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Pain in the Neonate

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on 29 June 2016

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Transcript of Pain in the Neonate

Pain in the Neonate
#1
Pain is Real

Pain pathways, as well as cortical and subcortical substrates are well developed late in gestation.
Physiology of the Perinatal Period, Vol. 2. 1970. pp 889-906
The density of nociceptive nerve endings in the skin of newborns is similar to or greater than that in adult skin.
Cutaneous sensory perception appears in the perioral area in the 7th week of gestation...
gradually spreading to the rest of the face, the palms of the hands, and the soles of the feet by the 11th week...
to the trunk and proximal parts of the arms and legs by the 15th week...
and to all cutaneous and mucous surfaces by the 20th week.
Prog Brain Res 1964;4:93-195
Nociceptive impulses in the peripheral nerves are conducted through unmyelinated and thinly myelinated fibers.
Is myelination necessary for pain perception?
Nociceptive nerve tracts in the central nervous system undergo complete myelination during the second and third trimesters of gestation.
Pain pathways to the brain stem and thalamus are completely myelinated by 30 weeks.
N Engl J Med 1987;317:1321-1329
Neocortex
Development begins at 8 weeks
By 20th week - full complement of 10 neurons.
9
Arborization of cortical neurons
Synaptic targets for incoming thalamocortical fibers and intracortical connections.
Crucial for cortical perception
Thalamocortical Connections
established with synaptogenesis occuring between the 20th and 24th week of gestation.
Neurosci Res Prog Bull 1982;20:433-451
#2 Pain and Pathology
Painful and Stressful procedures are common in the NICU
488 cumulative procedures for an infant born at 23 weeks
Clin Perinatol 2000;2:363-379
The highest risk neonates need the highest number of painful/stressful procedures
Neonates exhibit
increased
sensitivity to pain.

Lack of inhibitory controls
thresholds increase 11-fold from neonate to adult
Low Threshold - High Sensitivity
Excitatory mechanisms develop earlier than inhibitory
Repeated tactile stimulation
Significant lowering of threshold (sensitization) up to 35 weeks gestation.
Increased magnitude response
hormonal
metabolic
cardiovascular
Compared with older age groups
Higher plasma concentrations needed
analgesics
anesthetics
Low Threshold Accentuated
Increased excitability to any painful stimulus
Wind-Up Phenomenon
(NMDA receptors)
After a painful stimulus...
Even non-noxious stimuli are interpreted as pain
routine handling
physical examination
bathing
nursing procedures
noise
J Matern Fetal Neonatal Med September 2009;22(9):722-732
Physiologic Responses to Pain
Acute increases in...
heart rate
blood pressure
heart rate variability
intracranial pressure
Decreases in arterial oxygen saturation
Rapid Physiologic Responses
reperfusion injury
venous congestion and IVH or PVL
In ventilated neonates...
diaphragmatic splinting with changes in intrathoracic pressure, cerebral blood volume and flow.
Vagal Responses
feeding tube insertion
tracheal suctioning
heel sticks
Substantial changes in cerebral blood flow and oxygen delivery
Biol Neonate 1998;73:1-9
Biol Neonate 1998;73:1-9
"Behavioral and physiologic responses to repetitive pain may lead to an extension of the early IVH caused by perinatal factors, or directly contribute to the hypoxia, hypercarbia, acidosis, hyperglycemia, ventilator dissynchrony and pneumothoraces, all which have been correlated with late IVH or the extension of early IVH."
Biol Neonate 1998;73:1-9
J Matern Fetal Neonatal Med 2009;22(9):722-732
Long-term Effects of Pain
Pain "lingers" beyond the NICU
28 weeks and 4 weeks of NICU care
Animal Studies
Long-term Effects of Pain
After Unanesthetized Circumcision
Lower gray matter reduction and less white matter gain in preterm infants at 8 and 12 years of age
Parent's perception of their child's pain.
decreased behavioral responses to pain
increased cardiovascular responses
correlated with the number of painful procedures
Biol Neonate 1998;73:1-9
Increased behavioral response to pain of vaccination at 4-5 months of age.
Biol Neonate 1998;73:1-9
birth weight 500-1000 gm
bumps and scrapes at 18 months
significantly less reactive
Clin Perinatol 2002;29:373-394
Pediatrics 2009;123:503-511
Lower pain thresholds
increased preference for alcohol
anxiety
defensive withdrawal behavior
hypervigilance
cerebral apoptosis
Suicide Risk as Adults
Birth trauma associated with increased risk for males and females
Maternal opioids at delivery reduced risk to the same as the control group
Clin Perinatol 2000;2:363-379
Pain 1994;59:101-109
BMJ 1998;317:1346-1349
#3 The Drugs
“My mother groaned, my father wept,
into the dangerous world I leapt.”
― William Blake
"Whenever a doctor cannot do good, he must be kept from doing harm."
- Hippocrates
If pain can alter the CNS cell proliferation, migration, differentiation and selective cell survival...
then exposure to analgo-sedatives also modulates receptor-signaling-related brain development.
Seminars in Fetal & Neonatal Medicine 18 (2013) 42-47
Chronic morphine in animal studies
reduced brain volume
decreased neuronal packing density
less dendritic growth and branching
learning and motor disabilities
Opioid blockade leads to increased brain size and dendritic arborization.
Similar results with ...
benzodiazepines
ketamine
inhalational anesthetics
propofol
barbituates
combination therapy
Excitatory
Inhibitory
Pain
Analgo-Sedatives
Neuronal migration
Arborization
Synaptogenesis
Apotosis
Alcohol Induced Apoptosis
Fetal Alcohol Syndrome
Similar pattern of apoptosis seen in exposure to phenobarbital and diazepam
NMDA antagonists
GABAa agonists
Immunomodulation
Increased risk of sepsis and mortality associated with sedation.
Benzodiazapines
Opioids
Inhalational anesthetics
Crit Care Clin 25 (2009) 551-570
Neurodevelopmental Outcomes
"prolonged sedation and/or analgesia exposure has no major effect on neurological outcome." (at 5 years)
"This is currently a critical and controversial issue..."
Arch Pediatr Adolesc Med. 2008;162(8):728-733
Difficult to separate effects of the pathology that made sedation desirable.
e.g. NEC or PPHN
#4 Management
Effective pain management = quality of care
"Adequate pain management is not an isolated activity, but an integrated part of developmental care."
Seminars in Fetal & Neonatal Medicine 18 (2013) 42-47
"In our opinion, non-pharmacological methods... are the link between pharmacological analgesia and developmental-oriented care.
Seminars in Fetal & Neonatal Medicine 18 (2013) 42-47
Sedation for ventilated preterm infants
"There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns."
Arch Dis Child Fetal Neonatal Ed 2010;95:F241-F251.
longer to reach full enteral feedings
increased time on the ventilator
no improvement in pain scores
Continuous Fentanyl after surgery
Continuous infusion of Fentanyl is associated with pain control similar to that with bolus dosing regular intervals.
Possible increased need for ventilator support with continuous infusion.
Journal of Pediatric Surgery, Vol 31, No 12 (December), 1996: pp 1616-1823
Prevention
Limit procedures
Planned procedures
Planned care
Leave the baby alone!
IASP vol. XIX, Issue 6 December 2011
Nursing
N
eonatal
I
nfant
P
ain
S
cale
P
remature
I
nfant
P
ain
P
rofile
Communication
Documentation
Patient advocacy
Painful procedures - 12 per day
Stressful procedures - 16 per day
heel sticks
endotracheal suctioning
venous or arterial puncture
Even morphine does not alleviate the pain response
Eur J Pediatr (2009)168:765-770
First Two Weeks of Life
"One of the most effective strategies to relieve neonatal pain is the reduction n the number of procedures."
Non-pharmacological interventions
Document the most effective method to perform a given procedure
Hyperalgesia
- a second painful stimulus of similar magnitude resulting in a more pronounced pain response

Sensitization
- the observation that a preterm neonate displays a massive and disproportional response to an innocuous stimulus for or a period of time allowing a painful stimulus
Sensorial Saturation
"delicate tactile, vestibular, gustative, olfactory, auditory and visual stimuli."
Biol Neonate 2001;80:15-18
“Some pains are physical, and some pains are mental, but the one that's both is dental.”
― Ogden Nash
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