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Clinically relevant concentrations of beta agonists may stimulate alveolar fluid clearance in acute respiratory distress syndrome

Background

Acute respiratory distress syndrome (ARDS) is characterised by the development of noncardiogenic pulmonary oedema leading to refractory hypoxaemia. The early clearance of alveolar oedema is an important determinant of outcome in ARDS. β -agonists have been shown to upregulate alveolar fluid clearance (AFC). The primary aim of this study was to determine the concentration of salbutamol achieved in plasma after treatment with intravenous (IV) salbutamol. A second aim was to determine the concentration of airspace salbutamol required to stimulate AFC in the normal rat lung.

Methods

Patients with acute lung injury/ARDS were randomised to an infusion of IV salbutamol (15 μg/kg/hour) or placebo. Plasma salbutamol levels were measured by a commercially available ELISA before and 24 hours after starting the infusion. In a second series of experiments AFC was measured in rats in response to 10 -4 M to 10-8 M salbutamol as previously described [1].

Results

Twelve patients were recruited (six received placebo). Median plasma salbutamol levels were 408 ng/ml in the salbutamol-treated group (equivalent to 10-6 M) compared with undetectable in the placebo group (P = 0.001). Basal AFC in rats was 7.6 ± 2.2% hour. Salbutamol (10-6 to 10-5 M) increased AFC by 100% and 400%, respectively, above baseline (P < 0.05).

Discussion

The plasma concentration (10-6 M) following IV administration in patients with ARDS may be sufficient to stimulate AFC if a similar concentration reaches the airspaces. Aerosolised delivery of a beta-2 agonist can achieve higher concentrations in the distal airspaces and maximal AFC. Although both IV and aerosolised delivery of a β2-agonist can achieve an effective concentration, the optimal route of delivery for treating ARDS patients remains uncertain.

References

  1. 1.

    Rezaiguia S, et al.: J Clin Invest 1997, 99: 325-335.

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Perkins, G., McAuley, D., Frank, J. et al. Clinically relevant concentrations of beta agonists may stimulate alveolar fluid clearance in acute respiratory distress syndrome. Crit Care 8, P33 (2004). https://doi.org/10.1186/cc2500

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Keywords

  • Placebo
  • Pulmonary Oedema
  • Salbutamol
  • Acute Respiratory Distress Syndrome
  • Relevant Concentration