The treatment of asthma in the ICU combines pharmacological interventions and ventilatory support measures to reverse bronchospasm, reduce inflammation, and treat respiratory failure.1,2 According to the Spanish Guide for the Management of Asthma (GEMA 5.5), patients with moderate or severe exacerbations should receive oxygen without delay to maintain an oxygen saturation level above 90% (≥ 95% in pregnant women or patients with heart disease)2. Initial treatment includes short-acting beta agonists (SABAs, such as salbutamol) via spacer or nebulizer, with the addition of ipratropium bromide in moderate or severe cases. Systemic corticosteroids (methylprednisolone 40−50 mg/day for 5–7 days, p.o. or i.v.) should be initiated at the earliest possible opportunity.2

In severe crises, the administration of inhaled magnesium sulfate, in conjunction with SABA or SABA and ipratropium, has been shown to improve pulmonary function and reduce patient admissions. In cases where other methods have failed, the intravenous route is employed. Controlled oxygen therapy aims to achieve an oxygen saturation ≥94%.2,3 Noninvasive ventilation (NIV) is preferred over invasive ventilation because it has been shown to offer better results and lower mortality.1 If mechanical ventilation is required, it is essential to adjust the parameters to avoid dynamic hyperinflation (low respiratory rate, prolonged expiratory time, low tidal volume). Additionally, sedation with ketamine or propofol is recommended due to their bronchodilator properties.

HeliOx (a combination of helium and oxygen) is not a standard recommendation, but it may be considered for patients with refractory conditions.1 Similarly, the use of aminophylline or theophylline is not recommended. Extracorporeal membrane oxygenation (ECMO) is a valuable treatment option for severe, near-fatal asthma cases with persistent respiratory acidosis where adequate ventilation is not achieved.3–5

Up to 30% of patients with asthma in the ICU do not recover within five days despite the administration of high doses of corticosteroids and bronchodilators, due to persistent severe obstruction1,3,4. Systemic corticosteroid therapy is the mainstay of the management of severe asthma exacerbations.2 However, biological drugs (biologics) have been shown to improve control in severe asthma, even in refractory cases.4–10

A history of admission to the ICU is the main risk factor for recurrence and can be considered an indirect marker of type 2 (T2) inflammation.4,10 Such patients typically present with corticosteroid-resistant T2 inflammation associated with mucus plugs.4,10 Anti-T2 biologics act rapidly on this inflammation, reducing plug formation and overcoming corticosteroid resistance. This, in turn, improves the prognosis.4,10

In 2021, Bourdin et al.10 proposed the use of biologics in patients with asthmatic exacerbations admitted to the ICU. In Spain, the available biologics include benralizumab (anti-IL5R), mepolizumab and reslizumab (anti-IL5), dupilumab (anti-IL4R/13), omalizumab (anti-IgE), and tezepelumab (anti-TSLP). These biologics are indicated for severe asthma when conventional treatments fail.2

While none of these drugs have an approved indication for acute exacerbations, they have been used successfully through compassionate (off-label) use programs.2,4–10 The ABRA study (United Kingdom, 2021−2024) is the only clinical trial in this context. The study evaluated a 100 mg subcutaneous dose of benralizumab in 158 adults with eosinophilic exacerbations of asthma or COPD (≥300 eosinophils/μl). The results showed a significant decrease in treatment failures and symptom improvement versus prednisolone alone, with good tolerability.4 Case reports involving biological treatments (benralizumab, tezepelumab, mepolizumab, omalizumab, and reslizumab) in patients with asthmatic exacerbation admitted to the ICU (intubated with mechanical ventilation and some with VV ECMO) confirm the efficacy of these drugs in acute life-threatening episodes4–10 (Table 1). Some of the benefits reported after the administration of biologics in these patients were the disappearance of bronchospasm, normalization of pH, a decrease in eosinophil count and immunoglobulin E (IgE) levels, a decrease in peak pressure, respiratory resistance and driving pressure, an increase in patient tidal volume, and the possibility of starting weaning from ECMO and mechanical ventilation, with successful extubation of the patient a few hours/days after drug administration4–10 (Table 1).

There is an unmet need to improve the management of severe asthma exacerbations in patients admitted to the ICU, based on clinical trials evaluating the efficacy of biological drugs. Currently, there are no studies registered in ClinicalTrials.gov, and the available evidence comes from a small number of cases with heterogeneous treatments and follow-up periods.4–10 Controlled trials analyzing biomarkers of inflammation and their clinical correlation could determine whether these drugs improve the prognosis of patients with near-fatal asthma. Furthermore, conducting such studies would facilitate the optimization of resources, thus reducing mechanical ventilation and the use of corticosteroids and bronchodilators, and improving hospital stay and clinical outcomes.

Biologics have revolutionized the treatment of severe asthma as adjunctive maintenance therapy. This approach holds the potential to improve patient prognoses, minimize the necessity and dosage of corticosteroids, mitigate adverse effects, and optimize clinical outcomes for patients admitted due to near-fatal asthma exacerbation. However, the evidence on their efficacy and safety in this context is limited and is based on compassionate use. While they are not intended for administration in acute situations, their use in near-fatal asthma exacerbations in the ICU presents an opportunity for patients who have not responded to conventional treatment.

María Lozano-Espinosa: conceptualization; research; supervision; validation - verification, visualization - preparation, writing - original draft; writing - revision and editing.

Darío Antolín-Amérigo: supervision; validation - verification, visualization - preparation, writing - original draft; writing - revision and editing.

There has been no assistance or use of AI for drafting the manuscript, although Open Evidence was used to search for relevant literature.

The authors declare that there has been no funding for this manuscript.