Transcript Pain in neonates

Pain management in neonates
N. Ambalavanan MD
Oct 1999
Common misconceptions (“myths”)

Myth 1: The neuronal and endocrine systems of
the newborn infant are not developed to the stage
that allows for transmission of painful stimuli
(i.e. that they can’t feel pain)
 Myth 2: Newborn infants cannot “remember” pain
and, therefore, there can be no sequelae of pain
 Myth 3: Pain cannot be assessed in the newborn
infant
 Myth 4: Newborn infants are easily comforted
without analgesics
(Adapted from the CPS statement on neonatal pain)
Outline of this talk
Rationale : why do it?
 Definitions
 Problems with neonatal pain management
 Pain assessment
 Pain alleviation

Rationale: why do it?
Neonates and infants can perceive pain...
 …which can have adverse short-term
consequences…
 …and adverse long term consequences…
 …which may be attenuated by analgesia

Rationale: why do it ? (contd.)

Perception of pain:
– Neonates and infants perceive pain on behavioral,
physiological, and biochemical measures (KJS Anand
et al: PCNA 1989; 36:795-822 & NEJM 1987; 317: 1321-1329; Craig KD
et al: Pain 1993; 53: 287-299 & Pain 1987;28:395-410)
– Even the fetus in utero mounts a hormonal
(cortisol and b-endorphin) response to needling
(Giannakoulopoulos X et al. Lancet 1994; 344: 77-81)

Parental perception of pain:
– Vivid memories of parental stress (even 3 years post-NICU)
related to neonatal appearance and behavior, and the pain
and procedures endured.
Rationale: why do it ? (contd.)

Adverse short-term consequences:
– Stress hormone level inversely correlated with
severity of illness. Catecholamine levels higher
in non-survivors, who have a lower fall in
norepinephrine levels with sedation. (Barker DP et
al. Arch Dis Child Fetal Neonatal Ed. 1996; 75:F187-190)
– Exposure of preterm neonates to repetitive pain
and stress leads to clinical instability and
complications. (KJS Anand. Crit Care Med 1993; 21: S358359)
Rationale: why do it ? (contd.)

Adverse long-term consequences:
– Circumcision increases pain response to subsequent
vaccination (Taddio A et al: Lancet 1997;349: 599-603)
– Permanent structural and functional changes may occur
in infants exposed to multiple painful and stressful
events (Porter FL et al: J Dev Behav Pediatr 1999;20:253-61)
– ELBW children noted to have altered pain sensitivity
unrelated to temperament or parental style (Grunau RV et
al: Pain 1994; 58: 341-346)
– Neonatal pain and stress may program the brain’s
response to future stimuli (Winberg J. Acta Pediatr 1998;
87:723-5)
Basis for long-term effects

Development of HPA responses to stress is modified by
sensory experiences during the neonatal period
(Levine S et al. Physiol Behav 1967;2:55-64 & Science 1962; 135:795796; and Ader R et al. Physiol Behav 1969;4:303-305)

Mechanisms for these changes probably due to plasticity
in neonatal limbic structures and related to expression of
corticosteroid, vasopressin receptor systems regulating
HPA. (Francis D et al. Ann NY Acad Sci 1996;794:136-152)

Neonatal handling, maternal separation, infections,
pain/stress etc can lead to permanent changes in
endocrine, behavior, and immune systems. (Anand KJ: Biol
Neonate 1998;73:1-9)
Rationale: why do it ? (contd.)

Analgesia works!
– Anesthesia improves clinical outcomes in surgical
neonates (Anand KJS et al. Lancet 1987;1:243-248)
– EMLA pre-circumcision attenuated altered pain
response to subsequent vaccination (Taddio A et al: Lancet
1997;349: 599-603)
– Morphine analgesia given by continuous low-dose
infusion reduced the risk of poor neurologic outcome
(death/ IVH III or IV / PVL) from 24% in placebo group
and 32% in midazolam group to 4% in the morphine
group. (The NOPAIN pilot study. Anand KJS et al. Arch Pediatr Adol
Med 1999; 153; 331-338) (Previous studies showed no effect: small n?)
Some definitions...
Stress: A mentally or emotionally disruptive
condition occurring in response to adverse
external influences and capable of affecting
physical health, or a stimulus which leads to
such a condition
 Stress Response: The physiologic response,
including motor, visceral, humoral, and
behavioral responses of the neonate to stress
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More definitions…

Pain: An unpleasant sensory or emotional
experience associated with actual or potential
tissue damage, or described in terms of such
damage (International Association for the study of Pain:
IASP)

Discomfort: Something that would ordinarily be
considered to disturb one's comfort or cause
annoyance
Neonatal pain management: problems

Confusion regarding Stress vs. Pain
– Pain is always stressful
– Stress is not always due to pain or associated with pain

Pain assessment
– pain is subjective in its assessment
– no “gold standard” for evaluation of neonatal pain
– Indications for, and monitoring of, analgesia therefore
uncertain
Neonatal pain management: problems

Analgesia in the newborn period
– Pharmacodynamics and pharmacokinetics vary,
depending on the agent, gestational age, postnatal age,
underlying disease process, and many other factors

Focus on evidence-based medicine
– Lack of sufficient data on value of analgesia regarding
important short-term and long-term outcomes, and
reduction of costs in both full-term and preterm infants
– Absence of evidence is not evidence of absence!
Pain assessment methods
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Behavioral assessment
– Subjective - crying, agitation etc
– Semi-objective - scoring systems such as NIPS,
PIPP (also includes HR, SpO2) , NFCS etc
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Physiologic variables
– HR, BP, SpO2, intracranial pressure etc

Biochemical assessment
– Cortisol, catecholamines, b -endorphin etc
Pain assessment: which method to use?
Often a lack of significant correlation
between physiologic, biochemical, and
behavioral indicators of pain - there is no
“gold standard”
 Behavioral indicators often used as they are:

– easier to measure
– baseline better established
– non-invasive (esp. for repeated measurements)
– more “honest signal” of pain
Behavioral assessment

Sedation score:
–
–
–
–
(Jacqz-Aigrain et al, Lancet 344:646-650, 1994)
Facial expression- calm and relaxed (0) or pronounced (1)
sucking-absent (0) or strong and rhythmic (1)
spontaneous motor activity – normal(0) or agitated (1)
excitability, responsiveness to stimulation- normal (0) or tremulous,
clonic movements (1)
– excessive flexion of fingers and toes- absent (0) or present &
constant (1)
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
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Scores of 0 or 1 suggest satisfactory sedation
Primarily a score for sedation in intubated neonates.
Simple, rapid, and construct validity established
Behavioral assessment (contd.)
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Neonatal Infant Pain Scale (NIPS)
(Lawrence et al, Neonatal netw.12:59-66, 1993)
– Face: relaxed (0) or grimace (1) ; Cry: no (0), whimper (1), vigorous (2);
Breathing patterns: relaxed (0) or change in breathing (1) ; Arms:
relaxed/restrained (0) or flexed/extended (1); Legs: relaxed/restrained (0)
or flexed/extended (1); State of arousal: sleeping/awake (0) or fussy (1)

Scoring in one-minute intervals; x2 before time/ procedure, x 5 during
time/procedure, and x3 after time/procedure. Total scores for each minute
range from 0-7
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Response to acute painful stimuli in non-intubated babies.
Full validation done, but score is time-consuming, and items such
as breathing patterns and cry difficult to interpret in intubated
neonates

Behavioral assessment (contd.)
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Premature Infant Pain Profile (PIPP)
(Stevens B et al. Clin J Pain12: 13-22, 1996).
– Gestational age: >36 wks (0), 32-35.6 (1), 28-31.6 (2), < 28 wks (3)
– Behavioral state: active/awake, eyes open, facial movements (0), quiet/awake,
eyes open, no facial movements(1), active/sleep, eyes closed, facial movements
(2), quiet/sleep, eyes closed, no facial movements
– Heart rate: 0-4 bpm increase (0), 5-14 (1), 15-24(2), >25 increase (3)
– O2 saturation: 0-2.4% decrease (0), 2.4-4.9% (1), 5-7.4% (2), >7.5% decrease (3)
– Brow bulge: None, 0-9% of time (0), Minimum, 10-39% (1), Moderate (40-69%),
Maximum (>70%)
– Eye squeeze: None, 0-9% of time (0), Minimum, 10-39% (1), Moderate (40-69%),
Maximum (>70%)
– Nasolabial furrow: None, 0-9% of time (0), Minimum, 10-39% (1), Moderate (4069%), Maximum (>70%)
Behavioral assessment (contd.)

Premature Infant Pain Profile (PIPP) (contd.)
– Observe baseline HR, SpO2 in 15 s before event. Scoring in 30 s after
event.
– Scores for 7 indicators summed for total pain score. Max score dependent
on GA: youngest up to 21, larger up to 18.
– Scores of <6 indicate minimal or no pain, >12 moderate to severe pain.
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Validated research tool, cumbersome and time-consuming for
clinical purposes. Use in intubated neonates is questionable:
1. baseline obtained while infant is under chronic stress
2. if pre-intubation baseline is used, O2 saturation not an
indicator of pain but rather of disease process
3. items such as nasolabial furrow difficult to discern
Behavioral assessment (contd.)
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Neonatal Facial Coding System (NFCS)
(Grunau RVE, Craig KD: Pain expression in neonates. Pain 28: 395-410, 1987)
• Eight items:
– Brow bulge; Eye squeeze; Nasolabial furrow; Open lips; Stretch
mouth (vertical or horizontal); Lip purse; Taut tongue; Chin quiver
– Each present feature scores one, total score eight (modified
NFCS in Guinsburg et al. J Pediatr 132: 954-959, 1998)
• Some facial actions (lip purse, tongue protusion, chin
quiver) occur in non-pain situations. Other facial actions
(Horizontal or vertical mouth stretch, taut tongue) are
present less than 50% of the time in pain situations
• Difficult to assess face in intubated neonates
Other behavioral scales
• Modified post-operative comfort score (Attia J et al.
Intensive Care Med [abstract]13: 459, 1987)
• Pokela’s behavioral pain score (Pokela ML: Pediatrics 93:
379-383, 1994)
• Behavioral state score (adapted from Bruck et al. Biol
Neonate 4: 32, 1962 byOrsini et al. J Pediatr 129: 140-145,
1996)
• Infant Body Coding System (IBCS) (Craig KD et al. Pain
52: 287-300, 1993)
• Modified Behavioral Pain Scale (MBPS): developed from
CHEOPS by Taddio et al. (Taddio et al. J Pain Symptom
Manage 10:456-463, 1995)
Physiologic assessment
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Physiologic indicators (FT= full term; PT= preterm)
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Heart rate : usually increased (FT, PT)
SpO2: usually decreased (FT, PT)
Vagal tone: decreased (FT)
Resp rate: increased (FT)
ICP: increased (PT)
Variability in HR and RR: increased (PT)
Cannot be unequivocally interpreted as pain as
they are more clearly associated with stress
(Stevens B et al. Clin J Pain 12: 13-22, 1996)
Biochemical indicators
Catecholamines (Epinephrine,
Norepinephrine)
 Cortisol (blood, saliva, or urine can be used)
 b-Endorphin
 Growth hormone, glucose, and lactate have
also been studied

Pain management
Systematic approach to prevent pain
required, rather than “as needed” basis
 Risks and benefits of pain management
techniques must be considered and
individualized
 Prevention of :

– Acute pain (surgery, procedure)
– Pain due disease process/ postsurgical/ postprocedure
– Minimize stress due to noxious stimuli
Pain alleviation : basics
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Prevention
– Control stress (limit noxious stimuli)
– Limit painful procedures (only if necessary; use
non-invasive monitoring whenever possible; art lines or
CV lines rather than repeated punctures)
– Skilled caregivers with appropriate techniques
(venipuncture less painful than heel lancing)
– Swaddling, non-nutritive sucking, positioning
for minor procedures
(Prevention and management of stress and/or pain in
the newborn infant. CPS statement)
Prevention of acute pain

Anesthesia
– General
– Regional (epidural, nerve blocks etc)
– Local (lidocaine, EMLA etc)
• Lidocaine (DPNB) or EMLA effective for circumcision
• EMLA not effective for heel lancing
• EMLA does not cause methemoglobinemia with single
applications at > 26 wks GA
– Opioids (Morphine/Fentanyl)
Post-op / disease related pain
Regional blocks (e.g. intercostal block for
thoracotomy, caudal block for hernia)
 Systemic analgesics:

– Opioids : best to titrate dose to effect
– Acetaminophen: orally or rectally is safe but
efficacy not well studied
– Natural sweeteners: Sucrose or Glucose
effective for pain relief during minor procedures
Minimization of stress

Non-pharmacological:
– Avoid excessive noise, light. Comfort measures
such as swaddling, positioning, non-nutritive
sucking.

Pharmacological:
– Sedatives (benzodiazepines, barbiturates,
phenothiazines, chloral hydrate)
Analgesics: opioids

Morphine or Fentanyl most often used. Avoid
Demerol (Meperidine)
 Requires frequent and thorough assessment of
adequacy of pain relief and possible side effects
– Adverse effects include respiratory depression and
glottic/chest wall rigidity (due to fentanyl/alfentanil rapid
infusions: give slowly. If they occur, give muscle
relaxants/ narcan)
– Avoid use > 5 days. Wean 20% per day if > 5 days. Wean
by 10% per day if withdrawal symptoms.
– Continuous infusion (vs. bolus) decreases apnea, but
higher total dose may be required for analgesia.
Sedatives: benzodiazepines

Benzodiazepines are NOT analgesics. They have
sedative-hypnotic, amnesic, anxiolytic, muscle
relaxant, and anti-epileptic properties.
 Midazolam (Versed) has a short half-life and is
approved by the FDA for neonatal use. Although
shown to be an effective sedative, it can cause
abnormal movements and adverse hemodynamic
effects (unknown if due to benzyl alcohol).
 Insufficient data on lorazepam (Ativan).
 Diazepam not recommended due to long half-life.
Other sedatives

Chloral hydrate: Trichloroethanol (TCE) is the
active metabolite. TCE and its metabolite TCA
accumulate with repeated doses and can cause
CNS / CVS depression and hyperbilirubinemia.
Single doses are safe in neonates.
 Phenobarbital / phenothiazines: evidence of
benefit is lacking. Half-life may be very long.
Some final thoughts...
Neonatal pain relief by itself may be an
adequate and distinct objective or outcome,
in the absence of other benefits or adverse
effects
 If opioids are safe and effective and have
equivalent or better long term outcomes, it
may be ethical to tolerate a small increase
in short-term side effects (e.g. bowel
dysmotility or prolongation of ventilation)
for improved pain relief
