Rapid Communication
The incidence of severe symptoms of altitude illness among recreational climbers has reached 9%, of which 1% requires hospital treatment.1 Dexamethasone is the mainstay of pharmacological intervention in moderate-to-severe acute mountain sickness (AMS) and high-altitude cerebral oedema (HACE). It can be life-saving when immediate descent and oxygen therapy are not feasible. Although the mechanism by which dexamethasone exerts its therapeutic effects in the setting of AMS and HACE treatment remains unclear, it probably serves to ameliorate vasogenic oedema through the stabilization of the blood–brain barrier and the attenuation of anti-inflammatory responses.2 Dexamethasone can be administered intravenously, intramuscularly or orally. Its administration should include a loading dose of 8 mg (HACE), followed by a 4 mg dose every 6 h (AMS and HACE).2 Symptoms, such as nausea and vomiting, are common in AMS and HACE and impaired consciousness predominating in HACE precludes the oral administration of dexamethasone. Intravenous drug administration by climbers who are not medics is practically impossible. Intramuscular route can be used by climbers but requires training. As a result, a significant proportion of AMS and HACE patients cannot benefit from dexamethasone treatment under real conditions.
The nasal administration is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain.3 The intranasal route of administration is becoming increasingly popular in the prehospital setting. Intranasal administration of fentanyl, sufentanil, ketamine, hydromorphone, midazolam, haloperidol, naloxone and glucagon is a safe, effective and well-tolerated alternative to intramuscular or intravenous administration.4 The intranasal drug delivery has several advantages over intravenous and intramuscular administration, which include shorter environmental exposure, non-invasiveness, lower risk of provider needlestick, self-administration, simple technique available for non-healthcare professionals, shorter time to onset of effect, higher bioavailability due to avoidance of hepatic first-pass metabolism and potentially higher central nervous system drug availability due to bypassing the blood–brain barrier.3
Efficient crossing of the drug through the blood–brain barrier requires its physiologic pH, unionized state, high lipophilicity and small molecular weight. The volume administered should not exceed 1 ml per nostril to avoid runoff and swallowing. Medications should be administered during a few seconds and divided evenly between nostrils. Drug should be delivered preferably by the atomizer that sprays the large surface area of the nasal mucosa and does not require patient cooperation in head positioning.4 Instilling medication into nasal cavity with syringes or droppers is uncommon in prehospital and emergency department setting because it necessitates patient compliance and appropriate head positioning.
Dexamethasone sodium phosphate (dexamethasone KRKA, injectable solution, KRKA) is a highly soluble glucocorticoid with a pH = 7–8.5, which does not harm the nasal mucosa. Dexamethasone is available as a 4 mg/1 ml solution in 1 or 2 ml ampoules. A study performed on healthy volunteers demonstrated that the blood bioavailability of dexamethasone administered by intranasal atomization is comparable with that via intravenous administration.5 The authors suggested that the intranasal route can be used as a non-invasive alternative for intramuscular or intravenous drug delivery. Basing on chemical properties and available formulations of dexamethasone, the effectiveness of its intranasal vs intravenous administration to moderate-and-severe COVID-19 adult patients is being studied in an approved open-label, multicentre and randomized controlled trial.6
There are potential limitations to the intranasal use of dexamethasone in austere high altitude environment. Dexamethasone is cold resistant, but frozen and then thawed ampoules should not be used.7 Nasal congestion and symptoms of rhinitis, which are common complaints at high altitude, may limit nasal absorption of the drug.8
Conclusion
The intranasal route of dexamethasone administration should be considered as an alternative to the currently recommended intravenous and intramuscular route in the treatment of severe AMS and HACE by non-medics in an austere, high-altitude environment. Intranasal use of dexamethasone for altitude illness should be investigated in randomized controlled trial.
Funding
None.
Authors’ contributions
Robert K. Szymczak and Magdalena Sawicka equally contributed to the acquisition of data and drafting of the manuscript.
Conflict of interest
None declared.
Patient’s consent
Not applicable.
Contributor Information
Robert K Szymczak, Department of Emergency Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Mariana Smoluchowskiego 17, Gdańsk 80-214, Poland.
Magdalena Sawicka, Department of Neurology, Faculty of Medicine, Medical University of Gdańsk, Mariana Smoluchowskiego 17, Gdańsk 80-214, Poland.
References
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