1. Perinatal Palliative Care
Mike Harlos MD, CCFP, FCFP
Professor and Section Head, Palliative Medicine, University of Manitoba
Medical Director, Adult & Pediatric Palliative Care, Winnipeg Regional Health Authority

4. The presenter has no conflicts of interest to disclose

5. 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
To learn about the overall management of complex clinical scenarios in perinatal palliative care

7. WHO Definition of Palliative Care for Children
Palliative care for children is the active total care of the child's body, mind and spirit, and also involves giving support to the family.
It begins when illness is diagnosed, and continues regardless of whether or not a child receives treatment directed at the disease.
Health providers must evaluate and alleviate a child's physical, psychological, and social distress.
Effective palliative care requires a broad multidisciplinary approach that includes the family and makes use of available community resources; it can be successfully implemented even if resources are limited.
It can be provided in tertiary care facilities, in community health centres and even in children's homes.

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

9. Clinical Directives Timing Setting Choices in Palliative Care –
What considerations might
limit potential options?
Clinical
Directives
Timing
Setting

10. BACKGROUND
neonatal deaths remain a reality in health care, and with prenatal diagnosis a palliative approach to care can often be planned
UK Stats:
98% of neonatal deaths occur in an NICU
few are supported to die at home or in hospice
palliative care is only routinely provided for babies and children over 28 days old
If newborns could tell us what they thought of these stats, what would they say?....

12. Potential Palliative Scenarios
known lethal fetal anomalies exist; potential need for aggressive symptom management with noninvasive routes of administration
withdrawing life-sustaining treatment
withholding / non-escalation of interventions
comfort care during terminal phase of irreversible organ failure (e.g.. gut, renal, hepatic)… may be days to weeks

13. Wilkinson D, Thiele P, Watkins A, De Crespigny L. Fatally flawed
Wilkinson D, Thiele P, Watkins A, De Crespigny L. Fatally flawed? A review and ethical analysis of lethal congenital malformations. BJOG. 2012;119:

14. 2012 Report On The Ten Most Common Causes of Infant Deaths In U. S. A
2012 Report On The Ten Most Common Causes of Infant Deaths In U.S.A. In 2009 Kochanek KD, Kirmeyer SE, Martin JA, Strobino DM, Guyer B.Pediatrics Feb;129(2):338-48
Significant potential for anticipating palliative needs of newborn

15. Potential Roles For Neonatal Palliative Care
Explore potential “what-if” scenarios and inform the discussion about possible approaches
Regardless of the prognostic certainty or the approach taken, ensure vigilance towards:
Comfort of the newborn
Support of family
Support of team
Connections – siblings, other relatives
Legacy/Memory – footprints, photos, etc
Participate in dialogue around difficult ethical considerations
On occasion – consolidate information from multiple involved specialists; serve as a steady presence in the context of weekly turnover of attending physicians
Participate in exploration of alternate care settings

16. Life-And-Death Decisions?
In situations where death will be an inescapable outcome, family may nonetheless feel that their choices about care are life-and-death decisions (treating infections, hydrating, tube feeding, etc.)
It may be helpful to say something such as:
“I know that you’re being asked to make some very difficult choices about care, and it must feel that you’re having to make life-and-death decisions. You must remember that this is not a survivable condition, and none of the choices that you make can change that outcome. We know that because of her illness, she is on a path towards dying. We are asking you to help us choose the smoothest path, causing least distress for your baby”
Many of the choices presented to families in the context of end-of-life circumstances can result in them feeling as though they are deciding whether or not there loved one lives or dies. It can be helpful to reaffirm that the underlying condition is not survivable, and that none of the choices that they make can change that… they are being asked for input that will help make sure that the care provided is consistent with how their loved one would have guided it, while ensuring that comfort is addressed.
Such scenarios can sometimes be described as the illness being a play whose script has been written and which cannot be changed… we are the stage hands whose role is to ensure that it unfolds with as much comfort and dignity for the patient as possible. 16

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

20. Palliative Care… The “What If…?” Tour Guides
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 if…?
Disease-focused Care
(“Aggressive Care”)

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

22. Elements of Neonatal Palliative Care Best practice guidelines: Palliative care for the newborn in the United Kingdom L. de Rooy, N. Aladangady, E. Aidoo; Early Human Development 88 (2012) 73–77
Assessment: baby's current clinical state, focusing on pain, agitation, dyspnea and other symptoms
Communication: verbal/ written communication with parents
Review of medications: stop all medications which do not add to the baby's comfort, actively treat all symptoms.
Review of interventions: stop all unnecessary interventions and observations, actively consider interventions which can increase comfort, e.g. skin-to-skin contact.
Resuscitative care plan: record details of what should, and should not be provided in case of deterioration
Provision of hydration/nutrition: provide fluids/feeds through the least invasive route
Communication with MDT
Review: palliative care is a process not an event, review care plans and adjust as needed
Other care options: consider whether the baby may be best cared for in other settings e.g. hospice or home.

23. Approach To Prenatal Palliative Care Consult
Our program has had 68 prenatal consults since Nov. 2006
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 and expectations RE delivery
plan for potential threats to comfort (almost always dyspnea)
Consider pre-drawn medications (fentanyl) for nasal/buccal administration for possible pain, resp distress, restlessness
Home as a possible care setting if baby survives long enough
Autopsy/coroner/tissue donation
Bereavement follow-up

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

26. Helping Families At The Bedside: Physical Changes
physical changes of dying can be upsetting to those at the bedside:
skin colour – cyanosis, mottling
breathing patterns and rate
muscles used in breathing
these reflect inescapable physiological changes occurring in the dying process.
may be comforting for families to distinguish between who their loved one is - the person to whom they are so connected in thought and spirit - versus the physical changes that are happening to their loved one's body.

27. Potential Pitfalls Experienced Through Our Prenatal Involvement
Assumptions that pediatrics and/or neonatology does not need to be involved in delivery or in postnatal care if palliative care involved
Over-interpreting what the “palliative” label means about other aspects of care and support for the baby
Misconception that families can’t change their minds and opt for aggressive care

28. Meet Matthew… Prenatal Dx Trisomy 18
Prenatal palliative care consult May 22, 2008
reviewed potential outcomes and approaches
Induced July 14, on low-risk unit (LDRP)
Home within 16 hrs
Consult received from the NICU CNS, as Derek and Tracey were made aware of the pediatric palliative care service through a pharmacist at Children’s Hospital who worked in NICU. May 22, met prenatal Fetal Assessment Unit visit.
Matthew, their first child, had been diagnosed with Trisomy 18 and a VSD (ventricular septal defect). Further cardiac anomalies were not investigated. In the first meeting our team (physician and CNS) discussed the spectrum of what could be expected with Matthew: from a stillbirth to him living several months. We took the approach that should he be born alive, we would manage things in the first few minutes after his birth and then take the next few hours, and then the next few days. Spoke about issues r/t hydration, and the spectrum of possibilities. Also spoke of need to think about a funeral home and parents decided to pre-plan funeral and cemetery plot.
Derek and Tracey had developed a birth plan and wanted no attempts at resuscitation. Born in the LDRP unit (not their usual patient). PPC service called as Tracey induced and in labour, on July 14, Prepared several doses of Fentanyl and Midazolam in case of Matthew’s distress at birth. Preparation and support of LDRP staff. No meds needed. Matthew bottle feeding small amounts. The next day the parents wanted to go home. Initiated paperwork to get Matthew home: LAD in Home, ME Notification (parents had chosen funeral home prior to birth), and care plan for various HCP involved (palliative care program, pediatrician, public health nurse).

31. 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
Ensure responsiveness and availability at all times

36. Fentanyl highly potent opioid – small volumes needed
lipophilic – absorbed readily through transmucosal membranes and blood-brain barrier
expanding pediatric and adult literature on intranasal use of the injectable preparation for pain and dyspnea management

37. Intranasal Fentanyl TMAX 5 – 15 min.
compare with TMAX of 138 minutes for buccal morphine
therapeutic levels reported as short as 2 minutes
bioavailability 71 – 89%
not irritating to the nasal mucosa

38. Intranasal Meds Reasonable to start with recommended mg/kg
Drug
Tmax (min)
Bioavailability (%)
Midazolam1,2
11 – 14*
55 – 83
Fentanyl3,7 5
71 – 89
Sufentanil3 10 78
Hydromorphone4
20 – 25 55
Ketamine6 20 45
Reasonable to start with recommended mg/kg
for IV dosing and adjust empirically
* Available to the cerebral cortex 2 – 5 min. after nasal use5
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):501-7
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):759-70
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):117-23
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):123-6
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):37-43.
Foster D, Upton R, Christrup L, Popper L. Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl in patients with pain after oral surgery. Ann Pharmacother 2008;42: 1380e1387 38

39. MAD300® Device
Syringe is filled with an extra 0.1 ml medication to accommodate for device dead space
our practice is to reuse the device multiple times with the same patient
device is cleared with air to restore dead space prior to next dose

40. Example #1 Newborn with Trisomy 18 and a cardiac defect
Seen by palliative care team twice prenatally, when in labour and after birth of baby on LDRP
Lived 13 hours and 9 minutes
8 doses of Fentanyl administered for respiratory distress
First dose given at 58 min. Next doses at 1 hr + 4 min, at 2 hr + 52 min, then at 3 hr + 40 min. At 9 hr + 5 min: cluster of 4 doses given within 58 min. Increased dose, but no further fentanyl required
Last dose administered 3 hrs + 6 min prior to death
Charted as effective in calming baby

41. Example #2
Extremely premature infant with NEC and sepsis, intubated and ventilated
Seen by palliative care team in NICU 6 days prior to death, plan for withdrawal of life sustaining treatment
IJ line had been running Morphine continuous infusion for one month, switched to Fentanyl infusion 2 days prior to extubation. Lost IJ line immediately prior to planned extubation.
Given 4 doses of intranasal fentanyl. Two doses prior to extubation (32 min and 14 min prior). Two doses given after extubation at 3 min and then 26 min post-extubation (this last dose was given 81 minutes prior to death). One dose of Midazolam intranasally prior to extubation.
Died at 44 days of age in NICU (2 hr + 26 min after extubation)
Effective in managing respiratory distress – “well sedated and comfortable” and “Looks settled”

42. Common Concerns About Aggressive Use of Opioids at End-Of-Life
How do you know that the aggressive use of opioids for dyspnea doesn't actually bring about or speed up the patient's death?
“I gave the last dose of morphine and he died a few minutes later… did the medication cause the death?” 42

43. Literature: the literature supports that opioids administered in doses proportionate to the degree of distress do not hasten death and may in fact delay death
Clinical context: breathing patterns usually seen in progression towards dying (clusters with apnea, irreg. pattern) vs. opioid effects (progressive slowing, regular breathing; pinpoint pupils)
Medication history: usually “the last dose” is the same as those given throughout recent hours/days, and was well tolerated 43

44. Analgesia For Dying Infants Whose Life Support Is Withdrawn Or Withheld
Partridge JC, Wall SN; Pediatrics 99(1) 1997; 76-79
n = 121 deaths related to withholding (n=13) or withdrawing (n=108) life support

47. Intranasal Fentanyl Preparation Prior To Delivery
Based on Estimated Birth Weight
500 – 1000 gm
Based on Fetal Assessment or gestational age < 27 weeks
> 1000 gm
Based on Fetal Assessment or gestational age > 27 weeks
1 mcg/dose
0.1 ml of 10 mcg/ml
2 mcg/kg for 500 gm neonate and 1 mcg/kg for gm neonate
2.5 mcg/dose
0.1 ml of 25 mcg/ml
2 mcg/kg for 1250 gm neonate and 1 mcg/kg for gm neonate
administered q 10 min prn, up to 3 doses within a 30 min period