the extracellular compartment.[3] As a result of this event, electrolyte imbalance can occur,and this may lead to myoglobinuria and acute renal failure (ARF).
Rhabdomyolysis is most frequently described in adult patients, whereas- it is less frequently reported in children.[1],[4],[5] It is generally caused by following etiological factors: Muscle injury, increased muscular activity, ischemia, drugs, toxins, infection, inflammatory myopathies, metabolic disorders, and hereditary metabolic myopathies.[1]
Although hypernatremia is one of the causes of rhabdomyolysis, it is rarely reported in the literature.[1],[5] So, the authors wanted to present a case of hypodipsia-hypematremia syndrome who was admitted to their with acute renal failure and rhabdomyolysis.
Case Report
A 5-year-old girl was brought authors her parents with the complaints of high fever, vomiting and loss of conciousness. They reported that vomitting started one week ago and oral intake lessened gradually. She was feverish and unconscious for the past 2 days. In past medical history, she was diagnosed as hypodipsia-hypernatremia syndrome in their clinic four years ago, because of significant adipsia, recurrent hypernatremia attacks and midfacial defects. In cerebral magnetic resonance imaging, lobar holoprosencephaly was diagnosed. She had an operation for cleft lip and palate at the age of 8 months, and was hospitalized a few times with the complaints of fever and loss of conciuosness due to hypernatremic dehydratation. Nasogastric feeding was administered due to insufficient oral intake.
Physical examination was consistent with moderate-severe dehydratation. Her height (94 cm), weight (12.4 Kg) and head circumference (44 cm) were below third percentile for age. In neurological examination, she was unconscious. The rest of physical and neurological examination was unremarkable.
In laboratory examination, complete blood count was normal. Blood biochemistry was as follows: serum BUN 91 mg/dL, creatinine 3.0 mg/dL, AST 489 lU/L, ALT 87 lU/L, creatine kinase (CK) 9985 U/L, albumine 4.3 g/dL, glucose 300 mg/dL, calcium 8.0 mg/dL, phosphorus 7.6 mg/dL, uric acid 14.8 mg/dL, Na 195 mEq/L (corrected Na 198.2 mEq/L), K 5.8 mEq/L. Blood ketones were negative, blood osmolality was 474 mOsm/kg. In arterial blood gase analysis, blood pH was 7.23, HC03 17 mmol/L, and base excess -9.7 mmol/L. In urinalysis, protein reaction was 3+. But no erythrocyte was seen in microscopic examination. Myoglobinuria was not determined.
Treatment with intravenous hypotonic fluids (0.45% sodium chloride) and sodium bicarbonate was started immediately for fluid-electrolyte imbalance and metabolic acidosis. The correction rate of hypernatremia was regulated not exceeding 1 mEq/l/h. She was conscious at 24 hours. Urinary output normalized in 24 hours of the treatment. Serum Na level decreased to 177 and 163 mEq/L at 24 and 48 hours respectively. Serum CK increased to 48420 U/L at two days. It continued to raise upto the level of 69170 U/L and then 137290 U/L at four and five days, respectively. Serum Na levels were 151 and 147 mEq/L in the meantime. Na, K, BUN, creatinine, uric acid, AL T and glucose were normal at ten days while CK level was 44930 U/L, and AST was 158 lU/L. All laboratory values including CK level were normal at third weeks.
Discussion
Rhabdomyolysis caused by hypernatremia has been usually reported in adults whereas it has been rarely seen in children.[1],[4],[5] In this case, the other causes of rhabdomyolysis like muscle injury, increased muscular activity, ischemia, drugs, toxins, infection, inflammatory myopathies, and hereditary metabolic myopathies were excluded by historical, physical and laboratory findings.
Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, coxsackievirus A virus, influenza virus, streptococcus pneumoniae, mycoplasma pneumoniae, Salmonella More Details, and shigella are some of the infective agents which cause rhabdomyolysis.[6] Neither cultures nor viral serology was positive for these agents in our case. There were no clinical symptoms suggestive of infection. The authors also excluded metabolic diseases by serum and urine aminoacids and organic acid analysis in urine.
Rhabdomyolysis is also presented with other hyperosmolar situations like diabetic ketoacidosis and hyperosmolar coma.[7] Singhal et al[4] showed rhabdomyolysis in 31 patients with high blood osmolality. They also detected a linear correlation between serum CK versus serum Na and serum CK versus serum osmolality. The present had hyperglycemia of 300 mg/dL. But she had no diabetes mellitus. Furthermore, Krahe et al[5] reported the existence of hyperglycemia in rhabdomyolysis which may develop secondary to hypernatremicdehidration and increased catecholamines and glucocorticoids levels in the acute stress. The authros think that these explanations may also true for our case. Besides in different two studies by Morales[8], Hollander[9] and Carchman[10] rabdomyolysis related hyperglisemic hyperosmolor syndrome (HHS) in type 2 diabetes mellitus were reported in six, seven and four patients respectively.
How hypematremia causes rhabdomyolysis has not been exactly known. However, it has been thought to be related to inhibition of electrogenic sodium pump on muscle cells. Impairing sodium-calcium transport and resulting in an increased cytoplasmic calcium level. Persistently high intracellular calcium may result in activation of neutral proteases and leading to the destruction of muscle. As a result, muscle damage occurs and intracellular structures like CK and myoglobin get out of the cell into the extracellular area.[7],[11]
Creatine kinase is a reliable marker to determine the existence and intensity of muscle damage.[12] It by more than 100 times in rhabdomyolysis.[4] In this case, Na and serum CK were 195 mEq/L and 9985 U/L, at admission, respectively. By considering clinical and laboratory findings, our patient was diagnosed as rhabdomyolysis caused by severe hypernatremia. Opas et al[1] reported two cases whose ages were 9 months and 9 years with hypernatremia and rhabdomyolysis after dehydratation caused by gastroenteritis. Krahe et al[5] also presented a case of 6 months of age. Electrolytes also get out of the damaged muscle cells and result in hyperkalemia, hyperphosphatemia. Secondary hypocalcemia due to intracellular shift of calcium occur in rhabdomyolysis.[7] In this case, hyperphosphatemia, hyperkalemia and borderline hypocalcemia were present. Hypoalbuminemia has also been reported as a frequent sign of rhabdomyolysis.[13] In their patient, hypoalbuminemia was not present.
The most important complication of this disorder is ARF, which develops in up to 40% of patients with rhabdomyolysis.[13] It has been believed that the pathogenesis of ARF is multifactorial. These are renal vasoconstriction/hypo perfusion, renal tubular obstruction secondary to cast formation, and myoglobin-mediated tubular cytotoxicity.[14] Although rhabdomyolysis induced ARF can be prevented by appropriate fluid and alkali treatment, it may progress and lead to renal failure. Author this case had acute renal failure as a result of rhabdomyolysis. She improved regarding ARF by appropriate treatment.
In summary, rhabdomyolysis caused by hypernatremia is rarely seen in children. By presenting this patient with hypodipsia-hypernatremia syndrome, the authrs want to emphasize both the risk of rhabdomyolysis in this syndrome and draw the physicians' attention to the occurrence of rhabdomyolysis in hypernatremic situations. By increasing awareness of this, it may be expected that appropriate treatment can be started immediately.
References
1.Opas LM, Adler R, Robinson R, Lieberman E. Rhabdomyolysis with severe hypernatremia. J Pediatr 1997; 90: 713-716.
2.Moritz ML, Ayus JC. The changing pattern of hypernatremia in hospitalized children. Pediatrics 1999; 104: 435-439. [PUBMED] [FULLTEXT]
3.Neg YT, Johnston HM. Clinical rhabdomyolysis. J Pediatr Child Health 20 00; 36: 397-400.
4.Singhal PC, Abromovici M, Ayer S, Desroches L. Determinants of rhabdomyolysis in diabetic state. Am J Nephrol 1991; 11: 447-450.
5.Krahe J, Roll C, Hanssler L, Bonzel KE. Sekundare rhabdomyolyse und akutes nierenversagen bei gastroenteritis mit hypernatriamischer dehydratation. Monatsschr Kinderheilkd 1993; 141: 303-307. [PUBMED]
6.Minami K, Maeda H, Yanagawa T, Suzuki H, Izumi G, Yoshikawa N. Rhabdomyolysis associated with Mycoplasma pneumoniae infection. Pediatr Infect Dis J 2003; 22 :291-293. [PUBMED] [FULLTEXT]
7.Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin 1999; 15: 415-428. [PUBMED]
8.Morales AE, Rosenbloom AL. Death caused by hyperglycemic hyperosmolar state at the onset of type 2 diabetes. J Pediatr 2004; 144: 210-273. [PUBMED] [FULLTEXT]
9.Hollander AS, Olney RC, Blacket PR, Marshall BA. Fatal malignant hyperthermialike syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males. Pediatrics 2003; 111: 1447-1452.
10.Charchman RM, Dechert-Zeger M, Calikoglu AS, Harris BD. A new challenge in pediatric obesity: pediatric hyperglycemic hyperosmolar syndrome. Pediatr Crit Care Med 2005; 6: 20-24.
11.Abramovici MI, Singhal PC, Trachtman H. Hypernatremia and rhabdomyolysis. J Med 1992; 23: 55-62. [PUBMED]
12.V aholder R, Sever MS, Erek E, Lameire N. Acute renal failure related to the crush syndrome: towards an era of seismo-nephrology Nephrol Dial Transplant 2000; 15: 1517-1521.
13.Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol 2000; 8: 72-76. [PUBMED] [FULLTEXT]
14.Watanabe T. Rhabdomyolysis and acute renal failure in children. Pediatr Nephrol 2001; 16 : 1072-1075. [PUBMED] [FULLTEXT](Incecik Faruk, Herguner M Ozlem, Yildizd)
2 Cukurova University Medical Faculty, Department of PICU, Adana, Turkey
Rhabdomyolysis is a clinical picture which is rarely seen in children. In this case report here it is presented a patient who has biochemical and clinical signs of rhabdomyolysis and admitted to our clinic with hypernatremia. The authors think that it is necessary to be alert for rhabdomyolysis in severe hypernatremia cases.
Keywords: Hypernatremia; Rhabdomyolysis
Severe hypernatremia (serum sodium level> 190 mEq/L) may lead to neurological signs like agitation, convulsions, lethargy, and coma besides the common symptoms such as fever, vomiting, tachypnea, high-pitched crying, changes in skin turgor. Generalized muscle weakness is less frequently seen.[1],[2] Rhabdomyolysis is characterized by systemic signs and symptoms of the muscle cell injury which causes the intracellular components like myoglobin, enzymes, electrolytes to come out of muscle into the extracellular compartment.[3] As a result of this event, electrolyte imbalance can occur,and this may lead to myoglobinuria and acute renal failure (ARF).
Rhabdomyolysis is most frequently described in adult patients, whereas- it is less frequently reported in children.[1],[4],[5] It is generally caused by following etiological factors: Muscle injury, increased muscular activity, ischemia, drugs, toxins, infection, inflammatory myopathies, metabolic disorders, and hereditary metabolic myopathies.[1]
Although hypernatremia is one of the causes of rhabdomyolysis, it is rarely reported in the literature.[1],[5] So, the authors wanted to present a case of hypodipsia-hypematremia syndrome who was admitted to their with acute renal failure and rhabdomyolysis.
Case Report
A 5-year-old girl was brought authors her parents with the complaints of high fever, vomiting and loss of conciousness. They reported that vomitting started one week ago and oral intake lessened gradually. She was feverish and unconscious for the past 2 days. In past medical history, she was diagnosed as hypodipsia-hypernatremia syndrome in their clinic four years ago, because of significant adipsia, recurrent hypernatremia attacks and midfacial defects. In cerebral magnetic resonance imaging, lobar holoprosencephaly was diagnosed. She had an operation for cleft lip and palate at the age of 8 months, and was hospitalized a few times with the complaints of fever and loss of conciuosness due to hypernatremic dehydratation. Nasogastric feeding was administered due to insufficient oral intake.
Physical examination was consistent with moderate-severe dehydratation. Her height (94 cm), weight (12.4 Kg) and head circumference (44 cm) were below third percentile for age. In neurological examination, she was unconscious. The rest of physical and neurological examination was unremarkable.
In laboratory examination, complete blood count was normal. Blood biochemistry was as follows: serum BUN 91 mg/dL, creatinine 3.0 mg/dL, AST 489 lU/L, ALT 87 lU/L, creatine kinase (CK) 9985 U/L, albumine 4.3 g/dL, glucose 300 mg/dL, calcium 8.0 mg/dL, phosphorus 7.6 mg/dL, uric acid 14.8 mg/dL, Na 195 mEq/L (corrected Na 198.2 mEq/L), K 5.8 mEq/L. Blood ketones were negative, blood osmolality was 474 mOsm/kg. In arterial blood gase analysis, blood pH was 7.23, HC03 17 mmol/L, and base excess -9.7 mmol/L. In urinalysis, protein reaction was 3+. But no erythrocyte was seen in microscopic examination. Myoglobinuria was not determined.
Treatment with intravenous hypotonic fluids (0.45% sodium chloride) and sodium bicarbonate was started immediately for fluid-electrolyte imbalance and metabolic acidosis. The correction rate of hypernatremia was regulated not exceeding 1 mEq/l/h. She was conscious at 24 hours. Urinary output normalized in 24 hours of the treatment. Serum Na level decreased to 177 and 163 mEq/L at 24 and 48 hours respectively. Serum CK increased to 48420 U/L at two days. It continued to raise upto the level of 69170 U/L and then 137290 U/L at four and five days, respectively. Serum Na levels were 151 and 147 mEq/L in the meantime. Na, K, BUN, creatinine, uric acid, AL T and glucose were normal at ten days while CK level was 44930 U/L, and AST was 158 lU/L. All laboratory values including CK level were normal at third weeks.
Discussion
Rhabdomyolysis caused by hypernatremia has been usually reported in adults whereas it has been rarely seen in children.[1],[4],[5] In this case, the other causes of rhabdomyolysis like muscle injury, increased muscular activity, ischemia, drugs, toxins, infection, inflammatory myopathies, and hereditary metabolic myopathies were excluded by historical, physical and laboratory findings.
Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, coxsackievirus A virus, influenza virus, streptococcus pneumoniae, mycoplasma pneumoniae, Salmonella More Details, and shigella are some of the infective agents which cause rhabdomyolysis.[6] Neither cultures nor viral serology was positive for these agents in our case. There were no clinical symptoms suggestive of infection. The authors also excluded metabolic diseases by serum and urine aminoacids and organic acid analysis in urine.
Rhabdomyolysis is also presented with other hyperosmolar situations like diabetic ketoacidosis and hyperosmolar coma.[7] Singhal et al[4] showed rhabdomyolysis in 31 patients with high blood osmolality. They also detected a linear correlation between serum CK versus serum Na and serum CK versus serum osmolality. The present had hyperglycemia of 300 mg/dL. But she had no diabetes mellitus. Furthermore, Krahe et al[5] reported the existence of hyperglycemia in rhabdomyolysis which may develop secondary to hypernatremicdehidration and increased catecholamines and glucocorticoids levels in the acute stress. The authros think that these explanations may also true for our case. Besides in different two studies by Morales[8], Hollander[9] and Carchman[10] rabdomyolysis related hyperglisemic hyperosmolor syndrome (HHS) in type 2 diabetes mellitus were reported in six, seven and four patients respectively.
How hypematremia causes rhabdomyolysis has not been exactly known. However, it has been thought to be related to inhibition of electrogenic sodium pump on muscle cells. Impairing sodium-calcium transport and resulting in an increased cytoplasmic calcium level. Persistently high intracellular calcium may result in activation of neutral proteases and leading to the destruction of muscle. As a result, muscle damage occurs and intracellular structures like CK and myoglobin get out of the cell into the extracellular area.[7],[11]
Creatine kinase is a reliable marker to determine the existence and intensity of muscle damage.[12] It by more than 100 times in rhabdomyolysis.[4] In this case, Na and serum CK were 195 mEq/L and 9985 U/L, at admission, respectively. By considering clinical and laboratory findings, our patient was diagnosed as rhabdomyolysis caused by severe hypernatremia. Opas et al[1] reported two cases whose ages were 9 months and 9 years with hypernatremia and rhabdomyolysis after dehydratation caused by gastroenteritis. Krahe et al[5] also presented a case of 6 months of age. Electrolytes also get out of the damaged muscle cells and result in hyperkalemia, hyperphosphatemia. Secondary hypocalcemia due to intracellular shift of calcium occur in rhabdomyolysis.[7] In this case, hyperphosphatemia, hyperkalemia and borderline hypocalcemia were present. Hypoalbuminemia has also been reported as a frequent sign of rhabdomyolysis.[13] In their patient, hypoalbuminemia was not present.
The most important complication of this disorder is ARF, which develops in up to 40% of patients with rhabdomyolysis.[13] It has been believed that the pathogenesis of ARF is multifactorial. These are renal vasoconstriction/hypo perfusion, renal tubular obstruction secondary to cast formation, and myoglobin-mediated tubular cytotoxicity.[14] Although rhabdomyolysis induced ARF can be prevented by appropriate fluid and alkali treatment, it may progress and lead to renal failure. Author this case had acute renal failure as a result of rhabdomyolysis. She improved regarding ARF by appropriate treatment.
In summary, rhabdomyolysis caused by hypernatremia is rarely seen in children. By presenting this patient with hypodipsia-hypernatremia syndrome, the authrs want to emphasize both the risk of rhabdomyolysis in this syndrome and draw the physicians' attention to the occurrence of rhabdomyolysis in hypernatremic situations. By increasing awareness of this, it may be expected that appropriate treatment can be started immediately.
References
1.Opas LM, Adler R, Robinson R, Lieberman E. Rhabdomyolysis with severe hypernatremia. J Pediatr 1997; 90: 713-716.
2.Moritz ML, Ayus JC. The changing pattern of hypernatremia in hospitalized children. Pediatrics 1999; 104: 435-439. [PUBMED] [FULLTEXT]
3.Neg YT, Johnston HM. Clinical rhabdomyolysis. J Pediatr Child Health 20 00; 36: 397-400.
4.Singhal PC, Abromovici M, Ayer S, Desroches L. Determinants of rhabdomyolysis in diabetic state. Am J Nephrol 1991; 11: 447-450.
5.Krahe J, Roll C, Hanssler L, Bonzel KE. Sekundare rhabdomyolyse und akutes nierenversagen bei gastroenteritis mit hypernatriamischer dehydratation. Monatsschr Kinderheilkd 1993; 141: 303-307. [PUBMED]
6.Minami K, Maeda H, Yanagawa T, Suzuki H, Izumi G, Yoshikawa N. Rhabdomyolysis associated with Mycoplasma pneumoniae infection. Pediatr Infect Dis J 2003; 22 :291-293. [PUBMED] [FULLTEXT]
7.Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin 1999; 15: 415-428. [PUBMED]
8.Morales AE, Rosenbloom AL. Death caused by hyperglycemic hyperosmolar state at the onset of type 2 diabetes. J Pediatr 2004; 144: 210-273. [PUBMED] [FULLTEXT]
9.Hollander AS, Olney RC, Blacket PR, Marshall BA. Fatal malignant hyperthermialike syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males. Pediatrics 2003; 111: 1447-1452.
10.Charchman RM, Dechert-Zeger M, Calikoglu AS, Harris BD. A new challenge in pediatric obesity: pediatric hyperglycemic hyperosmolar syndrome. Pediatr Crit Care Med 2005; 6: 20-24.
11.Abramovici MI, Singhal PC, Trachtman H. Hypernatremia and rhabdomyolysis. J Med 1992; 23: 55-62. [PUBMED]
12.V aholder R, Sever MS, Erek E, Lameire N. Acute renal failure related to the crush syndrome: towards an era of seismo-nephrology Nephrol Dial Transplant 2000; 15: 1517-1521.
13.Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol 2000; 8: 72-76. [PUBMED] [FULLTEXT]
14.Watanabe T. Rhabdomyolysis and acute renal failure in children. Pediatr Nephrol 2001; 16 : 1072-1075. [PUBMED] [FULLTEXT](Incecik Faruk, Herguner M Ozlem, Yildizd)