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Pain management in neonates. N. Ambalavanan MD Oct 1999. Common mis conceptions (“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)

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pain management in neonates

Pain management in neonates

N. Ambalavanan MD

Oct 1999

common mis conceptions myths
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 comfortedwithoutanalgesics

(Adapted from the CPS statement on neonatal pain)

outline of this talk
Outline of this talk
  • Rationale : why do it?
  • Definitions
  • Problems with neonatal pain management
  • Pain assessment
  • Pain alleviation
rationale why do it
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
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 contd6
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: S358-359)
rationale why do it contd7
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
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; 135:795-796; 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 contd9
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
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
more definitions
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
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 problems13
Neonatal pain management: problems
  • Analgesia in the newborn period
    • Pharmacodynamics and pharmacokinetics vary, depending on the agent, gestational age, postnatal age, underlying diseaseprocess, 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
Pain assessment methods
  • Behavioral assessment
    • Subjective - crying, agitation etc
    • Semi-objective - scoring systems such as NIPS, PIPP (also includes HR, SpO2) , NFCS etc
  • Physiologic variables
    • HR, BP, SpO2, intracranial pressure etc
  • Biochemical assessment
    • Cortisol, catecholamines, b -endorphin etc
pain assessment which method to use
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
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)
  • 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
Behavioral assessment (contd.)
  • 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
  • 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 contd18
Behavioral assessment (contd.)
  • 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 (40-69%), Maximum (>70%)
behavioral assessment contd19
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.
  • 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 contd20
Behavioral assessment (contd.)
  • 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
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
Physiologic assessment
  • Physiologic indicators (FT= full term; PT= preterm)
      • 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
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
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
Pain alleviation : basics
  • 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
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
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
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
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
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
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
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