Intractable metabolic acidosis in a child with propionic acidemia undergoing liver transplantation -a case report-
A 22-month old male (body weight: 12.6 kg, height: 90 cm) with PA was scheduled for living donor LT. He was a full term infant born to a family with a history of genetic disease in which his elder sister died of a metabolic disorder at an age of 45 days. He was diagnosed with PA at 7 days of age when he was present with poor feeding and lethargy. Urine amino acid analysis and plasma amino acid analysis were positive for glycine. Urine organic acid analysis was positive for methylcitric acid, propionylglycine, 3-hydroxypropionic acid and triglycine. Plasma organic acid analysis was positive for 3-hydroxypropionic acid and propionylgycine. Specific mutations were identified in the PCC beta polypeptide gene. After the diagnosis, his medical management included low protein diet to reduce the load on amino acid catabolism and administration of sodium benzoate, L-carnitine, L-arginine thiazolidine carboxylate and biotin. He had been hospitalized in many occasions due to pneumonia, metabolic acidosis, and poor oral intake. One month prior to LDLT, he was admitted several times for decreased activity, altered mental status, hyperammonemia and ketoacidosis.\nPreoperative vital signs showed blood pressure of 100/47 mmHg, a heart rate of 104 beats/min, and a respiratory rate of 24 breaths/min. Preoperative laboratory results were as follows: white blood cell 4.8 × 103/µl, hemoglobin 11.1 g/dl, platelet 202 × 103/µl, prothrombin time (international normalized ratio) 0.96, activated partial thromboplastin time 36.0 sec, ammonia 103.6 µmol/L, albumin 1.8 g/dl, protein 4.9 g/dl, total bilirubin 0.3 mg/dl, aspartate aminotransferase 24 U/L, alanine aminotransferase 16 U/L, and creatinine 0.25 mg/dl. The results of arterial blood gas analysis (ABGA) were pH 7.415, PaCO2 36.8 mmHg, PaO2 64.2 mmHg, HCO3- 23.1 mEq/L, BE -1.1 mEq and glucose 102 mg/dl. Chest X-ray and doppler echocardiogram were within normal limits. The patient received 5% DNK3 at 40 ml/hr, preoperatively.\nAnesthesia was induced with midazolam 1 mg, thiopental sodium 75 mg, and rocuronium 10 mg and was maintained with desflurance in air and oxygen (inspiratory oxygen fraction of 0.5) and vecuronium (0.8 µg/kg/min). Ventilation was controlled with a tidal volume of 7-10 ml/kg and ventilatory rate was adjusted to maintain an end tidal CO2 of 35-40 mmHg. Anesthesia monitoring included electrocardiogram, noninvasive blood pressure, pulse oximetry, capnography, and esophageal core temperature. Invasive monitoring included continuous arterial pressures via radial and femoral arteries, femoral venous pressure, and central venous pressure via 5.5 Fr 3-lumen venous catheter placed in the right internal jugular vein. After the induction, the initial ABGA showed a glucose level of 58 mg/dl. We infused 5% dextrose 50 cc/hr, and 1 hour later, the glucose level increased to 122 mg/dl.\nThe operation started 40 minutes after the induction of anesthesia. During the preanhepatic period, the hemodynamic profile remained stable. 1 hour after the start of theoperation, ABGA showed pH 7.211 and BE -15.1 mEq/L, thus continuous infusion of bicarbonate 10 mEq/hr was started and titrated according to the hourly ABGA results. The anhepatic period began at 2 hour 15 minutes after the induction and continuous infusion of dopamine 8 µg/kg/min was initiated to maintain the mean BP above 55 mmHg. 1 hour after the start of the anhepatic period, the glucose level dropped to 45 mg/dl and we infused 5% dextrose 70 cc for 30 minutes. Reperfusion began at one hour and 10 minutes after portal vein clamping. Immediately after reperfusion, the mean BP dropped to 46 mmHg and then normalized within 3 minutes with bolus injections of atropine 0.3 mg and ephedrine 2 mg. During the postreperfusion period, metabolic acidosis still persisted thus requiring continued infusion of barcarbonate 10 mEq/hr. During the operation, the patient received 1,400 ml of crystalloid (normal saline), 450 ml of colloid (voluven®, Fresenius Kabi, Bad Homburg, Germany), and 1 unit of packed red blood cells. In this case, albumin was not administered in order to limit the exogenous source of protein intake. The total duration of operation was 8 hours and 51 minutes. Three hours and 30 minutes after the reperfusion, the patient was transferred to the intensive care unit. Intraoperative laboratory test results are summarized in .\nThe patient's postoperative course was complicated by persistent metabolic acidosis and hepatic failure due to hepatic vein obstruction (). On postoperative day (POD) 0, dopamine 20 µg/kg/min was continuously infused due to low BP and aliquots of bicarbonate 20 mEq were administered to correct metabolic acidosis. On POD 1, abdominal sonography revealed hepatic vein obstruction prompting the patient to undergo emergency re-operation for hepatic vein obstruction. Anesthesia was induced and maintained with isoflurane in air and oxygen (inspiratory oxygen fraction of 0.5) and vecuronium. Ventilation was controlled with a tidal volume of 7-10 ml/kg and ventilatory rate was adjusted to maintain an end tidal CO2 of 35-40 mmHg. After the induction, initial ABGA showed pH 7.135, BE -14.8mEq/L and a glucose level of 55 mg/dl. The patient received 5% dextrose 30 cc/hr and 0.45% normal saline 60 cc/hr. Dopamine 30 µg/kg/min was administered to maintain the mean BP above (55 mmHg) and continuous infusion of bicarbonate 8 mEq/hr was given for progressive metabolic acidosis. The surgery lasted for 2 hours, and the patient's ABGA at the end of surgery showed pH 7.179, BE -13.4 mEq/L and the glucose level of 55 mg/dl. In spite of re-operation, patient's liver function deteriorated further and metabolic acidosis worsened. Moreover, the patient developed hemodynamic compromise requiring continuous infusion of dopamine 30 µg/kg/min, epinephrine 1 µg/kg/min, and norepinephrine 5 µg/kg/min. On POD 4, the patient expired as a result of hepatic failure and subsequent severe metabolic acidosis.