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Aminophylline in severe, unresponsive asthma

Investigators in Australia determined that children with severe acuteasthma that is unresponsive to nebulized salbutamol can benefit from aminophylline,but at the cost of high frequency of adverse effects. The 163 children inthe trial, from 1 to 9 years of age, had been unresponsive to three nebulizeddoses of 5 mg of the b agent salbutamol. They were given standard care atthe investigators' institution and assigned to receive either aminophyllineor a sterile water placebo. Clinicians were blinded to assignment.

The addition of aminophylline to frequent inhaled b₂ sympathomimeticdrugs, ipratropium, and intravenous corticosteroids significantly improvedairway function initially and oxygenation for 24 hours and reduced the riskof endotracheal intubation. The drug did not change the hospital lengthof stay. Treated children required no fewer salbutamol nebulizations, butwere less likely to receive intravenous b agonists than children in theplacebo group. Aminophylline was associated with a significant risk of nauseaand vomiting (Yung M et al: Arch Dis Child 1998;79:405).

Commentary: I remember when a therapeutic aminophyllinelevel was required before a child with acute asthma would be accepted forinpatient admission. The shift toward anti-inflammatory treatments in asthma,increasing concerns about side effects of methylxanthines, and lack of goodstudies supporting acute use of aminophylline have made its inpatient usesomething of a rarity. In fact, in the 1997 revision of the National Institutesof Health Guidelines for the Diagnosis and Management of Asthma, aminophyllinehas been removed from the algorithm on hospital-based management of asthmaexacerbations.

Perhaps this article will move the pendulum in the other direction. Theauthors suggest that other treatments be used but that aminophylline beconsidered in severe asthmatics who fail to respond. That seems reasonableto me.

Newborn hearing screening: Making it work

Two studies­­one in England and one in Texas­­show thevalue of neonatal screening in identifying hearing impairment and what isessential to creating an effective program. The British study investigatedwhether neonatal screening, in addition to a "distraction test,"increases the rates of early referral, confirmation, and management of hearingloss. Using two pairs of hospitals, researchers compared results from fourfour-to-six-month periods during which newborns underwent neonatal screeningalong with the distraction test and four four-to-six-month periods duringwhich infants had the distraction test alone. Neonatal screening was performedwith a transient evoked otoacoustic emission test; babies who failed thetest had an automated auditory brainstem response test on the same day.In the distraction test, done on all infants at 8 months of age, one personattracted the infant's attention with a visual stimulus, then removed thevisual stimulus from the child's view while another tester tried to attractthe child's attention with a series of auditory stimuli.

A total of 53,781 babies were included in the trial. The number of babieswith hearing loss identified during neonatal screening was significantlyhigher than the number identified by 8-month distraction testing alone.The rate of false-negative results was 4% for neonatal screening and 27%for the distraction test. Early confirmation and management of hearing losssignificantly increased during the neonatal screening periods as well (WessexUniversal Neonatal Hearing Screening Trial Group: Lancet 1998;352:1957).

In the Texas study, investigators reviewed outcomes of screening forhearing in 54,228 newborns over three and a half years. They determinedthat nursery screening achieves low false-positive rates under three circumstances:

• Role of audiologist is understood. The audiologist manages the hearing screening program and coordinates services for families.
• Hospital support. Without the backing of top management, programs faltered or failed.
• Automated data and information management. Automated protocols provide immediate feedback without on-site supervision or later test interpretation. They also eliminate errors in interpretation.

Educating pediatricians and nursery staff on the importance of earlydetection of hearing loss also contributes to program success; if pediatricianstake screening seriously they encourage parents to return for follow-up(Finitzo T et al: Pediatrics 1998;102:1452).

Commentary: The first of these articles makes a strongargument for neonatal hearing screening. The second makes it clear thatarranging that screening and follow-up for 4 million US babies a year wouldbe no small feat. Proponents of neonatal hearing screening argue that theeffort will be worthwhile, allowing early evaluation and initiation of therapyin the first year of life. That is two years earlier than the average ageof identification of moderate to severe hearing loss in the US in 1993,two crucial years for language development.

EMLA safe in neonates

EMLA cream 5%, a eutectic mixture of lidocaine and prilocaine used tocontrol the pain of venipuncture and other minor procedures, has not beenrecommended for neonates because they are at risk for methemoglobinemiafollowing the use of prilocaine. Now a new study shows that while EMLA doesraise the concentration of methemoglobin in neonates, the level remainssafe.

Investigators established the safety of EMLA in 47 term neonates, aged0 to 3 months. On each infant, they applied 1 g of EMLA cream or placebocream divided between two sites. The cream was left on the skin for 60 to70 minutes, and the sites were kept covered. Venous methemoglobin levelswere determined at baseline and at three randomly assigned times, 0.5 hoursto 18 hours after application. After treatment, methemoglobin concentrationsranged from 0.50% to 2.53% in the EMLA group and from 0.50% to 1.53% inthe placebo group. The methemoglobin concentrations were significantly higherin the EMLA group than in the placebo group in the intervals from 3.5 hoursto 13 hours, but remained well below potentially harmful levels­­5%to 6% or higher (Brisman M et al: Acta Paediatr 1998; 87:1191).

Commentary: This is one of several studies published overthe last four years showing that EMLA can be used safely in neonates despitethe theoretical concern that it might induce methemoglobinemia. The Physicians'Desk Reference warns against EMLA use in infants younger than 12 monthswho are receiving treatment with methemoglobin-inducing agents, includingacetaminophen. Ten of the patients reported here were given both EMLA andacetaminophen and had no clinically significant rise in methemoglobin levels.According to these authors, a one-hour application of one gram of EMLA issafe even in young infants.

Antibiotic failure to eradicate group A strep

Investigators in Israel tested a hypothesis to explain why antibioticsfail to eradicate group A streptococci in up to 30% of patients with pharyngotonsillitis.They theorized that the presence of the fibronectin-binding protein genesprtF1 and sfbI might be linked to the ability of a strain to persist inthe throat after therapy. These genes are part of the process whereby somestrains of group A streptococci can enter respiratory epithelial cells,where they are inaccessible to antibiotics that cannot penetrate the cellmembrane, such as penicillins.

The study examined the frequency of prtF1-containing strains among 67patients, 2 to 18 years old, with pharyngotonsillitis who had been treatedwith ceftibuten or amoxicillin. Although all the patients were clinicallycured, 13 continued to have group A streptococci in the throat during orafter therapy. Twelve of the 13 (92%) had prtF1-containing strains in thethroat compared with 16 (30%) of the 54 patients in whom streptococci weresuccessfully eradicated. Although three of the 13 patients were recolonizedwith strains that differed from pretreatment strains, persisting strainscarried prtF1 in nine of the remaining 10 (90%). These findings suggestthat fibronectin-binding protein (F1) may be linked to the ability of astrain to persist in the throat after therapy (Neeman R et al: Lancet 1998;352:1974).

Commentary: The more we learn, the more we realize thecomplexity of the relationship between our bodies and the bacteria thatcolonize us. I wonder if an understanding of the role of these proteinscan be used to develop ways to transport antibiotics or other therapeuticproducts into cells.

JOURNAL CLUB.

Contemporary Pediatrics

1999;0:168.