1. Palliative Sedation at the End-of-Life Gary D. Ceneviva, MD Penn State Hershey Children’s Hospital

2. Objectives Describe the Patterns of Childhood Death Define Palliative Sedation Describe the Indications and Conditions of Palliative Sedation Discuss the Ethics of Sedation at the End of Life Describe Palliative Medication Selection, Dosing, and Titration

3. Epidemiology Approximately 500,000 children cope with life-threatening conditions annually in the United States 1 Over 50,000 infants and children die annually in the United States 2 1. Himelstein BP et al. N Eng J Med 2004; 350:1752 2. Hoyert DL et al. Pediatrics 2006; 117:168

4. Leading Causes of Infant Death Congenital & Chromosomal Anomalies Disorders related to SGA & LBW SIDS Maternal Complications of Pregnancy Complications of Placenta, Cord & Membranes Respiratory Distress Accidents Bacterial Sepsis Diseases of the Circulatory System Intrauterine Hypoxia & Birth Asphyxia Martin JA et al. Pediatrics 2005; 115:619

5. Leading Causes of Childhood Death (1- 19 years old) Accidents (unintentional injuries) Assault (homicide) Malignant Neoplasms Intentional Self Harm (suicide) Congenital & Chromosomal Anomalies Diseases of Heart Chronic Lower Respiratory Diseases Influenza and Pneumonia Septicemia Cerebrovascular Diseases Martin JA et al. Pediatrics 2005; 115:619

6. Epidemiology 1 in 5 Americans die using intensive care services Nationally, this translates to approximately 540,000 Americans each year Angus DC et al. Crit Care Med 2004: 32:638

7. Epidemiology Feudtner C et al Pediatrics 2006; 117:e932

8. Angus DC et al. Crit Care Med 2004; 32:638

9. Epidemiology Commonly these children die following a decision to either withdraw or limit life sustaining therapies Vernon DD et al. Crit Care Med 1993; 21:1798 Mink RB et al. Pediatrics 1992; 89:961

10. Sedation in Palliative Care – Definition and Terminology Sedation Terminal sedation Sedation for intractable distress in the imminently dying End of life sedation Total sedation Sedation in terminal or final stages of life Palliative sedation Palliative sedation therapy Morita T et al. J Pain Symptom Manage 2002;24:447 De Graeff A et al. J Palliat Med 2007;10:67

11. Terminal Sedation Often used in the USA literature Does not emphasize symptom palliation May be interpreted as an intention to terminate the patient’s life

12. Palliative Sedation The use of sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness Morita T et al. J Pain Symptom Manage 2002;24:447 De Graeff A et al. J Palliat Med 2007;10:67

13. Criteria for Palliative Sedation - Intolerable Suffering Subjective The patient can only determine the suffering to be intolerable If the patient is unable to express the degree the discomfort or suffering experienced a proxy judgment by family and care givers should be sought

14. Palliative Sedation The use of sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness Morita T et al. J Pain Symptom Manage 2002;24:447 De Graeff A et al. J Palliat Med 2007;10:67

15. Criteria for Palliative Sedation - Refractory Symptoms Further interventions are: Not capable of providing adequate relief Associated with excessive or intolerable morbidity Unlikely to provide relief within a tolerable time frame Implies an experienced colleague or palliative care specialist judge the symptom refractory Cherney NI et al. J Palliat Care 1994;10:31

16. Criteria for Palliative Sedation - Refractory Symptoms Dyspnea Pain Agitation Delirium Nausea or vomiting Seizures Myoclonus Levy MH et al. Semin Oncol 2005;32:237

17. Palliative Sedation The use of sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness Morita T et al. J Pain Symptom Manage 2002;24:447 De Graeff A et al. J Palliat Med 2007;10:67

18. Criteria for Palliative Sedation - Patient Selection Applies to patients with progressive or terminal diseases with a life expectancy of hours to days The illness is irreversible and death is expected imminently An order to withhold cardiopulmonary resuscitation must be obtained before sedation is instituted Levy M et al. Semin Oncol 2005;32:237

19. Case A 5 year old with stage 4 neuroblastoma has recurrent disease despite surgery, chemotherapy, and a bone marrow transplantation. She develops severe bone pain refractory to opioids and adjuvant analgesics. Palliative sedation was considered the most viable option for symptom control. The mother is told that the additive effects of these medications could predispose the patient to respiratory depression and death, even though this was not the primary aim of the treating doctor. Collins J. Ethics Rounds 1998;15:258

20. Nurses Perspectives with Palliative Sedation Some nurses thought palliative sedation had not accelerated death Others thought that it may have accelerated death but that this was justified when there was no other way of relieving discomfort. A third group thought that palliative sedation was close to the practice of euthanasia and they often found it difficult to be involved in its use. Rietjens J et al. Palliat Med 2007;21:643

21. Ethics of Palliative Sedation Is palliative sedation different form physician assisted suicide and euthanasia? Is palliative sedation ever ethically appropriate for patients who are not imminently dying? Should willingness to forgo life sustaining treatment be a condition for administering palliative sedation? May palliative sedation be provided to patients who lack decision making capacity? National Ethics Committee Am J Hosp Palliat Med 2007;23:483

22. Is Palliative Sedation Different From Physician Assisted Suicide and Euthanasia? Intention (Principle of Double Effect) The primary intention in physician assisted suicide and euthanasia is to cause the patient’s death; the patients suffering ends as a result The primary intention in palliative sedation is to relieve the patient’s suffering; death occurs as result of the underlying disease process Deep sedation is unlikely to hasten death Levy M et al. Semin Oncol 2005;32:237 Partridge et al. Pedatrics 1997;99;76 Chan JD et al. Chest 2004;126:286

23. Is Palliative Sedation Ethically Appropriate for Patients Who Are Not Imminently Dying Palliative sedation is understood to be an intervention of last resort at the end of life for terminally ill patients who are imminently dying Allowing palliative sedation when the patient can be expected to live for months risks eroding the distinction between palliative sedation and physician assisted suicide

24. Is Forgoing Life Sustaining Treatment a Condition for Palliative Sedation Consensus in the professional community is that candidates for palliative sedation should have a DNR order There is no compelling argument to limit other concurrent life sustaining interventions such as artificial nutrition & hydration for patients who receive palliative sedation

25. May palliative sedation be provided to patients who lack decision making capacity?

26. Decision Making Capacity & Competency Refers to the ability of a person to make decisions Involves 3 essential elements The ability to understand & communicate information relevant to a decision The ability to reason and deliberate concerning a decision The ability to apply a set of values to decision AAP Committee on Bioethics Pediatrics 1994; 93:532

27. Decision Making Capacity & Competency Surrogates Usually the parents May include other family members or court appointed guardians Emancipated minor Definition varies from state to state Examples: high school graduates, married, members of the armed forces, pregnant or parents, or those living apart independently from their parents Mature Minor Definition also varies among courts and legislatures > 14 years old assessed to have decision making capacity AAP Committee on Bioethics Pediatrics 1994; 93:532

28. Standards for Decision Making Substituted Judgment Standard Surrogates can make inferences about the preferences of previously competent patients Can be used for children who are emancipated or mature Best Interest Standard Serves as the basis for decisions for patients who never achieve decision making capacity Usually used by surrogates of infants and young children

29. May Palliative Sedation be Provided to Patient’s Lacking Decision Making Capacity Confining palliative sedation to patient who have decision making capacity risks excluding many patients whose suffering cannot be relieved by other means for whom surrogates are empowered to make all other treatment decisions

30. Case DG is a 6 week old premature infant with a past medical history of trisomy 18, moderate sized atrial & ventricular septal defects, pulmonary hypertension, ventricular tachycardia, and renal insufficiency who was admitted to the PICU following an out of hospital cardiopulmonary arrest. The hospital course was remarkable for severe multiple organ dysfunction. Following several discussions with DG’s family regarding her grave prognosis the family requested all life sustaining therapies be withdrawn

31. Respiratory Distress Versus Agonal Breathes Respiratory distress manifested by: Increased work of breathing A sense of shortness of breath (dyspnea) Signs of air hunger Agonal Respirations (terminal breathes) Breaths occur sporadically with long periods of apnea The patient is invariably unconscious reflexive

32. Choosing a Medication Regimen Plan needs to include Selection of medication(s) Starting doses of the medication(s) usually administered before extubation Titration of the medication(s) Needs to relieve all signs of discomfort including grimacing, agitation, anxiety, and physiologic signs of distress

33. Narcotics When used alone, are usually insufficient in the management of air hunger and respiratory distress at the end of life

34. Palliative Sedation Medications Anxiolytic Sedatives Midazolam, lorazepam Neuroleptics Haloperidol Barbituates Phenobarbital, thiopental, pentobarbital General Anesthetics Propofol, ketamine Levy MH et al. Semin Oncol 2005;32:237 De Graeff A et al. J Palliat Med 2007;10:67 Chater S et al. Palliat Med 1998;12:255

35. Palliative Sedation Medications

36. Sedation During Withdraw of Ventilation Burns JP et al Crit Care Med 2000;28:3060

37. Neuromuscular Blockade (NMB) NMBA may be required to facilitate mechanical ventilation NMBA possess no sedative or analgesic activity Prevents the assessment of a patient’s pain or level of sedation Truog RD et al. Crit Care Med 2001; 29:2332

38. Neuromuscular Blockade Agents Approximately 1/3 of pediatric intensivists & over 85% of other pediatric subspecialists were either uncertain or agreed that it was appropriate to provide NMB with analgesia before withdrawing a ventilator in a child whose death was imminent Solomon MZ et al. Pediatrics 2005; 116:872

39. Guidelines for the Use of NMB When Ventilation is Withdrawn NMB should never be introduced when mechanical ventilation is being withdrawn In patients who are already receiving NMB, neuromuscular function should be restored before the life support is withdrawn. Troug RD et al. New Engl J Med 2000; 342:582

40. Guidelines for the Use of NMB When Ventilation is Withdrawn The only exception to this rule should be: Death is expected to be both rapid and certain and the burden to the child & family of waiting for the neuromuscular blockade to diminish to a reversible level exceed the benefits of allowing better assessment of the patient's comfort and the possibility of interaction with loved ones. Troug RD et al. New Engl J Med 2000; 342:508

41. Guidelines for the Use of NMB When Ventilation is Withdrawn When death is expected to be both rapid and certain after the removal of ventilation, and When the burdens to the child & family of waiting for the neuromuscular blockade to diminish to a reversible level exceed the benefits of allowing better assessment of the patient's comfort and the possibility of interaction with loved ones. Troug RD et al. New Engl J Med 2000; 342:508

42. Conclusion Most pediatric deaths occur in intensive care settings following a decision to forgo life sustaining therapies Palliative Sedation is the use of sedative medications to relieve intolerable suffering from refractory symptoms in patients who are imminently dying