Discussion
Seizures have the ability to increase CK levels and even increase the rate of in-hospital mortality [2, 12, 13]. Bosch et al. proposed that less severe RM with few symptoms and no renal failure could be designated hyperCKemia [2]. No patient developed renal failure or needed renal replacement therapy in the present study. Therefore, in this study, it was appropriate to define elevated CK as hyperCKemia.
In the current study, patients did not experience any trauma, metabolic disorders, alcohol abuse, exposure to drugs or toxins, infection or sepsis, myocardial infarction, or other diseases associated with hyperCKemia [2, 7]. However, significant electrolyte disorders caused by bowel preparation, vomiting, and diarrhea were observed in patient 4 (hyponatremia and hypomagnesemia) and patient 6 (hypokalemia and hypomagnesemia). Among the different electrolyte disorders, hypokalemia and hypophosphatemia are known to cause damage to myocytes [1], but hypophosphatemia was not observed in our cases.
Some studies indicated that a potassium level less than 2.0 mmol/L observed in the initial evaluation could potentially cause RM [1, 16-18]. In the present study, it appeared that hypokalemia was not the primary cause of hyperCKemia in patient 6, who exhibited a potassium level of 2.66 mmol/L. No causal association has been established between desmopressin acetate-induced hyponatremia and muscle injury in animal studies [19]. In a clinical study, asymptomatic hyperCKemia was associated with hyponatremia caused by diuretics and polydipsia, which may have been complicated by AKI [20]. Compared to ultra-athletes with normonatremia, exercise-associated hyponatremia is prone to develop into exercise-associated RM [21]. Severe hyponatremia was observed in patient 6, and we considered that hyponatremia might promote the development of hyperCKemia. Hypomagnesemia was observed in two patients, which may have been due to gastrointestinal losses as they had a history of bowel preparation, vomiting, and diarrhea [22]. There was less possibility of other causes of hypomagnesemia because these patients did not have any history of hypomagnesemia, and their serum magnesium gradually recovered after supplementation. Therefore, for these two patients, hyperCKemia might have been caused synergistically by electrolyte disorders and seizures.
Consequently, it was likely that the seizures experienced by the patients in the present study caused the hyperCKemia. Other factors might have been involved in the pathophysiological process associated with muscle damage, especially the electrolyte disorders. Thus, we recommend performing serial testing for levels of CK and electrolytes after seizure onset.
Early and aggressive repletion of several liters of fluid to restore renal perfusion and increase the urine flow rate is the primary management for AKI [1, 2, 23]. We administered normal saline at 1,500 ml/day to the majority of patients with kidney function impairment in the cases in this study. Fluid was administered at a rate of 2,500 ml/day to patient 6 due to his history of vomiting and diarrhea. Only patient 6 had a lower eGFR (55.65 ml/min/1.73m2). However, patient 6 did not report any history of kidney function impairment, such as renal disease, toxin exposure, or sepsis [24]. Unfortunately, we could not investigate the reason for this outcome, as patient 6 did not have a follow-up examination.
Urinary alkalization and diuretic agents were administrated to the patients in this study. Alkaline urine might prevent lipid peroxidation, redox-cycling, and myoglobin cast formation [2, 23]. Diuresis might prevent the accumulation of debris in the renal tubules, increase renal perfusion, and improve myoglobin excretion [1, 24]. Mannitol should be avoided in anuric patients, and electrolytes should be monitored if loop diuretics are used [1, 25]. Fortunately, no patient in this study developed renal failure or required continuous renal replacement therapy, probably due to the rate for renal failure was lower in exertional RM or generalized tonic-clonic seizures [10, 12]. The eGFR for all patients increased after treatment even though the recovery level was less than 90 mL/min/1.73m2 at the time of discharge. It might be necessary to conduct a follow-up examination.