Left to Our Own Devices - Oregon Hospice

Left to Our Own Devices - Oregon Hospice

Left to Our Own Devices Katrina Hoffman, NP Laura Mavity, MD Clinical Director, St. Charles Health System Advanced Illness Management/Palliative Care Objectives Identify legal and ethical considerations in removing implanted devices at the end of life. List the basic steps and documentation required after a decision to deactivate an implanted device. Identify methods used for both planned and urgent implanted device deactivation. Identify measures to control recurrent seizures to promote patient comfort and ease caregiver/family distress. Katrinas slides

Case #1 Jeannie is a 53yo female who is enrolled in your hospice program with glioblastoma multiforme. She was diagnosed 3 years ago, initially did well after subtotal resection with Temodar and radiation, unfortunately had progression of disease 14 months later, did have further surgery for partial resection and had some improvement with Avastin for months, but now declining with MRI showing tumor progression with associated edema. She has had some issues with seizures around the time of surgeries and in between, which have been generally well controlled with Keppra 500mg po bid. She is now declining with less alertness, less ability to take PO, and family and her hospice team are appropriately concerned about managing her seizures for comfort at home. Case #2 Joe is a 64yo male hospitalized with progressive end stage liver disease due to alcoholic cirrhosis and Hepatitis C with complications including encephalopathy, recurrent ascites. He was living at home prior to admission, still drinking alcohol, living with his SO of many years, who is no longer able to care for him with increasing weakness and confusion. He is no longer eating and is now bedbound. He has never had seizures in the past. While your inpatient palliative care team is working with his SO to sort out care goals and plans and discussing the hospice benefit, he develops refractory seizure activity in the hospital. Phenobarbital/Valium/Ativan/Keppra are not effective at controlling his seizures. pe SEIZURE

CHARACTERISTICS TYPES Partial or focal seizures Simple: without loss of consciousness or Complex: with loss of consciousness Motor Sensory Autonomic Affective Generalized (with loss of consciousness) Primary or secondary (following partial seizure) With or without aura Nonconvulsive: Absence or petit mal Convulsive: Grand mal or tonic-clonic Clonic (upper limb, neck, and face contractions)

Myoclonic (limbs) Tonic (generalized rigidity and falls) Atonic (sudden loss of muscle tone) Caraceni A, Martini C, Simonetti F. Neurological problems in advanced cancer. In: Hanks G, Cherny NI, Christakis NA, Fallon M, Kaasa S, Portenoy RK, editors. Oxford textbook of palliative medicine. 4th ed. New York, NY: Oxford University Press; 2010. pp. 103458. Evaluation History and PE useful to determine cause Structural cause if aura, focal, versive eye movements during seizure, focal neurologic findings (may disappear within few hours) Review Medications any meds that lower seizure threshold

withdrawal from benzodiazepines or alcohol weaning from steroids subtherapeutic levels of anticonvulsants. opioid neurotoxicity (rare cause) Investigations CBC and CMP to identify reversible anomalies CSF for culture, cytologic examination Radiologic investigations ie CT scan with contrast or MRI (assess for mass, leptomeningeal disease, brain tumor progression, CVA)

Electroencephalogram if suspicion of subtle seizure activity re type SECOND-LINE TREATMENT SEIZURE TYPE FIRST-LINE TREATMENT Partial (with or without secondary generalized seizure): Carbamazepine Phenytoin Oxcarbazepine Valproic acid (for secondary generalized seizure) Phenobarbital Clobazam (for simple partial seizures) Gabapentin Topiramate Lamotrigine

Levetiracetam Absence Valproic acid Clonazepam Clobazam Topiramate Lamotrigine Myoclonic Valproic acid Clonazepam Clobazam Topiramate Tonic-clonic Carbamazepine Phenytoin Valproic acid Phenobarbital Oxcarbazepine Topiramate

Generalized: Beaulieu I, Nadeau C. Myoclonies et convulsions. In: Beausoleil M, Association des pharmaciens des tablissements de sant du Qubec, editor. Guide pratique des soins palliatifs: gestion de la douleur et autres symptmes. 4th ed. Montreal, QC: Association des pharmaciens des tablissements de sant du Qubec; 2008. pp. 28798. Caraceni A, Martini C, Simonetti F. Neurological problems in advanced cancer. In: Hanks G, Cherny NI, Christakis NA, Fallon M, Kaasa S, Portenoy RK, editors. Oxford textbook of palliative medicine. 4th ed. New York, NY: Oxford University Press; 2010. pp. 103458. cts parate wiANTICONVULSANT Phenytoin STARTING DOSE NA Carbamazepine 200 mg/d; increase by 200 mg/wk Valproic acid 15 mg/kg daily; 250500 mg/d, increased weekly by 250 mg/wk Oxcarbazepine 300600 mg/d

9002400 mg/d; decrease dose if renal Hyponatremia, dizziness, somnolence, failure occurs nausea, ataxia, diplopia Phenobarbital NA 60250 mg/d, maximum 600 mg/d (15 Drug-drug interactions, CNS depressor, mg/kg in adults) in single or divided respiratory depression, somnolence, doses; decrease dose if renal or hepatic rash failure occur Gabapentin NA 3003600 mg/d as monotherapy; up to 1800 mg/d as adjuvant therapy, in 34 divided doses; decrease dose if renal failure occurs Lamotrigine 50 mg/d for 2 wk, then increase by 25 100500 mg/d in 2 divided doses; 50 mg/wk decrease dose if renal or hepatic failure occur

25 mg/d; increase by 2550 mg/wk 75400 mg/d in 2 divided doses; decrease dose if renal failure occurs Rash, especially if dose escalation is rapid Levetiracetam 7501000 mg/d 10003000 mg/d in 2 divided doses; decrease dose if renal failure occurs Anxiety, aggressivity, somnolence, asthenia, dizziness Clobazam 10 mg/d 1030 mg/d, maximum 6080 mg/d in 2 divided doses Same as for benzodiazepines; rash Clonazepam NA

16 mg/d in 23 divided doses Same as for benzodiazepines; paradoxical excitation Topiramate USUAL EFFECTIVE DOSE 200500 mg/d in single or divided doses SIDE EFFECTS Drug-drug interactions including dexamethasone, CNS (ataxia), liver, GI, dermatologic, hirsutism, anemia, osteoporosis 3001600 mg/d in 34 divided doses or Drug-drug interactions, SIADH, CNS 2 divided doses if long-acting (sedation, vertigo, ataxia, diplopia), myelotoxicity 10003000 mg/d, up to 60 mg/kg daily Drug-drug interactions, CNS (ataxia, (check serum levels) in 3 divided doses tremors, sedation), weight gain, hair or 2 divided doses if long-acting; loss, GI, thrombocytopenia, liver decrease dose if hepatic failure occurs toxicity Interaction with antacids; decrease in memory and concentration;

somnolence, ataxia, dizziness, edema, weight gain Drug-drug interactions, somnolence, confusion, weight loss, metabolic acidosis, angle-closure glaucoma Benzodiazepine options for declining patients Plan for high prevalence of poor responsiveness and dysphagia leading to decreasing ability to take PO PO midazolam, alprazolam, lorazepam, diazepam, clonazepam SL liquid preparations of lorazepam and diazepam Intranasal (intranasal midazolam similar efficacy/safety to rectal diazepam and much preferred by CGs) PR diazepam

SQ/IM midazolam, lorazepam, diazepam IV midazolam infusion, lorazepam, diazepam Koekkoed, J et al, Antiepileptic drug treatment in the endoflife phase of glioma patients: a feasibility study, Support Care Cancer. 2016 24: 16331638. Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000321:8386. Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol. 200634:355359. Status Epilepticus Continuous or without full recovery, lasting more than 30 minutes. Refractory SE (does not respond to first- or second-line therapies (lorazepam/midazolam and fosphenytoin/phenytoin) occurs in approximately 30% of all SE cases Myoclonic status epilepticus is spontaneous, repetitive, unrelenting, generalized myoclonus involving the face, limbs, and axial musculature in comatose patient, portends

vast neurological damageand is not only a poor prognostic indicator but an agonal event Treatment guidelines for SE in general medical population include intravenous (IV) agents (see Table 1) and close monitoring that are often not available or typically appropriate in the palliative care setting. Dulin, JD et al, (2014) Management of Refractory Status Epilepticus in an Actively Dying Patient, Journal of Pain & Palliative Care Pharmacotherapy, Aug 2014, 28:3, 243-250 Virginia Commonwealth Universitys Thomas Palliative Care Unit Use palliative sedation guidelines/protocol for management of refractory seizure activity: Midazolam (IV or SQ), very short acting benzodiazepine (onset of action within 3-5 minutes after intravenous injection with peak effect seen in 20-60 minutes), 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. Usual maintenance dose range 20-120 mg/day. Propofol (IV only)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 310 minutes. The terminal elimination half-life is 200 minutes. Pain at the injection site is a common adverse reaction which can be minimized by and using a large vein if possible. Propofol also has antiemetic properties. Dosing Recommended bolus dose of 20mg over 5 minutes, usual starting dose 5-10 mg/hr titrate by 10mg/hr every15-20 minutes. Average range 500mg- 1100mg/day. Barbiturates 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, loading dose prior to starting infusion or maintenance dose. Many drug interactions.

Dosing Phenobarbital (IV or SQ) 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. Pentobarbital (IV only) - the typical loading of 2mg/kg (150mg) IV push over 5 minutes. Starting dose 1mg/hr (or 10ml/hr) and titrate upward to maintain sedation. Pediatric population Fear of apnea or over-sedation are main barriers to prompt symptom control. Experience of managing seizures at end-of-life is challenging and stressful for staff. Pharmacological approaches to seizure management in end-of-life care are variable, often exceeding dose recommendations, but usually effective Harris N, et al. Seizure management in end-of-life care for children. Archives of Disease in Childhood 2017;102:A203. Case #1 Jeannie is a 53yo female who is enrolled in your hospice program with glioblastoma multiforme. She was diagnosed 3 years ago, initially did well after subtotal resection with Temodar and radiation, unfortunately

had progression of disease 14 months later, did have further surgery for partial resection and had some improvement with Avastin for months, but now declining with MRI showing tumor progression with associated edema. She has had some issues with seizures around the time of surgeries and in between, which have been generally well controlled with Keppra 500mg po bid. She is now declining with less alertness, less ability to take PO, and family and her hospice team are appropriately concerned about managing her seizures for comfort at home. How would you manage this patients seizure disorder? Case #2 Joe is a 64yo male hospitalized with progressive end stage liver disease due to alcoholic cirrhosis and Hepatitis C with complications including encephalopathy, recurrent ascites. He was living at home prior to admission, still drinking alcohol, living with his SO of many years, who is no longer able to care for him with increasing weakness and confusion. He is no longer eating and is now bedbound. He has never had seizures in the past. While your inpatient palliative care team is working with his SO to sort out care goals and plans and discussing the hospice benefit, he develops refractory seizure activity in the hospital. Phenobarbital/Valium/Ativan/Keppra are not effective at controlling his seizures. How would you further manage this patients seizure disorder? ects BOTTOM LINE

Seizures might signal the progression of underlying brain lesions or, alternatively, be due to biochemical or drug imbalances. When a patient develops a seizure, a prompt history and physical examination are useful to determine the cause. The presence of seizures can be traumatizing for patients and their families. Proper management must include reassurance and education of patients and families, as well as prescriptions for the acute management of future episodes of seizures. Because the probability of spontaneous resolution of the seizure decreases with time, treatment of status epilepticus should be instituted when a convulsion lasts 5 minutes or more. Treatment might vary according to the patients location of care. Most seizures can be controlled with prompt treatment with benzodiazepines, and although status epilepticus might be a terminal event, it can be made to be as peaceful as possible.

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