Clin Exp Nephrol (2007) 11:88–91 DOI 10.1007/s10157-006-0449-0
© Japanese Society of Nephrology 2007
CASE REPORT Sanjay Vikrant · Deveshwar Pandey · Rajeev Raina Ashok Sharma
Deep vein thrombosis complicating severe hypernatremia, rhabdomyolysis, and acute renal failure in a patient with untreated seizure disorder
Received: August 21, 2006 / Accepted: October 7, 2006
Abstract We report a 22-year-old male patient with untreated seizure disorder, presenting with increased frequency of seizures followed by encephalopathy. Laboratory evaluation showed severe hypernatremia (175 meq/l sodium), rhabdomyolysis, and acute renal failure (ARF). Excessive insensible water loss in hot and humid weather, associated with an inability to obtain adequate water replacement, led to a hyperosmolar state (plasma osmolality, 398 mOsm/kg). He was vigorously treated with hypotonic fluid supplement and, further, needed dialysis therapy (peritoneal dialysis followed by hemodialysis) for acute renal insufficiency. The patient survived without any neurological sequelae, but the clinical course was complicated by acute deep vein thrombosis. This case represents what we believe is a unique report in the literature of severe hypernatremia developing via the pathogenic mechanism outlined above and the complication of acute peripheral venous thrombosis, which has not been reported in adults. The purpose of this report is to emphasize hyperosmolarity as a newly described cause of rhabdomyolysis, ARF, and a hypercoagulable state. Key words Acute renal failure · Hypernatremia · Rhabdomyolysis · Seizure disorder · Deep vein thrombosis
Introduction Hypernatremia in young adults is a rare condition.1 The few reported patients with severe hypernatremia had an adverse outcome, with high mortality and/or severe neurological sequelae.2–5 We describe a patient with untreated
S. Vikrant (*) · D. Pandey Department of Nephrology, Indira Gandhi Medical College, Shimla (Himachal Pradesh)-171001, India Tel. +91-177-2651108; Fax +91-177-2658339 e-mail:
[email protected] R. Raina · A. Sharma Department of Medicine, Indira Gandhi Medical College, Shimla (Himachal Pradesh)-171001, India
seizure disorder who survived severe hypernatremia (175 meq/l sodium), rhabdomyolysis, and acute renal failure (ARF). The clinical course was complicated by acute deep vein thrombosis (DVT), but the patient survived without any neurological sequelae. This case represents what we believe is a unique report in the literature of sever hypernatremia developing via this pathogenic mechanism and the complication of acute peripheral venous thrombosis.
Case report A 22-year-old man was admitted with a history of increasing frequency of seizures in the previous 10 days and altered sensorium for 1 day. The patient was having one to two episodes of generalized tonic-clonic (GTC) seizures daily. There was a history of excessive sweating leading to the wetting of clothes and bed sheets. There was no history of fever, headache, or focal neurological deficit. The patient was known to have had GTC seizures for the previous 5 years, with seizure episodes every 1–2 months, and was not on any antiepileptic drug therapy. On examination on admission, the patient was in a stupor and dehydrated, and his body temperature was elevated. He was hemodynamically stable: pulse was 88/min; blood pressure was 110/70 mmHg and respiratory rate was 20/min. On central nervous system examination, meningeal signs were absent, there was no focal neurological deficit, and deep tendon reflexes were elicitable. Fundus examination was normal. Results of emergency investigations done on day 1 were: hemoglobin, 12.5 g/dl and total WBC count, 12 800, with polymorphs 68% and lymphocytes 31%. Blood urea was 178 mg/dl; creatinine, 2.7 mg/dl; sodium, 155 meq/l; potassium, 5.3 meq/l; chloride, 116 meq/l; and random blood sugar, 205 mg/dl. Cerebrospinal fluid (CSF) analysis revealed: no cells; protein, 45 mg/dl; and sugar, 118 mg/dl. Chest X-ray and electrocardiogram (EKG) were normal. Noncontrast computerized tomogram (NCCT) of the head showed a very hyper dense mass, measuring 2.03 × 1.65 × 2 cm, in the
89 Fig. 1. Noncontrast computerized tomogram (NCCT) of the head, showing a very hyperdense mass, measuring 2.03 × 1.65 × 2 cm, in the left temporo-parietal region of the brain (density 700 HU) – possibly a calcified granuloma
left temporoparietal region of the brain (density 700 HU) – possibly a calcified granuloma (Fig. 1). Results of routine investigations were: hemoglobin, 14 g/ dl; total WBC count, 7300, with polymorphs 57%, lymphocytes 38%, and platelets 252 × 109/l; erythrocyte sedimentation rate (ESR), 10 mm first hour; peripheral blood smear, normal. Blood urea was 238 mg/dl; creatinine, 3.9 mg/dl; sodium, 175 meq/l; potassium, 6.9 meq/l; chloride, 128 meq/l; calculated plasma osmolality, 398 mOsm/kg; calcium, 8.4 mg/ dl; phosphorous, 8.5 mg/dl; uric acid, 11.2 mg/dl; protein, 7 g/dl; albumin, 3.9 g/dl; bilirubin, 0.8 mg/dl; aspartate aminotransferase (AST), 90 IU/l; alanine aminotransferase (ALT), 101 IU/l; alkaline phosphatase, 183 U/l; random blood sugar, 120 mg/dl; cholesterol, 148 mg/dl; serum creatine phosphokinase (CPK-MM), 2497 U/l (normal range, 24–170 U/l). Arterial blood gas (ABG) revealed pH 7.24; PaO2, 80 mmHg; PaCO2, 24 mmHg; HCO3, 10 meq/l; arterial oxygen saturation (SaO2), 95%. Urinalysis showed specific gravity, 1.020; albumin, +; RBCs, 1–3 per high-power field (HPF); WBCs, 3–5 HPF; cast, +; and urine sodium, 35 mmol/ l; urine culture was sterile. Ultrasound of the kidney, ureter, and bladder (KUB) region showed normal-sized kidneys with increased echo texture. Doppler study revealed deep vein thrombosis (DVT) of the left lower limb: The left common femoral vein was dilated and noncompressible and contained an echogenic thrombus. The superficial and deep femoral vessels also contained thrombus and did not give any signal. The popliteal vein was also dilated and noncompressible. The patient was admitted with a diagnosis of untreated seizure disorder and so was given a loading dose of phenytoin and hypotonic fluid, in the form of 5% dextrose, as per water deficit to correct hypernatremic dehydration. Routine investigation on day 2 revealed severe hypernatremia (sodium, 175 meq/l), hyperchloremia, hyperkalemia, azotemia (urea, 238 mg/dl; creatinine, 3.9 mg/dl), and high anion gap (AG) metabolic acidosis, however, and the patient was started on peritoneal dialysis. There was also evidence of rhabdomyolysis: increased creatine phosphokinase (CPK)A10 (MM), phosphorous, and uric acid, and decreased
calcium and albumin. Peritoneal dialysis (PD) was given for 40 cycles, during which the water deficit was corrected by creating a positive PD balance of 7.5 l. The hypernatremia was corrected on day 5 and there was also a gradual improvement in sensorium. But the patient developed swelling of the left lower limb and a doppler study revealed complete thrombotic obstruction of the femoral and popliteal veins. The patient was given low-molecular-weight heparin for 10 days and put on an oral anticoagulant. He required two hemodialysis sessions, and renal functions normalized on day 23 of his hospital stay (Table 1). The patient was discharged on phenytoin and an oral anticoagulant. At discharge, sensorium had normalized and the leftleg swelling had decreased. On follow-up at 2 weeks, the left-leg swelling had disappeared and the patient had completely recovered. He was advised to continue the antiepileptic drug therapy long-term and the oral anticoagulant for 3 months. He was seizure-free on follow-up at 6 months.
Discussion Partial and generalized seizures often affect autonomic function during seizures, as well as during the interictal and postictal periods. The autonomic dysfunction during or after seizures may cause excessive sweating.6 Further, the sodium concentration of sweat decreases with profuse perspiration, thereby increasing solute-free water loss.1 Our patient had a history of increased frequency of seizures and excessive sweating for the 10 days prior to admission. He developed a water deficit secondary to excessive insensible water loss, due to the increased frequency of seizures and excessive sweating, leading to hypotonic fluid during a period of hot, humid weather, associated with an inability to obtain adequate water replacement due to his acute illness and altered sensorium. On admission to the hospital, the patient was in a stupor and was clinically dehydrated. His laboratory values were consistent with a water deficit of
90 Table 1. Laboratory tests and urine output Day
1
2a
Hemoglobin (g/dl) Sodium (meq/l) Potassium (meq/l) Chloride (meq/l) Urea (mg/dl) Creatinine (/dl) Urine output (ml/day)
12.5
14
155
175
161
150
145
142
138
139
135
136
136
142
143
143
142
5.3
6.9
4.9
3.5
3.6
4.0
3.5
4.0
3.9
4.0
3.9
4.6
4.2
4.0
4.5
116
128
113
106
102
101
102
109
107
107
178
238
264
213
158
185
220
284
250
140
159
101
62
40
23
2.7
3.9
4.0
4.5
4.5
4.3
5.2
5.3
4.6
3.3
4.3
2.1
1.8
0.9
0.5
350
450
650
1080
1000
700
800
700
1900
2300
4300
2900
2000
1700
a b
3a
4a
5
6
7
9b
10b
12
11
13
18
20
11.8
110
23
Follow-up
11
Patient was treated with peritoneal dialysis Patient was treated with hemodialysis
approximately 25% (7.5 l) of body water. The patient also had ARF associated with advanced azotemia, hyperkalemia, and high anion gap (AG) metabolic acidosis. He was treated with PD, during which the water deficit was corrected by administering hypotonic fluid supplements and achieving a positive PD balance. Hypokalemia, hypocalcemia, hypophosphatemia, hyponatremia, and, particularly, hypernatremia and hyperosmotic conditions, have all been associated with rhabdomyolysis. The degree of rhabdomyolysis that can manifest ranges from a subclinical rise in creatine kinase (CK) to a medical emergency consisting of interstitial and muscle cell edema, contraction of intravascular volume, and pigment-induced ARF.7 The ARF due to rhabdomyolysis secondary to muscle injury is characterized by muscle tenderness, swelling and/or necrosis, pigmenturia (red-brown urine) resulting from myoglobinuria, oliguria, elevated blood levels of muscle enzymes (CPK and aldolase), and abnormalities in serum electrolytes (including hypocalcemia, hyperphosphatemia, hyperkalemia, hypermagnesemia, acidosis, and marked hyperuricemia). Transient moderate to severe elevation of liver enzymes and bilirubinemia may be seen in many patients with rhabdomyolysis. Leukocytosis is almost always present. Rhabdomyolysis may aggravate hypernatremia, because the intracellular breakdown of macromolecules into smaller molecules will promote the shift of water from the extracellular fluid (ECF) into muscle cells.7 Rhabdomyolysis and ARF as complications of severe hypernatremia were seen in our patient. The association of decreased ECF volume and rhabdomyolysis were likely causes of ARF in our patient. The patient reported herein developed a typical clinical picture of acute DVT which was confirmed by Doppler ultrasound. The pathogenesis of DVT of the lower limbs is related to factors included in the classic triad of stasis, vessel wall damage, and hypercoagulability.8 In particular, the association of hypercoagulability with venous stasis, which allows accumulation of activated coagulation factors in the venous valve sinuses of the calf, is regarded as the primary triggering mechanism in the development of most venous
thrombi.8 This combination occurs in circumstances such as surgical procedures, leg trauma or fracture, and prolonged immobilization of any cause. Chronic hypernatremia in patients with prolonged immobilization is associated with an increased risk of the development of DVT.9 Hypernatremia and increasing plasma arginine vasopressin (AVP) concentrations produce changes in hemostatic function consistent with a hypercoagulable state (Increase in factor VIII coagulant acitivity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity and fibrinopeptide A concentration with shortening of the activated partial thromboplastin time).10 The mechanisms of the effect are unclear. These changes in hemostatic function might contribute to the thromboembolic complications of conditions such as hyperosmolar coma in diabetes mellitus or severe heatstroke in which degrees of hypernatremia occur. In conclusion, the case we have reported represents what we believe is a unique report in the literature of severe hypernatremia developing via the pathogenic mechanism outlined above, and the complication of acute peripheral venous thrombosis in an adult patient. Patients with chronic hypernatremia and prolonged immobilization are at increased risk of the development of DVT, and such patients should be given DVT prophylaxis during their managed care.
References 1. Palevsky PM. Hypernatremia. In: Greenberg A, editor. Primer on kidney diseases. 2nd ed. San Diego, California: Academic; 1998;64–71. 2. Elisaf M, Litou H, Siamopoulos KC. Survival after severe iatrogenic hypernatremia. Am J Kidney Dis 1989;14:230–1. 3. Kamijo Y, Soma K, Hamanaka S, Nagai T, Kurihara K. Dural sinus thrombosis with severe hypernatremia developing in a patient on long-term lithium therapy. J Toxicol Clin Toxicol 2003;41:359–62. 4. Gomez-Daspet, Elko L, Grebenev D, Vesely DL. Survival with serum sodium level of 180 meq/l: permanent disorientation to place and time. Am J Med Sci 2002;324:321–5. 5. Lima EQ, Aguiar FC, Barbosa DM, Burdmann EA. Severe hypernatraemia (221 mEq/l), rhabdomyolysis and acute renal failure
91 after cerebral aneurysm surgery. Nephrol Dial Transplant 2004; 19:2126–9. 6. Devinsky O. Effects of seizures on autonomic and cardiovascular function. Epilepsy Curr 2004;4:43–6. 7. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000;11:1553–61. 8. Thomas DP. Pathogenesis of venous thrombosis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, editors. Hemostasis and throm-
bosis: basic principles and clinical practice. Philadelphia: JB Lippincott; 1987. p. 820–30. 9. Bergada I, Aversa L, Heinrich JJ. Peripheral venous thrombosis in children and adolescents with adipsic hypernatremia secondary to hypothalamic tumors. Horm Res 2004;61:108–10. 10. Grant PJ, Tate GM, Hughes JR, Davies JA, Prentice CR. Does hypernatraemia promote thrombosis? Thromb Res 1985;40: 393–9.
