Severe, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a rapid deterioration of the respiratory symptoms of patients with COPD, requiring hospital admission and escalation of pharmacological and nonpharmacological care including the more severe cases of respiratory failure and admission to an intensive care unit (ICU). These events severely impact patients' quality of life and prognosis. This review will describe the nonantibiotic, pharmacological treatment options available for critically ill patients with AECOPD. The aim of treatment is to alleviate symptoms, improve patient's functional and respiratory status, reduce mortality, reduce the risk or the duration of invasive mechanical ventilation, and prevent reexacerbations. Inhaled bronchodilators (i.e., short-acting β2-agonists and anticholinergics) and systemic corticosteroids are the main drugs used in the treatment of AECOPD. These drugs are also used in the treatment of stable COPD and in the treatment of AECOPD patients in the non-ICU or community setting. Other drugs are essentially only used in the ICU setting such as inhaled anesthetic agents, ketamine, intravenous methylxanthines, and magnesium. Finally, recently developed drugs, such as the specific phosphodiesterase-4 inhibitors, may play a role in the prevention of relapsing AECOPD following a critical event than the treatment of the exacerbation itself. Although they significantly improve the survival of critically ill patients with AECOPD, none of available drugs, alone or combined, is able to significantly modify the prognosis of patients with COPD. This remains an open challenge for the current and future generations of researchers and clinicians.
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