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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_37_библиотеки_им_акад_М_И_Перельмана
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TABLE
Suspensory
e
nerves
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12.13
Midazolam
(Versed)
CHAPTER 12 Pain and Pain Relief
ANALGESICS, SEDATIVES, AND REVERSAL AGENTS FOR THE NEONATE—CONT’D
NONBARBITURATES
0.05–0.15 mg/kg/dose IV (give over ≥5 min) q 2–4 hr PRN
Continuous IV infusion:
<32 wk: 0.03 mg/kg/hr or 0.5 mcg/kg/min
>32 wk: 0.06 mg/kg/hr or 1 mcg/kg/min
PO: 0.25 mg/kg/dose of oral syrup
Onset: IV—1–2 min;
PO—15–30 min
Duration: 1 hr after single IV dose
For procedural sedation: Give 0.05 mg/kg IV and repeat ×1 PRN
for procedure
Same as for lorazepam; continuous IV infusion enables
precise titration until sedative effect is obtained; calms
agitated infant on ventilator. Rapid bolus delivery and/
or use with fentanyl is associated with (1) myoclonus—
rhythmic twitching of all extremities that ceases with
discontinuation of drug and does not return, and (2)
respiratory depression and hypotension—caution use in
hypotensive and hypovolemic neonates.
A systematic review shows (1) increased incidence of
adverse neurologic outcomes (e.g., grade 3–4 IVH; PVL),
altered CBF; (2) longer duration of NICU stay with midazolam use; and (3) conclusion that there is insufficient
evidence to support IV midazolam use as a sedative for
neonates in the NICU.
295
infants who received midazolam in the NICU found
decreased hippocampal volume (and associated lower
cognitive scores) and increased mean diffusivity.
309
212,265
Recent study of very preterm
127
REVERSAL AGENTS
Naloxone (Narcan) 0.1 mg/kg Reverses effects of opioids (both side effects
and analgesia).
Flumazenil (Mazicon) 10 mcg/kg 10 mcg/kg Reverses effects of benzodiazepines (e.g.,
midazolam, diazepam, lorazepam).
*Not yet approved by the Food and Drug Administration for use in the United States.
CBF, Cerebral blood flow; CNS, central nervous system; EEG, electroencephalography; ELBW, extremely low-birth-weight; EMLA, eutectic mixture of lidocaine and prilocaine; ETT, endotracheal tube; G6PD, glucose-6-phosphate dehydrogenase; GI, gastrointestinal; IM, intramuscular; IV, intravenous; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; NICU,
neonatal intensive care unit; PICC, percutaneous insertion of central catheter; PO, per os; PR, per rectum; PRN, as needed; PVL, periventricular leukomalacia; ROP, retinopathy of prematurity;
sub-Q, subcutaneous; VLBW, very-low-birth-weight.
Eutectic Mixture of Local Anesthetic and Infiltration. EMLA is
Buck’s
fascia
Deep dorsal vein
Deep penil
nerves
Corpora
cavernosa
Corpus
spongiosum
Dorsal penile
ligament
FIGURE 12.7 Anatomic landmarks for placement of a dorsal penile nerve
block. (From McClain B, Anand KS. Neonatal pain management. In: Deshpande
J, Tobias J, eds. The Pediatric Pain Handbook. St Louis, MO: Mosby; 1996.)
a local anesthetic cream that anesthetizes the skin and
has been used for a variety of procedures (e.g., lumbar puncture, venipuncture, immunizations).
205,234,416
A study of EMLA, applied 60 to 90 minutes before
lumbar puncture, showed a significant decrease in pain
response during needle insertion and withdrawal but
not during positioning/handling of the newborn.
EMLA has been used for analgesia with circumcisions in newborns and has been shown to be
efficacious.
416
However, its analgesic properties
are not as effective as those of dorsal penile blocks
in relieving postoperative circumcision pain.*
228
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A meta-analysis of the efficacy of EMLA for a
variety of procedures in neonates found that EMLA
diminishes pain during circumcision, venipuncture,
arterial puncture, and placement of a peripheral/
central IV line.
389,416
For maximum effective-
ness, EMLA should be applied and left on for
at least 1 to 2 hours before starting an invasive
procedure. Unfortunately, EMLA does not appear
to alleviate pain resulting from heel sticks.
142,389,416
Infiltration of local anesthetic can help decrease
pain for procedures such as placement of percuta-
neous central lines, removal of Broviac catheters,
and circumcision. Methemoglobinemia does not
appear to be a problem when single daily doses of
0.5 g EMLA are left in place for 60 minutes,
389
but
studies are ongoing to address this issue.
Amethocaine gel (lysosome-encapsulated tetra-
caine) is a topical local anesthetic preparation that
provides more effective superficial analgesia than
EMLA in adults. Amethocaine has demonstrated similar efficacy to EMLA when appropriate application
times are used and has a more rapid onset and longer
duration of action than EMLA.
301
Studies have doc-
umented its effectiveness in neonates as follows:
• It relieves pain during venipuncture,
insertion, and injections of vitamin K.
• It does not relieve pain from heel sticks
213,260
357
315
IV
or
peripherally inserted central catheter (PICC)
insertion, unless combined with morphine use.
• It relieves circumcision pain.
416
388
• It does not cause methemoglobinemia.
• It is effective within 30 to 40 minutes of application.
A recent Cochrane review recommends more
research into the safety and efficacy of topical anesthetics, especially in the very preterm neonate and
for multiple applications.
OTHER MEDICATIONS
140
Acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) can be helpful in providing analgesia for mild to moderate pain (see
Table 12.13). These medications are more effective
when administered on a regular schedule, augment the effects of opioids, and may be delayed in
effect because of the rate of gastric emptying.
36,405
Acetaminophen given 2 hours before circumcision does not reduce pain during the procedure
but is effective in postoperative pain relief;
repeated doses every 4 to 6 hours for the first
24 hours after circumcision are recommended.
The analgesic effects of IV NSAIDs have not been
studied in preterm infants, and the adverse effects of
prolonged NSAID use may lead to renal, circulatory,
hepatic, gastrointestinal, and hematologic complica-
25,31
tions.
Ketorolac in a single dose has been studied
in infants as young as 2 months of age and found to
be safe and effective at relieving pain.
90,264
Although
use of acetaminophen as a prophylactic for febrile
response to immunizations is effective, there is a
significantly lower antibody response to vaccine
antigen when acetaminophen is used.
329
Sedatives can help decrease agitation and improve
comfort but do not by themselves provide anal-
gesia. Use of developmental care significantly
reduces the need of VLBW infants for sedative
411
drugs.
Sedatives are appropriate to induce sleep
for diagnostic procedures (e.g., MRI, computed
tomography [CT]), to calm chronically irritable
infants whose physiologic stability or ventilatory status is compromised by agitation, and for pain-related
agitation.
27,411
Sedatives have potential toxicities,
effect behavioral changes, and affect consciousness,
which deprive neonates of their ability to communicate and interact with their parents, caregivers, and
the environment.
412
Furthermore, the short-term
and long-term effects of frequent or continuous use
of sedatives on the developing brain are unknown.
Comfort/Nonpharmacologic
Measures
Comfort measures alone do not relieve pain;
however, their use reduces agitation, which
indirectly reduces pain by promoting behavioral
organization, relaxation, general comfort, and
sleep.13 Although comfort measures may prevent the intensification of pain (e.g., guarding
an abdominal incision by positioning is less
painful than four-point restraint), they may not
relieve moderate to severe pain. Comfort measures are helpful but inadequate by themselves,
considering the intensity of the noxious stimuli
causing moderate to severe pain.
Provision of nonpharmacologic interventions
for neonatal pain is an evidence-based nursing
practice that should be initiated by neonatal
nurses and parents.
151
A recent survey of NICU
nurses found that when rationing of nursing interventions (limiting or omitting interventions to particular patients) occurs, provision of comfort care is
“often” and “very often” rationed.
13,102
339
Another survey
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311
found that 64% of NICU caregivers used nonpharmacologic interventions for heel sticks or venipunctures.50 As partners in care, parents should be
encouraged, facilitated, and educated to engage in
providing comfort measures for their infants having painful procedures.68 Nonpharmacologic interventions that have been found to offer the most
comfort during a painful intervention include nonnutritive sucking, breastfeeding, skin-to-skin contact (kangaroo care) with the mother or another
immediate postpartum mother,
285,293
facilitated
tucking, rocking, and holding.* Who better than
parents can provide these interventions? Research
shows the efficacy of parental involvement.
Initiation of skin-to-skin contact,
168
taste, and
suckling was described in full-term infants receiving heel sticks for genetic screens, who experienced
less crying (91%) and grimacing (84%) when
being held and breastfed by their mothers.
75,167
Numerous studies show that very preterm,
healthy preterm, and term newborns (between
28 and 36 weeks’ PMA) who received heel
sticks experienced diminished behavioral and
physiologic pain response, less crying, and
quicker recovery when being held skin-to-skin
(e.g., kangaroo care) by their mothers for 15 to
30 minutes before and during the procedure. If
the preterm infant’s mother is not available, does
provision of skin-to-skin care by the father or an
unrelated woman result in lower pain responses?
This question has been researched in two published
studies with the following results: (1) fathers were
marginally less effective than mothers in decreasing
their preterm infant’s pain response,
219
(2) unrelated females had a small, although not negligible,
decrease in their ability to relieve infant pain, and
fathers are more acceptable to the baby’s mother
than an unrelated female to provide this intimate
216
care.
Animal studies show that the short-term
and long-term effects of repeated pain are ameliorated by the presence and ministrations of the
mother;
413
perhaps the presence of the human
mother or parent provides the same protection for the human neonate.* One study found
concordance between mother and infant cortisol
levels during heel lance, which supports the stress
* References 79, 84, 123, 194, 310, 314, 319, 359.
* References 48, 69, 79, 84, 95, 96, 99, 169, 219, 291,
300, 310, 314.
regulatory role of maternal skin-to-skin care during
painful procedures.
78
Skin-to-skin care is the most effective nonphar-
macologic intervention for neonatal pain,
193,321
and
barriers to use need to be identified and addressed.
One barrier to using skin-to-skin care and breastfeeding to relieve neonatal pain during invasive
procedures such as heel stick and injections is the
uncomfortable position of the professional performing the procedure. An ergonomically sound
protocol using an adjustable height stool has been
developed and tested in the clinical setting.97 This
protocol has resulted in a more comfortable position for the professional and more use of skin-toskin care and breastfeeding for neonatal pain relief
during the procedure.
97
Developmental care not only prevents pain
but also decreases behavioral and physiologic
pain scores in preterm infants.
79,365
A recent study
of a simple diaper change in VLBW preterm infants
showed less physiologic response (e.g., alteration in
heart rate, hypoxia, bradycardia, desaturation events)
and less pain response (measured with two pain
scales) when developmental care was used before
and during the procedure.
365
In this study, developmental supports such as opportunities for grasping,
hand swaddling, decreasing light and noise, NNS,
and body support and containment were used.
NONNUTRITIVE SUCKING
NNS (e.g., the infant’s own fingers or hands or a
pacifier) soothes by reducing the infant’s level of
arousal and duration of cry while promoting the
quiet alert state.69 NNS is effective in reducing
pain in preterm infants during heel stick, cir-
cumcision, immunizations, and ROP screening eye
examinations.59 The effect of NNS is immediate,
but the effect ceases immediately on cessation
of sucking/removal of the pacifier. Combining
NNS and sucrose before and during painful
procedures provides a synergistic effect on pain
relief for both term and preterm neonates.*
ORAL SUCROSE/GLUCOSE AND
BREASTFEEDING
Distressed infants who were offered oral sucrose
calmed quickly, stayed calm longer, and spent
more time in a quiet alert state than did infants
offered only a pacifier.55 Sucking soothes, reduces
* References 56, 73, 257, 259, 298, 383, 400.
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heart and metabolic rates, induces hand-to-mouth
behavior, and elevates the pain threshold through
opioid and nonopioid systems.55 Oral administra-
tion of sucrose within 2 to 3 minutes before an
invasive procedure (e.g., heel stick/venipuncture, bladder catheterization, ROP examination,
insertion of gavage tube, arterial stick, echocardiography, casting) has been shown to decrease
crying duration, heart rate, facial activity, and
EEG changes associated with pain in full-term
and preterm infants.* However, in the first ran-
domized clinical trial of 40 preterm and term
infants receiving oral sucrose (24%) for peripheral
intravenous catheter (PIV) placement, no efficacy
in relieving the neonate’s pain during the procedure
was seen.
100
Replication of this study is needed
before widespread application of these findings.
In these studies, the amount (0.05 to 2 mL) and
concentrations (24% to 50%) of sucrose varied, but
even the smallest dose administered once to preterm
infants of 26 to 34 weeks of gestation reduced
pain behaviors.
379
The small doses of concentrated
sucrose solution used to treat neonatal pain have
not been shown to cause hyperglycemia in preterm
infants.62 The AAP recommends that oral sucrose/
glucose used for pain relief must be ordered and
tracked as a medication.
13
When sucrose is paired with developmen-
tal interventions such as rocking, carrying,
101,422
NNS,
422
ing,
parental holding,
prone positioning, facilitated tuck-
radiant warmth,
166
89,157
swaddling
sucrose is more effec-
125,128,131
162
or
tive in decreasing behavioral pain responses.
Sensorial saturation (massaging the infant’s face,
gently talking to the infant, and instilling a sweet
solution on the tongue) is effective in newborn
pain relief during minor procedures.49 Sensorial
saturation is more effective than oral glucose alone,
but use of sensorial saturation without sweet solution is ineffective. A systematic review of sensorial
saturation (i.e., oral sucrose, massage, and caregiver’s
voice) found that it is more effective in heel stick
procedures in preterm and term infants than oral
sucrose/glucose alone.
259
Combining massage and
breastfeeding relieves the pain of venipuncture in
term and late preterm infants.
425
In healthy fullterm neonates, especially males, sensorial saturation
reduces pain scores and markers of oxidative stress
after heel stick.
* References 55, 212, 234, 285, 286, 329, 357, 383, 403.
317
Two RCTs of the combination of NNS, oral
sucrose, and facilitated tucking during heel stick in
preterm infants found reduced arousal during the
procedure, less crying and fussing, and better sleep
than routine care alone.
422
For intrusive procedures,
use of a supportive bundle (i.e., modulating the
infant’s state, NNS, facilitated tucking, and oral
sucrose) increased premature infants’ sleep time and
efficiency as well as decreased bouts of awakening
after the procedure.
246
In a systematic meta-anal-
ysis of 74 studies of sucrose use for analgesia,
sucrose was found to be safe, effective, and
cost-effective for single painful procedures (e.g.,
heel stick/venipuncture/intramuscular [IM]
injection) for preterm and term neonates.
addition of liposomal lidocaine to sucrose in one
study did not further decrease the pain of venipuncture in healthy term newborns.
394
Despite being
aware that sucrose relieves pain, only 10% of surveyed NICUs used sucrose before a heel stick, and
only 11% used sucrose before venipuncture.
other surveys found that (1) only 33% of responding
NICUs used sucrose before routine painful procedures, and (2) NICUs in eight European countries
found poor compliance with pain management
guidelines for heel stick and other invasive proce-
262
dures.
The use of sucrose for neonatal heel lance
increased by 84% after an educational intervention
for NICU staff.
359
A systematic review of eight studies for the safety
and efficacy of repeated oral sucrose for repeated
procedural pain found that (1) different study designs
prohibited a meta-analysis; (2) repeated sucrose was
effective in decreasing behavioral pain response and
composite pain scores; and (3) repeated sucrose
had variable efficacy in altering physiologic pain
response for preterm (less efficacy in two studies)
and term (less variability in one study) infants.
During repeated painful procedures, combining
NNS and sucrose provides better pain relief than
either intervention used alone,
149
and repeated
use of skin-to-skin care continues to provide
pain relief for preterm infants.
150
None of the
studies reported adverse outcomes from repeated
sucrose use. Neurodevelopmental outcomes were
mixed and included: (1) repeated sucrose use for
repeated procedural pain would not lead to poor
neurologic development (two studies); (2) preterm
infants less than 31 weeks’ GA who received more
than 10 doses of sucrose/24 hours in the first week
of life had poorer neurologic outcomes than infants
379
169
The
Two
148
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313
receiving fewer doses; and (3) no study reported
long-term neurodevelopmental outcomes. There
is limited research supporting the safety and efficacy of repeated sucrose for repeated procedural
pain, and multicenter, prospective, large RCTs are
needed.
148
The benefits of sucrose for pain relief have
been shown to provide comfort to the infant
during subsequent caregiving activities.
393
Two
hundred and forty neonates were randomized to
a placebo or sucrose-treated group for all needle procedures. After the painful procedure, those
infants receiving sucrose reacted to a diaper change
with lower pain scores than the infants receiving
only a placebo. The comforting benefits of sucrose
remained even after the painful procedure was
complete.
393
The Academy of Breastfeeding Medicine
supports that when available, breastfeeding
should be the first choice to alleviate procedural
pain in neonates.
52,337
When possible, breastfeeding throughout the procedure, rather than pumped
breast milk, offers more comfort because of the
synergism between skin-to-skin contact with the
mother, sucking, and reception of breast milk by
the infant.52 An RCT comparing breast milk with
sucrose for pain relief in 71 late preterm infants
(born at 32 to 37 weeks’ PMA) undergoing heel
lance was conducted in the Netherlands.
361
Using
the PIPP assessment scale, there was no significant
difference in pain scores between the preterm
infants receiving breast milk (directly breastfed or
bottle-fed) and those receiving sucrose. A randomized crossover study comparing expressed breast
milk and oral sucrose for relief of pain associated
with venipuncture found the same analgesic effect
in most preterm infants; however, sucrose had better pain relief in extremely preterm infants.92 An
RCT comparing the analgesic effect of sucrose
and breastfeeding during venipuncture in healthy
3-day-old newborns found equal pain relief for
both methods as measured by NIRS.
338
Salivary cortisol levels from birth to 1 year of
age are 40% higher in breastfed infants compared
with formula-fed infants.79 The analgesic effect of
breast milk may be a result of these higher cortisol
levels.70 Concerns about breastfeeding as a com-
fort measure during painful procedures have
been raised. To explore these concerns, a study of
57 preterm infants (30 to 36 weeks’ GA) were randomized to be breastfed or given a soother during
a blood collection procedure.
200
Preterm infants
with mature breastfeeding skills had lower pain
scores during the procedure, all breastfed infants
had lower pain scores after the procedure, and
use of breastfeeding as a comfort measure did
not interfere with the acquisition of breastfeeding skills.
200
A more recent study comparing breast
milk and sucrose for reducing the pain of ROP
examination found that preterm infants receiving
1 mL of breast milk recovered more quickly, and
their vital signs returned to baseline more quickly
than those preterm infants receiving sucrose.
352
Another study evaluated the use of breast milk versus
swaddling versus oral sucrose to relieve the pain of
ETT suctioning and found no difference between
them in relieving pain.
118
Breastfeeding for immunizations lowers pain scores and heart rates, shortens
the duration of crying, and prevents lower oxygen
saturations.
130
When compared with skin-to-skin
care and swaddling, breastfeeding was more effective
than either in reducing pain of immunizations in
healthy term neonates.
134
Several studies have compared the use of
glucose versus sucrose for pain relief, with conflicting results. A comparison of oral glucose versus
sucrose showed that glucose solution (33% to 50%)
was more effective in reducing pain response in
term newborns having heel sticks.
181
Another study
found that 30% sucrose solution was more effective
in reducing crying time than 10% to 30% glucose
solutions.
211
When (30%) oral glucose solution was
given to full-term newborns undergoing venipuncture compared with (1) EMLA cream
165
and (2)
subcutaneous injections,72 the infants treated with
glucose had significantly lower pain scores. Oral
glucose and facilitated tucking by parents was
found to be more effective and preferred over
the use of opioids in preterm infants receiving
heel sticks and pharyngeal suction.
43
A meta-analysis of 38 RCTs found that use
of 20% to 30% oral glucose solutions reduced
preterm infants’ pain scores and crying with both
heel lance and venipuncture,63 but was ineffective
for longer procedures such as eye examnations.
103
Another more recent study of the efficacy of
oral glucose (25%) versus oral sucrose (24%) use
for pain relief during heel lance in 94 preterm
neonates in the first 48 hours of life found comparable pain relief.
238
Various strengths of oral
glucose solutions are effective in relieving
neonatal pain: (1) a 25% solution is more effective
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at relieving pain from an IM injection than NNS
256
alone
; (2) 2 mL of a 10% solution relieves the
pain of venipuncture and nasopharyngeal suc-
270
tioning
; and (3) a 5% solution relieves pain,
decreases crying time and heart rate, and increases
oxygen saturation in preterm infants receiving IM
injections.
399
Efficacy of sweet solutions to relieve
neonatal pain has existed since the first trials and
reviewers of a recent meta-analysis recommend
that placebo/no-treatment trials be abandoned for
more ethical control groups.
TACTILE INTERVENTIONS
191
A reassuring human presence (of parents or
caregivers) during painful procedures for all
neonates in the NICU is mandatory.47 Body con-
tainment of extremities in a flexed position (e.g.,
holding, swaddling, nesting; providing an opportunity to grasp a finger or pacifier) decreases gross
motor movements that contribute to the infant’s
increased level of arousal, reduces physiologic and
behavioral stress, facilitates energy conservation in
the preterm infant, and lowers pain scores.
69,84,395
When swaddling and skin-to-skin care were
compared for the relief of pain during venipuncture in premature infants, pain was relieved
equally between the groups when compared
with the control group.
122
Premature infants
nested in the prone position experienced lower
pain scores and salivary cortisol levels after a
heel lance procedure compared with nesting in
the supine position.
225
Improper body positioning contributes to discomfort and pain. An RCT
combining five tactile interventions (i.e., swaddling,
side/stomach lying, shushing, swinging, and sucking) for infant immunizations resulted in less crying
time and lower pain scores; these outcomes were
greater than those obtained with sucrose alone.
190
Facilitated tucking—gentle containment of
flexed extremities in the midline on the trunk
while side-lying or supine—during a painful
procedure (e.g., heel stick) results in lower
heart rate, shorter crying time, less sleep disruption, and fewer sleep-state changes.
102,193,321
One study of facilitated tucking and usual positioning for heel stick found a “surprising” result: no
difference between the two positions in pain intensity for the premature infants.
112
Pairing facilitated
tucking with breast milk and NNS effectively
reduces pain in premature infants during heel
316
lance.
Several studies of facilitated tucking
during endotracheal tube suctioning have been
conducted with the results of lower pain scores
in the preterm infants receiving facilitated tucking, when compared with no intervention.
Facilitated tucking (provided by parents for endotracheal tube suctioning) showed that participation
by parents was a safe, effective pain management
strategy that provided parents with an active role in
their infant’s pain care and was also preferred by parents.42 A more recent study by the same researchers found lower pain scores with oral glucose
and facilitated tucking by parents during heel
stick and pharyngeal suction in very preterm
infants.43 Facilitated tucking was perceived pos-
itively by mothers who were either internally
motivated to provide it or were externally motivated by nurses who suggested their involvement.41
However, two other studies of facilitated tucking
and facilitated tucking and oral sucrose89 found that
using facilitated tucking alone was less effective in
pain management.
Use of a 2-minute massage of the ipsilateral leg
before heel stick in preterm infants was safe and
resulted in a decreased pain response (decreased
pain score and heart rate) compared with nonmassaged preterm infants.
214
Massage of the arms and
hands of infants for 2 minutes before an invasive
procedure such as heel stick or other needle stick,
including venipuncture, has been shown to reduce
pain scores.
84,85
A more recent pilot study of the
use of vibration on the lateral aspect of the leg
during heel lance resulted in lower N-PASS scores
and more stable heart rate during and 2 minutes
after the procedure when compared with the control group, without any physiologic or behavioral
adverse effects.
274
Motoric boundaries (e.g., containment of
extremities) assist a preterm infant to maintain
a more secure, controlled response and facilitate
self-regulation. Therapeutic interventions include
the use of positions that support flexion and
restraint in physiologic position, periodic release
of restraint and exercise of extremities, gentle
change in body position, and positioning to
guard operative sites. Along with comfort mea-
sures, minimizing stimulation in the NICU environment enables a neonate who is agitated or in
pain to use internal and external resources in organizing his or her behavior and develop self-soothing
strategies (see Chapter 13). Individualizing care and
handling to the infant’s likes and dislikes and listing
7,261
157
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315
these at the bedside help maintain consistency of
care and build trust in these developing neonates.
Picking up, holding, and rocking provide tactile
soothing, vestibular stimulation, and the calming
effect of rhythmic, repetitive movement. Use of
massage, rocking, and water mattresses provides tactile, vestibular, and kinesthetic stimuli that modify
and accelerate behavioral state control and decrease
stress behaviors (see Chapter 13).
AUDITORY INTERVENTIONS
Four small studies of the use of music therapy to
relieve the stress and pain of procedures evaluated
physiologic and behavioral responses in a total of 75
infants.9 In two studies, intubated preterm infants
were exposed to music/no music during routine
suctioning. Positive results in the music-exposed
preterm infants included (1) improved oxygen
saturation, (2) heart rates between 120 and 160
beats/min for a longer period, (3) more time
in sleep state, and (4) quicker recovery time
after suctioning.
64,87
Two other studies exposed
irritable, agitated, infants in a naturally occurring
inconsolable crying episode to music and measured
their responses. Again positive results of music therapy included (1) improved oxygen saturation, (2)
better respiratory and heart rates, (3) state change
to drowsy or quiet alert, and (4) fewer crying
episodes.
93,229
A more recent study of recorded
maternal voice played during heel lance resulted
in significantly lower PIPP scores and less oxygen desaturations with no side effects in the
group of preterm infants hearing their mothers’
voice, when compared with the control group.86
Playing the same music that mothers listened
to while pregnant resulted in less pain response
to heel lance in preterm infants.
239
Breastfeeding
full-term healthy neonates during a heel lance procedure effectively reduced their pain response, but
the addition of music therapy did not enhance pain
423
relief.
Additional data from well-designed studies
are required before use of music therapy for preterm
infants during painful, stressful conditions can be
recommended.
9
Combination of auditory therapies and other
nonpharmacologic interventions is more effective than use of single therapies to relieve
pain. A randomized study of 62 preterm infants
using a combination of music and touch during
painful procedures found similar cortisol concentrations at birth and at 2 weeks of life between
the experimental and control groups. However,
at the beginning of hospitalization and after 2
weeks, beta-endorphin levels were higher and
the PIPP scores lower in the group exposed to
the combination of music and touch.
330
Stable
neonates with a PMA of 35 weeks who were
exposed to recorded music and sucrose for heel
stick procedure were in less pain than when the
interventions were administered separately.
354
Preterm infant pain was relieved during venipuncture with the use of eye covering and playing
intrauterine ambient sounds.
COMPLEMENTARY HEALING
MODALITIES
6
Complementary healing (e.g., therapeutic touch
[TT], acupressure, acupuncture, Reiki) is gaining
increasing interest among neonatal health care
providers. Little research exists, but clinical reports
have depicted the benefits of pain relief with
integration of these modalities. A study conducted
with registered nurses (RNs) who provided TT
to preterm infants (25 to 37 weeks of gestation)
revealed that the infants’ responses to TT included
(1) decreased heart and respiratory rates; (2)
enhanced restful periods; (3) improved sucking,
swallowing, and breathing; and (4) a greater ability
to interact with the environment.
187
Two more
recent studies of the use of TT with a painful
procedure have been conducted. In the first study,
10 preterm infants (34 to 40 weeks’ conceptual
age) received TT during a low-intensity sensory
punctuate stimuli and responded with an increase
in cerebral oxygenation.
202
The researchers con-
cluded that TT may have a protective effect
on the autoregulation of cerebral blood flow
in the preterm infant during painful stimuli.
202
Another randomized study of the effects of TT
before and after procedural pain (heel lance)
found no comforting effect for 27 preterm infants
less than 30 weeks’ GA.
217
These researchers recommended use of other tactile interventions for
pain relief. Reiki uses healing energy to restore
balance within the body. Reiki has been used
for neonates experiencing neonatal abstinence
syndrome without adverse effects and resulted in
a slight decrease in heart rate, which may signify
relaxation.
331
Acupuncture and acupressure may be safely
used to treat pain, agitation, and drug withdrawal in the neonate.
160
A retrospective review
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of 10 hospitalized infants exposed to acupuncture found a decrease in the use of sedatives and
analgesics for agitation, successful weaning from
ventilators, and transitioning to oral intake after
oral aversion without adverse effects.
153
Use of
acupuncture in neonates in one NICU decreased
the amount of medication needed for agitation
and withdrawal, was well tolerated, and was without complications.
161
In a small RCT, acupressure before heel lance was shown to shorten the
procedure and the duration of crying in preterm
infants.1 However, in another study, use of noninvasive electrical stimulation of acupuncture needles
in term infants receiving heel sticks was not shown
to be effective in procedural pain relief.
284
Use of
noninvasive magnetic acupuncture on the outer
ears of newborns (mean gestational age 34 weeks)
receiving heel stick procedures resulted in lower
pain scores.82 Acupuncture used for 2-week-old
to 8-week-old infants with colic resulted in less
crying and less colicky crying than standard care by
the second week of treatment.
247
More research is
needed to validate the use of these modalities for
pain management.
153
Activation of cutaneous sensory nerves with a
transcutaneous electrical nerve stimulation (TENS)
unit and application of thermal topical skin refrigerant blocks transmission of peripheral pain impulses
from procedural pain. Low-frequency, monotonous
sounds (e.g., heartbeat, vacuums) quiet the infant
and increase behavioral organization. Use of music
(see Chapter 13) and recordings of family voices
soothe term and preterm infants, resulting in fewer
state changes, less time in the arousal state, and
increased behavioral organization. However, during
circumcision, music (with or without a pacifier) is
not an effective distraction or soothing strategy for
relief of the pain of the procedure. Another recent
study showed that preterm infants presented with
a familiar odor during venipuncture exhibited
significantly less crying and grimacing, compared
with the preterm infants presented with an unfamiliar odor or no odor.
164
However, scents (such
as amniotic fluid, breast milk, or maternal odors)
presented to premature infants during a heel stick
procedure did not reduce neonatal pain scores,
233
yet the odor of mother’s own milk did decrease
pain scores during venipuncture and crying after
the procedure.46 Another RCT of preterm infants
exposed to breast milk odor, or recorded maternal
voice or incubator cover during peripheral intravenous cannulation found that these interventions
were simple, safe, and supportive during painful
procedures.
5
END-OF-LIFE CARE
When the decision is made to terminate or
not begin aggressive medical intervention, the
neonate receives end-of-life care, also known
as comfort care or palliative care (see Chapter
32). Neonates who receive end-of-life care are at
the threshold of viability, have multiple congenital
anomalies that are incompatible with life, or are not
responding to NICU interventions (e.g., deterioration in condition despite medical efforts).
End-of-life care should combine comfort
measures, pharmacologic management, developmental care (see Chapter 13),
and psychosocial support for the neonate and
family (see Chapters 29 and 30).
Parents are acutely aware of (and able to recall) their
infant’s suffering, including perceiving the infant’s
pain at the end of life.
360
The family is provided
a quiet, private, homelike area in which to touch,
hold, and interact with their terminally ill neonate. Use of skin-to-skin care; soft, soothing music;
dimmed lighting; infant massage; holding; and
rocking provide both a comforting environment
for the infant and family, as well as parenting and
comforting opportunities.
83,383
Parents, siblings, and
extended family members remain with their infant
during and after death. Clergy may be present for
family support and may perform a religious service,
such as a baptism or blessing.
For comfort care, all invasive procedures,
including measurement of vital signs, monitors,
machines, and artificial feeding, are discontinued. The infant, cleaned and wrapped in a warm
blanket, is held by his or her family. Intravenous
access may remain in place for administration
of pain medications or sedatives. Medication is
administered in sufficient doses to provide comfort, relieve pain, and ensure that the infant
does not suffer at the end of his or her life.
In the earliest study documenting the use of
analgesia for dying infants whose life support was
withdrawn or withheld, 165 deaths in a universitybased NICU were reviewed.
313
Opioid analgesia
320,336
383
and spiritual
77,80,320,382,383
CHAPTER 12 Pain and Pain Relief
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317
was administered to 84% of infants when life support was withdrawn or withheld. Infants with major
congenital anomalies (93%) and necrotizing enterocolitis (100%) were more likely to receive opioids
than were ELBW infants (66% to 83%). Overall,
opioid analgesia was administered to at least 65%
of infants. Reasons for life support discontinuation
also influenced administration of opioids: (1) futility
of treatment (84% medicated), (2) severe lifelong
impairment (85% medicated), and (3) suffering
caused by treatment (100% medicated). The median
dose of opioids was within the usual pharmacologic
range in 64% of infants and greater in 36%. Of the
infants receiving a higher dose, 94% had previously
been receiving an analgesic and may have needed a
higher dose as a result of tolerance. The median time
until death from the discontinuation of life support
was 18 minutes for those who received the standard
dose and 20 minutes for those who received the
higher dose.
A recent study of end-of-life care found that
85% of infants received analgesic and/or sedative
medications before the withdrawal of treatment,
55% at withdrawal and 60% after treatment was
terminated.
139
The majority of medication was
given by continuous intravenous medications for
sedation and pain related to diagnosis. Use of nonpharmacologic interventions for end-of-life care/
pain was minimally documented in this exploratory, descriptive study. If there is no intravenous
access, intranasal fentanyl has also been used in
palliative care with dying newborns with no complications such as chest rigidity and drug-related
apnea. Neonatal restlessness and labored respiratory efforts were calmed after the intranasal fentanyl, with the average time from last dose to death
of 61 minutes.
188
A survey of hospital staff providing pediatric
palliative care found that 50% of physicians and
30% of nurses reported feeling inexperienced in
pain management.99 Providers also shared how
personally distressing it is to witness a child’s
suffering, especially when pain relief was possible but not available or delivered. In the same
study, families also described their anguish in watching their child experience and suffer any amount
of pain and discomfort. Unlike the health care
providers, families thought that everything had
been done to alleviate their child’s pain. Another
recent study found that insufficient education in
pain and palliative care of pediatric care providers
was a barrier to use of palliative care in children.
113
COMPLICATIONS
A neonate’s complex behavioral response to
pain has both short-term and long-term ramifications (Box 12.7).
These behavioral changes may disrupt parent-infant interaction and attachment, adaptation to
the postnatal environment, feeding behaviors, and
growth.
and maldevelopment of sensory systems can
occur when distorted or inappropriate sensory
input occurs during a critical period in development. Because of a neonate’s memory, painful
experiences increase the infant’s sensitivity to
subsequent medical encounters. These initial
experiences may affect the development of attitudes,
fears, anxiety, conflicts, wishes, expectations, and
patterns of interactions with others.*
term consequences (see Box 12.7) because there
is heightened sensitivity at earlier developmental stages. In the most immature preterm infants,
lower pain thresholds and the lack of inhibitory
controls influence hypersensitivity.
injury occurs early in development, increased
pain sensitivity develops both at the site of the
damage (primary hyperalgesia) and in the surrounding skin (secondary hyperalgesia) because
of hyperinnervation at the site.
pain threshold of the more preterm infant is also
influenced by repeated exposures.
sequences of this altered excitability include (1)
perceiving nonnoxious tactile stimuli as noxious,9
depending on the number of invasive procedures in
the previous 24 hours
chronic pain and discomfort; (3) associating earlier
pain with decreased behavioral responses to pain; (4)
variable physiologic responses
thresholds, pain tolerance, and higher pain intensity
in adolescence.
the importance of infant and family factors (Fig.
12.8) in ameliorating developmental alterations
initiated by early and repeated pain exposures.
* References 19, 21, 33, 61, 62, 139, 179, 183, 184, 271, 303,
321, 327, 337, 346, 373, 391, 394, 397, 406, 419.
29,408
An alteration in brain development
Younger infants are more susceptible to long-
171
When tissue
171,319
The lower
171
The con-
175
; (2) systemic responses of
171
; and (5) lower pain
65,404
Ongoing studies demonstrate
171
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BOX
12.7
• Less physiologic stability (e.g., alterations in heart and/or respira-
• Less postnatal growth (less weight gain and lower head circumfer-
• Alterations in basal cortisol levels in extremely low gestational age
• Cortisol dysregulation associated with lower IQ in 7-year-old boys
• Alterations in cerebral blood flow,
• Significantly thinner cerebral cortex, predominately in the frontal and
• Inappropriate sensory input (pain) disrupts neural activity, and
• In extremely preterm neonates, disrupts the development of brain
• Hyperinnervation (e.g., neural reorganization in the periphery and
• Altered pain responsiveness:
• Heightened responsiveness to pain (hyperalgesia)/lower pain
• Decreased responsiveness to pain (associated with more expo-
• Reduced tolerance, and lower pain thresholds and higher pain inten-
• Altered behavioral and neurodevelopment
• Temperamental difficulties at 3 months of age
• Altered hypothalamic-pituitary-adrenal (HPA) axis function up to
• Shortening of telomere (region of repetitive nucleotide structure at
* References 19–28,33,62,95,138,139,172–174,179,183,184,271,303,320,327,
345,353,372,389–393,396,405,417,418
Alteration of parent-infant interactions and relationships; temperament and pain expression
LONG-TERM CONSEQUENCES OF
REPETITIVE PAIN*
tory rates and blood pressure)
ence) in very preterm infants
preterm infants at 8 and 18 months that suggests a “resetting” of
the endocrine stress systems with potential for negative implications
for neurodevelopment and later health
born very preterm (but not girls) who have the brain-derived neurotropic factor gene variant
tricular hemorrhage and periventricular leukomalacia; altered white
matter microstructure
parietal lobes
chronic activation of neuroendocrine system results in abnormal brain
development.
regions involved in somatosensory processing (i.e., thalamic volume
loss; reduces thalamocortical maturation), which results in poor cognitive and motor function at 3 years corrected age.
the spinal cord) associated with increased pain behaviors such as
allodynia and hypersensitivity
sity in adolescence (after being born preterm)
school age in children born very preterm, especially in males.
each end of a chromosome) length in very preterm infants that is
associated with repeated NICU pain and stress
333,370
threshold
sure to painful experiences) in the NICU and later in infancy and
childhood
401,408
81
266
increasing the risk for intraven-
370
126
404
94,163
287
60
327
NICUs with a higher level of infant pain management are associated with better neurobehavioral performance (i.e., better attention and arousal,
less lethargy, and better reflexes as measured by the
NICU Network Neurobehavioral Scale [NNNS])
in very preterm infants.
286
Studies to evaluate the
long-term effects of pharmacologic and comfort
interventions are also needed.
61,171,182,183,278,334,408
As mentioned, unanesthetized surgery and/
or unrelieved pain causes suffering that might
itself be a risk to life.29 Maintaining metabolic
homeostasis by the appropriate use of anesthetics
and analgesics improves postoperative outcome
by preventing (1) protein wasting, (2) electrolyte
imbalance, (3) impaired immune function, (4)
sepsis, (5) metabolic acidosis, (6) pulmonary and
cardiac insufficiency, (7) hypermetabolic state, and
(8) death.
17,30,120,158
Increasing evidence con-
firms that exposure to prolonged, severe, or
untreated pain increases morbidity and alters
brain development and subsequent behavioral
and physiologic responses to pain.
66,138,172,268,408
13,16,19,20,22,29,
Opioid analgesics may produce respiratory
depression severe enough to require mechanical
ventilation. Naloxone (0.1 mg/kg IV or IM) is
the specific antidote for opioid overdose (see
Table 12.13). Lower doses of naloxone (0.001 to
0.01 mg/kg IV or IM) can be used for moderate
respiratory depression. Complete opioid reversal
with 0.1 mg/kg naloxone increases agitation and
stress response in neonates with ongoing pain.
Subsequently, it is more difficult to manage the
neonate’s pain until the effects of the naloxone wear
off. Lower doses of naloxone should be used and
the dose titrated to prevent this outcome. An
ampule of neonatal naloxone should always be
immediately available with the appropriate dose
precalculated on the infant’s emergency card.
Flumazenil is a specific antagonist for the benzodiazepines and should be used to treat respiratory depression (see Table 12.13). Respiratory
depression may produce hypoxemia, so a pulse
oximeter should be standard equipment along
with cardiorespiratory monitoring.
13,384
All
equipment for assisted ventilation should be at
the bedside.
13
An overdose of local anesthetics can cause
seizures, ventricular tachycardia, bradycardia, and cardiovascular collapse. Toxic doses for
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