Timing of Inhaled Adrenaline Matters in Infant Bronchiolitis

Jun 12, 2013

By Gene Emery

NEW YORK (Reuters Health) Jun 12 - When it comes to giving inhalation therapy to an infant with acute bronchiolitis, timing may be everything.

Doctors in Norway found that babies who periodically received inhaled racemic adrenaline did no better than those who inhaled aerosolized saline for the same amount of time.

Yet when the treatment was given on an as-needed basis -- whether it was the drug or saline -- it cut the in-hospital time by 23% (p=0.01). Babies assigned to on-demand inhalation also needed 21% less oxygen supplementation (p=0.04) and the benefits were most pronounced in infants aged three months and younger.

"The strategy of inhalation on demand appears to be superior to that of inhalation on a fixed schedule," Dr. Havard Ove Skjerven of Oslo University Hospital and colleagues concluded in a paper released online today by the New England Journal of Medicine.

In Norway, inhaled racemic adrenaline therapy "has been a standard treatment for the last 30 years or so. It's given between 14 and 15 times for each patient, on average, so it's a lot of treatments," Dr. Skjerven told Reuters Health in a telephone interview.

"Bronchodilators are overused in infants with bronchiolitis in spite of several trials and recommendations that it's not necessarily the best treatment to be used," said Dr. Alyssa Silver of The Children's Hospital at Montefiore Medical Center in New York, who was not connected with the study. "Having one more study to show that inhaled adrenaline is also ineffective is one more piece of evidence."

But Dr. Silver told Reuters Health she was surprised that the on-demand treatment produced such improvement.

Eight centers in southeastern Norway and 404 children under the age of one year participated in the randomized double-blind trial. Inhaled adrenaline, which reduces mucosal swelling, has been shown in outpatients to improve symptoms and lower the risk of hospitalization. It has not, however, been found to reduce hospital stay for inpatients. The Skjerven team wanted to test that, and whether on-demand care would be better than a fixed schedule.

"It's common to give it on a regular schedule, which would be every second or third hour, whether he seems to need it or not, and whether he's awake or not," said Dr. Skjerven.

With on-demand therapy, "the nurses continuously made the decision about whether the patient needed it or if it seemed to be helping," he said. "If the patient was stable or sleeping, you would not wake up that patient to give him a treatment."

Regardless of the schedule, when the researchers just looked at saline versus adrenaline, the length of hospital stay, supplemental oxygen use, clinical scores, and other measures were essentially the same.

Yet when they compared on-demand inhalation versus fixed-schedule treatment regardless of whether adrenaline was used, mean length of stay in the hospital went from 61.3 hours in the fixed-schedule group to 47.6 hours in the on-demand group.

The number of infants requiring oxygen supplementation went from 48.7% down to 38.3% with on-demand, and the average number of inhalation treatments was 17.0 in the fixed-schedule group but 12.0 in the on-demand group.

"The main reason for trying on-demand treatment was to see if we could give more individualized treatment" and fewer treatments," Dr. Skjerven said. "That it actually turned out better was a surprise for us."

"The effect was most predominant in the smallest children, those less than three months, and those are the ones causing the most trouble for us," he said. "It actually shortened hospital stay by 24 hours, which was a lot."

The treatment was discontinued in 20.5% of the children, mostly in the saline group and mostly because it appeared that the treatment had failed. But the difference in the discontinuation rates was not statistically significant between the groups.�

Why would on-demand therapy be better?

"Remember, we give it as 100% oxygen and a high dose of adrenaline with a tight mask fitting around the face up to every hour. It's very likely to give them a stress reaction. A lot of them start screaming and they're obviously not comfortable with this," Dr. Skjerven said.

"There's a concept called minimum handling in intensive care units where you try to cluster up procedures and give the longest periods of sleep as possible to help recovery as much as possible," he said. "We've hypothesized that this concept is transferable to small infants less than three months, which makes sense to us."

He said the results "are definitely causing a guideline change in Norway and we're waiting to see what kind of influence it might have globally."

Dr. Silver said bronchodilation therapy probably remains common "because we have no good treatment option. It's a disease process that affects a lot of babies. It's the number one reason for admission of infants less than one in the United States. You see these young babies struggling to breathe and people just want to do something."

SOURCE: http://bit.ly/12nmgr2

N Engl J Med 2013; 368:2286-2293.