Empirical Clinical Research in Continuous Deep Sedation at the End of Life  Mohamed Y. Rady, BChir, MB (Cantab), MA, MD (Cantab), FRCS (Eng & Edin), FRCP (UK), FCCM  Journal of Pain and Symptom Management  Volume 53, Issue 6, Pages e10-e12 (June 2017) DOI: 10.1016/j.jpainsymman.2017.01.006 Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

Fig. 1 Self-perpetuating cycle of life-shortening pathophysiologic events triggered in continuous deep sedation. Continuous deep sedation can cause early lethality because of acute depression of the cardiovascular system, airway reflexes, and/or respiratory drive. Sedatives can diminish voluntary control over the muscles in the face and throat causing poor pharyngeal and airway muscle tone. The inability to swallow or cough can accelerate the onset of pulmonary aspiration and hypoxia. The alteration in pharmacokinetics and pharmacodynamics of sedatives (e.g., midazolam) administered as a continuous infusion can contribute to late lethality. Prolonged continuous deep sedation can be associated with metabolic disturbances from dehydration and hypoxia. These metabolic disturbances exacerbate the adverse side-effects of sedatives such as restlessness, agitation, and delirium. Further increases in the doses of sedatives may be necessary to control these neurologic side-effects. The dose escalation and diminished metabolic clearance of sedatives in dehydrated and hypoxic patients can disproportionately depress circulation and respiration. From Rady MY, Verheijde JL. Continuous deep sedation until death: palliation or physician-assisted death? Am J Hosp Palliat Care 2010;27:205–214. Reproduced with permission. Journal of Pain and Symptom Management 2017 53, e10-e12DOI: (10.1016/j.jpainsymman.2017.01.006) Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions