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Initial therapy should begin with supplemental oxygen, application of monitoring devices, and vascular access. Evidence suggests that oxygen therapy should be carefully titrated to a SpO₂ goal of 94%‐98% in patients with general respiratory distress and to a goal of 88%‐92% in patients with known COPD [16].

Inhaled bronchodilators, including short‐acting inhaled β₂‐agonists (SABAs) and anticholinergics, are commonly included in protocols for respiratory distress of unclear etiology. Although there is usually little downside to their use, especially if a component of bronchospasm is suspected, SABAs can be potentially harmful in those with ADHF, acute coronary syndrome, and cardiac dysrhythmias, due to their chronotropic, inotropic, and vasoactive effects on the cardiovascular system. A review of the Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE) database revealed that 21% of patients ultimately diagnosed with ADHF exacerbations received SABA treatments by EMS or in the emergency department [17]. There was an association between bronchodilator administration and a subsequent need for IV vasodilators and intubation [17]. Additionally, cases of acute MI precipitated by bronchodilator use have been reported [18]. SABAs are known to decrease serum potassium concentration by approximately 0.5 meq/L, which could precipitate or worsen hypokalemia‐associated dysrhythmias. In addition, SABAs may temporarily worsen hypoxemia by increasing the ventilation/perfusion mismatch. Inhaled anticholinergics, such as ipratropium, are not absorbed systemically and have no cardiovascular toxicity. Prehospital studies supporting their use as bronchodilators are limited [19].

Two forms of NIPPV have become common for treating several respiratory distress etiologies [20]. (See Chapter 6.) A mask is used to deliver ventilation support either at a constant pressure (continuous positive airway pressure) or with a higher pressure during inspiration (bilevel positive airway pressure). Prehospital NIPPV has resulted in decreased mortality, reduced intubation rates, shorter ICU lengths of stay, and improved vital signs [20, 21]. Although NIPPV has been most studied in COPD and ADHF, a systematic review and meta‐analysis supports its use in all forms of undifferentiated acute respiratory failure [22]. NIPPV may also permit administration of a lower concentration of inspired oxygen, thereby decreasing the potentially deleterious effects of hyperoxia [23]. It is essential that EMS clinicians understand the limitations of this intervention, including patient factors that are specific contraindications to its use. NIPPV is inappropriate for patients who require immediate intubation, such as those who cannot protect their airways, are vomiting, have altered mentation, or cannot tolerate the pressure mask. The patient must also have an acceptable respiratory drive prior to the application of NIPPV.

Advanced airway management with supraglottic airways or endotracheal intubation is the final common pathway for most individuals with severe respiratory distress who have failed to respond to the strategies discussed above.