Article type : Review of Therapeutics

Accepted Article
Corresponding author mail id : kplake@purdue.edu

Opioid and Benzodiazepine Weaning in Pediatric Patients: Review of Current Literature

First author:
Norman E Fenn III
Purdue University College of Pharmacy
575 Stadium Mall Drive
West Lafayette, IN 47906
Phone: 765-494-3579

Corresponding author:
Kimberly S Plake
Purdue University College of Pharmacy
575 Stadium Mall Drive
West Lafayette, IN 47906
Phone: 765-494-5966

Keywords: opioid, benzodiazepine, wean, taper, pediatric

The authors claim that no sources of support were obtained or used in the creation of this manuscript.

Running head: Opioid and benzodiazepine weaning in pediatrics

Abstract

Pediatric opioid and benzodiazepine withdrawal are avoidable complications of pain and sedation

management that is well described in the literature. To prevent withdrawal from occurring,

practitioners regularly employ a steady decrease of pain and sedation medications, also known as a

weaning or tapering schedule. The weaning schedule is highly variable based on clinician preference

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/phar.2026
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 and is usually dependent on the clinician. The purpose of this review is to evaluate the current literature
Accepted Article
on the process of opioid and benzodiazepine weaning in pediatric patients and to assess the various

standardized protocols used to decrease withdrawal occurrences. We conducted a search of the

PubMed, MEDLINE, Cochrane Library, Cumulative Index of Nursing and Allied Health (CINAHL), Academic

Search Premier, and PsycInfo databases. Studies were included if they described a wean or taper in

pediatric patients aged 18 years or younger. Studies describing neonatal abstinence syndrome were

excluded from the review. A total of 97 studies published between 2000 and 2014 were retrieved; of

those, 15 studies met the inclusion criteria. Studies were evaluated for selection of withdrawal

assessment tool, wean protocol summary, preferred weaning agents, benzodiazepine withdrawal, and

wean-at-home regimen. The most common opioid-weaning protocol approaches described a 10–20%

dose decrease per day. Benzodiazepine weaning was not regularly standardized nor described. The use

of a standardized opioid-weaning protocol reduced withdrawal rates compared with nonstandardized

weaning plans. Benzodiazepine weaning was inconsistently evaluated and may have affected study

outcomes. Identified areas of improvement include the use of newer withdrawal assessment tools

validated in the older pediatric population and standardized withdrawal assessment and reporting.

Background

Pediatric opioid and benzodiazepine withdrawal are avoidable complications of pain and sedation

management that is well described in the literature.1-3 The reported occurrence of pediatric opioid

withdrawal ranges from 0-100%,4-9 with more recent literature citing 45-86%.9,10 Children are more at

risk of withdrawal when they have been exposed to opioids or benzodiazepines over an extended period

of time, and/or when they have received a significant amount of either or both agents depending on

institutional practice, which varies throughout the literature.11 To prevent withdrawal from occurring,

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 practitioners regularly employ a steady decrease of pain and sedation medications, also known as a
Accepted Article
weaning or tapering schedule. The weaning schedule is highly variable based on clinician preference and

usually dependent on the clinician. A change from an intravenous (IV) agent to an oral option may also

be a part of the weaning process. Some institutions have developed a standardized weaning plan to

decrease variation in prescribing among prescribers; however, variability in individual protocols and

patient response continue to be big confounders. 4,12-21

Children are not always able to verbalize their discomfort or pain. Some tools, like the Face, Legs,

Activity, Cry, Consolability (FLACC) scale, have been created and validated in children to assess

nonverbal pain.22-24 Practitioners use different, often nonverbal cues such as diarrhea, tremor, and fever

to appropriately determine if a child is experiencing withdrawal.11,25 Until recently, the only tool

available for withdrawal assessment in pediatric patients was the Finnegan Neonatal Abstinence Scoring

Tool (FNAST), but this tool was not specifically designed for older pediatric patients.26 The Opioid and

Benzodiazepine Withdrawal Score (OBWS) assessment tool was described in the literature but was not

further validated.21 Two newer withdrawal assessment tools include the Withdrawal Assessment Tool,

version 1 (WAT-1), and the Sophia Observation Withdrawal Symptoms–scale (SOS). The WAT-1 was

introduced in 2008 and validated in 2012 by Franck et al.11,25 Ista and colleagues introduced the SOS

scale in 2009, which was validated in 2013.27,28 Although similar, there are some key differences

between these two tools, including observation period (7 minutes for WAT-1 and 2 minutes for SOS) and

the exclusion of several neurologic symptoms from the SOS scale (e.g., high-pitched crying, sneezing,

yawning, hyperactive Moro reflex, seizures, frequent suctioning, and pupil dilation). To our knowledge,

no assessment tools have been identified and validated specifically for benzodiazepine withdrawal.

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 The purpose of this review is to evaluate the current available literature on the process of opioid and
Accepted Article
benzodiazepine weaning in pediatric patients and to assess the various standardized protocols used to

decrease withdrawal occurrences, as well as other key aspects of the weaning process.

Methods

We conducted a literature search of the PubMed, MEDLINE, Cochrane Library, Cumulative Index of

Nursing and Allied Health (CINAHL), Academic Search Premier, and PsycInfo databases. Search terms

used with each database were “opioid OR opiate OR benzodiazepine,” “wean OR taper," and "pediatric."

Abstracts were reviewed and assessed for inclusion or exclusion. Inclusion criteria were patients aged 18

years or younger and description of opioid/opiate or benzodiazepine weaning regardless of a formal

standardized protocol. Studies were also included if they focused on pediatric patients (mean age ≤18

yrs) but reported patients older than 18 years in their demographics as an outlier. Studies were excluded

if only neonatal abstinence syndrome or neonatal populations were evaluated; the intent of the study

was to wean off devices or medications other than opioids or benzodiazepines (e.g., cancer, epilepsy,

ventilation settings); no description of the weaning process was provided; alternative weaning agents

were studied (e.g., dexmedetomidine, clonidine) or described adverse events not specifically associated

with weaning (e.g., surgical complications); the study involved animals; or the study evaluated other

aspects of opioids or benzodiazepines that did not include a wean or taper. The study search process is

described in Figure 1.

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 Results
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Evaluated Studies

A total of 97 studies were retrieved from the database searches (72 from PubMed, 7 from the Cochrane

Library, and 18 from CINAHL/MEDLINE/Academic Search Premier/PsycInfo). Of these, 82 were excluded

according to the predefined exclusion criteria. The remaining 15 studies included both retrospective and

prospective studies, with one case report included due to the weaning description. A total of 567

patients ranging in age from 1 day to 18 years, spanning 16 years of practice (1998-2014) and 14 years

of publication (2000-2014) were evaluated in this review. A breakdown of the assessed studies,

including sample size and inclusion/exclusion criteria are provided in Table 1. Descriptions of the wean

protocols and withdrawal evaluation tools are shown in Table 2.

Withdrawal Assessment Tool Utilization

Withdrawal was assessed in all but two studies. Of those studies not evaluating withdrawal, one focused

on the actual protocol implementation looking at overall wean duration and need for sedation

medications at discharge,16 whereas the other described weaning practices at their institution but did

not account for withdrawal events.13

Withdrawal was assessed by a variety of assessment tools. Seven studies used a modified version of the

FNAST,4,12,15,18-20,31 whereas two studies used the WAT-113,14 and two used the OBWS.15,21 There were a

few instances of investigators utilizing other scoring tools that had not been controlled in terms of

consistency or validity. The studies published by Lugo et al.17 and Dominguez et al.8 used physician

clinical judgment, the latter for assessing benzodiazepine withdrawal. As there was no validated scoring

tool available to assess benzodiazepine withdrawal, this was likely the best option available to

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 investigators at the time, but consistency in prescribing was not controlled between attending
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physicians. Ducharme and colleagues used the behavioral distress score,6 which has been validated in

previous literature but is not commonly seen in practice and does not assess some known physical

symptoms of withdrawal in practice, such as diarrhea or sweating.29 One study did not report the

withdrawal assessment tool.30

Wean Protocol Summary

The studies included in this article evaluated several different approaches to wean a pediatric patient

from opioid and/or benzodiazepine agents. Eleven of the 15 studies described their standardized

weaning protocol, whereas the remaining four studies did not have a standardized protocol in place.

Overall, the reported weaning durations ranged from 2–40 days, with several weaning patients at a rate

of 10-20% per day. Berens, Meyer, and Robertson showed efficacy of initiating a 10-day wean, while

Berens and Robertson also compared the differences between 5-day and 10-day wean protocols.4,18,19

Kozin described a two-way wean protocol based on duration of infusion (7-14 days and >14 days).16 A

more aggressive benzodiazepine wean was described by Dominguez and colleagues, and called for a

50% dose decrease every 2 days over 6 days, corresponding to a ~18% daily decrease overall.8 Giby and

Jeffries reported the use of a dosing schedule for wean management, whereas Johnson stated that the

patient was referred to pharmacy services once criteria were met.13-15 All authors described their

respective wean plans as successful with infrequent withdrawal events. Table 2 lists the included wean

protocols and specific withdrawal rates for each study.

All providers in one study failed to follow its protocol appropriately, and the study reported a

withdrawal rate of 42%.14 Franck et al. reported nonadherence to their protocol in 73% of its patients,

and reported a withdrawal rate of 87%,21 the highest of any protocol-driven study. Those who were

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 more adherent to a standardized protocol had lower rates of withdrawal ranging from 5-22%. Studies
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that did not have a defined standardized protocol in place prior to the study reported higher withdrawal

rates ranging from 24-80%. Five studies failed to clearly define withdrawal, as this was not the focus of

their research; thus, their reported withdrawal rates may have been higher than anticipated.

Preferred Weaning Agents

Either IV or enteral methadone was used for weaning as the preferred opioid weaning agent in 10

studies, whereas four studies described using IV fentanyl, and one study used IV and enteral morphine.

Multiple opioid medication options for weaning were described in three articles, whereas five studies

allowed for multiple benzodiazepine agents. The benzodiazepine agents lorazepam, midazolam, and

diazepam were used in eight, six, and four studies, respectively. Clonazepam was also described in one

study.

Benzodiazepine Withdrawal

Only one study was identified that focused exclusively on benzodiazepine weaning.8 The investigators

found that 24% of patients experienced withdrawal symptoms associated with lorazepam weaning.

Unfortunately, this study did not have or use a standardized withdrawal assessment tool. Most studies

described weaning of benzodiazepine agents to some extent without any detail as to how they were

weaned, suggesting that this is more often a secondary consideration and not usually standardized.

Eight studies excluded patients receiving benzodiazepines,did not describe benzodiazepine use or

weaning, or mentioned concurrent use of benzodiazepines without further discussion on how the

medication was tapered.

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 Wean-At-Home Regimen
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The literature describing the benefits of continued weaning of opioids and benzodiazepines at home

after discharge is limited. Of the studies analyzed, only Meyer described a home wean, with 60% of their

patients being able to complete their methadone wean without difficulty.18 Kozin did not directly

address sedation weaning at home; however, their results did describe a significant decrease in

prescribing sedation medications for home wean completion, meaning that fewer sedation medications

were prescribed to complete the wean at home (81% in the nonprotocol arm vs 33% in the protocol

arm).16

Discussion

General Considerations

This review provides insight into the reported options and approaches to weaning a pediatric patient

from opioid and/or benzodiazepine agents. Multiple studies cited a 5-day or 10-day standardized wean

protocol for patients receiving continuous opioid infusions ≥5 days with decreased withdrawal events

compared to nonstandardized protocols. Most studies required patients to have received a continuous

infusion of either or both agents for at least 5 days to qualify for their wean protocol.

Standardized Wean Protocol Assessment

The results of the reviewed studies suggest that use of a standardized protocol results in a decreased

withdrawal rate compared with studies not using a standardized protocol. Further, protocol buy-in by all

members of the health care team is essential for success, as is adherence to the protocol. Two studies

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 demonstrated how lack of buy-in led to an increase in withdrawal events.14,21 The use of a standardized
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protocol demonstrated reduced exposure to analgesic and sedative medications, decreasing overall risk

and costs to the patient. Many of these studies approached weaning in a similar manner, with most

establishing a specific time frame for weaning therapy. Steineck and colleagues further identified

different risk categories according to the number of days of continuous infusion, ranging from low risk

to very high risk.20 The Institute for Healthcare Improvement (IHI) supports interprofessional

collaboration for reducing adverse events from pain and sedative agents and standardized protocol

development.32

There was variability in the utilization and type of assessment tool. Although the earlier studies used the

FNAST, there was considerable difference in the choice of assessment tool with the more recent studies.

Some of the more recent studies reflected on utilization of older assessment tools because the newer

tools, such as the WAT-1, were created and/or implemented at their facility during or after completion

of their study. Johnson et al. recommended using the WAT-1 over the OBWS for withdrawal assessment

due to its improved sensitivity.15

Additionally, there was a lack of identifying the extent of withdrawal occurrences in patients. Several

studies evaluated the number of withdrawal events globally, such as diarrhea or inconsolability, but did

not identify how many patients experienced a withdrawal event or how many withdrawal events each

patient experienced, in total or on average. This may have led to overreporting success and

underreporting consequences of the described weaning schedule or protocol. Future studies evaluating

characteristics of withdrawal should consider these points.

Evaluation of Withdrawal Assessment Tools

Variations in reported withdrawal rates may have been due to the utilized withdrawal assessment tools.

Many of the older studies utilized the FNAST, which was validated exclusively in the neonatal/infant

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 population and is not ideal for assessing older pediatric patients. Modified FNAST assessment tools may
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vary between institutions and do not allow for consistency outside the organization. The use of provider

clinical judgment in two studies does not control for variation between providers, and can over- or

underestimate the incidence of withdrawal. Two studies utilized the OBWS,15,21 whereas one used the

behavioral distress score (BDS).6 Use of the BDS is questionable for assessing withdrawal, as it does not

completely address neurologic or gastrointestinal events or other contributing factors known to reflect

withdrawal, such as diarrhea or dilated pupils. Its validation was performed in children who underwent

invasive medical procedures and did not evaluate adverse drug effects specifically.29

Ista E et al. evaluated the described withdrawal assessment tools for opioids and benzodiazepines and

found that four of the six utilized tools were validated in neonates only.33 The other two tools were the

Sedation Withdrawal Scale and the OBWS. Only the OBWS had the option of prospective validation, but

its low sensitivity did not make it an ideal option. Newer withdrawal assessment tools, such as the WAT-

1 and the SOS, assess the use of both opioids and benzodiazepines in patients for whom the FNAST

would be inappropriate. These tools have been validated in pediatric populations since their

introduction. Only two studies utilized the WAT-1 as their primary assessment tool. The SOS may be

more utilized in Europe where it was created and validated; however, we found no published literature

describing its use in our search.

Preferred Weaning Agents

Oral methadone was the preferred opioid weaning agent in the majority of evaluated studies, whereas

lorazepam, midazolam, and diazepam were used as benzodiazepine-weaning agents. Patients were

switched from IV opioid therapy to methadone, requiring dose adjustment calculations and

consideration for cross-sensitivity and interpatient variability. Despite the pharmacokinetic variance,

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 methadone remains a popular selection for weaning off IV opioid agents. An alternative option
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described in only one study was the use of oral morphine. Oral morphine is converted using a 2:1 or 3:1

ratio from IV morphine, depending on clinical practice, and does not require consideration for cross-

sensitivity or interpatient variability with a morphine IV to oral conversion.34

Benzodiazepine Weaning

There are very little data available to evaluate benzodiazepine withdrawal. Only one study specifically

evaluated weaning benzodiazepines, and it failed to identify risk factors for withdrawal.8 Of the other 14

studies included, only three did not identify benzodiazepine use. The remaining 11 studies did not

differentiate between opioid withdrawal and benzodiazepine withdrawal. This remains a complex

situation, as withdrawal identification may be tied to one or both agents.

In practice, patients are often receiving a continuous opioid infusion (e.g., morphine, fentanyl) for pain

concurrently with a continuous benzodiazepine infusion (e.g., midazolam, lorazepam) for sedation. Risks

to pediatric patients on long-term continuous benzodiazepine infusions, in addition to tolerance and

withdrawal, include propylene glycol toxicity (lorazepam, diazepam) and cognitive and developmental

problems, especially in children younger than 3 years.35-37 It may be reasonable to wean off sedation

medications more quickly than pain medications, in most cases with limited withdrawal events, as was

demonstrated by Dominguez and colleagues.8

Weaning at Home

The idea of weaning pain and sedation medications at home was first described by Tobias and

colleagues in 1994; however, its practice is still not commonplace.38 Some facilities require completion

of a wean in the hospital, whereas others allow for patients to complete the wean at home. Both

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 options are viable, although allowing for weaning at home can result in decreased health care costs and
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free up resources for more critically ill patients without compromising care. A study from the

Netherlands evaluated home weaning in neonates treated for congenital diaphragmatic hernia requiring

extracorporeal membrane oxygenation (ECMO).39 The investigators showed an overall decreased

hospital stay of 107 days and a cost savings of approximately €150,000 (approximately $156,000 US).

Several studies support the use of weaning opioid and sedative medications at home.2,38,40 Proper

teaching and education of the parents and child, if old enough, by pharmacists or other health care

providers could facilitate patient discharge while maintaining optimal care and reducing the risks of

treatment failure or possible overdosing of medication.

Development of a Standardized Protocol

Kozin and colleagues document an innovative approach using an IHI algorithm.16 The IHI has specific

recommendations for reducing adverse drug events with analgesic and sedative medications, although

these pertain primarily to initial management rather than tapering.32 However, the IHI

recommendations encourage collaborative involvement from all health care team members. By

delineating responsibilities for prescribers, nursing staff, and pharmacists, and obtaining agreement

from all members, the success of the project or protocol is increased. Pharmacists are a part of the

health care team, and are well suited for managing a wean protocol given their extensive knowledge on

pain and sedation medications.15,20

Limitations

This review does come with limitations. It is a review of the available literature published in pediatrics,

which is fairly sparse. However, it does contain a mixture of retrospective and prospective studies, as

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 well as a case report, thus providing some diversity. There are also differences in how facilities practice
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weaning of opioids and benzodiazepines. Hospitals may have different approaches to opioid withdrawal

and may or may not have a protocol or policy already in place. The time period over which the study

spans is lengthy, approximately 14 years. Within this time frame, there have been clinical advances in

how to manage weaning patients on opioid and benzodiazepine agents, including the introduction of

withdrawal assessment tools that provide a more thorough and comprehensive understanding of

withdrawal in pediatrics.

Supplemental weaning agents, such as propofol and clonidine, were not assessed. Although used

periodically in clinical practice, the pediatric literature discussing use of these agents is limited and was

not the focus of this review. Further research on these therapies is warranted.

Neonatal withdrawal was also excluded from this review, and therefore the FNAST or its use outside of

the studies reviewed was not assessed. There are numerous studies on neonatal withdrawal and the

FNAST that could and have been reviewed in previous literature.41-44 Finally, withdrawal was assessed

but not reported in three studies and was not assessed at all in two studies. By not reporting withdrawal

rates, the success of the weaning process in these studies may have been exaggerated.

Conclusion

To our knowledge, this is the first review article to assess both opioid and benzodiazepine weaning

practices in pediatrics. The implementation of a standardized weaning protocol would benefit patients

by appropriately reducing opioid and/or benzodiazepine exposure and prevent harm by avoiding

unnecessary prolonged exposure to these medications. Individual patient consideration must be given

for each case, and therapy must be adjusted according to patient response. Utilizing newer, validated

assessment tools may allow practitioners to better assess withdrawal and improve patient outcomes.

Allowing patients to complete their wean plan at home could allow for significant health care savings

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 without loss of care. Larger studies assessing the validity of weaning protocols would benefit our
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pediatric patients.

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375(25):2468-79.

42. Kaltenbach K, Jones HE. Neonatal abstinence syndrome: presentation and treatment

considerations. J Addict Med. 2016 Jul-Aug; 10(4):217-23.

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the mother and infant. Semin Perinatol. 2016 Apr; 40(3):203-12.

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 44. Wolff K, Perez-Montejano R. Opioid neonatal abstinence syndrome: controversies and
Accepted Article
implications for practice. Curr Drug Abuse Rev. 2014; 7(1):44-58.

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ccepted Article
Table 1. Study Designs and Inclusion/Exclusion Criteria of the Included Articles

Study authors Study design No. of Inclusion criteria Exclusion criteria

(year of evaluated
publication) patients
Berens R et.al. Prospective RCT 37 ≤18 yrs old, >120-hr continuous i.v. Neonates <36 wks’ gestational age; lack of
(2006)4 opioid infusion parental consent; acute CNS injury;
orotracheal, nasotracheal, or tracheostomy
tube; inability to transition
Bowens CD et al. Prospective, double- 78 Fentanyl infusion ≥5 days, tolerating Already receiving methadone or diazepam,
(2011)12 blind RCT enteral feeds, expected to be had a CNS injury, or allergic to study
extubated within 2-3 days of starting medication
the wean
Cho H et.al. Case report 1 NA NA
(2007)30
Dominguez KD et Prospective, 29 Admitted to PICU, receiving continuous Neurologic issue, ECMO, language barrier,
al. (2006)8 investigational, open- i.v. lorazepam for ≥72 hrs ward of the state, poor prognosis
label study (BZD only)
Ducharme C et al. Prospective multiple 27 Admitted to PICU, receiving continuous NA
(2005)6 case design QA project i.v. opioid ± BZD infusion
Fernandez-Carrion Retrospective cohort 48 Admitted to PICU, mechanically Received other sedative/opioid, received
F et al. (2013)31 study ventilated, receiving fentanyl and replacement drug for withdrawal
midazolam infusions ≥48 hrs prevention, deceased, moved to other
PICU, severe hemodynamic instability,
respiratory failure, serious neurologic
damage
Franck LS et al. Prospective, repeated 15 Received opioid ± benzodiazepine Significant neurologic insult (documented
(2004)21 measures study therapy for ≥5 days by EEG or head ultrasound), seizure
disorder
Giby K et al. Retrospective chart 30 ≤18 yrs old, continuous i.v. opioid Did not complete wean in hospital,
(2014)13 review infusion within 7 days of methadone, administration of opioids within 5 days of
received methadone for a minimum of last methadone dose
3 days, completed wean in hospital
Jeffries SA et al. Retrospective chart 43 ≤18 yrs old, >120-hr continuous i.v. Received methadone after continuous i.v.

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ccepted Article
(2012)14 review morphine infusion, started on
methadone in PICU
fentanyl or hydromorphone, received
methadone for Finnegan Neonatal
Abstinence Scoring Tool
Johnson MR et al. Prospective, single- 107 Patients who received methadone or Use of methadone or DTO for reason other
(2014)15 center interventional DTO in the NICU, PICU, or pediatric than withdrawal, in utero exposure to
evaluation ward, with exposure to opioids for ≥3 opioids + BZD, incomplete medical record,
days or in utero exposure unknown duration of wean
Kozin ED et al. Retrospective review of 29 Pediatric patients admitted for Lack of standardized wean document in
(2015)16 patient data laryngotracheal reconstruction, chart
qualified for wean
Lugo R et al. Retrospective chart 22 Pediatric patients who received Received previous course of fentanyl
17
(2001) review continuous fentanyl infusion for ≥9 and/or other opioid analgesic
days and received methadone
Meyer MT et al. Prospective, 29 Continuous fentanyl infusion, signs and Exposure to non-fentanyl opioid infusion,
18
(2001) observational study symptoms of withdrawal, extubation lack of parental consent,
from mechanical vent, enteral feeds
Robertson RC et al. Prospective, time 20 Continuous fentanyl/morphine infusion Methadone wean not completed, death, on
(2000)19 series study ≥7 days, receiving methadone, in PICU alternate agent used
Steineck K et al. Retrospective chart 52 Admitted to PICU, pediatric bone Admitted to NICU, no methadone use,
(2014)20 review marrow transplant unit, or pediatric death during taper, discharged during taper
medical/surgical unit; received
methadone for withdrawal
BZD = benzodiazepine; CNS = central nervous system; DTO = dilute tincture of opium; ECMO = extracorporeal membrane oxygenation; EEG =
electroencephalogram; OBWS = Opioid and Benzodiazepine Withdrawal Score; NA = not applicable; NICU = neonatal intensive care unit; PICU =
pediatric intensive care unit; QA = quality assurance; RCT = randomized controlled trial; WAT-1 = Withdrawal Assessment Tool, version 1.

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ccepted Article
Table 2. Descriptions of the Wean Protocols of the Included Articles

Study authors Standardized Wean protocol Opioid Benzodiazepine Withdrawal Withdrawal Withdrawal rates
(year of wean description weaning weaning agents evaluation assessed and
publication) protocol agents tool criteria used
Berens R et al. Yes 5 days (20% decrease per Enteral Lorazepam FNAST Yes; FNAST > 5-day protocol: 19%
(2006)4 day + 5 days of placebo) vs methadone 8x3 10-day protocol: 19%
10 days (10% per day) consecutive
scores
Bowens CD et Yes Low-dose (weight-based) Enteral Diazepam MNWS Yes; MNWS 22% (excessive
al. (2011)12 vs high-dose (weight- methadone (Modified >8 withdrawal)
based + fentanyl infusion FNAST)
rate–based dosing), both
over 10 days
Cho H et al. No 1% dose decrease per Fentanyl Midazolam, Not Yes 0%
(2007)30 hour up to 10% per day clonazepam described
Dominguez KD No 6 days (50% dose decrease Fentanyl, Lorazepam Physician Yes 24%
et al. (2006)8 every 2 days x 3 steps) methadone clinical
judgment
Ducharme C et No 3-20% dose decrease NA Midazolam Behavioral Yes Not measured
al. (2005)6 depending on length of distress
infusion score
Fernandez- No 2-21 days (median 8 days) Fentanyl Midazolam, FNAST Yes 50-80%
Carrion F et al. diazepam
(2012)31
Franck LS et al. No 20% dose decrease per Morphine, Lorazepam, OBWS Yes; OBWS 87%
(2004)21 day (5-14 days) or 10% fentanyl midazolam >8 x 3 scores
dose decrease per day
(>14 days)
Giby K et al. Yes 5-40 days (mean: 19.8 Enteral Lorazepam, WAT-1 Noa Not evaluated
(2014)13 days) methadone midazolam,
diazepam
Jeffries SA et Yes 5 days vs 10 days Enteral Not described WAT-1, State Yes; WAT-1 42%
al. (2012)14 methadone Behavioral score ≥3

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ccepted Article
Johnson MR et Yes 10-20% dose decrease per Enteral Lorazepam
Scale
FNAST (<6 Yes Not calculated
al. (2014)15 day depending on methadone months);
exposure OBWS (>6
months)
Kozin ED et al. Yes Short-term protocol: 7 NA NA NA No Not evaluated
(2015)16 days; long-term protocol:
11 days
Lugo R et al. Yes Methadone: start at 0.1 Enteral Lorazepam, Clinical Yes 5% (pre-methadone
(2001)17 mg/kg every 6 hrs; methadone diazepam judgment wean)
decrease to every 8 hrs x 2
days, every 12 hrs x 2
days, then 25% dose
decrease every 2-3 days
(~14 days)
Meyer MT et Yes 10 days (10% dose Enteral Lorazepam FNAST Yes; FNAST 11%
al. (2001)18 decrease per day) methadone >8 x 3
consecutive
scores; 4
patients
reported
withdrawal
Robertson RC Yes 5 days: 20% dose decrease i.v. Lorazepam, FNAST Yes 20% (protocol) vs
et al. (2000)19 daily; 10 days: 20% dose methadone midazolam (not 33% (nonprotocol)
decrease every other day on day 1; evaluated)
enteral
methadone
on day 2 and
onward
Steineck KJ et Yes Low risk (<5 days of opioid Enteral or Not described Modified Yes Not measured
al. (2014)20 infusion): 3-day wean i.v. FNAST
Moderate risk (5-9 days of methadone
opioid infusion): 14-day
wean

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ccepted Article High risk (≥10 days of
opioid infusion or
cumulative fentanyl dose
of 1500-2499 mcg/kg): 18-
day wean
Very high risk (≥28 days of
opioid infusion or
cumulative fentanyl dose
of ≥2500 mcg/kg): 24-day
wean
FNAST = Finnegan Neonatal Abstinence Scoring Tool; MNWS = Modified narcotic withdrawal scale; NA = not applicable; OBWS = opioid and
benzodiazepine withdrawal score; WAT-1 = Withdrawal Assessment Tool, version 1.
a
Since only 20% of patients had been assessed with WAT-1 when it was newly implemented at the study institution, withdrawal events were not
included in the analysis.

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Accepted Article

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