NEONATAL N ETWORK
12 © 2017 Springer Publishing Company JANUARY/FEBRUARY 2017, VOL. 36, NO. 1
Accepted for publication
Martin Schiavenato, PhD, RN,
is the inventor of a pain detec-
tion device for use in premature
infants. It is not commercial-
ized, but he may at some point
in the future potentially derive
royalties from it.
Liisa Holsti, BSR, PhD,
OT, is the lead inventor of a
medical device which could be
used for managing pain in
preterm infants. In partner-
ship with the Provincial Health
Services Association of British
Columbia, she could, in the
future, receive royalties as a
result of licensing agreements
made with private industry for
commercialization of the device.
To date, she has not received any
Procedural distress is a common occurrence in the NICU and is tied to attempts to support the life and
development of vulnerable premature infants. We discuss the epidemiology of procedural distress and
the potential negative consequences on infant neurodevelopment. We deﬁne procedural distress in the
NICU and outline three approaches to limit or to reduce its detrimental effects including minimizing
the number of procedures, instituting measures for developmentally supportive care, and using
preemptively pharmacologic and nonpharmacologic analgesia. Despite the pervasiveness of procedural
distress in the NICU, clinical and administrative measures are available to ameliorate possible harmful
Keywords: pain; premature; infant; prematurity; neurodevelopment; developmental care; NICU;
INFAN TS BOR N PR EM ATURELY AR E FACED
with conditions that differ vastly from
those of the relative safety of the intrauterine
environment. Procedural distress (PD) has
been deﬁned previously in the pediatric pop-
ulation as the sum of anxiety and pain associ-
ated with invasive interventions surrounding
treatment.1 However, this deﬁnition does not
address several nuances related to PD in the
context of premature neonates in the NICU.
Specifically, premature infants experience
a profound neurodevelopmental mismatch
between the plasticity of a rapidly developing
nervous system and the variety of environ-
mental and physical stimuli they encounter
that are required for clinical management
and which can induce signiﬁcant and often
ongoing stress responses that affect the pre-
mature infant in multiple systems. Our aim
is to deﬁne PD in the NICU by highlighting
relevant issues that create the unique condi-
tions that apply to the care of these vulner-
able infants, particularly those born at the
earliest gestational ages.
WITH DISTRESS IN THE NICU
Each year worldwide, over 15 million
infants are born preterm.2 W ith advances
in health care, even those born at very early
stages of development (75 percent of infants
born at 25 weeks gestation, and .90 percent
born at 27–28 weeks gestation) survive.3
Because infants born extremely preterm
require lifesaving medical diagnostic and
therapeutic procedures, iatrogenic pain in
the NICU is commonplace. In fact, these
infants are exposed routinely to 5–15 painful
procedures per day (e.g., blood tests); cumu-
lative exposure can be as high as 300–400
procedures over an admission.4,5
Routine NICU procedures include inser-
tion and removal of various catheters, tra-
cheal intubation, nasal suctioning, punctures
for drawing blood, and so on. Fifty-ﬁve pro-
cedures have been identiﬁed as “common in
the NICU,” but this count is not exhaus-
tive.6 Cignacco and colleagues7 analyzed
Dening Procedural Distress in the
NICU and What Can Be Done About It
Martin Schiavenato, PhD, RN
Liisa Holsti, BSR, PhD, OT
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VOL. 36, NO. 1, JANUARY/FEBRUARY 2017 13
NEONATAL N ETWORK
broadly as being the unseen potential and/or actual damage
to the developing nervous system.
In other words, the dichotomy of skin-breaking versus non–
skin-breaking procedures as a determinant of “pain versus no
pain” is not valid with respect to the consequences they have
on the infant; rather, they are used in an attempt to deﬁne a
speciﬁc context that can be used for research purposes but
which may be less relevant for clinical management. Indeed,
procedures that may not be considered painful or even invasive
by the clinician may be noxious to the infant. For example,
a seemingly innocuous procedure, such as a diaper change,
induces physiologic and behavioral reactions characteristic of
a painful response19; furthermore, this response is greater in
premature infants than it is in term infants.20 These extended
and heightened responses may occur for several reasons, the
most important of which is that these infants’ central nervous
systems do not distinguish between pain and tactile stimuli
until 35 weeks gestational age.21 Thus, the complex physi-
ologic chain of biochemical and behavioral reactions that can
occur during even the most routine procedures should be
considered to have the potential to induce PD.
Furthermore, philosophically speaking, pain is in the eye
of the beholder. This means that the recognition of “pain” in
these infants who are unable to describe or self-report rests
entirely on its identiﬁcation or recognition by the clinician or
parent. That is, in premature infants, “distress” (the sum of
anxiety and pain) may be experienced by the patient whether
or not “pain” is observed by the clinician. This problem may
be exacerbated by the disconnect or inconsistency between
the occurrence of routine pain assessments in the NICU and
the incidence of PD.22
Therefore, we deﬁne PD in the NICU as iatrogenic stress
induced by care interventions that causes or potentially causes
seen or unseen damage, including altered neurodevelopment.
The PD and its adverse effects may occur whether or not
the procedure is considered invasive or viewed or assessed
as painful by the clinician. In these terms, PD is a frequent
and often silent source of or contributor to pathology for the
WHAT CAN BE DONE ABOUT
The disparity between ideal circumstances for neurodevel-
opment and the NICU environment is not entirely avoidable.
However, three important avenues are available whereby cli-
nicians can limit, reduce, or avoid PD that can and should be
implemented in the NICU.
1. Decrease or minimize the number of procedures. An
obvious step to reduce PD is a decrease in the number
of procedures or attempts at procedures.5 Mountcastle23
outlines several practical measures to engender a culture
of “minimal pain” in the NICU, including judicious
planning of procedures (i.e., eliminating those deemed
unnecessary whenever possible); using umbilical lines and
27 procedures in the NICU, with clinicians rating 70 percent
of them as painful, whereas Newnham and colleagues8
studied 44 acute procedures in the NICU and found clini-
cians ranked the vast majority as moderately, very, or severely
stressful to infants. The most common painful procedure in
the NICU is heelstick.5 In addition, given the evident rela-
tionship between severity of illness and the need for inter-
ventions, the number of invasive procedures is inversely
correlated with gestational age; that is, more procedures are
performed on infants born of earlier gestation.9 Notably, the
great majority of procedures are considered distressful or
painful by clinicians.
THE VULNERABLE PREMATURE NEONATE
Pain is but one source of stress to the infant whose
otherwise-normal intrauterine development differs signiﬁ-
cantly from life in the NICU. For example, environment-
derived stressors, such as instability in temperature and
humidity, disruption of sleep cycles, various forms of touch,
presence of light and noise, and so on, all have to be pro-
cessed by an infant with ill-equipped, immature sensory
systems.10 This bombardment of sensory input, both envi-
ronmental and procedural, can be damaging to the brain
when experienced during the last trimester of fetal develop-
ment because this period is characterized by rapid growth
and change which leaves the infant particularly vulnerable
to noxious stimuli. A noxious stimulus is one deﬁned as “a
stimulus that is damaging or threatens damage to normal
tiss ues .”11 Although the exact mechanisms by which the
pain experience impacts neurodevelopment in the premature
infant are not yet fully understood,12 a growing body of evi-
dence shows that the repetitive exposure to noxious stimuli
in prematurity is associated with altered brain growth, as well
as negative cognitive, motor, and emotional development.13
Structural brain abnormalities associated with skin-break-
ing procedures include a decrease in white and gray matter
growth as well as reductions of cortical thickness in multiple
regions.14,15 Additional long-term adverse effects of early
pain on health include altered sensitivity to pain, behavioral
problems, learning disorders, vision problems, lower IQ, and
depression, among others.16–18
DEFINING PROCEDURAL DISTRESS
Common terminology used to characterize PD includes
words such as stress, pain, or distress; thus, some clariﬁcation
is required. First, PD is iatrogenic in nature, meaning that it
originates from what we do for these infants in an attempt
to save and sustain their lives. Second, we deﬁne PD based
on the stimulus being noxious; that is, based on the inter-
vention’s actual or potential ability to cause tissue damage.
Tissue damage is not limited to that which is visible to the
clinician (e.g., skin-breaking procedures such as heelsticks
and IV starts), but more important, it is also deﬁned more
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14 JANUARY/FEBRUARY 2017, VOL. 36, NO. 1
NEONATAL N ETWORK
peripherally inserted central catheters to decrease the need
for peripheral punctures; using specialized formal train-
ing for nurses in the NICU (e.g., nurse residencies); and
evaluating the role of pediatric residents and other novices
in the treatment of NICU patients. Another strategy is
to minimize the number of errors or mishaps associated
with the phlebotomy process. Although we could not
ﬁnd published data on NICU-speciﬁc phlebotomy inci-
dents in blood collection that require additional invasive
blood draws (e.g., clotting of sample, lost samples, insuf-
ﬁcient blood), the issue has been recognized in a general
patient population, and it would be logical to assume that
an evaluation of current processes in the NICU, identiﬁ-
cation of potential sources of errors, and deliberate inter-
ventions to address them may result in a decrease in the
need for additional invasive blood draws.24
Furthermore, both the net number of procedures and
the type of procedure affect distress, with some proce-
dures potentially being less painful than others. For
example, all things being equal, venipuncture is thought
to be less painful than heelstick and a preferred method
for blood collection.25 Finally, the wider use and applica-
tion of new and up-and-coming microsensor platforms
that use minimal or no blood in laboratory diagnostics
should markedly reduce the need for blood volume and
blood collection in the NICU.26,27 Thus, opportunities
to reduce or minimize PD by addressing the process of
blood collection and the number and type of procedures
performed seem plentiful (see Sidebar); however, they
require a concerted effort to assess and address in current
2. Adopt developmental care practices. By developmental
care (DC), we mean a clinical milieu that acknowledges
the premature infant as a vulnerable human out of his
or her normal intrauterine developmental trajectory and
one that fosters and maximizes adaptation and success-
ful growth and development. As a concept, DC in the
NICU has been deﬁned further as promoting parental/
family involvement in the care of the infant beginning
immediately after birth and characterized by multidis-
ciplinary collaboration.28 Gibbins and colleagues,29 in
their universe of developmental care (UDC), highlight
the connection between the infant and the environment,
or more speciﬁc to us, the relationship between neuro-
development and PD through a shared boundary, that
is, the skin, which they deﬁne from a neurodevelopmen-
tal perspective as the surface of the brain. Importantly,
care providers cannot view the developing brain directly;
nevertheless, clinicians and families can and do interact
routinely within the context of this shared boundary.
Therefore, the cues or responses that are observed in
infants, coupled with the behaviors that we bring to these
interactions, have a potential for positive or negative con-
tribution to infant development.30,31 In other words, even
with the need to perform a painful or distressful proce-
dure, measures are available that caregivers can adopt to
enhance the outcome of the interaction. This group out-
lines the core measures for developmentally supportive
care according to the UDC model, and they speciﬁcally
address PD (see Sidebar).32
3. Use analgesia preemptively. DC advocates the use of
preemptive analgesia, but, because of its breadth and
importance, we choose to emphasize it separately here.
The last 10–15 years have seen an about-face in the
appreciation to the need for and importance of provid-
ing analgesia to the premature infant and a growth in
knowledge and options of the beneﬁts and effects of avail-
able interventions. However, questions remain as to the
consistency with which these interventions are applied,
Measures to Decrease or Minimize
the Number of Distress-Inducing
Procedures in the NICU
• Judiciouslypla nprocedures; elimin ateproceduresif possible.
• Whenava ilable,useopt ionsthata relesspa inful than
heelsticks (e.g., peripheral lines, umbilical catheters).
• Increase clinicia nexpert isewith procedures,reduce
procedures by novices, and use formal specialized training.
• Asse sscurrent laboratorypract icesandinter venetoreduce
occurrence of mishaps that require additional blood draws
(e.g., clotting of sample, lost samples, insufficient blood).
• Considera ndapplytechnologica lsolutionst hatmightus e
minimal or no blood in laboratory diagnostics.
Developmentally Supportive Measures
for Procedural Distress in the NICU
• Takeamult idisciplina ryapproacha ndinvolve/con sulta
broad range of clinicians as needed.
• Asse ssinfa ntsforpai nordist ressduri ngallpro ceduresand
• Useava lid,stand ardizedpa inasse ssmenttoolanddoc ument
a pain score.
• Involveand informpa rentsofthepa in/distress management
plan of care for their infant(s).
• Encouragepa rents/familyto providecomfortto theinf ant.
Adapted from Coughlin, Gibbins, and Hoath.32
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VOL. 36, NO. 1, JANUARY/FEBRUARY 2017 15
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TABLE 2 n Survey of Pharmacologic Approaches to Minimize Procedural Distress in the NICU
Drug Comments Referencesa
Local and topical anesthetics Lidocaine infiltration is commonly used to relieve pain from
Eutectic mixture of local anesthetic (EMLA) cream is used for
procedures such as venipuncture and lumbar puncture;
however, it is not effective for heelsticks.
Committee on Fetus and Newborn and Section
on Anesthesiology and Pain Medicine.37
Hall and Anand.41
Opioids Morphine is commonly used as a continuous infusion in
postoperative or ventilated infants or intermittently for
acute pain/invasive procedures. Morphine side effects are
significant, and its effectiveness, benefits, and long-term effects
on neurodevelopment are controversial and remain under
Fentanyl is 50 –100 times more potent than morphine; it is not
recommended for routine use in mechanically ventilated
infants. Remifentanil, a short-acting fentanyl derivative, may be
an alternative for short-term procedures, but further studies are
needed to examine its long-term effects.
Benzodiazepines These are anxiolytics that provide sedation and muscle relaxation,
but it is impor tant to keep in mind that they have little or no
analgesic effects; they include midazolam and lorazepam.
Alternative medications Other agents such as propofol, ketamine, and dexmedetomidine
have been proposed; however, they should be used with
caution because of the lack of studies establishing their safety,
efficacy, and dosing.
Acetaminophen in oral, rectal, and intravenous formulations
has been used in preterm, it may help decrease the need for
morphine. However, more data are needed to establish safety,
efficacy, and dosing.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are potentially
useful to treat preterm procedural distress; however, these
drugs are generally used in closure of patent ductus ar teriosus,
and little data exist on their analgesic effects.
aConsult a current NICU drug guide for proper dosage, side effects, and other important considerations.
and signiﬁcant concerns remain regarding the long-term
effects of some.33 –36 Analgesic interventions can be classi-
ﬁed as pharmacologic and nonpharmacologic. Table 1 lists
a survey of several tools or approaches available to allevi-
ate or prevent PD that are not drug based. In general,
much has been published about the use, effectiveness,
and other clinical factors associated with these inter-
ventions which are outside the scope of this work; see
“References” column in Table 1. Similarly, Table 2 lists a
survey of common pharmacologic interventions, and the
reader is urged to consult the “References” section for
clinical details and speciﬁc application.
TABLE 1 n Survey of Nonpharmacologic Approaches to Minimize Procedural Distress in the NICU
Intervention Comments References
Sweet solutions Recent AAP guidelines recommend further study is
needed on dose and on long-term effect s of sweet
solutions administered repeatedly.
Committee on Fetus and Newborn and Section on
Anesthesiology and Pain Medicine.37
Stevens and colleagues.38
Johnston and colleagues.39
Pillai Riddell and colleagues.40
Nonnutritive sucking For preterm infants, nonnutritive sucking is usually
combined with other nonpharmacologic treatments
for additive effects.
Facilitated tucking Facilitated tucking is a holding strategy whereby a
nurse or other caregiver provides gentle but firm
containment of an infant’s limbs before, during, and
after a painful procedure. Facilitated tucking along
with a soother is the strategy used in many NICUs
Skin-to-skin holding/rocking Skin-to-skin holding or kangaroo care is a method
whereby a parent holds an infant on his or her chest
with direct skin-to-skin contact.
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The care of the premature infant often requires lifesaving
and life-sustaining interventions. Paradoxically, these proce-
dures carry a negative toll in this burgeoning and vulnerable
critical period of infant neurodevelopment. We deﬁne PD
in the NICU as care interventions that cause or potentially
cause physiologic damage (obvious or not) with short- and/
or long-term consequences, including altered neurodevelop-
ment and its associated sequelae. Procedural distress may or
may not be construed or assessed as “pain” by the clinician;
instead, PD is deﬁned by the noxious effect of the stimulus
or procedure on the infant. As such, PD is pervasive, and
mounting evidence points to it as a signiﬁcant contributor
to the negative outcomes of prematurity. However, clinicians
can intervene and mitigate the effects of PD. Options for
this include the preemptive use of analgesia through phar-
macologic or nonpharmacologic means, the focused delivery
of DC interventions to promote adaptation to the extrauter-
ine environment and effective growth and development, and
deliberate administrative and clinical efforts to decrease the
number of procedures needed. Procedures in the NICU are a
necessity; however, their noxious effects can be minimized or
eliminated with a combination of considered and purposeful
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About the Authors
Martin Schiavenato, PhD, RN, is a former NICU nurse and a
pediatric pain researcher. His research interests are at the intersection of
technology and the care of vulnerable infants. He is an associate profes-
sor at the College of Nursing, Washington State University.
Liisa Holsti, BSR, PhD, OT, worked clinically in the NICU and
in the Neonatal Follow-up Program as an occupational therapist for
almost 20 years. She now holds a Canada Research Chair in Neonatal
Health and Development and is an associate professor in Occupational
Science and Occupational Therapy at UBC and a scientist at the Child
and Family Research Institute. Her program of research focuses on
developing novel ways to support optimal development in these extremely
For further information, please contact:
Martin Schiavenato, PhD, RN
WSU College of Nursing
P.O. Box 1495
Spokane, WA 99210
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