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
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Slide1
Pain Prior to Birth
Robin Pierucci, MD, MA
Slide2Parents instinctively know, babies feel pain
Slide3Painful Definition Problem?
BabyPremieFetus
Slide4Both doctors and lawyers have a history of being confused
Slide5Outline: 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
Slide6Looking Back to Move Forward:
The evolution of Pain Management in Neonates
Slide7Current 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
Slide8How 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
Slide9Anesthesia—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/
Slide10Modern 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
Slide11Early 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
Slide12A 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”
Slide14Documented Ramifications to Causing Neonatal Pain:Neurophysiological measurable effects:BehavioralNeurochemical, Cardiac, Hormonal, and Metabolic changes
Anand, 1987 NEJM
Slide15Prospective: Lighter vs Deep Intraoperative Anesthesia
Slide16Results: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
Slide17So, why is there a debate?
Problem: how should pain be defined?
Slide18Defining “Pain”
Slide19What Defines Pain in Humans?
Physical
Emotional
Psychologic
Spiritual
Slide20International 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”
Slide21By definition pain is:
Unpleasant
Physical aspect
Emotional aspect
The experience consists of
actual or
potential tissue damage
Slide22Can a human have physical pain without an emotional response?
(Pain without conscious awareness?)
Slide23Arguments: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
Slide24Tabor’s Medical DictionaryPain includes not only the perception of an uncomfortable stimulus but also the response to that perception
BUT OUR RESPONSE IS VARIABLE…
Slide25Pain Perception, Depends…
Slide26The 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”,
Slide27Example: Comatose Patient
We never would intentionally burn the patientAnd claim there’s no pain because they can’t complain
Slide28The 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
Slide29While 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
Slide30Anatomical Requirements
for Pain Perception
Slide31Pain 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
Slide32Spinal 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
Slide33Fetal 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
Slide34Emotionally 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
Slide35Arguments: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
Slide36The 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
Slide37Hypothalamic-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
Slide38Fetal 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)
Slide39Results: 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]”
Slide40The 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
Slide41Anencephaly & 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
Slide42Medical 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.
Slide43They 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
Slide44Study: 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
Slide45Response to
HeelstickPremies in the NICU x4 weeks vs newbornsDecreased oxygen saturations in response to heel pricks. Johnston CC, Stevens, B,
Slide46Neuroprotection
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
Slide47Current 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.
Slide48Fetal vs
Premie
Physiology
Is there a difference?
Slide49Fetus
Definition:
The in utero period of development from from 8 weeks gestation
Slide50Embryo
Definition:
The developing human from 3 to 8 weeks after conception
Embryonic Period
Transformation of single cells to different organ systems
Slide51At different times, we look different
Slide52Human Development
Slide5324 Weeks Gestation
Slide54There’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
Slide553-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
Slide56Adjusted 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
Slide57SummaryWhether 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
Slide58ConclusionResearch 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
Slide59Conclusion
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.