Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.

BACKGROUND: Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset Pompe disease. METHODS: Patients were diagnosed at 6 months of age and younger and exhibited severe GAA deficiency and cardiomyopathy. Patients received IV infusions of rhGAA at 20 mg/kg (n = 9) or 40 mg/kg (n = 9) every other week. Analyses were performed 52 weeks after the last patient was randomized to treatment. RESULTS: All patients (100%) survived to 18 months of age. A Cox proportional hazards analysis demonstrated that treatment reduced the risk of death by 99%, reduced the risk of death or invasive ventilation by 92%, and reduced the risk of death or any type of ventilation by 88%, as compared to an untreated historical control group. There was no clear advantage of the 40-mg/kg dose with regard to efficacy. Eleven of the 18 patients experienced 164 infusion-associated reactions; all were mild or moderate in intensity. CONCLUSIONS: Recombinant human acid alpha-glucosidase is safe and effective for treatment of infantile-onset Pompe disease. Eleven patients experienced adverse events related to treatment, but none discontinued. The young age at which these patients initiated therapy may have contributed to their improved response compared to previous trials with recombinant human acid alpha-glucosidase in which patients were older.

Abdominal compartment syndrome in children.

OBJECTIVE: To investigate the frequency, predisposing factors, clinical presentation, and outcome of abdominal compartment syndrome (ACS) in critically ill pediatric patients. DESIGN: A prospective study over a 5-yr period. SETTING: Pediatric intensive care unit of a tertiary care, university hospital. PATIENTS: All patients admitted to the pediatric intensive care unit were screened for the presence of ACS and were treated with a uniform protocol. ACS was defined as abdominal distention with intra-abdominal pressure (IAP) > 15 mm Hg, accompanied by at least two of the following: oliguria or anuria; respiratory decompensation; hypotension or shock; metabolic acidosis. MEASUREMENTS AND MAIN RESULTS: Of 1762 patients admitted over 5 yrs, ten patients (0.6%) had a total of 15 episodes of ACS. Of 406 trauma cases, three had ACS (0.7%). Three of the ten patients had primary abdominal conditions (mesenteric vein thrombosis, intussusception, enterocolitis), three had abdominal surgery (trauma, Kasai operation, esophageal perforation and peritonitis), three had primary central nervous system involvement, and one had meningococcemia. At laparotomy, bowel ischemia or necrosis was found in four episodes of ACS (27%). Mean IAP at diagnosis of ACS was 23.9 +/- 3.8 (range 17-31) mm Hg. Physiologic parameters were compared during 4 hrs before the development of ACS, during ACS, and after abdominal decompression. Mean arterial pressure, Pao(2), Pao(2)/Fio(2) ratio, and urinary output decreased significantly, whereas Paco(2), peak inspiratory pressures, positive end-expiratory pressures, and base deficit increased significantly after the development of ACS. After decompressive laparotomy, the condition of the patients improved promptly and these variables returned to pre-ACS values. Overall mortality rate in this group was 60%. CONCLUSIONS: Although relatively infrequent compared with adults, ACS occurs in critically ill children. Timely decompression of the abdomen results in uniform improvement, but overall mortality is still high. In contrast with adults, children with ACS have diverse primary diagnoses, with a significant number of primary extra-abdominal-mainly central nervous system-conditions. Ischemia and reperfusion injury appear to be the major mechanisms for development of ACS in children. Clinical presentation is similar to adults, but children may develop ACS at a lower IAP (as low as 16 mm Hg).

Treatment of acute hyponatremia: ensuring the excretion of a predictable amount of electrolyte-free water.

BACKGROUND: Hypertonic saline is the recommended therapy to shrink swollen brain cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES: In the absence of hypertonic saline, hypertonic mannitol will shrink the cell volume. Because mannitol is excreted rapidly, our aim was to ensure that it would be excreted with electrolyte-free water (EFW) and to evaluate the renal mechanisms responsible for EFW excretion. DESIGN: A randomized, prospective, placebo-controlled study in rats was carried out in a research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group of rats (n = 6) was administered hypotonic saline, a loop diuretic, vasopressin, and glucose by the intraperitoneal route; in the experimental group (n = 6), glucose was replaced with mannitol. Plasma electrolytes were measured at 0 and 210 mins, and balances for water, sodium, and potassium were obtained from 0 to 90 mins and from 90 to 210 mins. MEASUREMENTS AND MAIN RESULTS: Virtually 100% of the administered mannitol was excreted within 210 mins, and half was excreted in the first 90 mins. The urine contained EFW only in the mannitol group because of a larger volume in the first 90 mins (EFW, 3.7 mL) and to a lower excretion of NaCl in the next 120 mins (EFW, 3.5 mL). CONCLUSIONS: The combined use of mannitol and a loop diuretic caused the excretion of a predictable volume of EFW because the urine was iso-osmotic to plasma and contained all the administered mannitol. The calculated decrease in intracellular fluid volume was equivalent when mannitol was retained or excreted.

Intratracheal pulmonary ventilation in premature infants and children with intractable hypercapnia.

The feasibility of intratracheal pulmonary ventilation (ITPV) was tested in five ventilated moribund neonatal and pediatric patients with uncontrollable hypercapnia: a 2-year-old child, a 52-day-old infant, and three premature infants (29, 29, and 26 weeks gestation; 1300 g, 1100 g and 890 g birth weight, respectively). ITPV was applied for 9.5, 8, 25, 58.5, and 47.5 hr, respectively. An intratracheal catheter (Cook Critical Care, Inc., Bloomington, IN) with a reversed continuous flow of gas at its tip (away from the lungs) allowed flushing of CO2 from the proximal dead space. Marked reductions in Paco2, ranging from 37% to 71% and improvement in pH were achieved within 4-6 hr of applying ITPV. During ITPV, the mean lowest Paco2 was significantly less than the pre-ITPV Paco2 (p < 0.0017), and the mean best pH was significantly higher than the pre-ITPV pH (p < 0.015). In four patients, despite significant reductions in Paco2, there was no substantial improvement in their baseline condition (shock and severe metabolic acidosis or coma) and they were switched back to conventional ventilation. This led to worsening hypercapnia to pre-ITPV values. These four patients subsequently died. It is possible that these patients were already too ill to derive significant benefit from the technique. One premature infant survived, was successfully weaned to conventional ventilation and was eventually discharged home. ITPV can alleviate uncontrollable hypercapnia in ventilated neonatal and pediatric patients.

Clostridium septicum infection in children with cyclic neutropenia.

Atraumatic Clostridium septicum infection is rare in infancy and childhood and is associated with a high mortality rate. Although in adults it has been reported to occur mainly in patients with gastrointestinal malignancy, pediatric cases were always associated with neutropenia. About 70% of the cases were described in children with neutropenia caused by chemotherapy and 30% were found in children with cyclic neutropenia. No case was described in children with other forms of congenital severe neutropenia. We describe three children with cyclic neutropenia and severe Clostridium septicum infection, discuss the various possibilities of causation, and the need for prompt and aggressive treatment of this serious condition.

Punch pulmonary valvectomy: another alternative to treat critical pulmonary stenosis.

For neonates with severe valvar stenosis, or valvar pulmonary atresia with an imperforate pulmonary valve, we present a simple but effective closed procedure using a specially designed valvectomy punch. Seven neonates, who were not suitable for any type of transcatheter procedure, were treated. There were two late deaths, neither directly related to the operation; 4 patients are developing well. This approach using the valvectomy punch is a fast, safe, and effective procedure.

[Effectiveness of selective hepatic artery embolization in a child after blunt hepatic trauma].

A 9-year-old boy was admitted after a bicycle fall. Abdominal CT-scan revealed severe liver injury (stage IV according to the liver injury scale of the American Association for Surgery Trauma), including ruptured intraparenchymal hematoma with active bleeding. The patient was hemodynamically stable and was treated conservatively for the first 2 days. On the 3rd day selective hepatic artery angiography was performed because of abdominal distension and the need for 7 pints of packed red blood cells. Active right hepatic artery bleeding was identified and treated successfully by embolization. We think that early angiography and selective embolization should always be considered for acute or continuous bleeding after liver injury.