Does salbutamol benefit the treatment of children with severe acute asthma?

Does salbutamol benefit the treatment of children with severe acute asthma?

In a recent study published in the journal European Journal of Pediatricsresearchers from the Netherlands found no clinical benefit from adding a loading dose of intravenous (IV) salbutamol continuous infusion in children with status asthmaticus (AME) admitted to Pediatric Intensive Care Units (PICU).

During an AME episode, effective administration of inhaled medications is unpredictable due to severe airway obstruction. Therefore, IV administration of salbutamol may be more effective. However, there is a paucity of data that address the effectiveness of this therapeutic strategy. Even the optimal dose regimen for IV treatment in pediatric patients with this diagnosis is still a matter of debate. Therefore, the primary objective of the study was to assess the efficacy of an additional loading dose of IV salbutamol in children admitted to the PICU with AME, versus the standard start of IV salbutamol, with maintenance dose, without attack.

Methodology

The researchers conducted a multicentre, randomized, placebo-controlled study in seven PICUs of four tertiary pediatric hospitals in the Netherlands. Pediatric patients aged 2 to 18 years admitted between 2017 and 2019 with a diagnosis of AME were included.

All children with AME between 2 and 18 years who did not respond to initial treatment and therefore had to receive continuous infusion of salbutamol according to Dutch guidelines were eligible (according to these guidelines, IV salbutamol should be considered if continuous inhalation with salbutamol has insufficient or no effect, with Qureshi asthma score et al. equal to or greater than 10 after three sprays). In fact, current Dutch national guidelines recommend admission to the PICU as soon as the child receives IV salbutamol, regardless of dosage.

The exclusion criteria were:

  • Heart disease that interferes with normal asthma treatment;
  • Pre-existing chronic lung condition other than asthma, such as cystic fibrosis, bronchopulmonary dysplasia, and bronchiolitis obliterans;
  • sdown syndrome;
  • Secondary immunodeficiency;
  • Have received a loading dose of IV salbutamol prior to study enrollment;
  • Have been admitted more than two hours before the start of the study;
  • Having received invasive mechanical ventilation (IMV) prior to receiving study medication or placebo (which would avoid assessment of the clinical asthma score).

Prior to admission to the PICU, each child received continuous nebulization with salbutamol, prednisone, and a bolus of magnesium sulfate (MgSO4) according to the Dutch national EMA guideline.

Children were randomized to receive a loading dose of IV albuterol (15 mcg/kg, maximum dose 750 mcg) or saline during continuous salbutamol infusion. The primary outcome measure was the Qureshi asthma score et al. within an hour after the intervention. Analysis of covariance models was used to assess sensitivity to change in asthma scores. In addition, serum concentrations of salbutamol were obtained.

the score of qureshi et al.

Variable

asthma score

1 point

2 points

3 points

FR (irpm)

Age

  • 2 to 3 years
  • 4 to 5 years
  • 6 to 12 years
  • >12 years

34

30

26

23

35 – 39

31 – 35

27 – 30

24 – 27

40

36

31

28

Oxygen saturation (%)

>95% in AA

90 – 95% in AA

<90% in AA or Otwo additional

Auscultation

Normal breathing or end-expiratory wheezing

expiratory wheezing

Inspiratory and expiratory wheezing, decreased breath sounds, or both

print runs

none or intercostal

Intercostal and substernal

Intercostal, substernal and supraclavicular

dyspnea Speaks in phrases or coos and babbles Speaks in partial sentences or makes short cries

Speaks in single words or short sentences or grunts

asthma severity

Light

moderate

Serious

Peak expiratory flow rate (% of predicted value)

>70

50 – 70

<50

asthma score

5 – 7

8 – 11

12 – 15

Subtitle: AA – ambient air;FR – respiratory rate;Otwo – oxygen; irpm – respiratory incursions per minute.

Source: Adapted from Qureshi et al. (1998) – free translation.

Results

58 patients were included (29 in the intervention group [GI] and 29 in the control group [GC]). The median age was five years in the IG and eight years in the CG (p = 0.03).

The median baseline asthma score was 12 in the IG and 11 in the CG (p=0.032). The asthma score one hour after the intervention did not differ significantly between groups (p=0.508, β-coefficient=0.283). The mean increase in plasma albuterol levels ten minutes after the intervention was 13 μg/L in the GI and 4 μg/L in the CG (p=0.001). Furthermore, the mean length of stay in the PICU was 58 hours in the IG and 55 hours in the CG (p=0.696).

Adjuvant therapies and ventilatory support were similar between the two groups. Only one patient in the CG required IMV (after administration of the study drug, since IMV was an exclusion criterion).

Hypotension (blood pressure, if available) was defined as a pressure lower than the 5th percentile of systolic blood pressure and was documented in 15 patients: 11 in the CG and 4 in the IG (p=0.077). No patient required inotropic support. One patient in the placebo group had supraventricular tachycardia and recovered without complications after discontinuing IV albuterol. In the IG, 29 patients developed hyperglycemia (>8 mmol/L), against 27 patients in the CG (p=0.150). None of the patients had been treated with insulin. Tachycardia was present in all but one patient during PICU admission. Side effects, therefore, were comparable between the two groups.

Conclusion

The investigators found no beneficial effect of a loading dose of IV albuterol in children with AME admitted to the PICU (most already on IV salbutamol infusion) with regard to clinical asthma score, use of other medications, ventilatory support, and length of stay. in the PICU. In addition, there were no significant side effects. However, the scientists emphasize that future studies should focus on the effectiveness of a loading dose of IV salbutamol in the emergency department, before or simultaneously with the start of continuous infusion, with the ultimate goal of preventing further deterioration of respiratory distress and admission to PICU Finally, they highlight the need for a validated asthma score to study the effectiveness of different interventions in the context of emergency care and intensive care.

Comment

As commented by the authors themselves, the Qureshi asthma score et al., although considered by many to be the best asthma severity score available, requires validation studies in different populations, which can be considered a limitation of the study. In fact, many sites do not even use any clinical severity score. I have a lot of practice with the use of the Wood-Downes score, which, despite being old, is still not widely disseminated, being more used for research purposes.

Read too: The Wood-Downes score in the assessment of asthma severity in pediatrics

Despite providing us with important data on the use of intravenous salbutamol attack, given this limitation, I still consider an individualized indication of IV salbutamol to be necessary. I’ve used attack in some situations in practice, with excellent results in specific situations.

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