Caring for critically ill patients receiving mechanical ventilation in the intensive care unit (ICU) is an immense challenge for clinicians. Interventions to maintain physiological stability and life itself can cause a number of adverse effects that have a marked impact on patients beyond the period of critical illness or injury. These ICU-acquired conditions include but are not limited to weakness, depression, and post–intensive care syndrome, all of which markedly affect patients’ quality of life after they leave the unit. How best to manage the many symptoms experienced by patients undergoing mechanical ventilation without contributing to adverse ICU-acquired sequelae remains a daunting charge for clinicians and requires innovative “out of the box” approaches to address these complex issues. Systematic, cutting-edge research is needed to challenge the “usual” way of managing ICU patients in order to provide the best available evidence for practice integration that minimizes adverse, ICU-acquired sequelae and improves outcomes for the most vulnerable patients. This article highlights a program of research focused on interventions for managing symptoms in critically ill patients receiving mechanical ventilatory support, including the appropriate empowerment of symptom self-management by patients undergoing mechanical ventilation. Development and testing of innovative, nontraditional interventions specifically tailored for ICU patients receiving mechanical ventilatory support are presented. Music listening is highlighted as a nonpharmacological, adjunctive intervention to reduce anxiety associated with mechanical ventilation. Patient-controlled sedation is discussed as an alternative method to meet patients’ highly individual needs for sedative therapy to promote comfort.

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