Diagnosis of hepatopulmonary syndrome in children

March 2014  Volume 164  Number 3

Diagnosis of hepatopulmonary syndrome in children — William F. Balistreri, MD

Instructions for dosing of prescribed liquid medications need improvement — Sarah S. Long, MD

Copyright ª 2014 by Elsevier Inc.

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he United Network for Organ Sharing developed a system for prioritizing candidates waiting for liver transplants based on statistical formulas that predict urgency. The Model for End Stage Liver Disease (MELD) is used for candidates $12 years of age, and the Pediatric End Stage Liver Disease Model (PELD) is used for younger patients (http://www.unos.org/docs/MELD_PELD.pdf). However, it has been recognized that the calculated MELD/PELD score may not truly reflect a candidate’s need for a liver transplant and that “exceptions” must be made so that additional points can be awarded. One of the complications that would qualify a candidate for automatic MELD/PELD exception points is the diagnosis of hepatopulmonary syndrome (HPS). This decision is based on the documented lower survival rate for affected patients. The burden is on the transplant center to accurately diagnose HPS, which may not be straightforward. HPS is characterized by an oxygenation defect induced by intrapulmonary vascular dilatation (IPVD) in the setting of liver cirrhosis or portal hypertension. The resultant ventilation-perfusion mismatch and arteriovenous shunting cause limited diffusion and impaired oxygen exchange. In both adults and children, HPS is defined by abnormal pulse oximetry (SO2 97%) and an increased alveolar arterial oxygen gradient (> 15 mm Hg). Clinically, HPS is associated with the insidious onset of progressive dyspnea. Contrast-enhanced transthoracic echocardiography is the most effective test to demonstrate IPVD. Another method for detecting IPVD is the radionuclide lung perfusion scanning, using technetium-labeled macroaggregated albumin particles. Pulse oximetry has been used as a non invasive screening test for HPS. However, in this issue of The Journal, Hoerning et al report that pulse oximetry is not suitable for preventive screening and early diagnosis in children. In this study, pulse oximetry detected “only late and severe forms of HPS at a stage where liver transplantation is a high-risk associated with severe complications affecting the postoperative survival.” The authors suggest that contrast-enhanced transthoracic echocardiography and capillary blood gas determination be utilitized in the evaluation of HPS in children with cirrhosis. Article page 546<

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nintended overdosing of liquid medications in children has been associated with life-threatening and even fatal consequences. The Centers for Disease Control and Prevention began in 2008 to engage stakeholders in describing strategies to reduce unintentional overdose in children (the PROTECT initiative) and recommended one key initiative in 2012—to communicate, prescribe, and label liquid medication doses only in milliliters (mL). Prescribing or labeling by teaspoon or tablespoon dosing alone or along with mL dosing may incorrectly suggest to caregivers that the use of household tableware for dispensing medication is appropriate. In this issue of The Journal, pharmacists in Philadelphia analyzed healthcare professionals’ (HCP) prescriptions and pharmacy-applied labels on 649 prescriptions filled for the top 10 liquid medications given to children in four Philadelphia community pharmacies during 3 months in early 2012. (Continues on next page) 431

In essence, they learned that a multiprong, multipartner education (of HCPs, pharmacists and caregivers) and pharmacy policies are needed urgently to attain safe practices. Lack of HCPs’ exclusive use of mL dosing, as well as pharmacist changes of mL dosing to teaspoon/tablespoon dosing or to include both measurement options, occurred frequently in the dispensing of medications studied. This study uncovers holes in our new healthcare patient safety net. Hospitals— accustomed to scrutinizing, changing, and applying universal medical staff policies, pharmacy policies, ordering policies, and prepopulating order sets—can implement new safety initiatives almost immediately. Education is important, but policies will be needed in outpatient settings (ie, pharmacies) to immediately protect children from unsafe behaviors in dosing and administering liquid medications. Article page 596<

Neuro protection for infants — Alan H. Jobe, MD, PhD

Trends in preventive care among insured adolescents — Robert W. Wilmott, MD

Biomarkers for hypoxic ischemic encephalopathy — Alan H. Jobe, MD, PhD 432

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nfants receive a variety of brain injuries—intraventricular hemorrhage in preterm infants, hypoxic ischemic encephalopathy in term infants, and often poorly defined events resulting in cerebral palsy and other neurodevelopmental abnormalities. Recently, specific neuroprotective therapies have been tested to improve, including antenatal magnesium treatment for preterm deliveries and therapeutic hypothermia for hypoxic ischemic encephalopathy. Numerous other neuroprotective treatments, including stem cell treatments and erythropoietin treatments, are being tested in animal models and erythropoietin treatments. In this issue of The Journal, Benders et al report that the treatment of term infants with perinatal arterial ischemic strokes with erythropoietin is safe and feasible. This pilot study should result in formal therapeutic trials. Such interventions are gaining traction as a number of neonatologists are teaming up with pediatric neurologists to develop neurologic neonatal intensive care units to better diagnose and develop treatments for infants at high-risk of brain injury. The use of newer imaging and monitoring tools makes these efforts very likely to succeed. Article page 481< he goal of the report published in this issue of The Journal by Tsai et al from the Centers for Disease Control and Prevention was to investigate patterns of preventive care visits among commercially-insured adolescents before and after the recommendation of the Advisory Committee on Immunization Practices (ACIP) of three vaccines targeted toward adolescents. The data were derived from the Market Scan database. Eleven to 21-year-olds who were continuously enrolled in the same insurance plan during 20032010 were included in the study. The proportion of individuals making at least one preventive visit increased from 25% to 41% between 2003 and 2010, and the rate of vaccination-related visits increased from 13% to 26%. The increases were greater during the years in which ACIP issued recommendations. Rates of preventive and vaccinationrelated visits were considerably higher among females, early adolescents, and those in managed-care plans. Without this stimulus for attendance, only 2.4% of 11- to 21year-olds had annual preventive visits during the 8 years. The data from this study show that yearly improvements in preventive care visits were substantial and that the recommendations of the ACIP may have stimulated this improvement. However, rates of immunizations are still relatively low and rates of attendance for preventive care are low in this age group, so there is still important work to be done. Article page 625<

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ith the advent of therapeutic hypothermia as an effective treatment for hypoxic ischemic encephalopathy associated with birth, the identification of which infants will benefit has become a research priority. Similarly, if investigators could identify the infants likely to have poor outcomes soon after birth, then additional promising therapies could be targeted to these infants at highest risk. (Continues on next page) Vol. 164, No. 3

In this issue of The Journal, Chalak et al report that glial fibrillary acidic protein, a protein specific to astrocytes, and ubiquitin carboxyl-terminal hydrolase L 1, a protein concentrated in dendrites, were elevated in cord blood plasma. Their levels correlated with neurologic outcomes at 15-18 months of age for a small group of infants treated with hypothermia. They also found that rewarming did not alter the levels of these proteins or selected cytokines. In an accompanying editorial, Ferriero and Bonifacio emphasize the complexity of the pathophysiology of neonatal brain injury and the difficulty to identify useful biomarkers to date. Productive studies to identify and validate biomarkers will need to be multicentered to have sufficient patient numbers for careful phenotyping of the infants with magnetic resonance imaging and 2-year outcomes. Article page 468< Editorial page 438<

Albumin and renal transplant outcome — Thomas R. Welch, MD

Endothelial colony forming cells in cord blood — Stephen R. Daniels, MD, PhD

March 2014

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ypoalbuminemia is a feature of a number of chronic disorders. Children with chronic kidney disease (CKD) have a number of reasons for low serum albumin: urinary losses, nutritional deficiencies, and chronic inflammation. Indeed, for many children with CKD, all three mechanisms are operative. In many conditions, including CKD, hypoalbuminemia is a useful predictive marker of poor outcome. In this issue of The Journal, Butani et al studied a national database of children undergoing kidney transplants to determine if low serum albumin was a marker for poor transplant outcome. Because many children with hypoproteinemia undergoing kidney transplants have nephrotic disorders with a propensity to recur in the new organ, their conclusion that low serum albumin at the time of listing for transplantation is a risk for graft failure is not surprising. However, even when controlling for the underlying cause of CKD, the predictive value of hypoalbuminemia for graft failure remained. It is very reasonable to hypothesize that ongoing chronic inflammation may be a major contributor to this. Although no clear “action item” can be drawn from this study, it does raise the serious question as to whether transplant may better be delayed in the face of low serum protein. The authors show that there already is wide regional variation in the practice of transplanting children with hypoalbuminemia, suggesting that some practitioners may already be taking such an approach. Article page 602<

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ndothelial colony-forming cells are circulating endothelial progenitor cells. Deleterious conditions during fetal life, such as maternal diabetes, can impair the number and function of these cells. This could be a mechanistic explanation for the influence of fetal exposures on long-term cardiovascular health. These cells also may have therapeutic potential. In this issue of The Journal, Moreno-Luna et al evaluated whether maternal body mass index (BMI) was related to the number and function of endothelial colony-forming cells. Interestingly, they found that as maternal BMI increased the number of cells in umbilical cord blood also went up. There was no relationship between maternal BMI and function of endothelial colony-forming cells. One caveat is that the mothers who participated in this study were non-obese and had normal pregnancies. Clearly, these results suggest the need to study these relationships across a broader range of maternal BMI and other maternal and pregnancy factors. Article page 566<

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