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Pain Prior to Birth Robin Pierucci, MD, MA Pain Prior to Birth Robin Pierucci, MD, MA

Pain Prior to Birth Robin Pierucci, MD, MA - PowerPoint Presentation

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Pain Prior to Birth Robin Pierucci, MD, MA - PPT Presentation

Parents instinctively know babies feel pain Painful Definition Problem Baby Premie Fetus Both doctors and lawyers have a history of being confused Outline Fetal Pain Evolution of Neonatal Pain Management ID: 781538

fetal pain babies amp pain fetal amp babies perception noxious response fetus medical anesthesia stress early emotional weeks definition

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Slide1

Pain Prior to Birth

Robin Pierucci, MD, MA

Slide2

Parents instinctively know, babies feel pain

Slide3

Painful Definition Problem?

BabyPremieFetus

Slide4

Both doctors and lawyers have a history of being confused

Slide5

Outline: Fetal PainEvolution of Neonatal Pain Management From:

“Babies don’t feel pain” To: Medical standardDefining PainThe Anatomy of PainFetal vs Premature PhysiologyA view from the bedside

Slide6

Looking Back to Move Forward:

The evolution of Pain Management in Neonates

Slide7

Current Standard of Care for Babies:Pain management “particularly in preterm infants is important not only because it is ethical, but also because exposure to repeated painful stimuli early in life is known to have short and long term adverse sequalae”.

“Prevention and Management of Procedural Pain in the Neonate: An Update”COMMITTEE ON FETUS AND NEWBORN and SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE. 2016, Pediatrics

Slide8

How do we know this?

“The sequalae include:Physiologic instability, Altered brain development, Abnormal neurodevelopment, somatosensory and stress response systems, Which can persist into childhood.”Committee on Fetus and Newborn 2016, Pediatrics

Slide9

Anesthesia—sort of

400 BC: Assyrians use carotid compression to produce brief unconsciousness before circumcision or cataract surgery. History of Anesthesia - Interactive Timelinehttps://www.woodlibrarymuseum.org/history-of-anesthesia/

Slide10

Modern Era of AnesthesiaEarly to mid 1800’s, introduction of ether and chloroform1846: Ether introduced at Mass General, Boston.Early reports justifiably alarming

“Complications included:sudden cardiac deathincomplete anesthesia,madness, death, and a variety of medical problems“ Meyer, 2015, J of Anesth

Slide11

Early Anesthesia

Dosing: more art than science“By reason of immature cardiovascular and respiratory systems, neonates were assumed to be too sensitive to the depressant effects of anesthetics” Kuratani 2015 , J Anesth

Slide12

A Century of Pediatric Medical AdvancesSignificantly increase in # of pediatric issues surgically addressedLonger OR times under anesthesiaYet, early 1990’s babies still operated on

without anesthesia“Whiskey nipple”: widely used as a sedative supplement to local anesthesia in infants undergoing abdominal procedures

Slide13

“Pain and its Effects in the Human Neonate and Fetus” Anand, Phil, & Hickey (1987) NEJM

The focus on pain perception & confusion over its differentiation from nociceptive activityhave obscured the mounting evidence that nociception is important in the biology of the neonate“This is true regardless of any philosophical view on consciousness and pain perception in newborns”

Slide14

Documented Ramifications to Causing Neonatal Pain:Neurophysiological measurable effects:BehavioralNeurochemical, Cardiac, Hormonal, and Metabolic changes

Anand, 1987 NEJM

Slide15

Prospective: Lighter vs Deep Intraoperative Anesthesia

Slide16

Results:Statistically significant differences in the measurable levels of stress hormones “beta-endorphin, norepinephrine, epinephrine, glucagon, aldosterone, cortisol and other steroid hormones”Decreased post-operative complications and improved survival for those who received deep anesthesia

Slide17

So, why is there a debate?

Problem: how should pain be defined?

Slide18

Defining “Pain”

Slide19

What Defines Pain in Humans?

Physical

Emotional

Psychologic

Spiritual

Slide20

International Association for the Study of Pain (IASP)Definition of pain:“An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”

Slide21

By definition pain is:

Unpleasant

Physical aspect

Emotional aspect

The experience consists of

actual or

potential tissue damage

Slide22

Can a human have physical pain without an emotional response?

(Pain without conscious awareness?)

Slide23

Arguments:Due to in-utero neuroinhibitors, the fetus is never awake or aware, and thus, unable to ”truly experience pain”Mellor 2005, Brain Research Reviews

“If a conceptual subjectivity is considered necessary for pain, then pain is not possible at any gestational age”Derbyshire 2010, Best Practice & Research Clinical Ob/Gyne

Slide24

Tabor’s Medical DictionaryPain includes not only the perception of an uncomfortable stimulus but also the response to that perception

BUT OUR RESPONSE IS VARIABLE…

Slide25

Pain Perception, Depends…

Slide26

The Science: Why Pain Perception Is SituationalInfluenced by: physical, mental, biochemical,physiologic, psychologic, social, cultural, and emotional factors

Tabor’s Cyclopedic Medical DictionaryResult:Same insult in two different settings could be perceived as either agonizing or a bumpThus: perception (even if conscious) is an unreliable indicator of “tissue damage”,

Slide27

Example: Comatose Patient

We never would intentionally burn the patientAnd claim there’s no pain because they can’t complain

Slide28

The IASP DefinitionModification:“The inability to communicate verbally does not negate the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment.”IASP definition correctly identifies that pain and emotion are linked BUT: a lack of emotion does not negate nociception

Slide29

While debate continues, it seems unreasonable to err on the side of denying pain relief to the vulnerable

And “confusion has obscured the mounting evidence that nociception is important in the biology of the neonate” Anand 1987, NEJM

Slide30

Anatomical Requirements

for Pain Perception

Slide31

Pain ReceptorsPain sensation (noxious stimulation) is initially received via receptors located in the skin. Timing of human fetal rcptr appearance:7th -8th

wk: perioral area~11th wk: rest of the face, palms of the hand, & soles of the feet~15th wk: trunk, proximal parts of arms and legs Lowery, 2007, Seminars in Perinatology

Slide32

Spinal Sensory Reflex

Noxious stim (via rcptr) activates peripheral sensory n.Sensory n. synapses within spinal cord with motor nMotor n signals muscle contraction and limb withdrawal

Slide33

Fetal Response to Noxious StimulationThis reflex (meaning: occurs without cortical/conscious awareness), protectively moves one’s body away from harm Observed as early as 8 weeks “at this stage, touching the perioral region will result in movement away”. Derbyshire 2010  

Emotionally linked pain is processed in anatomically and physiologically different areas. Lowery, et al 2007

Slide34

Emotionally Linked/Conscious PainIn adults:Noxious stim of peripheral sensory n. to spinal cord synapseWith spinothalamic n. that run the message up the spinal column to the thalamusIn the thalamus, additional connections with n., bring news of the painful stimulus out to the cerebral cortex

Result: conscious perception of pain Lowery et al, 2007

Slide35

Arguments:Due to timing of CNS connections occurring in the mid 2nd trimester, this is when some believe is the earliest possible point of pain perception

Others think even this is too early Due to chemicals within the uterus that keep the fetus in a sleep like state and claim that the fetus is never actually “awake” until after birth. Mellor, et al, 2005

Slide36

The Fetus is Not Asleep:

“Based on behavioral reactions to noxious stimulation” documented at 26 weeks “Neurotransmitters related to regulation of arousal are present at the 12th week of gestation”Serotonin (10th wk) Catecholamines (11th wk)Acetylcholiniesterase (12th wk) Sekulic 2016, J of Pain Res

Slide37

Hypothalamic-Pituitary-Adrenal Axis (HPA)

In adults: noxious stress activates the HPA, the link to pain’s emotional component. Lowery et al, 2007 B endorphin, a stress hormone known to be made from stimulation of the HPA, has been found in the fetus Giannakoulopoulos in 1994 and Gitau in 2001

Slide38

Fetal Stress Responses to Invasive Procedures

Gitau et al 2005, pg104Comparison of fetal and maternal levels of stress homrones (cortisol & B endorphin) pre & post transfusion via piercing the fetal chest to access the intrahaptic vein (IHV) vstransfusion via needling placental cord insertion (PCI)

Slide39

Results: Gitau et al, 2000Fetal response were independent of the mother’s which did not change during transfusion at either site“Fetal B-endorphin responses: apparent from 18 wks GA & independent of GA,

Whereas fetal cortisol responses: apparent at 20 wks & were GA dependent”Findings: “Consistent with the maturation of the fetal pituitary before the fetal adrenal [gland]”

Slide40

The Fetal Brain Responds to Noxious Stim!Findings of neurotransmitters & increased stress hormones levels after painful stim mean that:Babies in the fetal stage are neurologically activeEven without the peripheral nerves being directly connected to the cerebral cortex

Slide41

Anencephaly & Hydranencephaly

Sekulic’s

2016 review:

With minimal or absent cortex, these little ones:

React to noxious stimulus

Can be soothed with comfort measures

Express wake/sleep cycles

Slide42

Medical Task Force on Anencephaly: Found that “Anesthetic agents may eliminate the subcortical responses to noxious stimuli…”“but are not necessary to minimize or prevent suffering.” NEJM, 1990

Their literature review was written back when many babies were still being taken to surgery without anesthesia.

Slide43

They May Feel MORE Pain than Term BabiesThere is an inhibitory arm of the nociceptive pathway that does not mature until after birth. The lack of this part of the developing nervous system “suggests that the fetus is more sensitive to nociception than infants and may explain why newborns show exaggerated behavioral reaction to sensory provocation” Sekulic et al, 2016

pg 1035

Slide44

Study: Experience in NICU Affects Pain Response

Johnston & Stevens 199632 wk newborns vs 32 wk old premature babies (~4 weeks old)HR in the older babies statistically higher than the newborns

Slide45

Response to

HeelstickPremies in the NICU x4 weeks vs newbornsDecreased oxygen saturations in response to heel pricks. Johnston CC, Stevens, B,

Slide46

Neuroprotection

Today, NICU’s are relooking at all of the ways extremely premature babies are touched. New studies: neuroprotection includes not only minimizing obvious pain, but also tending to “a healing environment, partnering with families, positioning and handling, safeguarding sleep, protecting skin, and optimizing nutrition. Morris et al, 2015

Slide47

Current Practice/Performance Improvement in the NICU:Neonatologists are not asking if premature babies can feel pain, Rather, the focus is on how to better address the entire NICU environment & experience to improve neuroprotection.

Slide48

Fetal vs

Premie

Physiology

Is there a difference?

Slide49

Fetus

Definition:

The in utero period of development from from 8 weeks gestation

Slide50

Embryo

Definition:

The developing human from 3 to 8 weeks after conception

Embryonic Period

Transformation of single cells to different organ systems

Slide51

At different times, we look different

Slide52

Human Development

Slide53

24 Weeks Gestation

Slide54

There’s no “light-switch” moment

“there is no scientific evidence that function in the multi-layered networks underlying pain perception waits for some cue to be “turned-on”. Lowery, 2007

Slide55

3-Dimensional Imaging

“an adult-like pattern of skin innervation is established before the end of the first trimester “Belle, Godefroy, Couly, Tridimensional Visualization & Analysis of Early Human Development, Cell 2017

Slide56

Adjusted Pain DefintionPain is the sensation of noxious stimuli which can be linked with an immediate emotional response or instigate a future “procedural memory” that leads to an altered behavioral pattern

Slide57

SummaryWhether a baby is term or maturing through their fetal physiology, there is enough information to always assume noxious stimulation can be deleterious to their present and future health. Babies feel pain

Slide58

ConclusionResearch informed changes to the medical standard of care for the treatment of neonatal pain is currently inconsistent with what is still legally permissible. Good medicine is politically blind. Ditto for the defense of truth. Good law is also politically blind

Slide59

Conclusion

Given the accumulating truths that have driven the changes in neonatal pain treatment,

this is an invitation for the law to be informed by the same truths that inform today’s medical standard of care.