Rhabdomyolysis is a potentially life-threatening condition that can result into complications such as hypovolemia, hyperkalemia, metabolic acidosis, acute kidney injury (AKI) and disseminated intravascular coagulation (DIC) [1]. Viral myositis is the most frequent cause of rhabdomyolysis in children [2]. Management of rhabdomyolysis includes aggressive fluid resuscitation and hydration in order to maintain adequate urine output and prevent AKI, and early correction of potentially lethal electrolyte disturbances [3]. For children with ongoing AKI in spite of conservative management, renal replacement therapy is warranted.

A 6-year-old, previously healthy girl presented to us with a febrile illness and profound pain in lower extremities. There was no history of trauma, excessive exercise or insect bite. Investigations showed elevated creatine kinase (CK) level (5169 U/L) and negative dengue serology (NS-1 antigen, IgM and IgG). Child was started on intravenous hydration and oral paracetamol. Her serum creatinine was 0.41 mg/dL. The next day, patient had asystolic cardiac arrest that reverted with cardiopulmonary resuscitation for two minutes. She was put on mechanical ventilation. Child also had coagulopathy that was treated with fresh frozen plasma and platelet transfusions. She was noted to have severe metabolic acidosis, elevated hepatic transaminases (SGOT 10,786 U/L, SGPT 3131 U/L) as well as reduced ejection fraction (35%) on Two-dimension echocardiography (2D-Echo) examination. Her serum creatinine was 0.58 mg/dL. Subsequent laboratory investigations revealed hyperkalemia (serum K+ 5.9 mEq/L), hypoalbuminemia and further rise in CK level (23586 U/L). Urine microscopic examination revealed ocassional red blood cells and positive urine myoglobin. Sodium bicarbonate infusion was added for alkalization of her urine. Considering very high CK levels, positive fluid balance (3 liters) and dark colored urine, acute renal tubular injury was considered. The child was started on intermittent hemodialysis (HD) with high flux dialyzer (Fx 60). Due to hemodynamic instability, patient was shifted to continuous renal replacement therapy (CRRT) next day in Continuous Veno-Venous Hemofiltration (CVVH) mode. Cytosorb filter was added to remove myoglobin (molecular weight 17kDal) and CK (molecular weight 81kDal). After three days of Cytosorb and five days of continuous CRRT, patient was shifted to intermittent hemodialysis with F×60, as she was hemodynamically stable. Repeat CK and myoglobin levels revealed decreasing trends, with lowest being (CK 219 U/L, myoglobin 171 ng/mL) by day 27 and day 19, respectively. Pharyngeal swab showed Polymerase chain reaction (PCR) for influenza B and enterovirus positive. During the renal replacement therapy, there were no complications such as bleeding, infection, hypophosphatemia or hypokalemia.

Fig.1 Trend of serum creatinine kinase (a), myoglobin (b), and creatinine (c) in index patient.

Intermittent hemodialysis was stopped on day 33 as patient’s urine output improved; her creatinine also normalized (0.53 mg/dL) by day 44. The trend of CK, myoglobin and serum creatinine is summarized in Fig. 1. Patient was transferred to ward and subsequently discharged home after a week. On follow-up, six months after discharge, child had gained weight (1.5 kg). Her serum creatinine was 0.26 mg/dl and the estimated glomerular filtration rate (eGFR) was 271 mL/minute.

Incidence of AKI secondary to rhabdomyolysis has been reported variably from 17-35% in adults and 5-50% in children [2,4]. Although renal replacement therapy is rarely needed in rhabdomyolysis, it should be considered when there is severe and resistant hyperkalemia, persistent metabolic acidosis, uremia and ongoing AKI despite conservative treatment. In the present case, we managed AKI associated with rhabdomyolysis with the combination of CRRT and Cytosorb. We added Cytosorb in line with the CRRT circuit in pre-dialyzer position for first 72 hours during CRRT with the intention of removing myoglobin from blood.

Cytosorb is a cytokine adsorbing polymer filter, initially intended as adjunctive treatment for patients with elevated cytokine levels in the setting of severe sepsis and septic shock. It contains hemoadsorption beads made up of polystryrene-divinylbenzene porous particles with a biocompatible polyvinyl-pyrrolidone coating [5]. In addition to cytokines, it has been shown to reduce serum myoglobin in adults with rhabdomyolysis [6]. In the patient discussed, early weaning of inotropic support and rapid improvement in multiorgan dysfunction including coagulopathy suggests the role of extra-corporeal filter therapy.

CRRT in conjunction with CytoSorb represents a novel approach to the treatment of AKI associated with rhabdomyolysis in children. Although early initiation of extracorporeal therapy seems to improve the outcome, currently there is no absolute clarity on identifying patients with rhabdomyolysis needing renal replacement therapy, the levels of CK or serum myoglobin at which RRT should be initiated and the optimum duration of use of Cytosorb in these patients. Data on a larger number of children with rhabdomyolysis need to be evaluated before instituting the above therapy as a standard management protocol.

6. Wiegele M, Krenn CG. Cytosorb™ in a patient with legionella-pneumonia associated rhabdomyolysis: a case report. ASAIO J. 2015;61:e14-6.