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BOX
12.1
CRITICAL FINDINGS
NEONATAL PAIN RESPONSE*
Physiologic
• Increase in
• Heart rate
• Blood pressure (also fluctuations)
• Intracranial pressure/cerebral blood flow,
risk for intraventricular hemorrhage
• Respiratory rate
• Mean airway pressure
• Muscle tension
• Carbon dioxide (↑TcPco2; Pco2)
• Pulmonary vascular tone
• Oxygen consumption
• Decrease in
• Depth of respiration (shallow)
• Oxygenation (↓Po2; Sao2), which leads to apnea or bradycardia
• Vagal tone and peripheral blood flow
• Cerebral oxygenation with vigorous crying
• Pallor or flushing
• Diaphoresis or palmar sweating
• Dilated pupils
• Nausea, vomiting, gagging, and hiccoughing
266
which leads to higher
Behavioral
• Vocalizations
• Crying (higher pitched, tense, and harsh)
• Inaudible crying
• Whimpering
• Moaning
• Facial expressions
• Grimacing
• Furrowing or bulging of the brow
• Quivering chin
• Eye squeeze
• Nasal flaring
• Curling/curving of the tongue
• Facial twitching
• Lips open and pursed
• Body movements
• General diffuse body activity (flexing/extending extremities; extending legs; finger splay, fisting, hand on face)
• Limb withdrawal, swiping, thrashing
• Changes in tone
• Hypertonicity, rigidity, fist clenching
• Hypotonicity, flaccidity
• Touch aversion
• States
• Sleep-wake cycle changes, wakefulness
• Activity level changes: increased fussiness, irritability, listlessness, lethargy
• Feeding difficulties
• More difficult to comfort, soothe, quiet
• Disruption of interactive ability with parents
Hormonal/Catabolic Stress Response
• Increase in
• Plasma rennin activity
• Catecholamine levels (epinephrine and norepinephrine)
• Cortisol levels (serum and hair)
• Nitrogen excretion/protein catabolism
• Release of
• Growth hormone
• Glucagons
• Aldosterone
• Biomarkers of oxidative stress: Advanced oxidation protein products
and total hydroperoxides
• Serum levels of
• Glucose
• Lactate
• Pyruvate
• Ketones
• Nonesterified fatty acids
• Decrease in
• Insulin secretion
• Prolactin
• Immune responses
317
* References 17, 18, 30, 97, 99, 159, 177, 181, 195, 293, 302, 381, 387, 418, 421.
been shown to still be present in 3-month-old
(former) very preterm infants when reacting
to a socioemotional stressor.
have compared the biobehavioral pain responses
of ELBW infants with term controls. The studies
found that (1) at 4 months’ corrected age, behavioral
328
Two other studies
and cardiac autonomic responses were similar, with
less parasympathetic withdrawal and more sustained
sympathetic response during recovery in the ELBW
300
group,
and (2) at 8 months’ corrected age, behavioral response was similar to that in term infants but
less sustained (i.e., faster dampening); baseline heart
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rate was significantly higher in ELBW neonates.
The number of previous painful experiences in
the NICU was significantly related to subse-
178
ETIOLOGY
Invasive Procedures
quent pain reactivity in the ELBW infants, and
the ELBW infants who were exposed to higher
doses of morphine had heart rate recovery more
similar to that of the term infants.
178
Higher num-
bers of invasive procedures are significantly
associated with brain structure alterations, specifically reduced white matter and subcortical
gray matter maturation in preterm infants.
BOX
12.2
INVASIVE PROCEDURES SURGICAL PROCEDURES OTHERS
Intravenous cannulation
Venipuncture
Heel stick
Intramuscular injection
Arterial line, blood gas
Umbilical catheterization
Chest tube insertion or removal
Bone marrow aspiration
Lumbar puncture
Paracentesis
Endotracheal intubation/removal
Endotracheal or nasal288 suction
Laryngoscopy for less invasive
Mechanical ventilation
NCPAP
Bladder catheterization
Suprapubic aspiration
Ventricular tap
Endoscopy
Bronchoscopy
PICC line insertion/removal
Cutdown (arterial/venous) for access
CDH, Congenital diaphragmatic hernia; CNS, central nervous system; ECMO, extracorporeal membrane oxygenation; IV, intravenous; NCPAP, nasal continuous positive airway pressure; NG,
nasogastric; PDA, patent ductus arteriosus; PICC, peripherally inserted central catheter; ROP, retinopathy of prematurity; TEF, tracheoesophageal fistula.
Data from Anand KJ and the International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc
Med. 2001;155:173; Barker D, Rutter N. Exposure to invasive procedures in neonatal intensive care unit admissions. Arch Dis Child Fetal Neonatal Ed. 1995;72:F47; Bauchner H, May
A, Coates E. Use of analgesic agents for invasive medical procedures in pediatric and neonatal intensive care units. J Pediatr. 1992;4:647; Belda S, Pallas C, Dela Cruz J, et al. Screening
for retinopathy of prematurity: is it painful? Biol Neonate. 2004;86:195; Evans JC, Vogelpohl DG, Bourguignon CM, et al. Pain behaviors in LBW infants accompany some “nonpainful”
caregiving procedures. Neonatal Netw. 1997;16:33.
SELECTED COMMON CAUSES OF PAIN IN NEONATES
Central line placement
PDA ligation
TEF repair
Gastroschisis repair
Omphalocele repair
CDH repair
Inguinal hernia repair
Cardiac surgery
Circumcision
Broviac catheter insertion or removal
ECMO catheter insertion or removal
surfactant administration
56
61
Pain is produced with any invasive procedure
(Box 12.2).
22,363
Two studies of the first 14 days in
the NICU found (1) an average of 196 procedures
per neonate with 14 invasive procedures per day per
363
infant
and (2) a median of 115 procedures per
neonate with 16 invasive procedures per day per
infant.74 In a more recent study, one-third of the
Clavicle, rib fracture
Extremity fracture
Chest pain
Central pain syndrome (i.e., pain derived from CNS damage)
Echocardiogram
Spasticity
Abdominal pain resulting from short gut syndrome, multiple
abdominal surgeries; visceral hyperalgesia
Necrotizing enterocolitis
Bowel obstruction
Prolonged and/or improper positioning
Position changes
NG tube placement
Flushing lines
Dressing changes
Eye examination for ROP
IV administration of medications
Addition/withdrawal of fluid from umbilical catheter
Transient mechanical birth trauma (e.g., cephalic hematoma,
molding, bruising, forceps marks, petechiae)
Cryo/laser surgery for ROP
Chest physiotherapy
Changing tape/suture removal
Therapeutic hypothermia
3
38
195
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infants received treatment for painful procedures,
which included the following74:
1. Pharmacologic-only therapy (2.1%)
2. Nonpharmacologic-only therapy (18.2%)
3. Combination therapy (both No. 1 and No. 2)
(20.8%)
4. No specific analgesia (79.2%)
5. Concurrent analgesia/anesthesia for other purposes (34.2%)
A recent systematic analysis of 18 observa-
tional studies found an average of 7.5 to 17.3
painful procedures per NICU infant per day,
with the most frequent procedures being heel
lance, suctioning, venipuncture, and peripheral
intravenous (PIV) line insertion.
108
Another
study showed that neonates in their first 7 days in
the NICU underwent a mean of 6.6 invasive procedures per day, with only 32.5 % of them receiving
pharmacologic or nonpharmacologic interventions
for pain.
372
The Epidemiology of Procedural Pain
in Neonates (EPIPPAIN) study looked at pain and
pain management (for heel stick and venipuncture)
in 16 NICUs in Paris, France
106,107
from birth to
the first 2 weeks of life. The mean number of heel
sticks per neonate was 16,
107
and the mean number
of venipunctures per neonate was 3.8 for infants
with a mean gestational age of 33.3 weeks and 4.1
for neonates less than 33 weeks.
107
Although 75.2%
of heel sticks were performed with either continuous analgesia or specific pre-procedural analgesia,
the use of analgesia was not systematic.
106
In this
study, 76% of venipunctures were performed with
pre-procedural analgesia, and 23.2% were done
while the infant was receiving continuous anal-
106
gesia.
These researchers recommend strategies
to decrease the number of PIV attempts (38.3%
required more than one attempt) and promotion
of parental presence—both associated with lower
pain scores.
106
A study of neonates at increased risk for neurologic impairment found that these infants had
the highest number of invasive procedures but
received the least amount of analgesic on the first
day of life.
378
Despite how these studies indicate
an improvement in the use of pain relief for invasive procedures, considerable work is needed to
educate practitioners about the safety, efficacy,
and benefits of appropriate pain management
in neonates. Use of “better practices” strategies, clinical practice guidelines, and proven
quality improvement methods has resulted in
better pain management for neonates in the
116,241,244,251
NICU.
Endotracheal intubation is associated with
hypoxia, bradycardia, catabolism, increased
intracranial pressure, increased systemic and
pulmonary hypertension, and release of stress
hormones.
236
Recent research has shown that
use of premedication for elective, nonurgent intubations is safer and more effective
than awake intubations (see the Endotracheal
Intubation section in Chapter 23). Unmedicated
endotracheal intubation in the neonate should
be reserved for emergency resuscitation in the
delivery room.
236
There is currently no validated
scoring system to assess the level of sedation before
elective intubation.
115
No consensus exists about pain relief in the
mechanically ventilated neonate, and clinical practice varies widely.
71,184,226,277,424
A recent survey of
the use of sedatives and analgesics among a large
group of ventilated preterm infants found that the
use of opioids increased from 5% to 32%, and the
use of sedatives increased from 5% to 24% from
1997 to 2012.
424
Benefits of pain management
in the ventilated neonate include (1) improved
ventilator synchrony; (2) improved pulmonary
function; (3) less neuroendocrine (cortisol,
beta-endorphins, catecholamine) response; (4)
better oxygenation; and (5) potentially ameliorated adverse effects of mechanical ventilation
(Fig. 12.2) in the preterm infant.
184,277
Two
approaches to pain management in ventilated neonates are commonly used: (1) preemptive, continuous
opioid infusion and (2) as-needed (PRN) intermittent bolus administration of opioids.
34,109,226,278
The NOPAIN pilot study found poor neurologic
outcomes in only 4% of the ventilated preterm
infants receiving continuous morphine sulfate (MS)
for pain compared with 24% in the placebo group
and 32% in the midazolam group.27 In this study,
the MS-treated preterm infants were the only group
with significantly lower pain scores.
27
The European Pain Audit in Neonates
(EUROPAIN) study evaluated the use of sedatives and analgesics in the NICUs of 18 European
countries.71 Tracheal ventilation and noninva-
sive ventilation resulted in administration of
sedatives (midazolam) and analgesics (opiates)
in 82% and 18% of the neonates, respectively,
given by a continuous IV dose, intermittent
doses, or both. Use of sedatives and analgesics
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Mechanical Ventilation
Changes in HR;
BP variability
Long-term
alterations in
the HPA axis
FIGURE 12.2 Potential mechanisms leading to adverse effects from mechanical ventilation in preterm neonates. BP, Blood pressure; HPA,
hypothalamic-pituitary-adrenal; HR, heart rate; IVH, intraventricular hemorrhage. (Modified from Hall RW, Boyle E, Young T. Do ventilated
neonates require pain management? Semin Perinatol. 2007;31:289.)
Stress
Changes in
cerebral
blood flow
Adverse
neurodevelopmental
outcome and
cardiovascular disease
in the intubated neonates resulted in longer
mechanical ventilation.71 Using the same database,
assessment for continuous pain only occurred in less
than one-third of NICU admissions and daily in
only 10% of neonates. The presence of pain guidelines, preterm infants less than 32 weeks of gestation,
nursing champions, surgical admissions, mechanical
ventilation, and use of opiates, sedatives, and general
anesthesia resulted in more frequent assessments for
continuous pain.33 An analysis of the Italian data
from the EUROPAIN study also found wide variation in the use of analgesia and sedatives and pain
assessment among Italian NICUs.
242
The NEOPAIN double-blind, randomized controlled trial (RCT), conducted in 12 American and
4 European NICUs, studied whether preemptive
morphine analgesia would decrease early neurologic
injury in 898 ventilated preterm infants less than 32
weeks of gestation.28 There was a higher incidence
of severe intraventricular hemorrhage (IVH) in the
morphine-treated group of 27 to 29 weeks of gestation, possibly resulting from higher MS infusion
rates or less MS clearance in hypotensive infants.28
Further analysis of cohorts from the NEOPAIN
study found the following: (1) MS-treated preterm
infants had significantly longer ventilation, as well
as more air leaks and supplemental oxygen use in
Hypocarbia;
changes in
oxygenation and
acid-base status
Complications
(pneumothorax,
tube plugging)
IVH
preterm infants who received additional intermittent boluses of MS53; (2) MS delays the start of and
the full attainment of enteral feedings but does not
increase gastrointestinal complications
280
; (3) both
preemptive and additional MS and lower GA are
associated with hypotension
185
; (4) IVH (i.e., any
and severe) and death are associated with preexisting
hypotension, but morphine therapy did not contribute to these outcomes
185
; and (5) although MS infusions cause hypotension, they can safely be used for
most preterm neonates.
185
Use MS cautiously for
23- to 26-week preterm infants and those with
preexisting hypotension.
185
Another randomized,
double-blind, placebo-controlled trial of morphine
infusion for ventilated preterm infants showed that
(1) the analgesic effect was similar between the
treated and placebo group, (2) routine morphine
infusion decreased the incidence of IVH but did not
influence poor neurologic outcome, (3) routine use
of MS infusions is not supported by the lack of analgesic effect and the absence of any beneficial effect,
and (4) the long-term effects of MS on the neurologic outcomes of preterm infants need study.
364
Studies have also compared fentanyl with morphine and fentanyl with sufentanil for analgesia
during mechanical ventilation in neonates.
345,350
Fentanyl was equianalgesic with morphine, sufentanil
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283
was equianalgesic to fentanyl, and sufentanil did not
reduce the weaning period for ventilated (term)
345,350
infants.
Continuous fentanyl infusion (plus
open-label PRN boluses of fentanyl) for very
preterm ventilated infants has been shown to reduce
acute, but not prolonged, pain with more side effects
(longer ventilation and delayed meconium passage)
than use of PRN fentanyl boluses alone.34 A recent
follow-up of very preterm ventilated infants who
received continuous fentanyl and open-label boluses
found significantly poorer eye-hand coordination
at 24 months’ corrected age in the IV infusion
group.35 Morphine, fentanyl, and sufentanil
reduce the pain and stress of preterm infants
being mechanically ventilated but may prolong
the duration of ventilation.34 Only two studies
have investigated the effect of fentanyl analgesia on
acute brain outcomes, and no difference was found
in the incidence of IVH, PVL, or mortality.
240,345
Dexmedetomidine hydrochloride, an α-ad-
renergic receptor agonist, provides analgesia,
anesthesia, and sedation for mechanically ventilated neonates.
277,302
Advantages include (1) less
adjunctive sedation needed, compared with fentanyl;
(2) minimal effect on blood pressure, heart and respiratory rates, oxygen saturation, and gastric motility;
and (3) its safety and effectiveness for short-term pain
relief during invasive procedures in ventilated and
nonventilated neonates.
277,302
Only one study of the
effect of dexmedetomidine on brain injury has been
conducted. In a comparison of dexmedetomidine
versus fentanyl used for sedation in mechanically
ventilated preterm infants, there was no difference
in the incidence of severe IVH or PVL between the
two groups.
397
An RCT of the safety and efficacy of
dexmedetomidine hydrochloride and the short- and
long-term neurologic outcomes are needed.
88
Although use of analgesia in ventilated
infants is recommended,
13,21
a meta-analysis
concludes that there is insufficient evidence
for “routine use” of opioids during mechanical
ventilation.51 The meta-analysis states that opioids should be selectively used for individual
neonates based on clinical judgment and pain
assessment.51 Long-term neurologic outcomes of
MS analgesia for ventilated preterm infants are
being studied. A recent pilot study of 5- to 7-yearolds from the NEOPAIN cohort of ventilated
preterm infants who had received preemptive MS
found that they were 7% smaller in head circumference; were 4% less in body weight; took longer and
completed fewer (27%) short-term memory tasks;
and had more social problems, specifically with
creating and maintaining friendships.
136
This same
cohort was again studied at 8 to 9 years of age and
found to have significantly better executive function
as evaluated by parents and teachers.
114
The method
of pharmacologic pain relief, the appropriate drug
to use, the use of preemptive or bolus infusion based
on pain scores, and minimizing long-term adverse
outcomes remain clinical and research challenges.
Surgery
Painful stimuli, surgery, and traumatic injuries have
been shown in adults to trigger the “stress response,”
which causes the release of a variety of hormones,
including epinephrine, norepinephrine, corticosteroids, glucagon, and growth hormones. These hormones prepare the body for a fight-or-flight response
and cause, among other things, an increase in heart
rate, respiratory rate, glucose production, and muscle
and fat breakdown. This response allows the body
to deal with an insult in the short term. If the
insult continues or is untreated, the ongoing
catabolic stress response may become deleterious
to the body’s well-being by promoting more
tissue breakdown and preventing growth and
tissue repair. During the period of rapid brain
growth and development, the immature brain
of the preterm infant has heightened vulnerability to pain. The first study to link cumulative
neonatal pain stress to alteration in brain function
in extremely low-gestation (≤28 weeks) preterm
infants has recently been published. This study found
an association between cumulative neonatal
pain-related stress and alteration in cortical function resulting in visual-perceptual difficulties at
school age in this vulnerable population.
Both premature and full-term infants have a
decreased stress response with the use of appropriate analgesia both during and immediately
after surgery. Physiologic indicators (e.g., heart/
respiratory rate, blood pressure) of postoperative
pain may be unreliable or confounded by illness
severity and use of analgesics and neuromuscular
blocking agents*. Use of adequate operative
anesthesia
12,13
and postoperative analgesia is
mandatory, even if its use might prolong postoperative ventilatory support.
* References 16, 18, 23, 28, 30, 31, 67, 142.
124
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A special example of untreated operative pain
is newborn circumcision. In addition to the previously mentioned short-term effects of not treating
the pain associated with circumcision, male infants
who have undergone circumcision without
analgesia have an increased pain response to
vaccination at 4 to 6 months of age.
385,387
When
these infants were pretreated for their immunizations with a topical anesthetic, their pain
response was lessened.
387
Another study of 14- and
45-month-old children who had major surgery
with appropriate analgesia (in their first 3 months
of life) found that their biobehavioral pain response
to immunizations was not altered compared with a
matched group of toddlers who had not had sur-
318
gery.
However, prolonged exposure to early
hospitalization did contribute to an altered pain
response (in areas of prior tissue damage) that
“recovered” over time.
318,319
Although early pain-
ful memories may not be consciously recalled,
experiences of pain are “remembered” by the
developing nervous system.
19,20,32,319
Newborns
have a much greater capacity for memory than was
previously thought.
Other Causes
Rib, clavicular, and extremity fractures are not
uncommon and should be considered in the presence of prolonged crying and failure to move the
affected extremity.
Bronchopulmonary dysplasia (BPD) is a common problem in infants who were premature and
may cause chest pain, a syndrome known to occur
in some older patients with chronic lung disease.
Neurologic dysfunction can leave patients with
ongoing pain from central pain syndrome or excessive spasticity. One study showed that 27% of former
ELBW infants who were now teenagers had neurosensory impairment, and 9% reported moderate or
severe pain.
346
PREVENTION
Prevention of pain in the neonate and preterm
infant begins with a proactive plan of care
aimed at preventing the pain cycle. The key
approaches in this plan include (1) anticipation;
(2) comprehensive and ongoing assessment of the
variables; (3) distinguishing agitation and irritability
from pain expressions and responses of the preterm
infant; (4) ongoing communication among health
care providers, using input from the parents; (5)
advocating and implementing timely and effective
treatment for irritability, agitation, and pain (e.g.,
pharmacologic and comfort measures); (6) reducing
the number of painful procedures
74,123,291,410
; and
(7) ongoing reevaluation of this proactive plan of
care.2 Different types of common procedures
in the NICU can be anticipated to be painful.
Diagnostic procedures include arterial puncture, heel
stick, lumbar puncture, and retinopathy of prematurity (ROP) examination. Therapeutic procedures
include tracheal intubation and extubation, tracheal suctioning,
118
surfactant administration with
laryngoscopy,56 chest tube insertion, mechanical
ventilation, suture removal, therapeutic hypother-
195
mia,
and removal of adhesive tape. Some of the
common surgical procedures are circumcision, patent
ductus arteriosus (PDA) ligation, insertion of central venous catheters, and laser therapy for ROP.
Anticipation and prevention of pain during such
procedures can markedly affect the success of
the procedure and the condition of the infant.
Preventing, reducing, and relieving neonatal
pain constitute an essential health care provider
goal to maintain the sick neonate’s behavioral,
physiologic, and biochemical homeostasis.
22,349
Individualized behavioral and developmental
care is another important area in preventing
stress and sensory overload, which often contribute to an ongoing pain cycle.
105,287,349,365
These approaches help prevent disorganization
in the neonate. Several studies have shown that
clustering care, a common practice in the NICU
(see Chapter 13), actually results in an increase
in behavioral responses and cortisol secretion for
preterm infants of younger GA when exposed to a
painful procedure.
197,198,201
To facilitate stability
and self-regulation before and during an invasive painful procedure, (1) do not cluster care,
and provide a period of rest before the procedure; (2) assess the infant’s state, and facilitate a
change to an alert state; (3) contain extremities
(see Chapter 13); (4) provide a pacifier and an
opportunity to grasp (a finger, hand, or blanket); and (5) use another person (e.g., parent,
caregiver) to support, contain, and observe for
stress. After the procedure, provide support,
comfort, and slow withdrawal so that the infant
remains calm.
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The suffering of neonates can be avoided.
Needless suffering is prevented by an established
plan of care for assessment, management, and evaluation of pain and attempts to relieve pain. Neonates
depend on the skilled observations, assessments,
and interventions of care providers for prompt,
safe, and effective relief. A cooperative effort
among health care providers and parents in
the form of pain management teams
well-established pain protocols
116,349
273
and
prevents
unnecessary suffering of both neonates and
their families.
230
Controlling environmental stimuli
(e.g., dimming lights, controlling noise level, speaking softly, performing rounds outside of the unit),
although often difficult in the NICU, is crucial for
decreasing stress and preventing unnecessary agitation. Use of an individualized, developmentally
appropriate plan of care reduces the need for
sedation in severely ill, VLBW neonates.
17,365
Quieting techniques are also a useful way to
BOX
12.3
CRITICAL FINDINGS
INDICATORS OF IRRITABILITY AND AGITATION
Physiologic
• Increase in
• Heart rate and blood pressure only with activity
• Oxygenation (↑TcPco2; Po2; Sao2)
• Respiratory rate and effort
• Decrease in
• Oxygenation (↓Po2; Sao2) after prolonged agitation
• Heart rate (bradycardia)
• Respirations (apnea)
• Alterations in skin color: cyanosis, mottling, duskiness, pallor
• Diaphoresis
• Vomiting
• Poor pattern of weight gain
Behavioral
• Vocalizations
• Whining cry
• Intense, urgent cry
• High-pitched cry
• Resumes fussiness when consolation ceases
• Facial expressions
• Frowning
help control pain response in the neonate; these
include nonnutritive sucking (NNS), containment interventions, and rocking (see Chapter 13).
DATA COLLECTION
History
Neonates experiencing procedural, surgical,
and/or chronic pain must be provided measures to alleviate pain. Neonatal irritability
and agitation (Box 12.3) secondary to chronic
conditions (e.g., BPD, necrotizing enterocolitis,
short bowel syndrome, neurologic deficits) and/or
environmental overstimulation may also require
a combination of environmental interventions
and sedation.
Assessment of pain in neonates is often challeng-
ing because they cannot verbalize their subjective
• Worried facies
• Gaze aversion
• Closes eyes to tune out
• Body movements
• Random movements of head and body
• Hypertonic, rigid posturing; arching; hyperextended neck
• Flailing, thrashing, frantic activity of extremities during fuss or cry
• Decreased activity
• Tremulousness
• States
• Hyperalert—easily aroused from sleep; startles easily
• Rapid and frequent state changes to fuss or cry
• Unpredictable sleep-wake cycles
• Feeding difficulties
• Difficult to console, soothe
• High level of persistence
• Needs environmental structure to fall asleep; takes a long time to fall
asleep
• Ineffective self-consoling; requires vestibular stimulation or body containment to console; responds inconsistently to consolation
• Noncuddly
13
Modified from Broome ME, Tanzillo H. Differentiating between pain and agitation in premature neonates. J Perinat Neonat Nurs. 1990;4:53; Burdeau G, Kleiber C. Clinical indicators of
infant irritability. Neonat Netw. 1991;9:23; Franck LS. A national survey of the assessment and treatment of pain and agitation in the NICU. J Obstet Gynecol Neonat Nurs. 1987;16:387.
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BOX
12.4
• Assess and document pain, with vital signs every 4 to 6 hours or as
• Use standardized pain assessment tools and methods with evidence
• Use pain assessment tools that are sensitive and specific for infants
• Use pain assessment tools that are comprehensive and multidi-
• Assess the neonate’s pain after each potentially painful clinical
• Reassess and re-evaluate the neonate’s pain to assess the efficacy of
Modified from Anand KJ and the International Evidence-Based Group for Neonatal Pain.
Consensus statement for the prevention and management of pain in the newborn. Arch
Pediatr Adolesc Med. 2001;155:173; Prince W, Horns K, Latta T, et al. Treatment of
neonatal pain without a gold standard: the case for caregiving interventions and sucrose
administration. Neonatal Netw. 2004;23:33.
GUIDELINES FOR ASSESSING PAIN
indicated by pain scores and/or the clinical condition of the neonate.
of validity, reliability, and clinical utility.
of different gestational ages and/or with acute, chronic, or continuous pain (e.g., postoperative pain, inflammatory conditions).
mensional (e.g., measure behavioral, physiologic, and hormonal/
biochemical indicators of pain) within the context of pain experience.
intervention.
pharmacologic, behavioral, and environmental interventions.
experience.21 The four objectives in the assessment of
pain are (1) detecting the presence of pain, (2) assessing
its effect, (3) providing pain-relieving interventions,
and (4) evaluating the effectiveness of interventions.97
Guidelines for the assessment of pain are listed in
Box 12.4. Expression of pain through behavior is
one of the neonate’s only means of communicating about pain. Behavioral cues may include diffuse
or localized motor activity, facial grimacing, crying,
agitation, and change in level of activity (see Box 12.3) .
Female infants, both preterm and term, show more
facial expressions of pain compared with male infants.
374
In an analysis of the responses of 149 infants to a painful event, facial actions were found 40% of the time to
account for pain indicators in vulnerable neonates.
374
Assessment of pain in the neonate is com-
plicated by the infant’s level of neural development and maturation.* Infants of younger
GA have limited autonomic and self-regulatory
abilities. Developmental immaturity also results
in disorganized, ineffective responses to stimuli
and makes it more difficult for these immature
preterm infants to communicate pain. Fewer
facial changes related to painful stimuli have been
observed in young preterm infants.
155
However, cry-
ing, change in arousal state, and facial grimacing
have been found to be the most robust pain
behaviors.
420
Another study showed a change in
facial expression with heel lance in preterm infants
as young as 25 weeks of gestation.
368
However, in
this study, preterm infants less than 32 weeks’ PMA
took a significantly longer time to change their
facial expression than did older infants.*
A more immature, fragile neonate may manifest
alterations in sleep-wake cycles and habituate to the
overwhelming stimuli of the NICU (see Chapter
13) and thus cannot exhibit any response to pain.
Illness severity as an influence on pain response has
shown contradictory findings in research studies.
Some studies show altered pain response in more
severely ill neonates, whereas others show no alteration in the most severely ill.
96,376
Behavioral expressions of pain by the neonate
are further hampered by intubation, use of restraints,
and neuromuscular blockers.
299
Similarly, chronically
ill infants who have been exposed to repeated
painful procedures have difficulty generating a
pain response and exhibit a “dampened” pain
response.
98,154,155,174
Recent research shows that several body movements (e.g., fisting, flexing/extending
extremities, finger splay, hand on the face) commonly
assessed in the Newborn Individualized Care and
Assessment Program (NIDCAP) for developmental
care (see Chapter 13) are associated with acute pain
response in preterm infants
290
(see Box 12.1). Preterm
infants who have experienced more invasive procedures, who are lower in GA at birth, and who have
spent more days on ventilators have a diminished
behavioral and cardiac autonomic pain response to
acute pain at 32 weeks’ PCA.
indicates that both term and preterm neonates who
172,175
Another study
undergo handling and immobilization may exhibit
exaggerated behavioral and physiologic response to
later painful procedures.
184
Other studies have demonstrated no difference in biobehavioral response to pain
in preterm infants with neurologic injury.
298,368,420
Physiologic parameters also may indicate pain
(e.g., increased heart and respiratory rates, elevated
blood pressure, desaturation, apnea, palmar sweating). These symptoms are the result of sympathetic
nervous system activation (see Box 12.1). One study
found that some physiologic responses to pain (e.g.,
facial activity and state) moderately correlated to
* References 180, 199, 221, 272, 293, 336, 425.
* References 180, 199, 221, 293, 336, 372, 425.
Catecholamines, glucagon, cortisol,
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aldosterone, and other corticosteroids
Decrease in insulinProcess
CHAPTER 12 Pain and Pain Relief
Protein breakdownUtilization of fat store
287
Clinical findings
FIGURE 12.3 Hormonal response to pain in infants. 3-MH, 3-Methylhistidine. (From Johnston C, Stevens B. Pain in infants. In: Watt-
Watson J, Donovan M, eds. Pain Management: Nursing Perspective. St Louis, MO: Mosby; 1992.)
Hyperglycemia
Increased risk of morbidity and mortality
heart rate changes, whereas other behavioral expressions (e.g., finger splay) did not correlate with any
autonomic changes.
289
However, in the same study,
specific measures of cardiac autonomic modulation
did not correlate with behavioral changes, suggesting
that cardiac alterations are influenced by a multitude
of factors
pain in the preterm infant.
299
and may be independent measures of
289
A more recent study
found higher physiologic reactivity (i.e., heart rate
changes) in male preterm infants, but the evidence
was insufficient to confirm a gender difference in
pain responsivity.
400
Some preterm infants respond
to pain with more behavioral changes, whereas
others respond with more physiologic changes.
377
In the first week of life, all infants of different
GAs (e.g., <28 to 36 weeks) can differentiate
between mild and more invasive procedures.
325
At 36 weeks, these same infants exhibited differing
physiologic pain responses based on their GA at birth.
(e.g., infants born closer to term had lower increases
in heart rate than those born at a younger GA).
325,420
When pain is repetitive or persists for hours
or days, there is a decompensatory response,
resulting in hormonal and metabolic alterations
(Fig. 12.3; see Box 12.1). The fight-or-flight mech-
anism of the sympathetic nervous system can no
longer compensate, so an adaptation syndrome
begins with a return to baseline physiologic
parameters. The return of the heart rate, respira-
tions, and blood pressure to baseline parameters
makes assessment of the infant’s pain more difficult
and does not mean that the infant has “adjusted” to
or is no longer experiencing pain.
66
Total ketone bodies
Nonesterified fatty acids
Plasma amino acids
Nitrogen excretion
3-MH/creatinine ratios
The lack of an expression of pain through
physiologic and behavioral responses also does
not mean that the neonate is not experiencing
210
pain.
Pain responses may be delayed, cumulative, or absent. In the preterm infant, sustained
elevations in vital signs and decreased oxygenation
confirm the persistence of physiologic alterations
after painful stimuli.
376
Critically ill neonates
and immature preterm infants may be so weak
and overwhelmed that they have completely
exhausted their energy and cannot respond.
A recent study showed that only 65% of healthy
newborns (>37 weeks and <42 weeks of gestation) cried after heel stick, although 100% of them
showed a cortical peak response measured by
electroencephalography (EEG) to the heel stick.
The incidence of crying in response to painful or noxious stimuli is less than 50% in the
preterm infant.
376
Depending on GA, a preterm
infant’s behavioral responses to pain are similar to
those of the term infant.
19,177,376
A prospective
cohort study comparing full-term infants (e.g.,
of diabetic mothers who were exposed to
repeated heel sticks in the first 1 to 2 days of
life) showed that these infants learned by conditioning to anticipate pain after their heel was
swabbed with alcohol and exhibited a more
intense pain response to a later venipuncture
than infants who had not been exposed to
repeated painful procedures.
393
Pain responses of the neonate are also influenced by the number and timing of painful
procedures, the technique used, and the degree
177
267
UNIT TWO Support of the Neonate288
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of professional expertise.
13,98,393
Lack of a response
to a painful stimulus occurs more frequently in
younger newborns (both GA and PCA) who are
asleep and who have recently undergone another
painful procedure.
220,299,325
Pain scores may be
lower in preterm infants with higher severity of
illness and higher number of previous invasive
procedures,
rate response to repeated pain.
165
whereas there is a larger heart
322
Mechanical
lancets are preferred over manual devices for
capillary blood draws. A recent comparison of five
automatic lancets found that the Tenderfoot device
(Accriva Diagnostics, San Diego, CA) evoked the
least pain and was most effective in obtaining adequate blood with a single lance.
371
Venipuncture
has been shown to be associated with less pain in
the neonate than heel stick,
303,356
and a new blood
glucose device using the forearm has been found to
be less painful for term infants than heel sticks.
347
Assessment of neonatal pain is influenced
by the attitudes and beliefs of care providers;
amount of time spent observing for and having knowledge of pain responses; discrepancy
between attitudes and practice, knowledge, and
education of parents and professionals about
pain; prioritization of pain recognition and relief
in the NICU; interdisciplinary communication
and collaboration; and the social community.
If professionals (1) deny that newborns experience
pain, (2) become desensitized to newborns’ pain
experience, (3) rationalize reasons for not assessing
or treating pain, and (4) do not take responsibility
for inflicting pain, there can be no improvement in
neonatal pain management.
21,249,276
A qualitative study of the responses of neonatal
nurses to “inflicting pain” on extremely premature
neonates found three subthemes: (1) “when caring
and torture are the same thing,” (2) “why are we
doing this!” and (3) “comfort for baby and nurse.”
170
In this study, the Australian neonatal nurses are passionate about the need for pain relief for neonates.
When these nurses inflicted pain on extremely
premature infants, they experienced a profound
sense of distress, manifested as existential suffering. Instead of relieving pain, the necessity of
inflicting pain results in neonatal nurses questioning their role as compassionate caregivers:
“It’s agony for us as well.”
170
Numerous other social factors influencing pain
recognition and relief include the following: (1)
appearance, behavior, and responsiveness of a sick
neonate who varies markedly from the usual expectations about newborns; (2) lack of knowledge
about analgesia and belief that pain is secondary in
importance to the focus on survival; and (3) lack of
knowledge about the effect on morbidity, mortality,
and long-term consequences.*
Researchers have examined the beliefs and management techniques of 374 clinicians (both physicians
and nurses) about procedural pain in newborn infants.
Although the majority of clinicians believe that
infants experience pain in the same or greater degree
than adults, of 12 commonly performed bedside procedures (e.g., intubation, chest tube insertion, arterial
or venous catheter insertion, heel sticks) were rated as
“moderately to very painful.” Neither pharmacologic
nor comfort measures were frequently used.
recent surveys and studies of professional attitudes
have found the following: (1) assessment for neonatal pain is based on instinct rather than tested pain
4,67,91,104
tools
and lack of evidence-based guidelines
; (2) there is inadequate staff knowledge
4,67,91
; (3) level
of empathy, secondary trauma, and burnout of the
professional caregiver influences caregiving
there is difficulty translating knowledge to clinical
4,104,249
practice
; and (5) nurse-physician collaboration is a strong predictor of evidence-based procedural pain control.
22,249,276
A recent qualitative study
revealed NICU staff attitudes concerning neonatal
pain. Pain causes unnecessary suffering, and staff
members realized how multiple and repeated
procedures result in long-term consequences
from previous pain experiences. Second, health
care providers realized how approaches to pain relief
are based on feeling rather than facts. Furthermore,
while comforting the neonate and when suffering
is detected, health care providers have doubts and
concerns about the use and side effects of drugs for
pain relief. Lastly, staff members felt that the par-
ent’s presence and caretaking in the NICU had
the potential to decrease the neonate’s response
to painful stimuli.
147
Despite over 40 years of
research focusing on pain and pain control in
neonates, “clinical use of pain-control measures
in neonates undergoing invasive procedures
remains sporadic and suboptimal.”
IRRITABILITY AND AGITATION
31
Differentiation between pain and irritability or
agitation is a challenge (Fig. 12.4) . Agitation is a
* References 23, 147, 187, 225, 251, 279, 307, 379.
325
More
248
; (4)
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