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1
Analgesia and Iatrogenic Weaning –
Pediatric/Neonatal–
Inpatient/Ambulatory
Clinical Practice Guideline
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 3
METHODOLOGY ...................................................................................................................... 4
INTRODUCTION ....................................................................................................................... 4
RECOMMENDATIONS .............................................................................................................. 5
GENERAL RECOMMENDATIONS ........................................................................................... 5
IATROGENIC WEANING: OPIOIDS ........................................................................................ 8
FIGURE 1. NICU MANAGEMENT OF OPIOID TAPER ............................................................13
FIGURE 2. PICU MANAGEMENT OF OPIOID TAPER ............................................................14
IATROGENIC WEANING: BENZODIAZEPINES .....................................................................17
FIGURE 3. MANAGEMENT OF A BENZODIAZEPINE TAPER ..............................................18
UW HEALTH IMPLEMENTATION ............................................................................................20
APPENDIX A. ANALGESIC MEDICATIONS...........................................................................21
APPENDIX C. EVIDENCE GRADING SCHEME .....................................................................26
REFERENCES .........................................................................................................................27
CPG Contact for Changes: CPG Contact for Content:
Name: Philip Trapskin, PharmD, BCPS Name: Joshua Vanderloo, PharmD, BCPS
Phone Number: 608-263-1328 Phone Number: 608-890-5931
Email Address: ptrapskin@uwhealth.org Email Address: jvanderloo@uwhealth.org
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2
Guideline Update Authors:
Joshua Vanderloo, PharmD, BCPS; M. Bogenschutz, PharmD, BCPPS; B. Walker, MD
Coordinating Team Members:
Joshua Vanderloo, PharmD, BCPS
Review Individuals/Bodies:
J. Limjoco, MD; B. Walker, MD; M. Wilhelm, MD
J. Bender, PharmD, BCPPS; M. Bogenschutz, PharmD, BCPPS, BCPS; Hanna Christensen, PharmD; A.
Crawford, PharmD, BCPPS
P. Riley, RN, MN, MPH; L. Konkol, RN, MSN; D. Soetenga, RN
Committee Approvals/Dates:
Pharmacy & Therapeutics Committee (09/21/2017)
Release Date: October 2017
Next Review Date: September 2019
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3
Executive Summary
Guideline Overview
This guideline is intended to provide recommendations for the assessment, prevention, and treatment of
pain in neonates, infants, and pediatric patients as well as recommendations for evaluating the need for
iatrogenic weaning and managing iatrogenic weaning.
Key Recommendations (2017 Periodic Review)
1. Addition of iatrogenic weaning evaluation and management for opioids and benzodiazepines.
2. Expansion of analgesic recommendations to include older infants and children.
Key Practice Recommendations
1. General recommendations
• Pain assessment
• Pharmacologic and non-pharmacologic pain therapies
• Pharmacologic therapy for agitation and sedation
2. Iatrogenic weaning of opioids
3. Iatrogenic weaning of benzodiazepines
Companion Documents
• Quick References, Pain Fast Facts and Guidelines
• Pain Care Fast Facts: Sucrose Analgesia for Infants
• Neonatal/Infant Pain Scale (NIPS)
• Neonatal Pain, Agitation and Sedation Scale (N-PASS)
• Withdrawal Assessment Tool (WAT-1)
• Intravenous Administration of Formulary Medications – Pediatric/Neonatal – Inpatient/Ambulatory
Clinical Practice Guideline
Scope
Disease/Conditions: Treatment and prevention of pain in neonates, infants, and children; iatrogenic
weaning of opiates and/or benzodiazepines in neonates, infants, and children.
Clinical Specialty: Pediatrics and neonatology
Intended Users: Physicians, advanced practice providers, pharmacists, nurses
Objective: This clinical practice guideline is intended to provide information for the prevention and
management of pain in neonates, infants, and children through a step-wise approach and guidance for
discontinuing opioids or anxiolytics. In addition, the guideline encourages a standardized approach to
weaning opioids and benzodiazepines in children experiencing iatrogenic withdrawal.
Target Population: Inpatient and ambulatory neonates or infants at risk for or currently experiencing
pain. Inpatient and outpatient pediatric patients receiving scheduled or continuous medications for pain
or sedation that have the potential to cause iatrogenic withdrawal syndrome (opioids or benzodiazepines).
This guideline does not address management of patients experiencing Neonatal Abstinence Syndrome
(NAS). Management of NAS patients is addressed in other guidelines.
Interventions and Practices Considered:
The clinical interventions and practices recommended in this guideline are for the assessment, prevention
and management of pain in neonates, infants and children. Neonates, infants and children should be
assessed using an age-appropriate pain scale. Numerous pharmacologic and non-pharmacologic options
are available for treatment and prevention of pain. Indication for the various modalities depends on the
cause, duration and severity of pain.
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Major Outcomes Considered:
The major outcomes considered for this guideline include the assessment, prevention and management
of pediatric pain that is most appropriate based on age, developmental stage, cause, duration and
severity of pain as well as prevention and management of withdrawal from opioids and anxiolytics.
Guideline Metrics:
• Use of non-drug therapies
• Compliance with pain assessment and reassessment
• Occurrence of withdrawal
Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (i.e. PUBMED) were conducted and workgroup members queried to collect
evidence for review; for the 2017 revision, clinical evidence dating back to publication of the previous
revision was reviewed. Major external guidelines were reviewed for new clinical information. Additionally,
hand searches were performed within selected evidence for other relevant resources. Expert opinion,
clinical experience, and regard for patient safety/experience were also considered during discussions of
the evidence.
Methods Used to Formulate the Recommendations:
The workgroup members arrived at a consensus through discussion of the literature and expert
experience. All recommendations endorsed or developed by the guideline workgroup were reviewed and
approved by other stakeholders.
Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations, or those adopted from external sources without an assigned
evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading
of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1 in
Appendix D).
Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix D for the rating schemes used within this document.
Recognition of Potential Health Care Disparities: No disparities were identified.
Introduction
The prevention and treatment of pain in children is an ethical expectation.
1
Neonates, defined as newborn
infants in their first month of life, experience a greater sensitivity to pain compared to older age groups,
requiring more attention to discomfort and stress; however, pain is often undertreated in neonates.
2,3

Premature infants, the smallest and often the sickest, are at the greatest risk for neurodevelopmental
impairment since they are most likely to be exposed to the greatest number of painful stimuli.
4
It is
theorized that the central nervous system does not fully mature for several weeks after birth, preventing
neuromodulation of the pain signal in neonates.
5
Multimodal therapy can help reduce pain during minor
and major procedures.
Untreated pain is stressful to neonates and can have detrimental effects during the critical period of brain
development, and untreated pain at any age can result in the development of chronic pain later in life.
6

Unfortunately, the effects of analgesia with or without surgery can have detrimental effects on the
developing brain of neonates; therefore, its use must be monitored and used in appropriate situations.
7
Pain is subjective, and assessment in preverbal and nonverbal children can be challenging, so
management is often based off an assumption that they are experiencing pain; therefore, pain
assessment, intervention and reassessment is based on their condition or cause of pain, but performed
minimally every 8 hours. Pain assessment is based on the UW Health Clinical Policy #3.5.5. Physiological
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5
changes such as increases in blood pressure, heart rate, or respiration are non-specific to pain but may
be useful in evaluation of neonate pain.
6,8
Additional behavioral changes that may occur when a
nonverbal infant or child is in pain may include facial expressions, body movements and crying.
1

However, a lack of physiologic or behavioral responses, including crying and movement, does not
necessarily indicate a lack of pain.
9
With prolonged pain, neonates enter a state of energy conservation
with decreased heart and respiratory rate, expressionless face, limited movements and decreased
oxygen consumption. Being in this prolonged state of pain can also heighten future responses to pain.
1
Therefore, pain assessment should be multidimensional, including behavioral cues, physiological
indicators, and contextual to fully evaluate the pain.
2
Pain should be assessed as frequently as other vital
signs.
9

Neonatal body composition and pharmacokinetics differ appreciably from adults and age-dependent dose
adjustments are required. The pharmacokinetics of neonates and young infants are altered due to lower
body fat and higher body water content, which result in lower plasma drug concentrations.
10
In addition,
the immature blood-brain barrier in infants can result in enhanced effects of lipophilic analgesics.
Neonates and small infants have impaired responses to hypoxia and hypercarbia in comparison to older
children, making them more susceptible to respiratory depression from opioids. Drug clearance is also
altered in neonates and infants younger than 6 months old because hepatic and renal functions are not
fully mature. In general, preterm neonates require lower doses and/or longer dosing intervals than full
term neonates to maintain similar therapeutic concentrations since the metabolic function is immature.
6

Oral and intramuscular absorption rates are decreased due to a decrease in gastric emptying, intestinal
motility and muscular blood flow; therefore, time to reach maximum plasma levels is increased. On the
other hand, percutaneous absorption is increased due to the thinner stratum corneum. Neonates also
have a lower amount of plasma proteins resulting in increased free fraction of drug. Each neonate
matures at his/her individual rate; therefore, absorption, distribution, metabolism, and excretion changes
are variable since growth is not a linear process in the first decade of life.
10

Drug withdrawal is a risk for pediatric patients receiving frequent dosing or continuous infusions of
medications, including opioids and/or benzodiazepines, to provide analgesia, sedation, amnesia, and
anxiolysis. Unfortunately, with continuation of these medications beyond a few days physical
dependence may occur and withdrawal may manifest with discontinuation of these medications.
11-13

Neonates and small infants develop tolerance to opioids more rapidly than older children.
12
The American
Academy of Pediatrics recommends developing standardized institutional-level approaches for prevention
and treatment of iatrogenic withdrawal; national standards are not available as there is not clinical
evidence available at this time to develop national standards.
11
Numerous studies have described
differing medications (e.g. morphine or methadone) and differing taper protocols for management of these
patients.
14-16
Methadone has been utilized frequently for the management of iatrogenic medication
weaning and has been shown to decrease opioid exposure although an optimized regimen has not been
described.
17,18
Similarly, additional clinical data are required to better standardize benzodiazepine
withdrawal management given broad practice variation.
19

Recommendations
General recommendations
Pain Assessment
1. The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) is used to assess pain in patient in the
NICU. Neonatal/Infant Pain Scale (NIPS) should be used to assess pain in children younger than 1
year of age outside of the NICU.
20,21
(UW Health Strong Recommendation, Moderate Quality of
Evidence)
2. The Neonatal Pain, Agitation and Sedation Scale (N-PASS) or State Behavioral Scale (SBS) should
be used in patients who are receiving sedative medications in addition to analgesics.
22-24
(UW Health
Strong Recommendation, Moderate Quality of Evidence)
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3. The Face Legs Agitation Cry Consolability (FLACC) Scale is an observational tool and should be
used in normally developing children aged 1-4 years. The FLACC-Revised is appropriate for use in
cognitively-impaired children aged 1 year to adult.
25,26

4. The Faces Pain Scale – Revised (FPS-R) is a self-report tool and should be used for children who
can express their pain pictorially, which is typically 4-8 years old.
27

5. The Numeric Rating Scale (NRS) is also known as the “0-10 scale” with 0 = no pain and 10 = worst
pain possible ro the Mild-Moderate-Severe pain scale. They are appropriate for children aged 7 years
and older.
28

6. Pain assessment using one of the above scales should be documented regularly based on clinical
condition of the patient, at a minimum of every 8 hours.
9
(UW Health Strong Recommendation, Low
Quality of Evidence)

Non-pharmacological therapies
1. Environmental, behavioral and non-pharmacological therapies are recommended during all painful
procedures
1,2,29
(UW Health Strong Recommendation, Moderate Quality of Evidence)
2. Examples include:
2.1. Neonates and infants younger than 6 months old:
2.1.1. “Kangaroo Care” in which the mother or father have skin-to-skin contact with neonate
29

(UW Health Strong Recommendation, Low Quality of Evidence)
2.1.2. Cradling in the parents’ arms
29
(UW Health Strong Recommendation, Very Low Quality
of Evidence)
2.1.3. Swaddling (wrap in blanket) or facilitated tucking (arms and legs in tucked position)
2,29

(UW Health Strong Recommendation, Low Quality of Evidence)
2.1.4. Developmental care: lateral positioning, limiting environmental stimuli, using supportive
bedding, paying attention to behavioral clues
1
(UW Health Strong Recommendation,
Very Low Quality of Evidence)
2.1.5. Providing familiar odors such as maternal milk
30
(UW Health Strong Recommendation,
Low Quality of Evidence)
2.1.6. Playing instrumental music or intrauterine sounds along with non-nutritive sucking
29

(UW Health Strong Recommendation, Very Low Quality of Evidence)
2.1.7. Controlling or reducing light and noise
29
(UW Health Strong Recommendation, Very
Low Quality of Evidence)
2.1.8. Planning procedures around sleep cycles with quiet wakefulness before starting the
procedure
29
(UW Health Strong Recommendation, Very Low Quality of Evidence)
2.1.9. Planning procedures apart from mealtimes and allowing time for recovery between
other procedures
29
(UW Health Strong Recommendation, Very Low Quality of
Evidence)
2.1.10. Breastfeeding two minutes pre- and post-procedure, as well as during the procedure
if able to accomplish safely
9
(UW Health Strong Recommendation, Moderate Quality
of Evidence)
2.1.11. Containing infant in warm sheets
29
(UW Health Strong Recommendation, Very Low
Quality of Evidence)
2.1.12. Allowing the parent to accompany the infant during and after the procedure
29
(UW
Health Strong Recommendation, Very Low Quality of Evidence)
2.1.13. Mechanical vibration may be considered for minor painful procedures.
31
(UW Health
Weak/Conditional Recommendation, Low Quality of Evidence)
2.1.14. Use techniques to distract the neonate and provide stimuli to stop pain transmission
such as the mother or nurse massaging affected area and/or talking to the child
29

(UW Health Strong Recommendation, Very Low Quality of Evidence)
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2.2. Older infants and children:
2.2.1. Distraction (books, video, talking)is effective for redirecting the child’s attention during
painful procedures
3233
(UW Health Strong Recommendation, Moderate Quality of
Evidence)
2.2.2. Mechanical vibration and/or cold may be considered for minor painful procedures.
(UW Health Strong Recommendation, Moderate Quality of Evidence)
3. Sucrose
3.1. Sucrose is recommended for neonates and infants younger than 6 months to decrease pain
responses, especially for brief painful procedures.(UW Health Strong Recommendation, High
Quality of Evidence)
2,29,34-36

3.2. Dosing information is available in Appendix A.
Management of Pain and Pharmacologic therapy for analgesia
1. Appendix A highlights recommended therapies for pain relief based on the type of procedure, age of
patient, and expected severity of pain.
2. The pain intensity, duration and physiological cause of pain should be evaluated and treatment
should be selected based on the severity of pain.
1,2,5,6,9,29
(UW Health Strong Recommendation, Low
Quality of Evidence)
3. A multimodal approach to analgesia is safest and most effective. For persistent pain, nonopioids
should be scheduled and opioids administered on a prn basis. The goal of this approach is to
minimize opioid requirements and opioid side effects.
37
(UW Health Strong Recommendation, High
Quality of Evidence)
3.1. The use of both nonpharmacologic and pharmacologic therapies is recommended.
1,2,5,6,9,29
(UW
Health Strong Recommendation, Moderate Quality of Evidence)
3.2. For moderate-severe pain, nonopioids analgesics (e.g., acetaminophen, NSAIDS) should be
given on a scheduled basis and opioids administered on an as-needed basis.
38

3.3. In developmentally normal patients over 6 years old, patient-controlled analgesia (PCA) may be
appropriate if significant opioid need is anticipated. In younger or developmentally delayed
children, nurse-controlled analgesia (NCA) or PCA-by-proxy may be appropriate. (UW Health
Strong Recommendation, Low Quality of Evidence) Reference Pain Care Fast Facts PCA in the
Pediatric Patient and Pediatric PCA Order Set [1437].
3.3.1. Non-opioid analgesics should be administered on a scheduled basis when possible
with PCA therapy. (UW Health Strong Recommendation, Low Quality of Evidence)
4. Opioid-related side effects may be treated with as-needed antiemetics (e.g., ondansetron,
metoclopramide) and antipruritics (e.g. nalbuphine, ondansetron).
39
(UW Health Strong
Recommendation, Moderate Quality of Evidence)
4.1. There is no histamine component associated with opioids, so antihistamines (e.g.
diphenhydramine) will not be effective, other than their sedative effects to break the scratch-itch
cycle.
4.2. Opioid-related sedation will often precede respiratory depression (or arrest). Children with a
sedation score of 3 or greater should not receive an increase in opioid therapy. Nonsedating
analgesics should be optimized, and opioid dosing should be reassessed. A trial of a different
opioid may be useful. (UW Health Strong Recommendation, Low Quality of Evidence)
5. Certain patient populations (postoperative, localized extremity or abdominal/thoracic pain) may
benefit from regional anesthesia techniques in consultation with the Pediatric Acute Pain Service.
6. Children with complex or chronic pain have additional therapeutic considerations and will benefit from
consultation with the Pediatric Inpatient Pain Management Service.
7. Avoid use for analgesia in neonates and infants younger than 6 months old:
7.1. Aspirin
40
(UW Health Strong Recommendation, High Quality of Evidence)
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8
7.2. NSAIDs (UW Health Strong Recommendation, Low Quality of Evidence)
7.3. Ketamine
41,42
(UW Health Strong Recommendation, Low Quality of Evidence)
7.4. Intranasal opioid administration (UW Health Strong Recommendation, Low Quality of Evidence).
There is limited evidence to support the use of intranasal administration of opioids in neonates.
8. Avoid use in all children:
8.1. Combination analgesic products (UW Health Strong Recommendation, Low Quality of Evidence
8.1.1. This includes, but is not limited to oxycodone-acetaminophen, hydrocodone-
acetaminophen, codeine-acetaminophen
8.1.2. Combination acetaminophen result in suboptimal acetaminophen dosing (as the
dosing is not scheduled) and increases the risk for acetaminophen toxicity.
8.2. Codeine
43
(UW Health Strong Recommendation, High Quality of Evidence)
8.3. Tramadol
43
(UW Health Strong Recommendation, Moderate Quality of Evidence)
Pharmacologic therapy for agitation and sedation
1. If agitation persists despite adequate pain control, then a sedative is indicated. (UW Health Strong
Recommendation, High Quality of Evidence)
2. Recommended pharmacologic therapy – See Appendix A.
Iatrogenic weaning: Opioids
Determining if a wean is necessary and when to initiate a wean
1. Opioid dependence may develop in as few as 72 hours after starting opioid therapy and withdrawal
symptoms may precipitate with abrupt discontinuation of opioids.
12,44
2. For patients who have received any analgesic or sedation continuous infusion (regardless of duration)
it is reasonable to monitor for at least 24 hours for withdrawal. (UW Health Strong Recommendation,
Very Low Quality of Evidence)
3. For patients who received analgesic or sedation continuous infusion for longer than 72 hours it is
reasonable to monitor for withdrawal for at least 72 hours after tapering analgesic and/or sedative
completely. (UW Health Strong Recommendation, Very Low Quality of Evidence)
3.1. If a patient discharges before the 72 hours of monitoring have elapsed, it is recommended to
send family home with HFFY #6646: Withdrawal to Medications in Children. (UW Health Strong
Recommendation, Low Quality of Evidence)
4. Patients who may be considered for iatrogenic weaning are those who have received analgesia and
sedation for subacute to chronic management with analgesics and/or sedatives for more than 72
hours. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
5. Patients receiving continuous infusion opioid or sedatives fewer than five days may not require a
structured wean and, rather, only require withdrawal scoring (WAT-1 or Finnegan) with symptomatic
treatment as needed. (UW Health Weak/Conditional Recommendation, Very Low Quality of
Evidence)
6. Consider transitioning to intermittent doses when (UW Health Weak/Conditional Recommendation,
Very Low Quality of Evidence):
• Continuous infusion rates at or below:
o Fentanyl 0.5 mcg/kg/hr IV to 1 mcg/kg/hr
o Morphine 0.01 mg/kg/hr IV (10 mcg/kg/hr)
• As-needed boluses are being used infrequently
• Patient’s clinical situation will require less sedation, which may include (but is not limited to):
extubation, reduced postoperative pain
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7. Risk factors associated with iatrogenic withdrawal include: rapid tapering; abrupt discontinuation;
prolonged exposure; and high total cumulative dose.
13

7.1. Withdrawal symptoms may be variable in the pediatric population with respect to age, but are
largely consistent across age ranges.
12,45

7.1.1. Patients should be considered experiencing withdrawal or at risk of withdrawal if:
• Finnegan scores of eight or greater in three or more consecutive scores;
• Finnegan scores of twelve or greater in two or more consecutive scores;
• WAT-1 scores greater than three
7.1.2. Behavioral changes are often the primary manifestations of withdrawal and include
anxiety, agitation, insomnia, and tremors.
7.1.3. Physiologic changes may include increased muscle tone, nausea, vomiting, diarrhea,
decreased appetite, tachypnea, tachycardia, fever, sweating, and hypertension.

Opioid selection and opioid management
1. Selection of methadone or morphine for an iatrogenic wean depends on the duration of a patient’s
continuous opioid infusion leading up to the initiation of an iatrogenic wean. (UW Health
Weak/Conditional Recommendation, Very Low Quality of Evidence)
2. Methadone is reasonable for managing iatrogenic weaning of patients.
11,12,15,16,46-48
(UW Health
Strong Recommendation, Low Quality of Evidence)
3. Methadone may be preferred for managing an iatrogenic wean if patient has received an opioid
continuous infusion for longer than two to three weeks.
49,50
(UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
3.1. The methadone half-life is much longer than the morphine half-life, therefore the duration of
action of methadone is longer. Additionally, due to the prolonged methadone half-life full clinical
effect of a dose change may not be fully demonstrated for up to approximately 48 hours
following a dose change, whereas clinical effect of a morphine dose change is fully revealed
within approximately 24 hours.
3.2. Comparatively, morphine has fewer drug interactions and side effects than methadone.
3.3. Methadone prolongs QTc interval.
3.3.1. EKG-based QTc monitoring should be considered prior to methadone initiation.
3.3.2. Methadone should probably be avoided in patients with prolonged QTc.
3.4. Methadone may be dosed less frequently than morphine, which may be desirable for outpatient
management of an iatrogenic wean.
4. If morphine is chosen for managing an iatrogenic wean, opioid withdrawal symptoms will manifest
more quickly with tapering progression due to shorter half-life in comparison to methadone.
4.1. Morphine may offer advantages as it can be rapidly titrated based on clinical response.
5. Patient factors which may favor methadone weaning (versus morphine weaning) include (but are not
limited to (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence):
• Anticipated hospitalization shorter than 14 days; methadone taper is reasonable to facilitate
transition to home with completion of taper at home
• Trisomy, CDH, prior history of weaning difficulty, or seizure history (increased withdrawal
risk)
6. When transitioning from an opioid infusion, it is reasonable to start methadone at a dose of 0.05 to
0.1 mg/kg PO every 6 to 8 hours (max dose 5 mg). In patients receiving very high doses of
continuous infusion opioids, consider increasing the starting methadone dose to 0.15-0.2 mg/kg PO
every 6 hours (max dose 5 mg). (UW Health Weak/Conditional Recommendation, Very Low Quality
of Evidence)
6.1. Factors that may lead to consideration of higher methadone starting doses include:
• higher morphine or fentanyl infusion doses;
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10
• prolonged duration of opioid exposure prior to wean initiation;
• frequent or multiple “as needed” boluses required for patients also receiving continuous
infusion opioids;
• patients with airway obstruction;
• patients with single ventricle physiology;
• patients with spasticity disorder
6.2. Factors that may lead to consideration of lower methadone starting doses include:
• patients who are expected to tolerate weaning;
• rare “as needed” boluses (outside of routine procedural doses)
6.3. In patients receiving very high doses of continuous infusion opioids, consider increasing the
starting methadone dose to 0.15-0.2 mg/kg PO every 6 hours (max dose 5 mg).
6.4. Due to prolonged methadone half life, overlap the continuous opioid infusion for 24 hours after
starting the oral methadone regimen before terminating the continuous opioid infusion.
6.5. Conversion from oral to IV methadone is variable due to wide range of methadone bioavailability
(30%-100%). A reasonable starting conversion may be 1 mg PO = 0.5 mg IV.
6.6. As-needed morphine doses should be available to treat withdrawal symptoms. See Figure 1 for
dosing recommendations.

Determining a wean schedule
1. Withdrawal is better than more drug exposure due to the risk of affecting brain development with
opioid exposure.
11
(UW Health Strong Recommendation, Low Quality of Evidence)
2. When considering initiation of a wean, clinical factors to consider include current rate of continuous
infusion medications, current sedation scores, as-needed analgesic/sedation doses required, and
respiratory status.
3. In patients receiving both a continuous infusion opioid and benzodiazepine, weaning by rate decrease
of alternating opioid and benzodiazepine may be reasonable. (UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
3.1. It is reasonable to select methadone or morphine in managing a wean for opioids and lorazepam
in managing a wean for benzodiazepines. (UW Health Strong Recommendation, Very Low
Quality of Evidence)
4. Reference Figure 1 for intermittent weaning schedules for opiates. (UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
4.1. For each patient undergoing a wean, as-needed doses of short-acting oral morphine of
lorazepam may be considered to treat acute withdrawal; oral is preferred, but intravenous may
be utilized if the oral route is unavailable.
4.1.1. This rescue dose should be 30% to 100% of the current scheduled dose.

Determining Total Daily Dose (TDD) and Conversions
1. Prior to initiating a wean, the total daily dose (TDD) of analgesics and/or sedatives should be
completed. (UW Health Strong Recommendation, Low Quality of Evidence)
1.1. TDD reflects the 24-hour summation of all opioids (oral, injectable, and continuous) after
converting individual drug dose to a standard equivalent, usually morphine equivalents and
lorazepam equivalents.
1.2. When converting between different opioids, TDD should be empirically reduced by 25-50% to
account for incomplete cross tolerance between different opioids. (UW Health Strong
Recommendation, Low Quality of Evidence)
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11
1.2.1. For patients having received long duration of analgesia, a smaller empiric reduction of
10% may be appropriate. (UW Health Strong Recommendation, Very Low Quality of
Evidence)
1.2.2. Patients with who are extubated with stable airway a larger empiric reduction of up to
50% may be appropriate; these patients are more likely to require intermittent boluses.
(UW Health Strong Recommendation, Very Low Quality of Evidence)
1.3. Intermittent dosing of opioids by oral route is preferred. Intravenous morphine may be
considered in patients unable to tolerate oral medications. (UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
• Morphine: 3 mg PO is equivalent to 1 mg IV

Management of a wean
1. Iatrogenic weaning strategies are presented in Figure 1 (NICU) and Figure 2 (PICU).
1.1. Weaning may be continued and completed in general care settings after initiation in the NICU or
PICU setting. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
2. Iatrogenic weaning should be monitored utilizing the Modified Finnegan’s Neonatal Abstinence
Scoring Tool or the Withdrawal Assessment Tool -1 (WAT-1).
11,51
(UW Health Strong
Recommendation, High Quality of Evidence)
3. In patients receiving both a continuous infusion opioid and benzodiazepine, weaning by rate decrease
of alternating opioid and benzodiazepine may be reasonable. (UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
3.1. It is reasonable to select morphine and/or methadone in managing a wean for opioids and
lorazepam in managing a wean for benzodiazepines. (UW Health Strong Recommendation,
Very Low Quality of Evidence)
4. In the NICU setting, it is reasonable to monitor the progression of the wean by utilizing Finnegan
scoring every three hours. (UW Health Strong Recommendation, Very Low Quality of Evidence)
4.1. It is reasonable to advance the wean every 24-48 hours.
4.2. If the patient has three consecutive Finnegan score of eight or more OR two consecutive WAT-1
scores of two or more, it is reasonable to hold wean advancement or to consider increasing the
dose of the opioid or benzodiazepine being used in the wean.
5. In the PICU setting, it is reasonable to monitor the progression of the wean by utilizing WAT-1 scoring
every 12 hours. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
5.1. It is reasonable to continue to advance the wean in patients scoring three or fewer on WAT-1
scoring.
5.2. It is reasonable to consider WAT-1 scores greater than three as reflective of withdrawal. In
these cases, it is reasonable to not advance wean and to establish a WAT-1 goal score to direct
progression of the wean.
6. Treatment of withdrawal symptoms during a wean (UW Health Weak/Conditional Recommendation,
Very Low Quality of Evidence)
6.1. Consider other changes in support or clinical care that may be promoting or contributing to
withdrawal symptoms.
6.2. Nonpharmacological therapies should be considered as first line prior to rescue drugs for
withdrawal management.
6.3. Intermittent rescue doses of 0.1 to 0.3 mg/kg/dose oral morphine (max dose 5 mg; max IV dose
2 mg) every one to two hours as needed for breakthrough withdrawal symptoms are
reasonable.
47
(UW Health Strong Recommendation, Very Low Quality of Evidence)
6.3.1. Rescue dose should be 30%-100% of the current scheduled dose.
6.4. Rescue doses of morphine may be reduced near the end of the taper. (UW Health Strong
Recommendation, Very Low Quality of Evidence)
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12
6.5. If a patient requires three or more rescue doses of morphine in a 24-hour period, the patient
should remain at the current step in the taper until patient no longer requires frequent rescue
doses. (UW Health Strong Recommendation, Low Quality of Evidence)
6.5.1. Finnegan and WAT scores should also reflect withdrawal symptoms. Investigation
should occur to confirm that rescue doses are being given to manage withdrawal
symptoms.
7. Iatrogenic weaning of analgesia and sedation should coincide with initiation of ventilatory weaning.
(UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
8. Nonpharmacologic interventions for iatrogenic weaning that may be considered include
1,2,29
(UW
Health Weak/Conditional Recommendation, Very Low Quality of Evidence):
• swaddling
• rocking
• minimal sensory or environmental stimulation
• temperature stability
• feeding (alternating bottle and pacifier during feeding to compensate for excessive sucking and
potentially prevent emesis)
• breast milk feedings
9. Adjunctive medications may be considered for patients not tolerating weaning of maintenance
medications. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
9.1. Initiating clonidine 1 mcg/kg/dose by mouth every 6 to 8 hours as needed may be considered as
first-line adjunctive therapy. (UW Health Weak/Conditional Recommendation, Very Low Quality
of Evidence)
9.1.1. For patients requiring all three clonidine doses in the first 24 hours, scheduling clonidine
1 mcg/kg/dose by both every 8 hours may be considered.
9.1.2. If scheduled clonidine is initiated, tapering on a schedule with other medications or
continuing clonidine without dose adjustment until opioid and/or benzodiazepine taper is
complete may be considered.
10. Weans initiated in intensive care setting (e.g. PICU and NICU) may be continued, as clinically
appropriate, to completion if a patient transfers to a general level of care. (UW Health
Weak/Conditional Recommendation, Very Low Quality of Evidence)

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13
Figure 1. NICU management of opioid taper (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
Continuous Infusion
Opioid Use
Use fewer than 3
days
Use 4-7 days
Use longer than 30
days
No opioid taper
necessary.
No opioid
withdrawal
expected
Use 8-29 days
Perform regular Finnegan or WAT-1
scoring for withdrawal symptoms.
Taper morphine infusion by 0.005-0.01
mg/kg/hr (or fentanyl equivalent) Q12-
24H to off as tolerated.
A
Perform regular Finnegan or WAT-1 scoring
for withdrawal symptoms.
Taper morphine infusion by 0.005-0.01 mg/
kg/hr (or fentanyl equivalent) Q12-24H to
rate of 0.01 mg/kg/hr (if fentanyl 0.01 mcg/
kg/hr) as tolerated.
A
Perform regular Finnegan or WAT-1 scoring
for withdrawal symptoms.
Taper morphine infusion by 0.005 mg/kg/hr
(or fentanyl equivalent) Q12-24H to rate of
0.02 mg/kg/hr (if fentanyl 0.02 mcg/kg/hr)
then taper by 0.002-0.003 mg/kg/hr (or
fentanyl equivalent) Q24H to rate of 0.01 mg/
kg/hr (0.01 mcg/kg/hr if fentanyl) as
tolerated.
A
When morphine infusion is at 0.005-0.01 mg/kg/hr, transition to intermittent methadone or morphine dosing to initiate taper. Evaluate for
extubation readiness.
Enteral taper is preferred, but IV may be used.
Follow Table 1 Fast Methadone Taper or
Table 2 Fast Morphine Taper
Continuous infusion opioid use fewer than 10 days
Follow Table 1 Slow Methadone Taper
Continuous infusion opioid use longer than 20 days
Evaluate Finnegan or WAT-1 scores and signs/symptoms of
withdrawal
• Treat acute withdrawal symptoms with
non-pharmacologic approaches and
morphine: 0.05-0.1 mg/kg PO or 0.05-0.1
mg/kg IV Q2H PRN OR 30-50% of the
current scheduled morphine dose
• Do not advance taper for 24-48 hours
• Remain at same dose or increase to
previous dose until Finnegan score <8 or
WAT-1 score <2 for 12-24 hours, then
resume taper
• Continue taper until complete
• Once taper completed, continue regular
Finnegan or WAT-1 scoring until 48 hours
after taper has been completed
Follow Table 1 Standard Methadone Taper
Continuous infusion opioid 10-20 days
Three consecutive Finnegan scores
of ≥8 or two consecutive Finnegan
scores of ≥12?
YesNo

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14
Figure 2. PICU management of opioid taper (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
Continuous Infusion
Opioid Use
Use fewer than 3
days
Use 4-7 days
No opioid taper
necessary.
No opioid withdrawal
expected
Follow Table 1 Fast Methadone Taper
Evaluate Finnegan or WAT-1 scores and signs/symptoms of
withdrawal
• Treat acute withdrawal symptoms with
non-pharmacologic approaches and
morphine: 0.1-0.3 mg/kg PO or 0.05-0.1
mg/kg IV Q2H PRN OR 30-50% of the
current scheduled morphine dose
• Do not advance taper for 24-48 hours
• Remain at same dose or increase to
previous dose until Finnegan score <8 or
WAT-1 score <2 for 12-24 hours, then
resume taper
• Continue taper until complete
• Once taper completed, continue regular
Finnegan or WAT-1 scoring until 48 hours
after taper has been completed
Continuous infusion opioid 7-20 days: follow Table 1 Standard Methadone
Taper
Continuous infusion opioid use longer than 20 days: follow Table 1 Slow
Methadone Taper
Finnegan score <8
WAT-1 score <2
Finnegan score ≥8
Two consecutive WAT-1 scores ≥2
Perform WAT-1 scoring for withdrawal symptoms.
Discontinue opioid infusion. Use 0.05-0.1 mg/kg
morphine PO as needed for management of withdrawal
symptoms.
Consider fast methadone taper if >4 PRN morphine doses given
Use longer than 7 days. Determine plan for
extubation or continued intubation
Planned extubation
within the next 48 to
72 hours
Plan to continue
intubation
Begin methadone taper based on duration of opioid
infusion. Decrease infusion rate by as much as 25% with
every methadone dose. Perform WAT-1 scoring for
withdrawal symptoms. Use 0.05-0.1 mg/kg morphine
PO as needed for management of withdrawal
symptoms.
Hold wean/taper advancement if more than two as
needed doses required in 6 hours; reinitiate
advancement of wean/taper after first 6 hour period
without PRN use
Attempt to wean opioid infusion; with acute
illness resolution, protracted intubation may
not require prolonged continuous opioid
infusion. Initiate methadone taper to manage
opioid dependence; if more than 3 PRN doses
in 12 hours, hold advancement of wean/taper.
Utilize lower methadone dose given
anticipated long duration of taper.

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15
Table 1. Methadone taper schedules (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
Taper
Step
Fast Methadone Taper: opioid exposure <10
days
A,B
Standard Methadone Taper: opioid exposure
10-20 days
A,B

Slow Methadone Taper: opioid exposure >20
days
B

1
100% of original dose
every 6 hours
A
Start Step 1 1-2 days
before extubation; wean
continuous sedation
after 2
nd
methadone
dose or as tolerated
100% of original dose
every 6 hours
A
Start Step 1 2-3 days
before extubation;
wean continuous
sedation after 4
th

methadone dose or as
tolerated
100% of original dose
every 6 hours
(starting methadone
dose 0.1 mg/kg, max
5 mg)
Start Step 1 2-3 days
before extubation;
wean continuous
sedation after 4th
methadone dose or as
tolerated
2
100% of original dose
every 8 hours
1-2 days
80% of original dose
every 6 hours
2 days
90% of original dose
every 6 hours
2 days
3
75% of original dose
every 8 hours
1-2 days
60% of original dose
every 6 hours
2 days
80% of original dose
every 6 hours
2 days
4
50% of original dose
every 12 hours
1-2 days
60% of original dose
every 8 hours
2 days
70% of original dose
every 6 hours
2 days
5
50 % of original dose
every 24 hours
1-2 days
60% of original dose
every 12 hours
2 days
60% of original dose
every 6 hours
2 days
6
STOP
30% of original dose
every 12 hours
1-2 days
60% of original dose
every 8 hours
2 days
7
30% of original dose
every 24 hours
1-2 days
40% of original dose
every 8 hours
2 days
8
STOP
40% of original dose
every 12 hours
2 days
9
20% of original dose
every 12 hours
1-2 days
10
20% of original dose
every 24 hours
1-2 days
11 STOP
A
Starting methadone dose 0.05-0.1 mg/kg (maximum starting dose = 5 mg). If needed, use IV:PO conversion of 1:1 as once orders to replace enteral doses.
B
Evaluate for excess sedation vs. symptoms of withdrawal daily. If patient tolerating wean, wean daily, if patient needing rescue doses for signs/symptoms of
withdrawal wean every other day (maximum 2-3 days at each step).
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16
Table 2. Fast morphine taper (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
Taper
Step
Morphine Dose
A
Frequency Duration (Number of Doses)
1 0.35 mg/kg PO Q4H 6
2 0.3 mg/kg PO Q4H 6
3 0.25 mg/kg PO Q4H 6
4 0.2 mg/kg PO Q4H 6
5 0.15 mg/kg PO Q4H 6
6 0.1 mg/kg PO Q4H 6
7 0.05 mg/kg PO Q4H 6
8 0.05 mg/kg PO Q6H 4
9 0.05 mg/kg PO Q12H 2
10 0.05 mg/kg PO Q24H 1
A
Maximum single morphine dose 5 mg

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17
Iatrogenic weaning: Benzodiazepines

Determining if a wean is necessary and when to initiate a wean
1. Patients receiving scheduled or continuous IV infusion benzodiazepines longer than 10 days are at
risk of benzodiazepine withdrawal. (UW Health Weak/Conditional Recommendation, Very Low
Quality of Evidence)
2. Patients receiving scheduled or continuous IV infusion benzodiazepines for durations fewer than 5 to
10 days are at lower risk of benzodiazepine withdrawal. (UW Health Weak/Conditional
Recommendation, Very Low Quality of Evidence)
2.1. These patients may be monitored for withdrawal symptoms and managed with enteral
lorazepam as-needed doses.
3. Factors for considering transitioning from continuous infusion to intermittent dosing include:
• Midazolam 0.05 mg/kg/hr to 0.1 mg/kg/hr IV
• As-needed boluses are being used infrequently
• Patient’s clinical situation will require less sedation, which may include (but is not limited to):
extubation, reduced postoperative pain
4. The scheduled intermittent starting doses that may be reasonable is lorazepam 0.03 mg/kg PO every
three to four hours. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)

Benzodiazepine selection and benzodiazepine management
1. Lorazepam is preferred for managing a benzodiazepine taper as it may be given enterally or
parenterally. (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
1.1. Enteral lorazepam is preferred
2. Higher initial benzodiazepine doses may be considered for patients receiving higher benzodiazepine
doses by continuous infusion or those patients receiving prolonged duration of benzodiazepine
infusion.
3. When converting between different benzodiazepines, TDD does not need to be empirically reduced
as there is no need to account for cross tolerance (unlike opiates)
3.1. TDD reflects the 24-hour summation of all benzodiazepines (oral, injectable, and continuous)
after converting individual drug dose to a standard equivalent, usually lorazepam equivalents
3.2. Intermittent dosing of opioids or benzodiazepines by oral route is preferred. Intravenous
lorazepam may be considered in patients unable to tolerate oral medications. (UW Health
Weak/Conditional Recommendation, Very Low Quality of Evidence)
3.3. Lorazepam: 1 mg PO is equivalent to 1 mg IV
3.4. Single dose of midazolam 1 mg is equivalent to single dose of lorazepam 0.5 mg

Determining a wean schedule
1. The progression and duration of the benzodiazepine taper should be determined by the duration of
benzodiazepine use prior to initiation of the wean. (UW Health Weak/Conditional Recommendation,
Very Low Quality of Evidence) See Figure 3.


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18
Figure 3. Management of a benzodiazepine taper (UW Health Weak/Conditional Recommendation, Very Low Quality of
Evidence)

Scheduled Benzodiazepine Use
A
Taper benzodiazpine over 3-5 days based
on clinical status
Utilize enteral dosing if possible
Scheduled use <5 days
• Wean benzodiazepine by ~10-30%
daily based on clinical status
• Utilize Table 3 to determine tapering
schedule
• Order PRN PO lorazepam for
treatment of withdrawal
• Utilize enteral dosing if possible
Scheduled use 5-10 days
Monitor for signs/symptoms of benzodiazepene
withdrawal:
• CNS: hypertonicity, tremors, irritability
• GI: disorganized sucking, vomiting, diarrhea
Signs of benzodiazepine withdrawal may not occur for 24-
36 hours after a taper dose decrease
A
Notes
• Lorazepam PO 1 mg = Lorazepam IV 1 mg
• Single-dose lorazepam 0.5 mg = single-dose
midazolam 1 mg
Lorazepam is preferred for benzodiazepine tapers
• Schedule lorazepam doses
• Consider Slow Lorazepam Taper
schedule in Table 3.
• Wean benzodiazepine by ~10-30%
daily based on clinical status
• Utilize enteral dosing if possible
Scheduled use >10 days
No PRN lorazepam or rare PRN lorazepam use
Two or more PRN lorazepam
doses in 24 hours

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19
Table 3. Lorazepam taper schedules (UW Health Weak/Conditional Recommendation, Very Low Quality of Evidence)
Taper
Step
Fast Lorazepam Taper: benzodiazepine
exposure <10 days
A,B
Standard Lorazepam Taper: benzodiazepine
exposure 10-20 days
A,B

Slow Lorazepam Taper: benzodiazepine
exposure >20 days
B

1
100% of original dose
every 6 hours
A

Start Step 1 1-2 days
before extubation; wean
continuous sedation
after 2
nd
lorazepam dose
or as tolerated
100% of original dose
every 6 hours
A
Start Step 1 2-3 days
before extubation;
wean continuous
sedation after 4
th

lorazepam dose or as
tolerated
100% of original dose
every 6 hours; starting
lorazepam dose of
0.1 mg/kg
Start Step 1 2-3 days
before extubation;
wean continuous
sedation after 4th
lorazepam dose or as
tolerated
2
100% of original dose
every 8 hours
1-2 days
80% of original dose
every 6 hours
2 days
90% of original dose
every 6 hours
2 days
3
75% of original dose
every 8 hours
1-2 days
60% of original dose
every 6 hours
2 days
80% of original dose
every 6 hours
2 days
4
50% of original dose
every 12 hours
1-2 days
60% of original dose
every 8 hours
2 days
70% of original dose
every 6 hours
2 days
5
50 % of original dose
every 24 hours
1-2 days
60% of original dose
every 12 hours
2 days
60% of original dose
every 6 hours
2 days
6
STOP
30% of original dose
every 12 hours
1-2 days
60% of original dose
every 8 hours
2 days
7
30% of original dose
every 24 hours
1-2 days
40% of original dose
every 8 hours
2 days
8
STOP
40% of original dose
every 12 hours
2 days
9
20% of original dose
every 12 hours
1-2 days
10
20% of original dose
every 24 hours
1-2 days
11 STOP
A
Starting lorazepam dose 0.05-0.1 mg/kg (maximum starting dose = 5 mg). If needed, use IV:PO conversion of 1:1 as once orders to replace enteral doses.
B
Evaluate for excess sedation vs. symptoms of withdrawal daily. If patient tolerating wean, wean daily, if patient needing rescue doses for signs/symptoms of
withdrawal wean every other day (maximum 2-3 days at each step).
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20
UW Health Implementation
Potential Benefits:
The benefits of this guideline include reducing the burden of pain experienced by neonates, infants, or
children by providing evidence-based recommendations for evaluating, preventing, and treating pain in
this population as well as reducing the risk of withdrawal due to analgesic or sedative exposure.

Potential Harms:
While it is anticipated that pain and iatrogenic weaning management in neonates and infants will improve
with standardization through recommendations provided in this guideline, it is understood that clinical
judgement should be utilized and a thorough assessment of risks and benefits should be done when
selecting appropriate therapy for management in this population.

Pertinent UW Health Policies and Procedures
• UW Health Clinical Policy 3.5.5: Pain management

Patient Resources
• Health Facts For You #6646: Withdrawal to Medications

Implementation Plan/Clinical Tools
1. Guideline will be posted on UConnect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be disseminated through physician champions
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the guideline
recommendations (such as the following) will be reviewed for consistency and modified as
appropriate.

Order Sets
• IP - Methadone Taper – Pediatric – Supplemental [5456]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of
patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a
clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit
the clinical condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.

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21
Appendix A. Analgesic medications
Table 1. Analgesic medication properties in neonates, infants, and children
5,52,53

Medication Dose Onset/Duration of Action Comments
Non-pharmacologic
Breast milk
55-57

 5 mL expressed breast milk
 Allow infant to breastfeed during
procedure while being held by
mother
 Administer or begin
breastfeeding 2 minutes prior
to procedure
 Rapid onset, lasts about 2
minutes
 Breastfeeding should
be continued
throughout the
procedure if possible
Non-categorized
Sucrose
1,2,5,9,29,34,58

 0.05-2 mL of 24% sucrose
(SweetEase®)
 Effect is almost immediate and
lasts about 2 minutes
 Administer dose 2
minutes prior to
procedure. May repeat
dose one to two
minutes after.
 Not recommended in
gestational age <32
weeks or if older than
six months
 Sucrose may be more
effective when given in
combination with a
pacifier and non-
nutritive sucking
9,36
Acetaminophen
2,52

 Oral:
o Usual dose: 10 -15 mg/kg
per dose (max dose 75
mg/kg/day; single max dose
650-1000 mg)
 Rectal:
o Usual dose: 10-20 mg/kg
per dose (max dose 650
mg)
o Perioperative analgesia:
single loading dose of 30
mg/kg
 IV:
59
o Infants between 32 and 44
weeks: Loading dose of 20
mg/kg, followed by a
maintenance dose of 10
mg/kg
o Older infants and children:
15 mg/kg/dose (max 650
mg)
 Maintenance intervals for oral,
rectal, and IV:
o Term infants: Q 6 hr
o Preterm infants ≥ 32 weeks:
Q 8 hr
o Preterm infants < 32 weeks:
Q 12 hr
o Children: Q 6 hr
 Oral: Peak effect occurs within
about 1 hour and lasts
approximately 4-6 hours
 Rectal: absorption is erratic
and onset of action may be
prolonged.
 IV: Onset is about 5-10
minutes and duration is
approximately 4-6 hours
 Liver toxicity is more
likely to occur with
excessive doses or
after prolonged
administration (>48
hours) of therapeutic
doses.
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22
Medication Dose Onset/Duration of Action Comments
Ibuprofen
 Oral: 5-10 mg/kg/dose (max 800
mg) every 6-8 hours
 Onset 30-60 minutes and
duration 2-4 hours
 Avoid in children
younger than 6 months
Ketorolac
 IV: 0.5 mg/kg/dose (max 15-30
mg) every 6 hours
 Onset 30-60 minutes and
duration 4-6 hours
 Caution with prolonged
use or concurrent
nephrotoxic
medications that may
contribute to AKI
development (see
NINJA Medication List)
Lidocaine
5,29,52

 Lidocaine 4% cream:
o Apply 0.5-1 g per site

 1% injection:
o 2-5 mg/kg SQ
 Onset is about 30 minutes,
effects last about 90 minutes
after cream removal
 Infiltrate the site 3-8 minutes
prior to procedure
5


 Remove cream and
cleanse prior to
beginning the
procedure
5

 Max of 1 g per site
 ≤5 kg: 1 site per hour
 >5 kg: 2 sites per hour
Opioid Analgesics and Reversal Agent
Adverse effect treatment
 Constipation: Infant glycerin suppositories may be administered for constipation (UW Health Strong
Recommendation, Low Quality of Evidence)
 Reversal of respiratory depression: Naloxone
Naloxone
52,60


(Opioid reversal)
 Reversal of respiratory
depression
o 1-5 mcg/kg/dose and titrate
to effect
 Emergent reversal
o 0.1 mg/kg/dose IV or IO


 Onset within 2 minutes
 Duration between 20-60
minutes
 Repeat doses of
naloxone may be
required
 Naloxone can
precipitate withdrawal
in patients receiving
opioids for longer than
4 days
9

 Intranasal Medication
Guideline
Fentanyl
2,5,52,58
 Intermittent slow IV push: 0.5-2
mcg/kg/dose over 5-10 min,
repeat as required, usually every
2 to 4 hr; max single dose 50
mcg
 Continuous IV Infusion: 0.05 to 5
mcg/kg/hr
 PCA: Reference Pain Care Fast
Facts PCA in the Pediatric
Patient and Pediatric PCA Order
Set [1437]
 Onset of action is almost
immediate and lasts about 1
hour
 Respiratory depression
may occur
unexpectedly because
of redistribution.
 Chest wall rigidity has
occurred in 4% of
neonates who received
2.2 to 6.5 mcg/kg per
dose, occasionally
associated with
laryngospasm.
 Intranasal Medication
Guideline
Morphine
5,52,58
 Oral: 0.05-0.1 mg/kg/dose every
4 hr; max single dose 15-30 mg
 Intermittent IV: 0.05 to 0.1 mg/kg
per dose, usually every 1-4 hr;
max single dose 2-4 mg
 Continuous IV infusion: 0.01-0.05
mg/kg/hr
 PCA: Reference Pain Care Fast
Facts PCA in the Pediatric
Patient and Pediatric PCA Order
Set [1437]
 Oral: Peak effect occurs in
about 1 hour
 IV: Onset of about 5 minutes,
with peak effect in about 15
minutes
 Increased entero-
hepatic circulation
prolongs half-life in
preterm infants
 May also be given IM
or SQ (only when
IV/PO access is
unavailable)
 Do not administer by
intranasal route

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23
Medication Dose Onset/Duration of Action Comments
Hydromorphone  Oral:
 Infants: 0.03-0.06 mg/kg/dose
every 4 hours
 Children: 0.03-0.08
mg/kg/dose; max single dose
2-4 mg
 Intermittent IV: 0.01-0.02
mg/kg/dose every 1-4 hours
 Continuous IV infusion: 2-10
mcg/kg/hr
 PCA: Reference Pain Care Fast
Facts PCA in the Pediatric
Patient and Pediatric PCA Order
Set [1437]
 Oral: Onset 15-30 minutes
with duration of 3-4 hours
 IV: Onset 5 minutes with
duration of 3-4 hours
 Intranasal Medication
Guideline
Oxycodone  Oral: 0.05-0.2 mg/kg/dose every
3-6 hours; max single dose small
children and infants 5-10 mg;
max single dose older children 5-
15 mg
 Onset 10-15 minutes with
duration of 3-6 hours

Analgesics with Anxiolytic Properties
Dexmedetomidine
52
,61

 IV infusion: Initiate at 0.25
mcg/kg/hr; increase by 0.25
mcg/kg/hr every 2-4 hours as
needed; usual dosing range
0.25-1 mcg/kg/hr
 Onset is approximately 30
minutes, peak effect in about
60 minutes

 May cause
bradycardia,
hypotension,
hypertension,
bronchospasm
 Intranasal Medication
Guideline
Sedatives and Reversal Agent
 Reversal of respiratory depression: Flumazenil
Flumazenil
52


(Benzodiazepine
reversal)
 IV: 0.01 mg/kg every 1 minute to
a maximum of 0.05 mg/kg total
dose
 Intranasal: 0.01-0.04 mg/kg/dose
 Rectal: 0.015-0.03 mg/kg/dose

 Onset within 1-3 minutes
 Duration usually < 1 hour
 Repeat doses of
flumazenil may be
required
 Flumazenil should not
be administered when
benzodiazepines are
administered to stop a
seizure
 Intranasal Medication
Guideline
Midazolam
52,62,63


 Oral: 0.25-0.5 mg/kg/dose every
2 hours; maximum single dose
20 mg
 Intermittent IV: 0.05-0.15
mg/kg/dose every 2 hrs
 Continuous IV infusion: 0.01-0.1
mg/kg/hr
 Intranasal: 0.2-0.5 mg/kg/dose;
max single dose 10 mg
 Onset is rapid
 Oral: Lasts about 2-6 hours
 IV: Lasts 20-30 minutes
 Intranasal: Lasts 30-60
minutes

 May cause
hypotension,
respiratory depression
 Intranasal Medication
Guideline
Lorazepam
52,54
 Oral: 0.05-0.1 mg/kg/dose every
2-4 hr
 Intermittent IV: 0.05-0.1 mg/kg
per dose over 2-5 minutes every
2-4 hr
 Oral: Onset within 60 minutes
 IV: Onset of action occurs
within 5 minutes, peak effects
in 45 minutes and last 3-24 hr

Dosing and pharmacokinetic information compiled from Pediatric Lexicomp,
52
NeoFax
54
, and the
Newborn Pain Assessment and Management Guideline for Practice
5
and as cited in the table.
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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
10/2017CCKM@uwhealth.org



24
Table 2. Recommendations for neonatal/infant pain management based on anticipated severity of
pain
Indications Minor Procedures Major procedures Post-operative Pain
Examples
• Heel stick
• Venipuncture
• IM or SQ injection
• Suctioning
• Tape removal
• Lumbar puncture
• Umbilical catheterization
• Circumcision*
• Intercostal drains
• Chest tube insertion and
removal
• Intubation
• Retinal exams
• IV catheter insertion
• Central line placement
• Pain associated with
surgery
Recommended
Therapies
1,2,5,9,29,58,64,65

• Non-pharmacological
methods such as
swaddling, containment
or facilitated tucking (UW
Health Strong
Recommendation,
Moderate Quality of
Evidence)

• Pacifier with sucrose and
non-nutritive sucking (UW
Health Strong
Recommendation,
Moderate Quality of
Evidence)

• Consider local
anesthetics, such as
topical lidocaine at site of
injection (UW Health
Weak/Conditional
Recommendation, Very
Low Quality of Evidence)
• Non-pharmacological
methods such as
swaddling, containment or
facilitated tucking as able
(UW Health Strong
Recommendation, Low
Quality of Evidence)

• Pacifier with sucrose and
non-nutritive sucking (UW
Health Strong
Recommendation,
Moderate Quality of
Evidence)

• Apply topical local
anesthetic if indicated
based on urgency or type
of procedure (UW Health
Strong Recommendation,
Very Low Quality of
Evidence)

• Consider bolus dose of
opioid (UW Health
Weak/Conditional
Recommendation, Low
Quality of Evidence)

• Acetaminophen may be
used for post-procedural
pain (UW Health Strong
Recommendation, Low
Quality of Evidence)

* Dorsal penile nerve block or
other regional block should be
performed with circumcision
66

(UW Health Strong
Recommendation, Low
Quality of Evidence)
• Non-pharmacological
methods such as
swaddling, containment or
facilitated tucking should
be provided as able (UW
Health Strong
Recommendation, Low
Quality of Evidence)

• Pacifier with sucrose and
non-nutritive sucking (UW
Health Strong
Recommendation,
Moderate Quality of
Evidence)

• Opioids (UW Health
Strong Recommendation,
Low Quality of Evidence)

• Acetaminophen for
multimodal therapy (UW
Health Strong
Recommendation, Low
Quality of Evidence)

• Regional analgesia (UW
Health Strong
Recommendation, Very
Low Quality of Evidence)

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31
Appendix B. Slow morphine taper table
Taper
Step
Morphine Dose Frequency
Duration (Number of
Doses)
1 0.35 mg/kg Q4H 12
2 0.3 mg/kg Q4H 12
3 0.275 mg/kg Q4H 12
4 0.25 mg/kg Q4H 12
5 0.225 mg/kg Q4H 12
6 0.2 mg/kg Q4H 12
7 0.175 mg/kg Q4H 12
8 0.15 mg/kg Q4H 12
9 0.125 mg/kg Q4H 12
10 0.1 mg/kg Q4H 12
11 0.1 mg/kg Q6H 8
12 0.05 mg/kg Q6H 8
13 0.05 mg/kg Q8H 6
14 0.05 mg/kg Q12H 4
15 0.05 mg/kg Q24H 2
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32
Appendix C. Evidence Grading Scheme
Figure 1. GRADE Methodology adapted by UW Health
GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate
We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.
GRADE Ratings for Recommendations For or Against Practice
Strong
The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.
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33
References
1. Batton DG, Barrington KJ, Wallman C. Prevention and management of pain in the neonate: an
update. Pediatrics. Nov 2006;118(5):2231-2241.
2. Anand KJ. Consensus statement for the prevention and management of pain in the newborn.
Arch Pediatr Adolesc Med. Feb 2001;155(2):173-180.
3. Simons SH, van Dijk M, Anand KS, Roofthooft D, van Lingen RA, Tibboel D. Do we still hurt
newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr
Adolesc Med. Nov 2003;157(11):1058-1064.
4. Stevens B, McGrath P, Gibbins S, et al. Procedural pain in newborns at risk for neurologic
impairment. Pain. Sep 2003;105(1-2):27-35.
5. Walden M, Gibbins S. Newborn Pain Assessment and Management: Guideline for Practice.
Glenview, IL: National Association of Neonatal Nurses; 2012.
6. Stevens BJ, Franck LS. Assessment and management of pain in neonates. Paediatr Drugs.
2001;3(7):539-558.
7. Carbajal R, Rousset A, Danan C, et al. Epidemiology and treatment of painful procedures in
neonates in intensive care units. JAMA. Jul 2 2008;300(1):60-70.
8. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. The New England
journal of medicine. Nov 19 1987;317(21):1321-1329.
9. Spence K, Henderson-Smart D, New K, Evans C, Whitelaw J, Woolnough R. Evidenced-based
clinical practice guideline for management of newborn pain. J Paediatr Child Health. Apr
2010;46(4):184-192.
10. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE.
Developmental pharmacology--drug disposition, action, and therapy in infants and children. The
New England journal of medicine. Sep 18 2003;349(12):1157-1167.
11. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. Feb 2012;129(2):e540-560.
12. Anand KJ, Willson DF, Berger J, et al. Tolerance and withdrawal from prolonged opioid use in
critically ill children. Pediatrics. May 2010;125(5):e1208-1225.
13. Cramton RE, Gruchala NE. Babies breaking bad: neonatal and iatrogenic withdrawal syndromes.
Curr Opin Pediatr. Aug 2013;25(4):532-542.
14. Tobias JD, Schleien CL, Haun SE. Methadone as treatment for iatrogenic narcotic dependency in
pediatric intensive care unit patients. Crit Care Med. Nov 1990;18(11):1292-1293.
15. Meyer MM, Berens RJ. Efficacy of an enteral 10-day methadone wean to prevent opioid
withdrawal in fentanyl-tolerant pediatric intensive care unit patients. Pediatr Crit Care Med. Oct
2001;2(4):329-333.
16. Robertson RC, Darsey E, Fortenberry JD, Pettignano R, Hartley G. Evaluation of an opiate-
weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care
Med. Oct 2000;1(2):119-123.
17. Abdouni R, Reyburn-Orne T, Youssef TH, Haddad IY, Gerkin RD. Impact of a Standardized
Treatment Guideline for Pediatric Iatrogenic Opioid Dependence: A Quality Improvement
Initiative. J Pediatr Pharmacol Ther. Jan-Feb 2016;21(1):54-65.
18. Dervan LA, Yaghmai B, Watson RS, Wolf FM. The use of methadone to facilitate opioid weaning
in pediatric critical care patients: a systematic review of the literature and meta-analysis. Paediatr
Anaesth. Mar 2017;27(3):228-239.
19. Best KM, Boullata JI, Curley MA. Risk factors associated with iatrogenic opioid and
benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual
model. Pediatr Crit Care Med. Feb 2015;16(2):175-183.
20. Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool
to assess neonatal pain. Neonatal Netw. Sep 1993;12(6):59-66.
21. Voepel-Lewis T, Merkel S, Tait AR, Trzcinka A, Malviya S. The reliability and validity of the Face,
Legs, Activity, Cry, Consolability observational tool as a measure of pain in children with cognitive
impairment. Anesth Analg. Nov 2002;95(5):1224-1229, table of contents.
22. Hummel P, Lawlor-Klean P, Weiss MG. Validity and reliability of the N-PASS assessment tool
with acute pain. J Perinatol. Jul 2010;30(7):474-478.
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2017CCKM@uwhealth.org



34
23. Hummel P, Puchalski M, Creech SD, Weiss MG. Clinical reliability and validity of the N-PASS:
neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol. Jan 2008;28(1):55-
60.
24. Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State Behavioral Scale: a sedation
assessment instrument for infants and young children supported on mechanical ventilation.
Pediatr Crit Care Med. Mar 2006;7(2):107-114.
25. Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring
postoperative pain in young children. Pediatric nursing. May-Jun 1997;23(3):293-297.
26. Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC observational pain
tool: improved reliability and validity for pain assessment in children with cognitive impairment.
Paediatric anaesthesia. Mar 2006;16(3):258-265.
27. Chambers CT, Hardial J, Craig KD, Court C, Montgomery C. Faces scales for the measurement
of postoperative pain intensity in children following minor surgery. The Clinical journal of pain.
May-Jun 2005;21(3):277-285.
28. von Baeyer CL, Spagrud LJ, McCormick JC, Choo E, Neville K, Connelly MA. Three new
datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain
intensity. Pain. Jun 2009;143(3):223-227.
29. Lago P, Garetti E, Merazzi D, et al. Guidelines for procedural pain in the newborn. Acta Paediatr.
Jun 2009;98(6):932-939.
30. Rattaz C, Goubet N, Bullinger A. The calming effect of a familiar odor on full-term newborns. J
Dev Behav Pediatr. Apr 2005;26(2):86-92.
31. Baba LR, McGrath JM, Liu J. The efficacy of mechanical vibration analgesia for relief of heel stick
pain in neonates: a novel approach. The Journal of perinatal & neonatal nursing. Jul-Sep
2010;24(3):274-283.
32. Uman LS, Chambers CT, McGrath PJ, Kisely S. A systematic review of randomized controlled
trials examining psychological interventions for needle-related procedural pain and distress in
children and adolescents: an abbreviated cochrane review. Journal of pediatric psychology. Sep
2008;33(8):842-854.
33. Ali S, McGrath T, Drendel AL. An Evidence-Based Approach to Minimizing Acute Procedural Pain
in the Emergency Department and Beyond. Pediatric emergency care. Jan 2016;32(1):36-42;
quiz 43-34.
34. Lefrak L, Burch K, Caravantes R, et al. Sucrose analgesia: identifying potentially better practices.
Pediatrics. Nov 2006;118 Suppl 2:S197-202.
35. Stevens B, Yamada J, Lee GY, Ohlsson A. Sucrose for analgesia in newborn infants undergoing
painful procedures. The Cochrane database of systematic reviews. 2013;1:Cd001069.
36. Zempsky WT, Cravero JP. Relief of pain and anxiety in pediatric patients in emergency medical
systems. Pediatrics. Nov 2004;114(5):1348-1356.
37. Voepel-Lewis T, Wagner D, Burke C, et al. Early adjuvant use of nonopioids associated with
reduced odds of serious postoperative opioid adverse events and need for rescue in children.
Paediatric anaesthesia. Feb 2013;23(2):162-169.
38. Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and
nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatric anaesthesia. Jun
2013;23(6):475-495.
39. Ganesh A, Maxwell LG. Pathophysiology and management of opioid-induced pruritus. Drugs.
2007;67(16):2323-2333.
40. Beutler AI, Chesnut GT, Mattingly JC, Jamieson B. FPIN's Clinical Inquiries. Aspirin use in
children for fever or viral syndromes. Am Fam Physician. Dec 15 2009;80(12):1472.
41. Bhutta AT. Ketamine: a controversial drug for neonates. Semin Perinatol. Oct 2007;31(5):303-
308.
42. Treston G, Bell A, Cardwell R, Fincher G, Chand D, Cashion G. What is the nature of the
emergence phenomenon when using intravenous or intramuscular ketamine for paediatric
procedural sedation? Emerg Med Australas. Aug 2009;21(4):315-322.
43. FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough
medicines and tramadol pain medicines in children; recommends against use in breastfeeding
women. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm (Accessed August
24, 2017).
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
10/2017CCKM@uwhealth.org



35
44. Galinkin J, Koh JL. Recognition and management of iatrogenically induced opioid dependence
and withdrawal in children. Pediatrics. Jan 2014;133(1):152-155.
45. Ista E, van Dijk M, Gamel C, Tibboel D, de Hoog M. Withdrawal symptoms in children after long-
term administration of sedatives and/or analgesics: a literature review. "Assessment remains
troublesome". Intensive Care Med. Aug 2007;33(8):1396-1406.
46. Steineck KJ, Skoglund AK, Carlson MK, Gupta S. Evaluation of a pharmacist-managed
methadone taper*. Pediatr Crit Care Med. Mar 2014;15(3):206-210.
47. Berens RJ, Meyer MT, Mikhailov TA, et al. A prospective evaluation of opioid weaning in opioid-
dependent pediatric critical care patients. Anesth Analg. Apr 2006;102(4):1045-1050.
48. Bowens CD, Thompson JA, Thompson MT, Breitzka RL, Thompson DG, Sheeran PW. A trial of
methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged
sedative infusions. Pediatr Crit Care Med. Nov 11 2010.
49. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care
Pharmacother. 2005;19(4):13-24.
50. Ward RM, Drover DR, Hammer GB, et al. The pharmacokinetics of methadone and its
metabolites in neonates, infants, and children. Paediatr Anaesth. Jun 2014;24(6):591-601.
51. Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1
(WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal
symptoms in pediatric patients. Pediatr Crit Care Med. Nov 2008;9(6):573-580.
52. Pediatric and Neonatal Lexi-Drugs. Hudson, OH: Lexicomp - Wolters Kluwer Health; 2015.
53. Young T, Mangum B. NEOFAX 2010. 11th ed. New York, NY: Thompson Reuters; 2010.
54. Young TE, Mangum B. NEOFAX 2010. 11th ed. New York, NY: Thomson Reuters; 2010.
55. Upadhyay A, Aggarwal R, Narayan S, Joshi M, Paul VK, Deorari AK. Analgesic effect of
expressed breast milk in procedural pain in term neonates: a randomized, placebo-controlled,
double-blind trial. Acta Paediatr. Apr 2004;93(4):518-522.
56. Gray L, Miller LW, Philipp BL, Blass EM. Breastfeeding is analgesic in healthy newborns.
Pediatrics. Apr 2002;109(4):590-593.
57. Carbajal R, Veerapen S, Couderc S, Jugie M, Ville Y. Analgesic effect of breast feeding in term
neonates: randomised controlled trial. BMJ. Jan 4 2003;326(7379):13.
58. Walter-Nicolet E, Annequin D, Biran V, Mitanchez D, Tourniaire B. Pain management in
newborns: from prevention to treatment. Paediatr Drugs. Dec 1 2010;12(6):353-365.
59. Veyckemans F, Anderson BJ, Wolf AR, Allegaert K. Intravenous paracetamol dosage in the
neonate and small infant. Br J Anaesth. Vol 112. England2014:380-381.
60. Kleinman ME, Chameides L, Schexnayder SM, et al. Pediatric advanced life support: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Pediatrics. Nov 2010;126(5):e1361-1399.
61. O'Mara K, Gal P, Ransommd JL, et al. Successful use of dexmedetomidine for sedation in a 24-
week gestational age neonate. Ann Pharmacother. Oct 2009;43(10):1707-1713.
62. Kumar P, Denson SE, Mancuso TJ. Premedication for nonemergency endotracheal intubation in
the neonate. Pediatrics. Mar 2010;125(3):608-615.
63. Durrmeyer X, Daoud P, Decobert F, et al. Premedication for neonatal endotracheal intubation:
results from the epidemiology of procedural pain in neonates study. Pediatr Crit Care Med. May
2013;14(4):e169-175.
64. Anand KJ. Pharmacological approaches to the management of pain in the neonatal intensive
care unit. J Perinatol. May 2007;27 Suppl 1:S4-S11.
65. Hall RW. Anesthesia and analgesia in the NICU. Clin Perinatol. Mar 2012;39(1):239-254.
66. Circumcision policy statement. American Academy of Pediatrics. Task Force on Circumcision.
Pediatrics. Mar 1999;103(3):686-693.


Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
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