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Consensus Statement for the Prevention and Management of Pain in the Newborn
K. J. S. Anand, MBBS, DPhil;
and the International Evidence-Based Group for Neonatal Pain
Arch Pediatr Adolesc Med. 2001;155:173-180.
ABSTRACT
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Objective To develop evidence-based guidelines for preventing or treating neonatal
pain and its adverse consequences. Compared with older children and adults,
neonates are more sensitive to pain and vulnerable to its long-term effects.
Despite the clinical importance of neonatal pain, current medical practices
continue to expose infants to repetitive, acute, or prolonged pain.
Design Experts representing several different countries, professional disciplines,
and practice settings used systematic reviews, data synthesis, and open discussion
to develop a consensus on clinical practices that were supported by published
evidence or were commonly used, the latter based on extrapolation of evidence
from older age groups. A practical format was used to describe the analgesic
management for specific invasive procedures and for ongoing pain in neonates.
Results Recognition of the sources of pain and routine assessments of neonatal
pain should dictate the avoidance of recurrent painful stimuli and the use
of specific environmental, behavioral, and pharmacological interventions.
Individualized care plans and analgesic protocols for specific clinical situations,
patients, and health care settings can be developed from these guidelines.
By clearly outlining areas where evidence is not available, these guidelines
may also stimulate further research. To use the recommended therapeutic approaches,
clinicians must be familiar with their adverse effects and the potential for
drug interactions.
Conclusion Management of pain must be considered an important component of the
health care provided to all neonates, regardless of their gestational age
or severity of illness.
INTRODUCTION
NEWBORNS routinely experience pain associated with invasive procedures
such as blood sampling, immunization, vitamin K injection, or circumcision.
The sick or preterm infant may experience repetitive or prolonged pain resulting
from many diagnostic, surgical, or therapeutic procedures.1, 2, 3, 4
Multiple lines of evidence suggest an increased sensitivity to pain
in neonates compared with older age groups.5, 6
This pain sensitivity is further accentuated in preterm neonates, and may
not be clinically evident.5, 6, 7, 8
Critically ill and preterm neonates do not mount vigorous behavioral responses
to pain, and therefore require particularly detailed assessment.6, 7, 8
The pain modulation systems that operate in older children and adults do not
appear to be fully functional in newborns9, 10, 11
or may function only during maternal contact in healthy newborns.12 Even the most immature preterm neonates mount increasing
responses to the pain caused by mild, moderate, or highly invasive procedures,
and the magnitude of their responses increase with postnatal age.6, 7, 13 Compared with older
children, neonates exhibit greater hormonal, metabolic, and cardiovascular
responses to surgical operations, and may require relatively higher doses
of anesthetics and analgesics for adequate pain control.5, 14, 15, 16, 17
The metabolism and clearance rates of most analgesic agents in preterm neonates
are slower than in term neonates, but increase rapidly with age.18, 19
Management of pain in the newborn is hampered by the lack of awareness
among health care professionals that the neonate is capable of experiencing
pain, and by fears about the adverse effects associated with analgesic use.
Current evidence supports the general principles listed in Table 1 for the routine management of neonates using safe and effective
environmental, behavioral, and pharmacological interventions for relieving
pain and for preventing its adverse consequences.20
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Table 1. General Principles for the Prevention and Management of Pain
in Newborns
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METHODS
These guidelines were developed from 2 consensus development meetings
(in April 1998 and August 1999). A detailed search of the published literature
on neonatal pain was conducted to identify the experts who were invited to
these meetings. Databases searched were MEDLINE, Embase, and PubMed using
the following terms: pain, nociception, stress, infant-newborn, and infant-premature. Faculty members were
selected by the chairman (K.J.S.A.) based on their expertise in specific topics
related to neonatal pain, coupled with a concerted effort to include professionals
trained in different disciplines and representing different countries and
distinct practice settings (eg, children's hospitals, general hospitals, office
practices). The disciplines represented were pediatrics, neonatology, child
psychology, anesthesiology, neuroscience, endocrinology, neonatal nursing,
pharmacy/pharmacology, rehabilitation medicine, critical care medicine, rheumatology/immunology,
and others. At the time of these meetings, faculty members were affiliated
to academic institutions in Australia, Brazil, Canada, Denmark, France, Germany,
Israel, Italy, Poland, Sweden, Switzerland, the Netherlands, United Kingdom,
and the United States.
Faculty members performed a systematic review of the published literature
on their specific topic, critically evaluated the quality of published data,
and synthesized these findings. Data from all relevant studies were presented
at these meetings and were discussed by the experts present. Other faculty
members were encouraged to present additional data and ample time was allowed
for detailed discussion. Guidelines were developed after reaching a consensus
on the clinical practices that were prevalent in most countries. As such,
these guidelines were based on a combination of published evidence (from randomized
controlled trials, systematic reviews, or meta-analyses of trials) and its
critical evaluation by the faculty members. Between September 1999 and April
2000, 3 separate draft versions of this statement were circulated and modified
by all members of the participating faculty. Approval of all faculty members
was obtained for the final version of the consensus statement, which is organized
around broad general principles (Table 1) and evidence-based guidelines for neonatal pain management. The
pharmacological interventions recommended in these guidelines are not the
exclusive products of the pharmaceutical company that funded these meetings,
and the representatives of this company have had no input in the format or
content of these guidelines.
RESULTS
EVIDENCE-BASED GUIDELINES FOR THE MANAGEMENT OF NEONATAL PAIN
Recognition of the Sources of Pain
Some of the painful procedures commonly performed on neonates in the
neonatal intensive care unit (NICU) include heel lancing, venipuncture, venous
or arterial catheter insertion, chest tube placement, tracheal intubation
or suctioning, lumbar puncture, and subcutaneous or intramuscular injections
(see Table 2 for additional procedures).1, 2, 3, 4 Other
sources of pain may include areas of inflammation and hyperalgesia around
previous tissue injury, postoperative pain, localized infection or inflammation,
and skin burns or abrasions caused by transcutaneous probes, monitoring leads,
or topical agents.
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Table 2. Painful Procedures Commonly Performed in the Neonatal Intensive
Care Unit
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Assessment of Pain
- Concomitantly with the vital signs, assessment of neonatal pain
must be undertaken and documented every 4 to 6 hours or as indicated by the
pain scores or clinical condition of the neonate.21, 22, 23, 24
- Standardized pain assessment methods with evidence of validity,
reliability, and clinical utility should be used25, 26, 27, 28, 29, 30, 31, 32
(Table 3).
- Pain assessment instruments should be sensitive and specific for
infants of different gestational ages and/or with acute, recurrent, or continuous
pain.13, 32, 33 Examples
of ongoing, continuous pain may include postoperative pain or inflammatory
conditions.1, 3, 33
- Pain assessment should be comprehensive and multidimensional,
including contextual, behavioral, and physiological indicators.8, 13, 21, 22, 23
- Pain assessment must be performed after each potentially painful
clinical intervention and to evaluate the efficacy of behavioral, environmental,
and pharmacological agents.21, 23, 33, 34
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Table 3. Commonly Used Methods for Assessment of Pain in Newborns
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Management of Pain in the Newborn
- Strategies for prevention, particularly by avoiding recurrent
painful stimuli.20, 33
- Use of environmental interventions to reduce stress in the NICU.33, 35, 36
- Behavioral methods, including sucrose and nonnutritive sucking.12, 20, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56
- Pharmacological agents for preemptive analgesia20, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76
(Table 4).
- Pharmacological therapy for ongoing pain17, 19, 34, 58, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80
(Table 4).
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Table 4. Recommended Analgesic Doses for Neonates*
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SUGGESTED MANAGEMENT APPROACHES FOR NEONATAL PAIN
In the following sections, an asterisk indicates that evidence from
studies in neonates is available to support the proposed intervention. The
combined use of multiple interventions may have additive or synergistic clinical
effects.
Heel Lance
- Consider use of venipuncture instead of heel lance in full-term
neonates and more mature preterm neonates* (because it is less painful, more
efficient and requires less resampling).62, 81, 82, 83, 84, 85, 86, 87
This approach may not apply to the care of extremely preterm infants.
- Use a pacifier* with sucrose* (concentration 12%-24%) given 2
minutes before the procedure.39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 51, 52, 53, 54, 55
- Use swaddling, containment,* or facilitated tucking.37, 38
- Consider skin-to-skin contact with the mother.*12
- Use a mechanical spring-loaded lance, eg, Autolance.*62, 85, 86
EMLA (a eutectic mixture of local anesthetics: lidocaine and prilocaine
hydrochloride in an emulsion base), acetaminophen, and warming the heel are
ineffective for heel lancing*; squeezing for blood collection is the most
painful part of the procedure.70, 81, 82, 83, 84, 85, 87
Percutaneous Venous Catheter Insertion
- Use a pacifier* with sucrose.*39, 41, 70, 81, 82, 83, 84
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA* to the proposed site (when nonurgent).60, 82, 88, 89
- Consider opioid dose(s),* if intravenous access is available.58, 73
- Consider a similar approach for venipuncture.88, 89
Percutaneous Arterial Catheter Insertion
- Use a pacifier* with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA to the proposed site.60, 70
- Consider subcutaneous infiltration of lidocaine.58, 70
- Consider a similar approach for arterial puncture.
Peripheral Arterial or Venous Cutdown
- Use a pacifier with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA to the proposed site.58, 60, 70
- Consider subcutaneous infiltration of lidocaine; avoid intravascular
injection.58, 70
- Consider opioid dose(s), if intravenous access is available.15, 58, 76
Central Venous Line Placement
- Use a pacifier* with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA to the proposed site, if nonurgent.60, 90
- Consider subcutaneous infiltration of lidocaine.58, 70
- Consider slow intravenous opioid infusion (morphine sulfate* or
fentanyl citrate*).73, 76
- Consider using general anesthesia for the procedure.15, 70, 76, 91
Umbilical Catheter Insertion (Umbilical Arterial/Umbilical Venous)
- Consider the use of a pacifier with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Avoid the placement of sutures or hemostat clamps on the skin
around the umbilicus.
Peripherally Inserted Central Catheter Placement
- Use a pacifier with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA* to the proposed site (when nonurgent).58, 60, 90
- Consider opioid dose(s), if intravenous access is available.58, 76, 91
Lumbar Puncture
- Use a pacifier* with sucrose.39, 41
- Apply EMLA to the proposed site.60
- Consider subcutaneous infiltration of lidocaine.58, 70
- Because containment is not possible, careful physical handling
is advised.
Subcutaneous or Intramuscular Injection
- Avoid subcutaneous and intramuscular injections; give drugs intravenously
whenever possible.
If necessary:
- Use a pacifier with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Apply EMLA to the proposed site (evidence for this approach is
available from studies in children, but not from studies in neonates).92, 93, 94
Endotracheal Intubation
Many variations in clinical approach have been noted; the superior efficacy
of any one technique is not supported by current evidence33, 58, 70, 95, 96, 97:
- Use combination of atropine sulfate and ketamine hydrochloride*95
- Use combination of atropine, thiopental sodium,* and succinylcholine
chloride.97
- Use combination of atropine, morphine, or fentanyl, and nondepolarizing
muscle relaxant (pancuronium, vercuronium, rorcuronium).15, 58
- Consider using a topical lidocaine spray, if available.98, 99
- Other drug combinations are frequently used.58, 70
Tracheal intubation without the use of analgesia or sedation should
be performed only for resuscitation in the delivery room or for other life-threatening
situations associated with the unavailability of intravenous access.95, 96, 97
Endotracheal Suction
This is considered a stressful procedure and may be associated with
the same physiological responses that accompany other painful procedures71, 100, 101, 102, 103, 104:
- Use a pacifier; may consider giving sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Consider continuous intravenous infusion of opioids (morphine*)71 or slow injection of intermittent opioid doses (fentanyl,*
meperidine,* or alfentanil*).100, 101, 102, 103, 104
Nasogastric or Orogastric Tube Insertion
- Use a pacifier with sucrose.39, 41
- Use swaddling, containment, or facilitated tucking.37, 38
- Use a gentle technique and appropriate lubrication.105
Chest Tube Insertion
- Anticipate the need for intubation and ventilation in neonates
breathing spontaneously.58
- Use a pacifier with sucrose.39, 41
- Consider subcutaneous infiltration of lidocaine.58, 70
- Consider slow intravenous opioid infusion (morphine or fentanyl;
see Table 4 for dosages).15, 58
- Other approaches may include the use of short-acting anesthetic
agents.15, 58, 76
The use of intravenous midazolam is not recommended.106, 107
Circumcision
If deemed necessary108, 109:
- Use an appropriate clamp (Mogen clamp preferred over Gomco*).110, 111
- Apply EMLA* to the proposed site.57, 60, 111
- Place a dorsal penile nerve block,*64, 111, 112
ring block,*65, 66 or caudal block,67, 68, 113, 114, 115, 116
using plain or buffered lidocaine.*117, 118, 119
- Use a pacifier* with sucrose.*39, 41, 56, 111, 118
- Consider acetaminophen for postoperative pain.*69
Analgesics can be combined for maximum efficacy,67, 110, 111, 118
although the addition of sodium bicarbonate to lidocaine does not alter the
neonatal responses to lidocaine injection.117, 118, 119
Ongoing Analgesia for Routine NICU Care and Procedures
- Use swaddling, containment, or facilitated tucking.37, 38
- Use a pacifier; may consider giving sucrose.39, 41
- Low-dose continuous infusion of morphine* or fentanyl* if patient
is ventilated.71, 72, 73, 74, 75
There is no evidence to show that neonates can be safely sedated for
several weeks or months20, 71, 72, 74, 75
and the use of midazolam is not recommended.71, 106, 107
- Consider acetaminophen therapy.
The efficacy and safety
of repeated acetaminophen doses is unknown, rectal absorption is variable,
and intravenous propacetamol is not available in the United States.77, 78, 79, 80, 87
- Reduce acoustic, thermal, and other environmental stresses.33, 35, 36
COMMENT
Recognition of the clinical importance of neonatal pain and stress has
been delayed5, 20 by outdated professional
attitudes (that newborns are less sensitive to pain),120, 121, 122, 123, 124, 125, 126
lack of education,127, 128 need
for accurate assessment methods, and lack of evidence for the safety and efficacy
of management approaches that can be applied to the routine care of neonates.
This is a preliminary attempt to present the available evidence so that it
may be useful to the clinicians at the bedside. We hope to stimulate further
research by clearly outlining the areas where current evidence is not available
for defining the efficacy of specific therapeutic approaches. Although these
management approaches are mainly applicable for established NICUs that provide
advanced medical and nursing care for critically ill neonates, they can be
adapted for management of neonatal pain in other clinical settings or geographical
locations.
Adverse effects that may result from these therapies are listed in Table 5,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158
and all clinicians using these guidelines must be familiar with the safe use
of analgesic agents in healthy or critically ill, term and preterm neonates.
Professionals working with neonates are expected to be knowledgeable about
the current assessment and management approaches through participation in
ongoing pain education, interaction with pain experts, attention to the most
recent research evidence, and adherence to professional standards and clinical
guidelines.159 We strongly support the initiative
taken by national professional organizations for the prevention and management
of neonatal pain20, 108, 109
and for the development of standards for health care professionals and institutions.
This consensus statement provides evidence-based protocols for developing
neonatal pain management guidelines that can be uniquely designed for various
clinical situations and diverse practice settings. Adherence to such guidelines
will not only improve the clinical care provided to all neonates, but may
also have a positive impact on their subsequent health and behaviors during
childhood and adolescence.160
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Table 5. Adverse Effects of Analgesic Agents in Neonates
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AUTHOR INFORMATION
Accepted for publication October 16, 2000.
These efforts were supported by an unrestricted educational grant from
Astra Pharmaceuticals (now AstraZeneca Inc, London, England) and were developed
at 2 meetings of the International Evidence-Based Group for Neonatal Pain
(Nice, France, April 21-23, 1998, and Baden, Austria, August 20-22, 1999).
The group gratefully acknowledges Jonas Nylander, Nadia Hammouda (AstraZeneca,
Inc), Brian Parsons, Anna Welsh (Colwood Healthworld, London, England), Sarah
Knott, and Daphne Steptoe (Wells Medical, Royal Tunbridge Wells, Kent, England)
for helping in the development of these guidelines.
Participants (listed alphabetically) of the International Evidence-Based
Group for Neonatal Pain are the following: Huda Huijer Abu-Saad, Maastricht,
the Netherlands; K. J. S. Anand, Little Rock, Ark (chair); Albert Aynsley-Green,
London, England; Eduardo Bancalari, Miami, Fla; Franca Benini, Padova, Italy;
G. David Champion, Darlinghurst, Australia; Kenneth D. Craig, Vancouver, British
Columbia; Tomasz S. Dangel, Warszawa, Poland; Elisabeth Fournier-Charrière,
Kremlin-Bicetre, France; Linda S. Franck, London, England; Ruth Eckstein Grunau,
Vancouver, British Columbia; Steen A. Hertel, Copenhagen, Denmark; Evelyne
Jacqz-Aigrain, Paris, France; Gerhard Jorch, Magdeburg, Germany; Benjamin
I. Kopelman, São Paulo, Brazil; Gideon Koren, Toronto, Ontario; Björn
Larsson, Stockholm, Sweden; Neil Marlow, Nottingham, England; Neil McIntosh,
Edinburgh, Scotland; Arne Ohlsson, Toronto, Ontario; Gunnar Olsson, Stockholm,
Sweden; Fran Porter, St Louis, Mo; Renate Richter, Erlangen, Germany; Bonnie
Stevens, Toronto, Ontario; and Anna Taddio, Toronto, Ontario.
Corresponding author and reprints: K. J. S. Anand, MD, Arkansas Children's
Hospital, S-431, 800 Marshall St, Little Rock, AR 72202 (e-mail: anandsunny{at}exchange.uams.edu).
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