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The process of dying is a ubiquitous milestone that allows patients and family members a time of reconciliation, growth, and spiritual enrichment as life enters its final chapter ^{[1, 2]}. Lamentably, it can also be a time of considerable suffering, precipitating physical and emotional anguish and fomenting desperate and unnecessary requests for physician-assisted death.
Even though symptoms can be adequately managed in most dying patients, suffering in all its do-mains may be refractory to standard palliative measures. When such suffering occurs, the goals of care are often modified so that the relief of symptoms may prevail over all other considerations, including the maintenance of consciousness. For that reason, when palliative therapies have been exhausted and symptoms remain refractory, palliative sedation is a valuable therapeutic adjunct that affords a more comfortable and dignified death ^[1]. Nevertheless, palliative sedation remains somewhat contentious, due to lack of a consistent and universal definition, disparity in clinical use, ethical and moral apprehensions, confusion regarding sedative medications, and a paucity of well-controlled research.

Definition and Epidemiology
Palliative sedation has not been universally and definitively defined ^{[3, 4],} making interpretation, comparison, and extrapolation of many studies and case analyses problematic. Several definitions have been proffered, of which three will be put forward for illustration:
§ Broeckaert and Olarte ^[5]define palliative sedation as the intentional administration of sedative drugs in dosages and combinations required to reduce the consciousness of a terminal patient as much as necessary to adequately relieve one or more refractory symptoms.
§ The Hospice and Palliative Nurses Association ^[6]defines palliative sedation as the monitored use of medications intended to induce varying degrees of unconsciousness, but not death, for relief of refractory and unendurable symptoms in imminently dying patients.
§ The American Academy of Hospice and Palliative Medicine ^[7] forgoes a formal definition but suggests the use of sedating medications is intended to decrease a patient’s level of consciousness to mitigate the experience of suffering, but not to hasten the end of life.
While these definitions are acceptable, many clinicians argue that palliative sedation does not necessarily mandate sedation to total unconsciousness and, instead, suggest there are variable degrees of sedation as well as duration of sedation. Although Morita and associates ^[8] propose a concise definition of palliative sedation similar to the above -mentioned definitions, they suggest subcategories of palliative sedation based upon degree and duration of sedation.

Nevertheless, it may be better to include subcategories in the definition of palliative sedation to preclude confusion and variation in the study and practice of palliative sedation. Consequently, palliative sedation may be more clearly defined and clinically characterized as the primary intention of deliberately inducing a temporary or permanent light-to-deep sleep, but not deliberately causing death, in patients with terminal illness and specific refractory symptoms.

Although palliative sedation is unquestionably a valuable and efficacious palliative intervention and was fundamentally sanctioned by the United States Supreme Court decision opposing a constitutional right to physician-assisted suicide [9–12], its use remains somewhat nebulous, with a reported incidence ranging from 2% to 52% [13–15].

Mr. Jones was a 73-year-old male with extensive metastatic cancer of the pharyngotonsillar region, complicated by significant chronic obstructive pulmonary disease and diabetes mellitus. His symptoms were relatively well controlled with sustained-release morphine (150 mg twice daily); immediate-release morphine sulfate (75 mg,) for breakthrough pain; and, on an“as needed” basis, haloperidol (0.5 mg) for nausea and vomiting, lorazepam (0.5 mg) for anxiety, and inhalant albuterol and ipratropium for dyspnea.

Mr. Jones did quite well on this regimen for several months,but as the disease progressed,his dyspnea worsened secondary to gradual tracheal compression from a large metastatic lesion, culminating in admission to an inpatient hospice unit for symptom control.Upon admission, numerous interventions were attempted in an effort to assuage Mr. Jones’ dyspnea, including conversion from oral morphine to a continuous subcutaneous infusion (4 mg/h); individually scheduled, small-volume nebulizations of albuterol, ipratropium, morphine, and furosemide; lorazepam (0.5 mg every 4 hours); chlorpromazine (25 mg every 6 hours); oxygen via a nasal cannula; and a fan gently blowing on his face.

Unfortunately, none of the treatments alleviated or attenuated his sense of dyspnea, and, in fact, stridor became apparent, aggravating his labored respirations. At this point, endotracheal intubation with mechanical ventilation was discussed with Mr. Jones and his family; however, they elected to forgo artificial respiratory support and chose to continue with symptomatic treatment, invoking the patient’s do-not-resuscitate election in light of the futility of intubation and assisted ventilation.

Since his dyspnea was refractory to all palliative measures, and impending respiratory failure

admission to an inpatient hospice unit for symptom control.Upon admission, numerous interventions were attempted in an effort to assuage Mr. Jones’ dyspnea, including conversion from oral morphine to a continuous subcutaneous infusion (4 mg/h); individually scheduled, small-volume nebulizations of albuterol, ipratropium, morphine, and furosemide; lorazepam (0.5 mg every 4 hours); chlorpromazine (25 mg every 6 hours); oxygen via a nasal cannula; and a fan gently blowing on his face.

Since his dyspnea was refractory to all palliative measures, and impending respiratory failure

was clinically evident,palliative sedation was pro-posed as a humane and compassionate approach to allay his suffering.After explanation of the procedure, both he and his family readily agreed to deep and continuous palliative sedation. An informed consent document was signed,and a note describing the indications and plans for palliative sedation was recorded in the patient’s chart. A 5-mg subcutaneous bolus of midazolam was then administered, followed by a continuous subcutaneous infusion of 1 mg of midazolam per hour. The Ramsay Sedation Scale was utilized to monitor depth of sedation, and the dosage of midazolam was titrated upward to maintain a deep level of sedation (a 5-mg bolus every 30–60 minutes,as needed,was utilized,with the continuous infusion increased by 1 mg/h after each bolus).

Within 5 minutes he was sedated, but after 30 minutes he was still arousable with verbal stimulation, so a second bolus of midazolam was ad-ministered and his infusion increased to 2 mg/h. Titration continued over the next few hours until he was deeply sedated, with an eventual dose of 5 mg/h required to maintain deep and continuous sedation.He died 2 days later,sedated,peaceful, and with his family at his bedside.

Midazolam was chosen to provide Mr. Jones’ sedation because of its short half-life.In addition, there is extensive clinical experience with its use as sedative pharmacotherapy at the end of life. Phenobarbital is also a cost-effective and efficacious agent that can be used as a first- or second-line medication and would have been added to Mr. Jones’ regimen had a high-dose (ie, 120–200 mg/d) of midazolam failed to provide adequate sedation.Propofol has also been touted as a valuable agent for palliative sedation;however,its cost and intravenous route of administration limit its use outside of an intensive care unit.

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