Management of Refractory Status Epilepticus in an Actively Dying Patient

ABSTRACT

No consensus guidelines exist for the treatment of refractory myoclonic status epilepticus or refractory myoclonus in the palliative care setting. Evidence-based guidelines for the general medical population are often neither practical nor applicable at the end of life. Many challenges, including medication availability, route of administration, monitoring, and work-up are all unique to the palliative care setting. Two patients with refractory myoclonus versus refractory myoclonic status epilepticus are described here, illustrating the challenges involved in treatment as well the need for further research for therapy in the palliative care setting.

KEYWORDS :

• myoclonus
• palliative care
• refractory
• status epilepticus
• propofol
• seizures

APPENDIX 1

APPENDIX 2

Thomas Palliative Care Guidelines Palliative Sedation

• Purpose:

  To establish a guideline for the delivery of parenteral or subcutaneous sedation to provide comfort during the final phase of life for patients who:

  • Have an established “Do Not Resuscitate” order,

  • Are Terminally ill,

  • Are experiencing refractory symptoms, seizures and/or restlessness

  • Whose treatment options have been discusses with members of the interdisciplinary team and with the patient and/or family

Team member consults that should be sought include: palliative care attending, fellow/advanced practice nurse, staff nurse, and chaplain. The depth and duration of sedation needed may vary, depending on the symptoms being palliated and the goals of treatment. This treatment will be administered only on the Palliative Care Unit. Drugs that may be used include: midazolam, propofol, and phenobarbital or pentobarbital. The purpose of this intervention is to relieve symptoms and suffering and not to hasten death. It is not a form of conscious sedation, euthanasia or physician assisted suicide.

• Definitions:

  1. Controlled sedation is the judicious controlled application of medications to reduce or alter consciousness in order to relieve refractory symptoms or suffering that are not responsive to less aggressive interventions. The level of sedation may be increased or decreased due to patient and family needs or concerns.

  2. This guideline addresses the use of midazolam, propofol, or barbiturates for the purposes of palliation of symptoms, seizures, and/or restlessness that have been refractory to standard palliative therapy.

  3. A refractory symptom is one that cannot be adequately controlled despite aggressive efforts to identify a tolerable therapy that does not compromise consciousness. In deciding when a symptom is refractory, the clinician must perceive that further invasive and non-invasive interventions are incapable of providing adequate relief, are associated with excessive and intolerable acute or chronic morbidity, or are unlikely to provide relief within a tolerable time frame.

  4. Opioids should be continued, in conjunction with the use of sedation, to avoid withdrawal and for the treatment of presumed pain.

• Pharmaceutical Consideration:

  • Midazolam (IV or SQ)

    1. Description –Versed is a very short acting benzodiazepine (onset of action within 3-5 minutes after intravenous injection with peak effect seen in 20-60 minutes), used most frequently as an induction agent for general anesthesia or to provide conscious sedation during brief invasive diagnostic procedures. Versed infusion has also been shown to be a safe and effective therapy in palliative care for the management of symptoms, including anxiety, pain control, seizures and restlessness that have been refractory to standard therapy. This drug is stable in solution for 30 days, so the PCA technicians can prepare the bags in advance (1:1 concentration in 100ml bags) and one will be stored on the palliative care unit. Midazolam is administered via a PCA pump.

    2. Dosing - Starting dose is midazolam 0.5-1mg per hour continuous infusion following a loading dose of 2.5-5 mg. Midazolam may be bolused at a dose equal to the hourly basal rate every 15 minutes as needed. If symptoms are unrelieved, the basal rate may be titrated every 4 hours based on the average hourly needs for the previous 4 hours until relief is achieved. Usual maintenance dose ranges 20-120 mg/day.

  • Propofol (IV only)

    1. Description - Propofol is an injectable sedative hypnotic agent used for general anesthesia. In much lower doses it is used for its sedative properties. The onset of effect is within 30 seconds and the duration of effect of a bolus dose is 3-10 minutes. The terminal elimination half-life is 200 minutes. Pain at the injection site is a common adverse reaction which can be minimized by dilution (no less than 2mg/ml) and using a large vein if possible. Propofol also has antiemetic properties. The drug will be given by the IV route with an infusion pump (not pca) since it must be in a glass bottle with nitroglycerin tubing. It should be ordered from the pharmacy as an IV infusion of 10mg/mL.

    2. Dosing –Recommended bolus dose of 20mg over 5 minutes (the pump would be set at 24 ml/hr x 5 minutes with an RN in attendance). Usual starting dose 5-10 mg/hr (0.5-1mL/hr). May titrate by 10mg/hr every 15-20 minutes. Average range 500mg-1100mg/day.

  • Barbiturates

    1. Description –Phenobarbital and Pentobarbital are intermediate-duration barbiturates used for insomnia, anxiety, and as anticonvulsants. The onset of effect is within 15-30 minutes after IV injection and the half-life is approximately 19 hours. An IV pump (not a PCA) will be used when giving by IV route due to short stability times. Will need a loading dose prior to starting infusion or maintenance dose. Barbiturates can be potent inducers of hepatic enzymes (be aware of potential drug interactions).

    2. Dosing

       1. Phenobarbital (IV or SQ) comes in a 130mg/mL vial. Loading dose 100mg-200mg (can easily give 130mg or entire vial), followed by 100-320 mg slow IV infusion 2-3 times/day. Average maintenance dose 600 mg/day.

       2. Pentobarbital (IV only) - the typical loading of 2mg/kg (∼150mg) would be given IV push over 5 minutes. The infusion would be ordered from pharmacy as 25mg in 250ml NS or D5W (0.1mg/ml). Starting dose 1mg/hr (or 10ml/hr) and titrate upward to maintain sedation.

• Protocol:

  1. Controlled sedation, administered by subcutaneous or intravenous routes, may be used on the Palliative Care unit only, for the treatment of refractory symptoms, seizures and/or restlessness. This protocol does not address the use of midazolam, propofol, or barbiturates in other clinical areas.

  2. In more difficult cases, more than one medication may be needed to sedate a patient adequately.

  3. The medication dose should not be increased unless there is evidence of inadequate sedation.

  4. Vital signs with pulse oximetry will be assessed prior to administration of the drug and then as ordered.

  5. Infusion pumps will be labeled “Sedation” with tape as a safety precaution.

  6. An orientation, education and competency program for nurses employed on the Palliative Care Unit regarding the appropriate and safe use and monitoring of controlled sedation is required.

  7. Only Registered Nurses oriented, educated and who have achieved competency for controlled sedation can be assigned to a patient receiving this therapy.

• References

  1. Cherny NI. The use of sedation in the management of refractory pain. Principles and practice of supportive oncology Updates. 2000 3:1-11

  2. Cherny NI and Portenoy RK. Sedation in the management of refractory symptoms: guidelines for evaluation and treatment, J. Pall. Care 10:2/1994; 31-38.

  3. Cherny, N., Commentary: Sedation in response to Refractory Existential Distress: Walking the Fine Line, J Pain Symptom Manage, 1998 Dec; 16(6): 404-5.

  4. Cherny, NI, Sedation for the Care of Patients with Advanced Cancer, Nat Clin Pract Oncol. 2006 Sept; 3(9):492-500.

  5. Charter S et al. Sedation for intractable distress in the dying-a survey of experts. Pall Med 1998; 12:255-269.

  6. Braun TC et al. Development of a clinical practice guideline for palliative sedation. J Pall Med 2003; 6:345-350.

  7. Hallenbeck, J., Terminal sedation for intractable distress, West J Med. 1999 Oct; 171(4):222-3.

  8. Muller-Busch, H., etal, Sedation in palliative care? A critical analysis of 7 years experience, BMC Palliative Care. 2003 May 13; 2(1):2.

  9. Rousseau, P., Existential suffering and palliative sedation: a brief commentary with a proposal for clinical guidelines, Am J Hosp Palliat Care, 2001 May-Jun; 18(3): 151-3.

  10. Rousseau, P., Palliative Sedation I the Management of Refractory Symptoms, Supportive Oncology. 2004 March/April; 2(2): 181-186.

  11. Berger, AM, Ed, et al, Principles and Practice of Palliative Care and Supportive Oncology, Philadelphia, PA: Lippincott Williams & Wilkins, 2002.

  12. Quill, TE, Responding to Intractable Terminal Suffering: The Role of Terminal Sedation and Voluntary Refusal of Food and Fluids, Ann Intern Med, 2000; 132: 408-414.

  13. Sykes, N., Sedative Use in the Last Week of Life and the Implications for End-of-Life Decision Making. Arch Intern Med, 2003 Feb 10; 163: 341-344

  14. deGraeff, A and Dean, M., Palliative Sedation Therapy in the Last Weeks of Life: A Literature Review and Recommendations for Standards, J Palliative Med. 2007, 10(1): 67-85.

  15. Del Fabbro, E., et al. Palliative Sedation: When the Family and Consulting Service See no Alternative, J Pall Med, 2007; 10(2):488-492.

  16. Rousseau, P, The Ethical Validity and Clinical Experience of Palliative Sedation, Mayo Clin Proc. 2000;75: 1064-1069.

  17. Cheng, C. et al, When Midazolam Fails, J Pain and Symptom Management. 2002; 23(3): 256-265.

  18. Knight,P., and Espinosa, L., Sedation for Refeactory Symptoms and Terminal Weaning. Oxford Textbook of Palliative Nusing, Oxford University Press 2010 pp 525-543.

  19. HPNA Position Statement on Palliative Sedation http://www.hpna.org/DisplayPage. aspx?Title=Position%20Statements