Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report
A 29-year-old man presented at a emergency room in a stupor.\nThe patient had started psychiatric treatment after being diagnosed with personality disorder and hypochondriasis by the department of psychiatry in our hospital 4 years ago. After about 1 year of treatment, olanzapine was administered due to the patient's symptoms of social withdrawal and distrust of people. After the initiation of olanzapine, the patient's body weight increased by ≥30 kg, and hyperthermia occurred together with nausea and vomiting 1 week prior to the visit to our hospital. The patient received a prescription from a neighboring hospital and had taken antipyretics, but did not show any improvement. Then the patient showed mental deterioration and was admitted to our hospital via the emergency room.\nBoth parents were moderately built, and none of the family members, including siblings, had a metabolic disease such as diabetes.\nThe patient was on medication due to incidences of personality disorder, hypochondriasis, and psychotic tendency, taking olanzapine 10 mg, valproic acid 500 mg, clonazepam 0.5 mg, and lorazepam 1 mg on a daily basis. The aforementioned medication regimen was maintained for over 1 year without any dosage change, and the intake period of olanzapine was 32 months. There was no other underlying disease than the aforementioned, and there were no abnormal test results based on blood assay, including an assay for fasting plasma glucose, which was performed prior to administration of antipsychotics.\nThe patient had no history of smoking or alcohol drinking and was unemployed since completion of military service as social service personnel.\nIn physical examination, the patient showed acute signs of illness and was in a coma. His vital signs measured at the time of visit to our hospital were 110/70 mm Hg for blood pressure (BP), 120 beats per minute for pulse rate, 24 times per minute for respiratory rate, and 37.2℃ for body temperature. The patient's height was 181 cm, weight was 104 kg and body mass index (BMI) was 31.7 kg/m2. His consciousness state was stupor with normal light reflexes, and senses as well as spontaneous motions of extremities were maintained. Chest auscultation revealed that the heart rate was fast, but there was no murmur, and the patient had tachypnea, but had no crackles or wheezing sound auscultated. There was neither notable tenderness nor rebound tenderness from the abdomen. The patient's skin was dry overall.\nPeripheral blood assay showed the following results: white blood cell 6,560/mm3 (neutrophil 72%), hemoglobin 20.2 g/dL, hematocrit 60.8%, and platelets 228,000/mm3. Taking the findings of physical examination into account, dehydration-induced hemoconcentration was suspected. The results of serum biochemical assay revealed that the plasma glucose level had increased to 1,216 mg/dL, the blood urea nitrogen level was 31 mg/dL, and creatinine level was 2.4 mg/dL. The result also showed the following: sodium, 149 mEq/L; potassium, 4.5 mEq/L; chloride, 96 mEq/L; total protein, 8.7 g/dL; albumin, 5.0 mg/dL; aspartate aminotransferase, 28 IU/L; alanine aminotransferase, 44 IU/L; total bilirubin, 0.6 mg/dL; calcium, 11.5 mg/dL; phosphate, 6.1 mg/dL; and creatine phosphokinase (CPK), 80 U/L (reference range, 30 to 170). Dipstick-utilized urine assay showed a positive reaction to ketone, and increases in amylase and lipase to 545 IU/L (reference range, 28 to 100) and 1,435 U/L (reference range, 13 to 60), respectively. Arterial blood gas analysis (ABGA) showed that the pH was 7.25, pCO2 was 18.9 mm Hg, pO2 was 86.1 mm Hg, HCO3- was 8.2 mEq/L, and oxygen saturation was 95.7%, presenting metabolic acidosis with 44.8 mEq/L of anion gap. The glycosylated hemoglobin level was 13.8%, while the serum C-peptide level tested during the administration of insulin were 0.38 ng/mL. So the patient was presumed to be in DKA and acute renal failure.\nElectrocardiography findings showed sinus tachycardia with rate of 150 beats per minute.\nThere were no specific findings from the chest X-ray examination, and there was no evidence of ileus other than fecal impaction shown on abdominal X-ray examination. An abdominal computed tomography scan showed no findings of edema or necrosis or fluid retention in the pancreatic parenchyme and its periphery ().\nAlthough there was no sign of BP reduction, the patient showed severe dehydration induced by extreme hyperglycemia and metabolic acidosis. We administered ≥4 L per day of fluid through intravenous infusion and immediately began insulin pump therapy. Within 24 hours of insulin therapy, the plasma glucose level was reduced to less than 300 mg/dL (), the anion gap level was reduced to normal range and ABGA showed that the patient was out of metabolic acidosis. But, in spite of fluid infusion of ≥2 L per day, hyperthermia occurred and the levels of CPK and creatinine began to increase rapidly to 16,161 U/L and 4.1 mg/dL, respectively, on the 3rd day of hospitalization. Also, the urinary myoglobin level was 1,879 ng/mL. In addition, the patient was in a confused mental state with severe muscle stiffness and rigidity, and increased uptake at upper and lower proximal limb was shown on bone scan (). Even with fluid treatment for acute renal failure, the level of creatinine continued to increase, so we started continuous renal replacement therapy (CRRT) on the 5th day of hospitalization (). After initiation of CRRT, the patient showed remarkable improvement in fever and consciousness, so we converted dialysis modality to intermittent hemodialysis 3 days later and maintained the treatment until the 12th day of hospitalization. The urine output was normalized and there was no additional elevation in creatinine and CPK concentrations, so we discontinued hemodialysis (). The patient presented consciousness deterioration, muscle stiffness, and high fever that did not respond to antipyretics and fluid infusion with history of taking antipsychotics, so we determined that the patient had NMS, and implemented supportive therapy including discontinuation of causative medication. We used the insulin pump for glycemic control in the early stage, and changed to multiple daily injections of insulin to manage the patient's condition. We could discontinue the administration of insulin on the 41st day after the first visit to our hospital as the insulin demand had gradually decreased. And we changed to metformin monotherapy. We stopped the administration of oral hypoglycemic agents on the 52nd day. On follow-up examination, we confirmed a notable reduction in glycosylated hemoglobin and a remarkable restoration of the serum C-peptide level (). Currently, the patient is maintaining very good glycemic control only by life style modification and is under prognostic observation as an outpatient.