Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience

Background

Supportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS®).

Methods

Retrospective data from children receiving therapy using MARS® from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS® session, technical modalities and adverse events were recorded.

Results

A total of six children underwent 17 MARS® sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX® and four infants were treated with the MiniMARS® filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11–33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS® from an initial 89?±?29 to 58?±?35 mcmol/L (p?=?0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation.

Conclusion

In our experience, treatment with MARS® is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.     

Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study

Background

The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients.

Methods

Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7–19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC_0–24), minimum whole-blood concentration (C_min), maximum whole-blood concentration (C_max), and time to achieve maximum whole-blood concentration (t_max)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.

Results

Both AUC_0–24 and C_min decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p?=?0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC_0–24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized C_min with the twice-daily formulation only.

Conclusions

Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC_0–24 and C_min after the conversion, requiring close pharmacokinetic monitoring during the conversion period.     

Köbberling type of familial partial lipodystrophy: an underrecognized syndrome

OBJECTIVE: The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought. RESEARCH DESIGN AND METHODS: Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes. RESULTS: Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-gamma. CONCLUSIONS: FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.     

Comparison of signal quality between EASI and Mason-Likar 12-lead electrocardiograms during physical activity.

BACKGROUND: Myoelectric noise and baseline wander, artifacts that appear when patients move during electrocardiographic monitoring, can cause false alarms. This problem can be addressed by using a reduced lead set and placing electrodes on the anterior part of the torso only. The Mason-Likar modification of the standard 12-lead electrocardiogram and the EASI lead system are 2 alternative systems for lead placement. OBJECTIVES: To test the hypothesis that the EASI lead system is less susceptible to artifacts than is the Mason-Likar modification of the standard 12-lead electrocardiogram. METHODS: Baseline wander and myoelectric noise amplitudes of EASI and Mason-Likar 12-lead electrocardiograms were compared. Twenty healthy volunteers participated. Both lead systems were recorded simultaneously for different types of physical activities. For each lead in each subject, baseline wander and myoelectric noise were measured for both systems, at rest and during each physical activity. RESULTS: The outcome for baseline wander was mixed. For myoelectric noise content, the EASI system performed better for the limb leads in the different physical activities. In the precordial leads, the differences were minimal or mixed. However, for supine-to-right turning, EASI performed worse than the Mason-Likar system. CONCLUSIONS: The 2 systems have similar susceptibilities to baseline wander. The EASI system is, however, less susceptible to myoelectric noise than is the Mason-Likar system. EASI performed worse than Mason-Likar for turning supine to right, because only the EASI system uses an electrode in the right-midaxillary line.     

The outcome of children admitted to intensive care with meningococcal septicaemia

Objective To review our experience of children with meningococcal septicaemia, and to validate, in our group, severity scores used in different populations to predict outcome.Design Retrospective review of case notes and charts.Patients A total of 35 children were admitted to the paediatric intensive care unit (ICU) in the Royal Children's Hospital (RCH) in the 8 years between January 1985 and December 1992 with proven meningococcal septicaemia.Results Ages ranged from 4 months to 16 years, with a median age of 20 months. The median meningococcal score was 4 and the median PRISM score was 20, with scores above these being significantly associated with death (P<0.0001). Thirty-two children (91%) received infusions of colloid for hypovolaemia and twenty-nine (83%) received one or more inotropic drugs. Twenty-one children (60%) required mechanical ventilation for a median of 16.5 h (range 7–574). Seven children (20%) underwent plasmapheresis. Six children (17%) underwent haemofiltration and two (6%), peritoneal dialysis. One patient received extracorporeal membrane oxygenation (ECMO) because of circulatory failure. Twenty-one children (60%) developed disseminated intravascular coagulation, renal failure and/or skin or limb necrosis. The overall survival was 66%, and all survivors are functionally normal.Conclusion The mortality from the disease remains at 34% despite the technological advances in intensive care. The PRISM and meningococcal scores are useful in predicting outcome. Novel methods of treatment (e.g., plasmapheresis or ECMO) may be valuable.