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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

The safety of nebulization with 3 to 5 ml of adrenaline (1:1000) in children: an evidence based review

L Zhang and LS Sanguebsche.

Review published: 2005.

Link to full article: [Journal publisher]

CRD summary

This review assessed the safety of 3 to 5 mL of nebulised adrenaline (1:1,000) in children with acute inflammatory airways obstruction. The authors concluded that 3 to 5 mL of nebulised adrenaline is safe. The evidence appears to support the authors' conclusion. However, the limited number of generally small studies and the lack of an assessment of study quality make the reliability of the results uncertain.

Authors' objectives

To assess the safety of 3 to 5 mL of nebulised adrenaline (1:1,000) used in the treatment of children with acute inflammatory airways obstruction.

Searching

MEDLINE (1949 to July 2004) was searched using the reported search terms. In addition, LILACS and the Cochrane CENTRAL Register were searched and the reference lists of identified studies were screened.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies of adrenaline (1:1,000) delivered by nebuliser were eligible for inclusion. The included studies used varying doses of adrenaline (1:1,000): from 0.5 to 5 mL, given either as a single or repeated dose. The included studies compared nebulised adrenaline with nebulisation using saline, racemic adrenaline (0.5 mL of 2.25%), salbutamol (0.5%) or budesonide (0.05%).

Participants included in the review

Studies in children (aged 18 years or younger) with a diagnosis of bronchiolitis or laryngotracheobronchitis were eligible for inclusion.

Outcomes assessed in the review

It was clear that the review focused on safety outcomes. The review assessed heart rate, systemic arterial pressure and other side-effects.

How were decisions on the relevance of primary studies made?

Two reviewers independently selected studies for inclusion. Any disagreements were resolved by consensus and inter-observer agreement was assessed using the kappa statistic.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Two reviewers independently extracted the data and the results were compared. For each study, data on side-effects were extracted.

Methods of synthesis

How were the studies combined?

The studies were grouped by outcome and combined in a narrative.

How were differences between studies investigated?

The results were discussed with respect to the dose of adrenaline. Other differences were apparent from the tables.

Results of the review

Seven RCTs (n=373) were included. The sample size ranged from 28 to 95.

Heart rate (7 trials).

Two of 6 trials using at least 3 mL of adrenaline found significant increases in heart rate. The first of these trials found significant increases in heart rate an hour after the last of three nebulisations with 4 mL adrenaline compared with saline control (151 versus 138 beats per minute, bpm, P<0.001). The second positive trial found a significant increase in heart rate 40 minutes after nebulisation with 3 mL adrenaline compared with before nebulisation (7 bpm increase, P<0.05). One of the other trials found a reduction (of 5 to 10 bpm) in heart rate after 5 mL adrenaline, but the statistical significance was not reported. The other 3 trials showed no significant effects of 3 to 4 mL adrenaline on heart rate. The trial using 0.5 mL adrenaline also found no significant effects on heart rate.

Systemic arterial pressure (2 trials).

Neither trial found any statistically significant effect of adrenaline on systemic arterial pressure.

Other adverse effects.

Pallor (3 trials): one of the 3 trials using at least 3 mL of adrenaline found an increase in pallor after nebulisation with two doses of adrenaline compared with salbutamol (47.6% versus 14.3% at 30 minutes, P<0.05; 38.1% versus 14.3% after 60 minutes, P=0.06). Other: one trial reported a similar number of patients with other adverse effects with adrenaline and budesonide. Six of 31 patients (19%) treated with 4 mL adrenaline versus 6 of 35 patients (17%) treated with budesonide had adverse effects such as hyperactivity, vomiting, erythema, diarrhoea, wheezing and epistaxis.

Authors' conclusions

Three to 5 mL of nebulised adrenaline (1:1,000) is a safe treatment for children with acute inflammatory airways obstruction.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, intervention and study design. Inclusion criteria for the outcomes were not defined but it was clear that the focus was on safety outcomes. Three relevant databases were searched and some attempts wee made to locate unpublished studies, thus minimising the potential for publication bias. It was unclear whether any language limitations had been applied, so the potential for language bias could not be assessed. The authors conducted study selection and data extraction procedures in duplicate in order to minimise reviewer errors and bias. Although only RCTs were included, study validity was not assessed and so the results from these studies and any synthesis may not be reliable.

Given differences between the studies in the participants' diagnosis, dose of adrenaline and comparators, a narrative synthesis of the studies was appropriate. The results tended to be reported as before-and-after adrenaline comparisons rather than for adrenaline compared with the various controls. Several of the studies had small sample sizes and could have been too small to detect a statistically significant difference; this limitation of the included studies was not discussed. The evidence appears to support the authors' conclusion. However, the limited number of generally small studies and the lack of an assessment of study quality make the reliability of the results uncertain.

Implications of the review for practice and research

Practice: The authors recommended the use of nebulisation with 3 to 5 mL adrenaline (1:1,000) for children with acute inflammatory airways obstruction. However, the review only assessed safety and did not assess efficacy.

Research: The authors did not state any implications for further research.

Bibliographic details

Zhang L, Sanguebsche L S. The safety of nebulization with 3 to 5 ml of adrenaline (1:1000) in children: an evidence based review Jornal de Pediatria 2005; 81(3): 193-197. [PubMed: 15951902]

Indexing Status

Subject indexing assigned by NLM

MeSH

Acute Disease; Administration, Inhalation; Airway Obstruction /drug therapy /etiology; Blood Pressure /drug effects; Bronchiolitis /complications; Bronchodilator Agents /administration & dosage /adverse effects; Child; Child, Preschool; Epinephrine /administration & dosage /adverse effects; Evidence-Based Medicine; Heart Rate /drug effects; Humans; Infant; Infant, Newborn; Laryngitis /complications; Randomized Controlled Trials as Topic; Tracheitis /complications

AccessionNumber

12006003026

Database entry date

30/11/2006

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15951902