Acute Rhabdomyolysis in a Child with Multiple Suspicious Gene Variants.

Rhabdomyolysis is diagnosed with creatinine kinase (CK) elevation beyond 1000 U/L or ten times above the normal upper limit. Severe episodes can be fatal from electrolyte imbalance, acute renal failure, and disseminated intravascular coagulation. A 13-month-old child was admitted with a CK of 82,090 U/L in the setting of respiratory tract infection-related hyperthermia of 106.9° farenheit. His medical history was significant for prematurity, dystonia, and recurrent rhabdomyolysis. His home medications clonazepam, clonidine, and baclofen were continued upon admission. He exhibited uncontrolled dystonia despite treatment for dystonia. Therefore, sedative infusions and forced alkaline diuresis were begun to prevent heme pigment-induced renal injury. Despite these interventions, his CK peaked at 145,920 U/L, which is rarely reported in this age group. The patient also developed pulmonary edema despite diuresis and required mechanical ventilation. Sedative infusions were not enough for dystonia management, and he needed the addition of a neuromuscular blocking infusion. He finally responded to these interventions, and the CK normalized after a month. He required a month of mechanical ventilation and two and a half months of hospitalization and extensive rehabilitation. We were able to avert renal replacement therapy despite pulmonary edema and an estimated glomerular filtration rate nadir of 21 mL/min/1.73 m2 based on the bedside Schwartz formula. He made a complete recovery and was discharged home. His growth and development were satisfactory for two years after that event. His extensive diagnostic workup was negative. Unfortunately, he died from septic and cardiogenic shock with mild rhabdomyolysis two years later. Prompt recognition, early institution of appropriate therapies, identification of underlying disease, and triggering events are pivotal in rhabdomyolysis management. Evidence-based guidelines are needed in this context.

Mothball Ingestion in the Setting of G6PD Deficiency Causing Severe Hemolytic Anemia, Methemoglobinemia, and Multiple Organ Failure in a Toddler.

Mothballs containing naphthalene or paradichlorobenzene are known to cause hemolysis and methemoglobinemia. They can also affect the other organs, including the kidneys, liver, lungs, and skeletal muscles. The involvement of 1 or 2 organs at a time has been commonly reported. However, more than 2 organ dysfunction in mothball intoxication is rare and usually indicates severe illness. The intoxication can have more pronounced symptoms in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report this case of a previously healthy 13-month-old patient who presented with severe hemolysis, lactic acidosis, methemoglobinemia, acute renal failure, hepatic dysfunction, and rhabdomyolysis. He required aggressive fluid resuscitation, blood transfusions, and mechanical ventilation. The underlying etiology of his illness was initially unclear; however, upon repeated questioning, the father recalled the patient chewing on a mothball 3-4 days before admission. Hence, mothball intoxication was considered the most plausible clinical diagnosis in this patient. He was given N-acetylcysteine, instead of methylene blue, because of hepatic dysfunction and the fact that G6PD deficiency could not be ruled out in the presence of acute hemolysis. The patient made a full recovery after 2 weeks of intensive care unit management. G6PD testing after 3 months confirmed the deficiency. These mothballs are available in Hawai'i, but this is the first report of such a severe presentation to our knowledge. The presence of methemoglobinemia, severe hemolysis, and thorough history-taking helped us determine the diagnosis of mothball intoxication and enabled definitive treatment.

Evaluation of self-dissolving needles containing low molecular weight heparin (LMWH) in rats.

Feasibility study of self-dissolving needles containing polysaccharide was performed. Low molecular weight heparin (LMWH) was used as a representative polysaccharide. Using chondroitin, dextran and dextrin as the base, self-dissolving needles (SDN) were prepared. The obtained SDNs were evaluated in rat absorption experiment, where pharmacological availability (PA) was calculated by comparing the plasma anti-Xa activity vs. time curves between SDNs and i.v. solution. After the insertion of SDNs to rats skin where the doses of LMWH were 25, 50 and 100 IU/kg, plasma samples were collected for 6h and anti-Xa activity was measured as the pharmacological index of LMWH. The anti-Xa level was maintained above 0.2 IU/ml, the therapeutic level, for about 2h at a dose of 100 IU/kg. Almost the same PAs of LMWH were obtained with dextran and dextrin SDNs, 97.7% and 102.3%, though lower PA was obtained with chondroitin SDN, 81.5%. In vitro dissolution experiment showed that LMWH was released from dextran, dextrin and chondroitin SDNs within 10 min. The T(50%)s were 0.84+/-0.06 min for dextran SDN, 1.07+/-0.12 min for chondroitin SDN and 2.11+/-0.31 min for dextrin SDN, respectively. Plasma anti-Xa activity vs. time profiles showed good dose-dependency in the 25-100 IU/kg range and high PAs were obtained, 90.0% for 25 IU/kg, 95.4% for 50 IU/kg and 97.7% for 100 IU/kg from dextran SDNs. Stability experiment was performed with dextran SDNs for 3 months. Above 97% of LMWH were remained in SDNs under three different conditions, -80, 4 and 40 degrees C. These results suggest the usefulness of SDN to polysaccharide drug.