Palliative Care Considerations with a Prenatal Diagnosis of a Potentially Non-survivable Fetal Condition Mike Harlos MD, CCFP, FCFP Simone Stenekes RN, MN, CHPCN(c) David Lambert MD, BSc, FRCPC Chris Hohl MD, FRCPC Winnipeg Regional Health Authority Palliative Care Program - Pediatric Symptom Management & Palliative Care Service

Objectives To consider where pediatric palliative care may fit in the care of those with a potentially non-survivable fetal condition To consider an approach to communication with families regarding perinatal palliative care To review considerations for the management of symptoms in the newborn with an anticipated non-survivable condition

“Thank you for giving me aliveness” Jonathan – 6 yr old boy terminally ill boy Ref: “Armfuls of Time”; Barbara Sourkes

“What if…? What would things look like? Time frame? Where care might take place What should the patient/family expect (perhaps demand?) regarding care? How might the palliative care team help patient, family, health care team? What would things look like? Time frame? Where care might take place What should the patient/family expect (perhaps demand?) regarding care? How might the palliative care team help patient, family, health care team? Palliative Care… The “What If…?” Tour Guides Disease-focused Care (“Aggressive Care”) Disease-focused Care (“Aggressive Care”)

The fetus-to-infant care when lethal anomalies are present is commonly fragmented due to the involvement of a variety of specialty areas. What if infants could tell us what they think of this?

Approach To Prenatal Palliative Care Consult  Explore parents’ understanding of condition and potential outcomes (e.g.. intrauterine death, death during labour/delivery, death following delivery – potential time frames, possible symptoms, goals of care, opportunities for care settings)  If needed, develop an approach to discussing with siblings  Discuss care setting for delivery and expectations/birth plan  Consider pre-drawn medications (typically fentanyl and/or midazolam) for nasal/buccal administration for possible pain, air hunger, restlessness  Home as a possible care setting if baby survives for a few hours/days  Autopsy/coroner/tissue donation  Bereavement follow-up

Communicating with families Exploring decisions Coordinating care

Patient/Family Understanding and Expectations Health Care Team’s Assessment and Expectations What if…?

1.Normalize “Often people in circumstances similar to this have concerns about __________” 2.Explore “I’m wondering if that is something you had been thinking about?” 3.Seek Permission Would you like to talk about that? Initiating Conversations

use gentle, but direct language around death and dying these are typically non-survivable conditions… the parents should not feel as though they are deciding whether their child will live or die – this has already been determined by the condition physical changes can be disturbing (colour, secretions, breathing patterns)… these are strictly physical changes that happen as the body’s systems shut down; they are not who their child is and do not reflect the experience of the child palliative care is not “doing nothing”, or “comfort care only”, but re-focusing of active and aggressive care in the context of a non-survivable condition

Live Birth Approach to comfort in first few minutes Next 1 – 2 hours Try feedingTry feeding Connections & legacyConnections & legacy Next 3 – 4 hours Feeding/hydration decisions if not feeding Feeding/hydration decisions if not feeding By 12 – 24 hours Explore options for care setting e.g. palliative care at home? Begin the path home

Medications Used In Symptom Management

Morphine Mu-1 and mu-2 opioid receptor agonist Metabolized in liver to morphine-3- glucuronide & morphine-6- glucuronide –Premature infants preferrentially metabolize to M-3-G Excretion via kidneys

Morphine Uses: –Analgesia –Dyspnea –Sedation –Anti-tussive Safety short & long term established in infants Side effects –Nausea –Constipation & delayed GI motility –CNS depression –Respiratory depression –Hypotension

Morphine Duration of action approximately 4 hours PO –30-50% bioavailablility –Onset min with peak 60 min Transmucosal –~55% bioavailability –Onset 2-5 min with peak min Intravenous –100% bioavailability –Onset 5 min with peak <30 min

Hydromorphone Uses & side effects similar to morphine –Main metabolite is hydromorphone-3- glucuronide with similar characteristics to M3G –No production of H6G More lipophilic Potency 3-10 times that of morphine –Typically use 5:1 for conversion

Hydromorphone Duration of action approximately 4 hours PO –62% bioavailablility –Onset min with peak min Transmucosal –55% bioavailability –Onset 5 min with peak min Intravenous –Onset 5 min with peak min

Fentanyl Synthetic opioid Agonist to mu-1 and delta opioid receptors Usually considered to be times potency of morphine –May be only times potency in infants Metabolized in liver to inactive compounds –Less histamine release –Chest wall rigidity (usually anesthetic doses) Infants may develop more tolerance

Fentanyl Not efficacious PO due to metabolism Duration up to 60 min Intravenous –Onset 1-3 minutes with peak 6 minutes Transmucosal –Bioavailability ~70% –5-15 min with peak at 13 min Transdermal –Doses generally not appropriate for infants

Midazolam Uses –Sedation/sleep –Amnesia –Anxiolysis –Muscle relaxation –Seizures Action via gamma- amino butyric acid Metabolized to 1- hydroxy-midazolam Side effects –Hypotension & respiratory depression (esp with opioids) –Myoclonus in infants –Temporary nasal irritation without physical damage

Midazolam Duration of action approximately minutes PO midazolam –25-35% bioavailablility –Onset min with peak min Transmucosal –50-83% bioavailability –Onset 2-5 min with peak min Intravenous –Onset 1-5 min with peak 15 min

Methotrimeprazine Originally used as an antipsychotic in 1950’s Uses –Sedation/sleep –Analgesia –Anxiolysis –Delirium/agitation –Nausea –Dyspnea Metabolized in liver Side effects –Sedation –Orthostatic hypotension with IV use –Dystonic reactions, TD, NMS Reactions similar to atypical antipsychotics –Anti-cholinergic side effects (dry mouth, flushing, constipation)

Methotrimeprazine DrugD2Alpha-1H1mAch-15HT2 Haldol Chlorpromazine Nozinan Olanzapine+++ +

Methotrimeprazine Little data given how old medication is Duration 2-4 hours regardless of administration PO –50% bioavailability –10-15 minute onset with peak in 1-3 hours Transmucosal –No experimental data –Onset rapid clinically (<10 minutes) Intravenous –Rapid (minutes) onset with peak at 30 minutes

Glycopyrrolate Muscarinic-cholinergic antagonist Uses –Decrease secretions –Prevent vagally-induced bradycardia Does not cross blood-brain barrier Renally excreted (reduce dose in renal failure)

Glycopyrrolate Poor data given blood levels do not correlate to clinical response Oral –Poor absorption (~5% bioavailability) –Onset 50 minutes with peak at minutes –8-12 hour duration for anti-sialogogue Transmucosal –No data Intravenous –Onset 1 min with peak in <10 min –Duration 2-3 hours

Scopolamine Non-selective muscarinic-cholinergic antagonist Crosses blood-brain barrier Use –Decrease secretions –Sedation desired (or at least not unwanted)

Scopolamine PO –Poor bioavailability (3-27%) –Onset + peak in min with 4-6 hour duration Transdermal –Onset 6-8 hours with duration of effect 72 hours Transmucosal –83% bioavailable –Peak drug at 22 min (effect 1 hour) Intravenous –Onset + peak in 4-10 min with 2 hour duration

DrugSL/IN DoseOnsetPeak/TmaxDuration Morphine mg/kg/dose 5 min15-45 min4 hours Hydromorphone mg/kg/dose 5 min20-25 min4 hours Fentanyl mcg/kg/dose 5 min13 min30-60 min Midazolam mg/kg/dose 2-5 min10-15 min30-60 min Nozinan mg/kg/dose 5-10 min~30 min2-4 hours Glycopyrrolate 5 mcg/kg/dose5 min~10 min>2 hours Scopolamine 5 mcg/kg/dose5 min22 min>2 hours Developed by Chris Hohl MD, FRCPC NB: limited or no published data regarding info in shaded areas

Intranasal Meds DrugT max (min)Bioavailability (%) Midazolam 1,2 11 – 14*55 – 83 Fentanyl Sufentanil Hydromorphone 4 20 – 2555 Ketamine P. D.Knoester ; Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers ; Br J Clin Pharmacol May;53(5): Rey E. et al; Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration ; Eur J Clin Pharmacol 41(4) 1991; Dale O, Hjortkjaer R, Kharasch ED; Nasal administration of opioids for pain management in adults ; Acta Anaesthesiol Scand Aug;46(7): Coda BA, Rudy AC, Archer SM, Wermeling DP; Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers ; Anesth Analg Jul;97(1): Fisgin T et al; Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study ; J Child Neurol Feb;17(2): Yanagihara Y et al; Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers; Biopharm Drug Dispos Jan;24(1): * Available to the cerebral cortex 2 – 5 min. after nasal use 5 Reasonable to start with recommended mg/kg for IV dosing and adjust empirically

Palliative Care in the Community  What needs to be considered? –Family awareness and desire to take child home  Who is involved? –Pediatrician / Family Physician –Specialists –Home Care –Palliative Care Team  What is involved? –Develop a care plan Letter of Anticipated Home Death Advance care plan with DNAR discussion of autopsy/tissue donation anticipate symptoms and evaluate routes of medication administration –Preparation of family –Insure responsiveness and availability at all times