blancingtheuseofsedativeandanalgesiainneonates-220622214028-96d3ce06.ppt

blancing the use of sedative and analgesia in neonates

1. Balancing the Use of Sedatives andBalancing the Use of Sedatives and
Analgesics in Neonates: Risks andAnalgesics in Neonates: Risks and
Associated Neurodevelopmental Associated Neurodevelopmental
OutcomesOutcomes
BY BY
DR. Magdy Shafik DR. Magdy Shafik
Senior Pediatric ConsultantSenior Pediatric Consultant
Diploma, M.S ,Ph.D of PediatricDiploma, M.S ,Ph.D of Pediatric

2. ObjectivesObjectives

Describe the impact of pain experiences and theDescribe the impact of pain experiences and the
developing braindeveloping brain

Summarize pain assessment tools used withSummarize pain assessment tools used with
newbornsnewborns

Discuss sedationanalgesia strategies
‐
Discuss sedationanalgesia strategies
‐

– – Nonpharmacologic pain control in newborns
‐
Nonpharmacologic pain control in newborns
‐

– – Review of frequently used medications in the NICUReview of frequently used medications in the NICU

Examine the short and longterm effects anesthesia
‐
Examine the short and longterm effects anesthesia
‐
exposureexposure

Identify recommendations to guide provisionIdentify recommendations to guide provision
sedationanalgesia in the NICU
‐
sedationanalgesia in the NICU
‐

3. 
Stress is defined as a physical, chemical, or Stress is defined as a physical, chemical, or
emotional factor that causes bodily or mental emotional factor that causes bodily or mental
tension and may be a factor in disease causation. tension and may be a factor in disease causation.

Pain is always stressful, but stress is not Pain is always stressful, but stress is not
necessarily painfulnecessarily painful..

4. Pain and the Developing BrainPain and the Developing Brain
• • Newborn period Newborn period is a time of is a time of rapid brain growthrapid brain growth, ,
development and particular vulnerabilitydevelopment and particular vulnerability
• •
On average a preterm neonate experiences On average a preterm neonate experiences ~ 515
‐
~ 515
‐
painful painful
procedures procedures per day (~ 7/d from admission per day (~ 7/d from admission to terme to terme
quivalent age or discharge)quivalent age or discharge)


Exposure to pain in preterm infants is Exposure to pain in preterm infants is multifactorialmultifactorial

Increased stress associated with Increased stress associated with decreased frontal lobedecreased frontal lobe
width,width, abnormal temporal abnormal temporal lobe diffusion and neurallobe diffusion and neural
networksnetworks

5. 
Preterm infants thought to have diminished pain Preterm infants thought to have diminished pain
perceptionperception
due to CNS immaturitydue to CNS immaturity

– – Sensory receptors and nerve fibers appear in the perioral Sensory receptors and nerve fibers appear in the perioral
area by 7area by 7
thth
week of gestation and spread to: week of gestation and spread to:

• • Face, palms and soles by week 11Face, palms and soles by week 11

• • Trunk, arms and legs by week 15Trunk, arms and legs by week 15

• • All cutaneous surfaces by week 20All cutaneous surfaces by week 20

• • Integrated nociceptive pathways are functional by 24 to 28Integrated nociceptive pathways are functional by 24 to 28
weeks’ gestationweeks’ gestation

6. How Pain is Transmitted to the How Pain is Transmitted to the
BrainBrain

7. Neonatal pain and developmental outcomes inNeonatal pain and developmental outcomes in
children born pretermchildren born preterm

Greater number of painful procedures in infants Greater number of painful procedures in infants
born extremely preterm (< 29 w GA) associated born extremely preterm (< 29 w GA) associated
withwith

– – Delayed postnatal growthDelayed postnatal growth

– – Poor early developmentPoor early development

– – High cortical activationHigh cortical activation

– – Altered brain developmentAltered brain development

– – Poor quality cognitive and motor development at Poor quality cognitive and motor development at
1 y age1 y age

– – Changes in cortical rhythmicity and cortical Changes in cortical rhythmicity and cortical
thickness in children at age 7thickness in children at age 7

8. OUTLINEOUTLINE

Pain and the developing brainPain and the developing brain

– – Effects of pain on the developing brainEffects of pain on the developing brain

• • Assessment of pain in newbornsAssessment of pain in newborns

• • Pain ManagementPain Management

– – Nonpharmacologic pain control in newborns
‐
Nonpharmacologic pain control in newborns
‐

– – Review of frequently used medications in the NICReview of frequently used medications in the NIC

• • Review of Weiler NICU practicesReview of Weiler NICU practices

• • SummarySummary

• • RecommendationsRecommendations

9. Effect of Pain and Inadequate Pain Control on theEffect of Pain and Inadequate Pain Control on the
Developing BrainDeveloping Brain

Immaturity of dorsal horn synaptic connectivity Immaturity of dorsal horn synaptic connectivity and and
descending inhibitory circuits in neonates results in:descending inhibitory circuits in neonates results in:
– – Poor localization and discrimination of sensory input Poor localization and discrimination of sensory input
and poor noxious inhibitory modulationand poor noxious inhibitory modulation

• • Repetitive noxious stimuli can Repetitive noxious stimuli can lead to acute lead to acute
physiologic and biochemical markers of stress that can physiologic and biochemical markers of stress that can
lead to:lead to:
– – Impaired ventilation, changes in intra thoracic & Impaired ventilation, changes in intra thoracic &
arterial pressures, IVH, PVLarterial pressures, IVH, PVL
– – Emotional/behavioral problems in childhood such as Emotional/behavioral problems in childhood such as
anxiety, depression, and suicidal tendenciesanxiety, depression, and suicidal tendencies

11. 
Exposure to procedural pain has been associated Exposure to procedural pain has been associated
with poorer cognitive & motor outcomes, reduced with poorer cognitive & motor outcomes, reduced
white matter & subcortical grey matter maturation, white matter & subcortical grey matter maturation,
altered corticospinal tract structure & growth altered corticospinal tract structure & growth
impairment.impairment.

Functional brain MRI of former preterm neonates Functional brain MRI of former preterm neonates
showed greater activation of sensory areas in showed greater activation of sensory areas in
response to pain compared to former full term response to pain compared to former full term
controls.controls.

Early neonatal painrelated stress are associated with
‐
Early neonatal painrelated stress are associated with
‐
reduced white matter and subcortical grey matter reduced white matter and subcortical grey matter
maturation on MRImaturation on MRI

12. Painful Procedures in the NICUPainful Procedures in the NICU





DiagnosticDiagnostic (e.g., arterial puncture, (e.g., arterial puncture,

venipuncture, venipuncture,

heel prick, heel prick,

lumbar puncture)lumbar puncture)





Therapeutic Therapeutic (e.g., umbilical catheterization, (e.g., umbilical catheterization,
chest physiotherapy,chest physiotherapy,
dressing change,dressing change,
removal of adhesive tape, removal of adhesive tape,
nasogastric tube insertion, nasogastric tube insertion,
peripheral venous catheterization,peripheral venous catheterization,
tracheal intubation/extubation and tracheal suctioning)tracheal intubation/extubation and tracheal suctioning)

13. ASSESSMENT OF PAIN IN NEONATESASSESSMENT OF PAIN IN NEONATES

Physiologic parameter changesPhysiologic parameter changes::
– – Changes in HR, RR, BP, SaO2 Changes in HR, RR, BP, SaO2
– – Vagal toneVagal tone
– – Breathing patternBreathing pattern
– – Palmar sweatingPalmar sweating
– – Skin colorSkin color
– – Pupillary sizePupillary size

Behavioral responses:Behavioral responses:
– – Crying patternsCrying patterns
– – Facial expressionsFacial expressions
– – Hand and body movements – Muscle toneHand and body movements – Muscle tone
– – Sleep patterns, behavioral state changesSleep patterns, behavioral state changes
– – ConsolabilityConsolability

14. Multidimensional Pain Assessment ToolsMultidimensional Pain Assessment Tools

15. Recommended assessment toolsRecommended assessment tools::
► ► Premature Infant Pain profile (PIPP): Premature Infant Pain profile (PIPP): the only the only
validated method for pain assessment among preterm validated method for pain assessment among preterm
infantsinfants
► ► Behavioral Pain Score (BPS)Behavioral Pain Score (BPS)
► ► Neonatal Infant Pain Scale (NIPSNeonatal Infant Pain Scale (NIPS))

19. NPASS (Neonatal Pain, Agitation and Sedation
‐
NPASS (Neonatal Pain, Agitation and Sedation
‐
Scale)Scale)
N PASS score < 4 = mild pain (non pharm rx); > 5 = mod
‐ ‐
severe pain (non pharm + pharmacologic measures
‐

20. Nonpharmacological Pain Control in
‐
Nonpharmacological Pain Control in
‐
NewbornsNewborns




BreastfeedingBreastfeeding in combination w/ in combination w/ skin to skin
‐ ‐
skin to skin
‐ ‐
(STS) (STS)
contactcontact




Non nutritive sucking
‐
Non nutritive sucking
‐
: oral sucrose or glucose solution: oral sucrose or glucose solution




Swaddling or facilitated tucking Swaddling or facilitated tucking (defined as gently (defined as gently
maintaining the arms and legs in a flexed position)maintaining the arms and legs in a flexed position)




Skin to skin contact
‐ ‐
Skin to skin contact
‐ ‐
(e.g., kangaroo care)(e.g., kangaroo care)




Sensorial Sensorial saturationsaturation (use of touch, massage, voice, and (use of touch, massage, voice, and
smell)smell)
• • Combinations of non pharmacologic
‐
Combinations of non pharmacologic
‐
measures (sucrose and measures (sucrose and
skin to skin contact) have additive
‐ ‐
skin to skin contact) have additive
‐ ‐
or synergistic effectsor synergistic effects..

SucroseSucrose : 24-50%, 0.1-2 ml orally; 2 minutes before : 24-50%, 0.1-2 ml orally; 2 minutes before
procedure via syringe or pacifierprocedure via syringe or pacifier

GlucoseGlucose : 30%, 0.3-1 ml orally; 1-2 minutes before procedure : 30%, 0.3-1 ml orally; 1-2 minutes before procedure

21. Stepwise approach for the management ofStepwise approach for the management of
acute pain in neonatesacute pain in neonates

22. 
• • Local Analgesia:Local Analgesia:
– – EMLAEMLA cream cream or tetracaine gel in addition to the or tetracaine gel in addition to the
administration of oral glucose to reduce pain associated administration of oral glucose to reduce pain associated
with venous, arterial, or lumbar punctures, and with venous, arterial, or lumbar punctures, and
peripheral venous or arterial catheter insertion.peripheral venous or arterial catheter insertion.
– – Lidocaine infiltrationLidocaine infiltration is used during surgical is used during surgical
operations including circumcision to reduce the operations including circumcision to reduce the
postoperative hyperalgesia.postoperative hyperalgesia.

23. 
Systemic AnalgesiaSystemic Analgesia

NSAID:NSAID:
– – Not generally used Not generally used for neonatal analgesia because for neonatal analgesia because
effective and safer agents are availableeffective and safer agents are available
– – Use of NSAIDs was Use of NSAIDs was associateassociated with gastrointestinal d with gastrointestinal
bleedingbleeding, platelet , platelet dysfunctiondysfunction, and decreased , and decreased
glomerular filtration rateglomerular filtration rate
– – Increased risk of bleeding in newborns < 21 days old Increased risk of bleeding in newborns < 21 days old
or < 37 weeks’ corrected GAor < 37 weeks’ corrected GA

24. 
MorphineMorphine
Most commonly used opioid for analgesia in Most commonly used opioid for analgesia in
neonatesneonates
• • Morphine is metabolized in the liver to morphine 3
‐ ‐
Morphine is metabolized in the liver to morphine 3
‐ ‐
glucoronide (antagonist) and morphine6
‐ ‐
glucoronide (antagonist) and morphine6
‐ ‐
glucuronide (agonist)glucuronide (agonist)
• • Morphine associated respiratory depression is greater Morphine associated respiratory depression is greater
in premature infants b/o immaturity of respiratory in premature infants b/o immaturity of respiratory
center responses to hypoxia and hypercarbiacenter responses to hypoxia and hypercarbia

25. Effect of Morphine During DevelopmentEffect of Morphine During Development

• • Chronic morphine exposure during prenatal and Chronic morphine exposure during prenatal and
early postnatal periods – Induces early postnatal periods – Induces significant significant
reduction in brain volume,reduction in brain volume, neuronal packing neuronal packing
density, and dendritic growthdensity, and dendritic growth

– – Leads to Leads to longterm alterations in pain threshold
‐
longterm alterations in pain threshold
‐
, ,
impairments in learning abilities, and locomotor impairments in learning abilities, and locomotor
activityactivity

Repeated morphine exposure leads to:Repeated morphine exposure leads to:
– – Persistent effects on the reorganization of synaptic Persistent effects on the reorganization of synaptic
connectionconnections s in areas that regulate motivation, in areas that regulate motivation,
reward, and learning reward, and learning throughout adult lifethroughout adult life

26. FentanylFentanyl

Continuous infusions in ventilated PT neonates are Continuous infusions in ventilated PT neonates are
not routinely usednot routinely used

• • In ventilated very PT infants continuous fentanyl In ventilated very PT infants continuous fentanyl
infusion plus openlabel boluses of fentanyl does not infusion plus openlabel boluses of fentanyl does not
reduce prolonged painreduce prolonged pain

Resulting Resulting respiratory depression respiratory depression prolongs the initial prolongs the initial
ventilatory course.ventilatory course.

Higher Higher cumulativecumulative fentanyl fentanyl dose in PTI dose in PTI correlated correlated
with with higher incidence cerebellar injury higher incidence cerebellar injury and lower and lower
cerebellar diameter at term equivalent.cerebellar diameter at term equivalent.

27. MidazolamMidazolam

Continuous midazolam infusion associated with an Continuous midazolam infusion associated with an
increase in IVHincrease in IVH

– – Decreases cerebral blood flow velocityDecreases cerebral blood flow velocity

– – Prolongs length of stay in the NICUProlongs length of stay in the NICU

30. AcetaminophenAcetaminophen

Acetaminophen alone is Acetaminophen alone is not not effective enough to reduce effective enough to reduce
acute pain.acute pain.

• • Acetaminophen with other analgesic Acetaminophen with other analgesic agents agents reduces reduces
the overall amount of administered opioidthe overall amount of administered opioid

• • Intravenous IV acetaminophen Intravenous IV acetaminophen reduced the reduced the
cumulative morphine dose following cumulative morphine dose following major major
thoracic thoracic (noncardiac) or abdominal surgery.
‐
(noncardiac) or abdominal surgery.
‐

31. Shortterm and long term outcome effects of untreated
‐ ‐
Shortterm and long term outcome effects of untreated
‐ ‐
neonatal pain/stress, or exposure to opioids or paracetamol neonatal pain/stress, or exposure to opioids or paracetamol
in (pre)term neonates (Smits, et al., in (pre)term neonates (Smits, et al., J Pharm Pharmacol J Pharm Pharmacol 20162016

32. SummarySummary

• • Research Research in nociception developmental physiology in nociception developmental physiology
demonstrates demonstrates the ability of preterm infants to perceive painthe ability of preterm infants to perceive pain

• • Preclinical and clinical Preclinical and clinical studiesstudies confirmed the adverse confirmed the adverse
consequences of untreated pain and stress on brain consequences of untreated pain and stress on brain
developmentdevelopment

• • Based on the availableBased on the available evidence, treatment evidence, treatment is is indicated for indicated for
acute events acute events ranging from minor procedural pain to majorranging from minor procedural pain to major
surgery as well as chronic stressful experiences surgery as well as chronic stressful experiences including including
mechanical ventilationmechanical ventilation

• • Sedation & analgesics Sedation & analgesics are indicated for amelioratingare indicated for ameliorating
moderate severe pai
‐
moderate severe pai
‐
n n • • Concerning preclinical and clinical data Concerning preclinical and clinical data
suggest these agents may promote suggest these agents may promote apoptosisapoptosis and and impact impact
neurodevelopmentneurodevelopment

33. Analgesia for procedural pain in Analgesia for procedural pain in
neonatesneonates
Procedures Management
Heel prick Sucrose with pacifier, swaddling, containment, skin-to-skin
contact with mother and use of mechanical lancet
Venipuncture Sucrose with pacifier, swaddling, containment facilitated
Tucking, EMLA cream at the site
Arterial puncture Sucrose with pacifier, swaddling, containment, facilitated
tucking, EMLA cream at the site, consider local subcutaneous
lidocaine locally
Lumbar puncture Sucrose with pacifier, EMLA cream at the site, consider
subcutaneous
lidocaine locally
Intubation Combination of opioid analgesics, sedatives, and muscle
relaxants, consider topical lidocaine spray (if not urgent)

34. Injection Avoid subcutaneous/intramuscular injections, prefer intravenous
route, sucrose with pacifier, swaddling, containment,
EMLA cream
Chest tube Sucrose with pacifier, subcutaneous lidocaine, consider opioid
analgesics or short-acting anesthetic agents
Umbilical catheterSucrose with pacifier, swaddling, containment, facilitated
tucking, avoid sutures or hemostat clamps on the skin around
the umbilicus
Central lineSucrose with pacifier, swaddling, containment, facilitated
tucking, EMLA to the site, subcutaneous lidocaine,
opioid analgesics
Endotracheal suctionSucrose with pacifier, swaddling, containment, facilitated
tucking, consider opioid analgesics
Nasogastric tubeSucrose with pacifier, swaddling, containment, facilitated
tucking, gentle technique, apply lubrication
Circumcision Sucrose with pacifier, EMLA cream to the site, dorsal nerve block
or penile ring block using lidocaine, consider acetaminophen for
postoperative pain

35. Eye examinationSucrose with pacifier, local anesthetic eye
drops
Mechanical
ventilation


First 24 hrs
(unless extubation is
anticipated in 4 hrs)


>24
Fentanyl or morphine IV/4 hrs and as needed,
or fentanyl
infusion 0.2-2 μg/kg/hr (start at low rate)

36. RecommendationsRecommendations

Stepwise approach in the management of neonatal Stepwise approach in the management of neonatal
pain depending on the clinical setting is pain depending on the clinical setting is
recommendedrecommended

• • Consider changing assessment tools to more Consider changing assessment tools to more
effectively assess the degree of pain/agitateffectively assess the degree of pain/agitation versus ion versus
level of sedation/sedation needslevel of sedation/sedation needs

• • Using nonpharmacologic measures
‐
Using nonpharmacologic measures
‐
(e.g., facilitated (e.g., facilitated
tucking or skinto skin contact)
‐
tucking or skinto skin contact)
‐
to improve analgesia to improve analgesia
for any painful procedure, when feasiblefor any painful procedure, when feasible

• • Oral sucrose with nonpharmacological measures for
‐
Oral sucrose with nonpharmacological measures for
‐
painful skin break procedurespainful skin break procedures

37. 
Invasive procedures require local anesthesia Invasive procedures require local anesthesia
& systemic analgesia& systemic analgesia

• • Postoperative pain Postoperative pain management can be management can be
achieved by using achieved by using acetaminophenacetaminophen as an as an
adjunctadjunct to opioid therapy to opioid therapy

• • Morphine or fentanyl infusion for routine Morphine or fentanyl infusion for routine
sedation sedation or pain control in ventilated or pain control in ventilated
neonates neonates is not recommendedis not recommended