Scientific Rationale for the Use of Alpha-adrenergic Agonists and Glucocorticoids in the Therapy of Pediatric Stridor

Overview

Journal Int J Otolaryngol

Specialty Otorhinolaryngology

Date 2012 Jan 6

PMID 22220172

Authors

Gustavo Nino

Orkun Baloglu

Maria J Gutierrez

Michael Schwartz

Affiliations

Soon will be listed here.

Abstract

Purpose. The most common pharmacological therapies used in the treatment of stridor in children are glucocorticosteroids (GC) and alpha-adrenergic (αAR) agonists. Despite the long-standing reported efficacy of these medications, there is a paucity of data relating to their actual mechanisms of action in the upper airway. Summary. There is compelling scientific evidence supporting the use of αAR-agonists and GCs in pediatric stridor. αAR signaling and GCs regulate the vasomotor tone in the upper airway mucosa. The latter translates into better airflow dynamics, as delineated by human and nonhuman upper airway physiological models. In turn, clinical trials have demonstrated that GCs and the nonselective αAR agonist, epinephrine, improve respiratory distress scores and reduce the need for further medical care in children with stridor. Future research is needed to investigate the role of selective αAR agonists and the potential synergism of GCs and αAR-signaling in the treatment of upper airway obstruction and stridor.

References

Khemani R, Randolph A, Markovitz B . Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults. Cochrane Database Syst Rev. 2009; (3):CD001000. PMC: 7096779. DOI: 10.1002/14651858.CD001000.pub3. View

Cotecchia S . The α1-adrenergic receptors: diversity of signaling networks and regulation. J Recept Signal Transduct Res. 2010; 30(6):410-9. PMC: 3018134. DOI: 10.3109/10799893.2010.518152. View

Cheng K, Hou C, Huang H, Lin S, Zhang H . Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients. Crit Care Med. 2006; 34(5):1345-50. DOI: 10.1097/01.CCM.0000214678.92134.BD. View

Couser R, Ferrara T, Falde B, Johnson K, Schilling C, Hoekstra R . Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr. 1992; 121(4):591-6. DOI: 10.1016/s0022-3476(05)81154-0. View

Geelhoed G . Budesonide offers no advantage when added to oral dexamethasone in the treatment of croup. Pediatr Emerg Care. 2005; 21(6):359-62. DOI: 10.1097/01.pec.0000166724.99555.de. View

Garcia-Sainz J, del Carmen Medina L . Alpha 1-adrenoceptors: function and phosphorylation. Eur J Pharmacol. 2000; 389(1):1-12. DOI: 10.1016/s0014-2999(99)00896-1. View

Baroody F, Brown D, Gavanescu L, DeTineo M, Naclerio R . Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2011; 127(4):927-34. DOI: 10.1016/j.jaci.2011.01.037. View

Morris S, Eccles R, Martez S, Riker D, Witek T . An evaluation of nasal response following different treatment regimes of oxymetazoline with reference to rebound congestion. Am J Rhinol. 1997; 11(2):109-15. DOI: 10.2500/105065897782537197. View

Mironneau J . Modulation of Ca2+ channels by alpha 1A- and alpha 2A-adrenoceptors in vascular myocytes: involvement of different transduction pathways. Cell Signal. 1995; 7(5):471-9. DOI: 10.1016/0898-6568(95)00014-g. View

10.

Corkey C, Barker G, Edmonds J, Mok P, Newth C . Radiographic tracheal diameter measurements in acute infectious croup: an objective scoring system. Crit Care Med. 1981; 9(8):587-90. DOI: 10.1097/00003246-198108000-00007. View

11.

Chiba Y, Oshita M, Matsuo K, Sakai H, Misawa M . Comparison of norepinephrine responsiveness of mucosal veins in vivo with that of isolated mucosal tissue in vitro in guinea pig nasal mucosa. Am J Rhinol. 2006; 20(3):349-52. DOI: 10.2500/ajr.2006.20.2853. View

12.

Barnes P . Glucocorticosteroids: current and future directions. Br J Pharmacol. 2011; 163(1):29-43. PMC: 3085866. DOI: 10.1111/j.1476-5381.2010.01199.x. View

13.

Hudgel D . Variable site of airway narrowing among obstructive sleep apnea patients. J Appl Physiol (1985). 1986; 61(4):1403-9. DOI: 10.1152/jappl.1986.61.4.1403. View

14.

Harel Y, Vardi A, Quigley R, Brink L, Manning S, Carmody T . Extubation failure due to post-extubation stridor is better correlated with neurologic impairment than with upper airway lesions in critically ill pediatric patients. Int J Pediatr Otorhinolaryngol. 1997; 39(2):147-58. DOI: 10.1016/s0165-5876(97)01488-2. View

15.

Tanimitsu N, Yajin K, Sasa M, Tsuru H . alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature. Eur J Pharmacol. 2000; 387(1):73-8. DOI: 10.1016/s0014-2999(99)00783-9. View

16.

Chang C, Wang S, Huang Z, Wang O, Huang M, Lu L . Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids. J Cell Physiol. 2010; 223(3):679-86. DOI: 10.1002/jcp.22070. View

17.

Rittichier K, Ledwith C . Outpatient treatment of moderate croup with dexamethasone: intramuscular versus oral dosing. Pediatrics. 2000; 106(6):1344-8. DOI: 10.1542/peds.106.6.1344. View

18.

Remaury A, Larrouy D, Daviaud D, Rouot B, Paris H . Coupling of the alpha 2-adrenergic receptor to the inhibitory G-protein Gi and adenylate cyclase in HT29 cells. Biochem J. 1993; 292 ( Pt 1):283-8. PMC: 1134302. DOI: 10.1042/bj2920283. View

19.

Lin C, Cheng P, Fang S . Mucosal changes in rhinitis medicamentosa. Ann Otol Rhinol Laryngol. 2004; 113(2):147-51. DOI: 10.1177/000348940411300213. View

20.

Verriere V, Hynes D, Faherty S, Devaney J, Bousquet J, Harvey B . Rapid effects of dexamethasone on intracellular pH and Na+/H+ exchanger activity in human bronchial epithelial cells. J Biol Chem. 2005; 280(43):35807-14. DOI: 10.1074/jbc.M506584200. View